[{"title": "Analysis of Protein Purification (Part II).txt", "text": "Another procedure, gel filtration Chromatography, in which we separate the proteins based on size."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And so following that, we extract that sample, we place it into this weld, and this is the band that we get."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And so this band disappears, other bands disappeared."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So what that means is we're slowly purifying the protein where we're moving those unwanted proteins as shown by padded increase in the band distribution number."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So that is what should be shown by this table."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So let's calculate this box."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "In this box, as always, the specific activity is 85,000 divided by 100."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "The two zeros cancel out and we have 850 divided by one and that gives us 850."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Now, what about this quantity?"}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So to calculate this, we simply take this divided by that."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So the specific activity of that mixture divided by the original mixture and we get 85."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So because this divided by this gives us 85."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And let's use purple for that."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Okay?"}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So what that means is this extracted mixture, following these processes up to this point is 85 times as pure as this initial mixture."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And finally, let's carry out the final one."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So in the final step, in step E, we take our extracted mixture of proteins and we expose it to affinity Chromatography."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And in affinity Chromatography, we separate our proteins based on their specific ability to bind to these special molecules."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And this usually creates a very high specific activity value because as we know, enzymes only bind to specific substrate to specific molecules."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So let's see if that's true by taking the extracted mixture and placing it into our last well."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So what we produce is a band distribution that only contains a single band."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And what that usually means is we have isolated that protein of interest because this band consists of a protein that has a specific type of mass, a specific type of size."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Now let's owe and by the way, let's calculate what the yield in this case was."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "To calculate the yield, we follow this equation."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So this divided by this gives us 85 divided by 200, which is 42.5 divided by 100 multiplied by 100, that gives us a percent of 42.5."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Okay?"}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So let's go back to this step."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So this basically means that we have successfully isolated that protein."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "We basically have this protein that consists of a single type of mass."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Now let's see that the specific activity increases and this increases."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And let's make sure that the yield didn't decrease by too much."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So if we have at least 30% here, that is a good procedure."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So let's take a look at E to calculate this."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "We take this divided by two and we get 35,000."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So we see that in fact, this procedure has a high specific activity."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And that makes sense because affinity Chromatography separates these enzymes based on their ability to bind to specific enzymes."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And so in our mixture, when we run our mixture proteins along that column of that affinity chromatography setup, only the protein that we want to study will bind to our beads inside that column, the other proteins will essentially go down because enzymes only bind to specific types of proteins."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And so that's why this is such a high value, because usually affinity chromatography separates by a very, very large margin."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Now, what about the purification level?"}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So this divided by this gives us 3500."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And what that means is, after all the procedures that we conducted, the final extracted mixture is 3500 times as pure as that initial sample, and that is a high amount."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "Now, for this set of procedures to actually be good, this yield has to be a high enough yield."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So let's see what that yield is."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So we take 70,000 divided by 200,000."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "That gives us 70 divided by 200 or 35 divided by 100."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "We multiply that ratio by 100 and we get 35%."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And this is a high enough yield."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So 35% is enough to basically mean we can work with that extracted sample, the protein, to basically study that protein in different ways."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So these are the five quantities that we have to calculate every time we carry out one of these procedures."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And then we also normally expose our extracted portion to SDS page to basically help us visualize if our technique is actually working."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And if we combine these two methods, that gives us a very good idea if the purification technique is working."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So normally, as we go from A to E, the number of bands should decrease."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And what that means is we're getting rid of those unwanted proteins and we're focusing in on that protein that we actually want to study."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And that is confirmed by these measurements because as we purify the sample, the specific activity has to increase and so should our purification level."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "And we also have to keep track of the yield."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "We don't want our yield to drop to a very small amount."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "For example, if following our procedure, this yield would have been, let's say 5%, then this procedure would not have been efficient because at the end, even though we would have had a high purification value, that yield is not enough."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "5% would not have been enough to basically create a mixture protein that is actually usable and workable in a laboratory setting."}, {"title": "Analysis of Protein Purification (Part II).txt", "text": "So whenever we're purifying proteins, we have to make sure that the purification level is high and that yield is high enough for us to actually work with that final purified mixture of protein."}, {"title": "RNA Polymerase .txt", "text": "Although DNA molecules contain the genetic information that is needed to build proteins the DNA molecules themselves are not used directly in protein synthesis."}, {"title": "RNA Polymerase .txt", "text": "And that's because we want to actually prevent damage to the DNA molecules."}, {"title": "RNA Polymerase .txt", "text": "And so what we do is in a process known as transcription we synthesize RNA molecules from DNA molecules."}, {"title": "RNA Polymerase .txt", "text": "And what these RNA molecules are they're copies of specific segments of the DNA molecule and these segments usually contain important genes."}, {"title": "RNA Polymerase .txt", "text": "So before we can synthesize proteins RNA molecules must be synthesized from DNA molecules in a process known as transcription."}, {"title": "RNA Polymerase .txt", "text": "And just like the process of DNA replication involves this protein known as DNA polymerase that catalyzes the formation of a phosphodiastor bond in the process of transcription."}, {"title": "RNA Polymerase .txt", "text": "When we form the RNA from the DNA there is a molecule, a protein known as RNA polymerase that catalyzes the formation of the phosphodia Esther Bond."}, {"title": "RNA Polymerase .txt", "text": "So RNA polymerase catalyzes the initiation and the elongation of that RNA polynucleotide chain."}, {"title": "RNA Polymerase .txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "RNA Polymerase .txt", "text": "So in the diagram in this chemical equation we basically describe how this reaction takes place and what RNA polymerase does."}, {"title": "RNA Polymerase .txt", "text": "So let's suppose we have an RNA chain and we're extending that RNA chain."}, {"title": "RNA Polymerase .txt", "text": "So we're building our RNA molecule."}, {"title": "RNA Polymerase .txt", "text": "Now, so far in our RNA molecule we have N number of nucleotides."}, {"title": "RNA Polymerase .txt", "text": "And let's suppose we want to add one more nucleotide."}, {"title": "RNA Polymerase .txt", "text": "We want to add one more ribonucleotide triphosphate."}, {"title": "RNA Polymerase .txt", "text": "Now, what RNA polymerase does and we'll discuss this in much more detail in just a moment what RNA polymerase does is it essentially attaches the ribonucleocide triphosphate onto the RNA molecule to form an RNA molecule that is extended by one nucleotide."}, {"title": "RNA Polymerase .txt", "text": "So here we have N number of ribonucleotide triphosphates but here we have N plus one."}, {"title": "RNA Polymerase .txt", "text": "And in the process we build this phosphodiastor bond between the ribonucleotide triphosphate and the RNA chain and we release a single pyrophosphate molecule."}, {"title": "RNA Polymerase .txt", "text": "So PP stands for a Pyrophosphate and in fact it's the breakdown of the Pyrophosphate that drives this transcription reaction forward as we'll discuss in much more detail when we'll discuss the process of transcription."}, {"title": "RNA Polymerase .txt", "text": "So this is the general equation that describes RNA polymerase."}, {"title": "RNA Polymerase .txt", "text": "Now, to actually work, what does RNA polymerase actually need?"}, {"title": "RNA Polymerase .txt", "text": "Well, it needs three different things."}, {"title": "RNA Polymerase .txt", "text": "It basically means the building blocks, the ribonucleotide triphosphates and there are four different types."}, {"title": "RNA Polymerase .txt", "text": "So we have adenosine five triphosphate we have guanosine five triphosphate we have citadine five prime triphosphate and we have uridine five prime triphosphate."}, {"title": "RNA Polymerase .txt", "text": "And these building blocks are needed to actually synthesize and elongate that polynucleotide chain."}, {"title": "RNA Polymerase .txt", "text": "Now, number two, it actually needs a preexisting DNA template molecule."}, {"title": "RNA Polymerase .txt", "text": "So usually we're dealing with a double stranded DNA molecule and a double stranded DNA molecule works the best."}, {"title": "RNA Polymerase .txt", "text": "But in some cases we can also use single stranded DNA molecules as templates."}, {"title": "RNA Polymerase .txt", "text": "Now, why do we need a template molecule?"}, {"title": "RNA Polymerase .txt", "text": "Well, we need the DNA template to basically copy that genetic information."}, {"title": "RNA Polymerase .txt", "text": "And it's the template, that DNA template that is used to basically bring those complementary bases to that elongated polynucleotide chain."}, {"title": "RNA Polymerase .txt", "text": "So although single stranded DNA molecules work, double stranded DNA molecules are more effective and more common as templates."}, {"title": "RNA Polymerase .txt", "text": "So RNA polymerase uses this DNA template to basically build a polynucleotide chain that contains complementary bases as we'll see in just a moment."}, {"title": "RNA Polymerase .txt", "text": "And finally, inside the RNA polymerase molecule at the center there is a pocket that can fit a divalent metal atom."}, {"title": "RNA Polymerase .txt", "text": "Now, what is a divalent metal atom?"}, {"title": "RNA Polymerase .txt", "text": "Well, it's a metal atom that can gain a positive charge, a charge of positive two."}, {"title": "RNA Polymerase .txt", "text": "So he can lose two electrons and gain a positive charge of two."}, {"title": "RNA Polymerase .txt", "text": "And two types of atoms that work in this particular case are magnesium so, Mg and Manganese MN."}, {"title": "RNA Polymerase .txt", "text": "And the reason we need this metal atom is because it acts as a cofactor, it increases the efficiency of this enzymes activity."}, {"title": "RNA Polymerase .txt", "text": "Now let's take a look at the following diagram that basically describes in detail how that bond is formed."}, {"title": "RNA Polymerase .txt", "text": "And notice this phosphodiasta bond is formed in a very similar way to how the phosphodiesta bond is formed when DNA polymerase replicates that DNA molecule."}, {"title": "RNA Polymerase .txt", "text": "So in this particular case, this is our DNA template that the RNA polymerase molecule is actually using."}, {"title": "RNA Polymerase .txt", "text": "So this is the three end and this is the five end."}, {"title": "RNA Polymerase .txt", "text": "Now, what our RNA polymerase does is it binds onto that DNA molecule and it reads the DNA template from the three to the five end and that means it builds it from the five to three end."}, {"title": "RNA Polymerase .txt", "text": "So this is the RNA chain that the RNA polymerase already built."}, {"title": "RNA Polymerase .txt", "text": "So let's imagine that inside this chain we have N number of nucleotides and this is the N plus one nucleotide that is being added onto that growing RNA chain."}, {"title": "RNA Polymerase .txt", "text": "So what the RNA polymerase does is it essentially hovers around this section and it brings that complementary ribonucleocide triphosphate which is complementary to this base that is found on the DNA template."}, {"title": "RNA Polymerase .txt", "text": "Now, how do we know when it's complementary?"}, {"title": "RNA Polymerase .txt", "text": "Well, basically when the bonding is just perfect, this molecule will stay in this location for long enough for this bond to actually take place."}, {"title": "RNA Polymerase .txt", "text": "So it will stay long enough for the bond to form."}, {"title": "RNA Polymerase .txt", "text": "And the way that the bond forms is so we can label these carbon atoms as carbon atom one, carbon atom two, carbon atom three, carbon atom four, and carbon atom five on this sugar molecule."}, {"title": "RNA Polymerase .txt", "text": "And we have the three prime hydroxyl group acts as a nucleophile and attacks this innermost phosphorus atom of this incoming nucleuside triphosphate."}, {"title": "RNA Polymerase .txt", "text": "And it forms a covalent bond between the oxygen and this phosphorus."}, {"title": "RNA Polymerase .txt", "text": "Now eventually this H atom is removed and this Pyrophosphate molecule is kicked off."}, {"title": "RNA Polymerase .txt", "text": "And so in the process when we form the phosphodieester bond and we form this polynucleotide chain, we essentially release a single pyrophosphate molecule and as we'll see in a future lecture the hydrolysis of the pyrophosphate molecule essentially drives this reaction forward."}, {"title": "RNA Polymerase .txt", "text": "So RNA polymerase catalyzes the formation of phosphodiasta bond."}, {"title": "RNA Polymerase .txt", "text": "It brings the complementary nucleotide triphosphate this nucleotide that is complementary to this base into the mixture and then our RNA polymerase holds this in place and it catalyzes the formation of this bond as shown in the following diagram and the pyrophosphate is released as a result."}, {"title": "RNA Polymerase .txt", "text": "Now, as I mentioned before the RNA polymerase reads the DNA template from the three to five end but it synthesizes that polynucleotide chain in the five to three end and this is the same exact method that DNA polymerase uses."}, {"title": "RNA Polymerase .txt", "text": "Remember, DNA polymerase also reads that DNA template from the three to five end and it synthesizes that DNA molecule from the five to three in the same way that RNA polymerase does."}, {"title": "RNA Polymerase .txt", "text": "Now, the difference between RNA polymerase and DNA polymerase is in RNA polymerase."}, {"title": "RNA Polymerase .txt", "text": "Notice we do not need a primer sequence to actually initiate the process."}, {"title": "RNA Polymerase .txt", "text": "So in DNA polymerase we said that DNA polymerase requires that primer sequence but RNA polymerase does not."}, {"title": "RNA Polymerase .txt", "text": "Now, unlike DNA polymerase which has the endonuclease activity has the ability to essentially correct the mistakes it makes."}, {"title": "RNA Polymerase .txt", "text": "RNA polymerase cannot correct the mistakes it makes."}, {"title": "RNA Polymerase .txt", "text": "So if it incorrectly pairs up two bases it will not be able to correct that mistake."}, {"title": "RNA Polymerase .txt", "text": "And that means RNA polymerase makes many more mistakes as compared to DNA polymerase which makes less mistakes."}, {"title": "RNA Polymerase .txt", "text": "So this is the RNA polymerase molecule that essentially is involved in forming that RNA molecule during the process of transcription when we essentially copied the code found in the DNA and form these RNA molecules."}, {"title": "RNA Polymerase .txt", "text": "For example transfer RNA molecules, messenger RNA molecules and ribosomal RNA molecules."}, {"title": "RNA Polymerase .txt", "text": "Now, the last thing I'd like to mention is in E. Coli cells so in prokaryotic cells, for example, bacterial cells a single RNA polymerase forms all the different types of RNA molecules the mRNA tRNA and RNA."}, {"title": "RNA Polymerase .txt", "text": "But in our own cells, in the human cells we have three different we have three different RNA polymerases as we'll discuss in a future lecture."}, {"title": "RNA Polymerase .txt", "text": "And each one of these RNA polymerases actually synthesizes a specific type of RNA molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "Carbon atoms."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So 1234."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So two of those carbon atoms basically came from these this acetyl coenzyme A molecule and the other two came from this acetyl coenzyme A molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "Now, what happens next?"}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "Because ultimately we said that fatty acid synthase can generate a 16 carbon fatty acid molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So what happens next is is this cycle basically takes place six more times."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "And when it takes place six more times, it generates a 16 carbon palmitate a 16 carbon palmitate fatty acid molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So quickly, let's talk about how that actually takes place."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So in the next step, once we generate this, what will happen is this entire group here, this four carbon group will be moved onto this cysteine in the same way that we move this group onto this holding 16 molecules shown here."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So in the next step, we're going to use another Malcolm coenzyme A to attach it onto the ACP that now does not contain this."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "And now we're going to continue via these steps."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "We have a condensation reduction dehydration and a second reduction step."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "And now we'll generate a six carbon intermediate and this will take place five more times until we generate that 16 carbon palmatoil intermediate molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "And once we generate that palmatoil intermediate molecule, an enzyme known as Thio esterase will cleave that bond that will release that 16 carbon palmitate fatty acid molecule."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "And that pretty much completes that fatty acid elongation step."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So these are the steps involved in synthesizing fatty acid molecules."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "Again, the first elongation step involves steps one through step seven."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "But then these steps from two and onward have to take place six more times to actually help is generate that 16 carbon fatty acid molecule that does not contain any double bond."}, {"title": "Fatty Acid Synthesis Part II .txt", "text": "So it's a fully saturated 16 carbon fatty acid molecule."}, {"title": "Gap Junctions.txt", "text": "So far in our discussion on on channels, we focused on two types of on channels."}, {"title": "Gap Junctions.txt", "text": "We discussed voltage gated on channels and ligand gated on channels."}, {"title": "Gap Junctions.txt", "text": "Now, we move on to a slightly different category, vine channels we call gap junctions."}, {"title": "Gap Junctions.txt", "text": "Now, gap junctions are also known as cell to cell channels, and we'll see why in just a moment."}, {"title": "Gap Junctions.txt", "text": "Now, although gap junctions are in fact on channels, they have very different properties from the properties of voltage gated and ligand gated on channels."}, {"title": "Gap Junctions.txt", "text": "And there are five important things that differentiate gap junctions from voltage gated and ligand gated on channels."}, {"title": "Gap Junctions.txt", "text": "So let's begin by comparing and contrasting these different types of on channels."}, {"title": "Gap Junctions.txt", "text": "So voltage gated channels and ligand gated channels are actually closed when that membrane is the rest, and they're only open when that membrane is excited by some type of stimulus."}, {"title": "Gap Junctions.txt", "text": "Now, when they do open, they're only open for a very short period of time, about a milliseconds or so, and then they're quickly closed off or they're inactivated."}, {"title": "Gap Junctions.txt", "text": "And the size of the pore inside these channels is actually very small."}, {"title": "Gap Junctions.txt", "text": "And that's why only small inorganic ions can pass across."}, {"title": "Gap Junctions.txt", "text": "And finally, these ion channels are usually very specific to the type of ions they allow across that membrane."}, {"title": "Gap Junctions.txt", "text": "Now, what about gap junctions?"}, {"title": "Gap Junctions.txt", "text": "Well, unlike voltage gated and ligand gate on channels, these gap junctions actually have relatively large pore sizes, so the diameter is about 20 angstroms."}, {"title": "Gap Junctions.txt", "text": "On top of that, they also allowed the movement of not only inorganic ions, so ions like calcium, sodium, potassium, chloride ions across that particular channel, but they also allow the movement of organic substances such as glucose molecules, amino acids, as well as nucleotides."}, {"title": "Gap Junctions.txt", "text": "So we see, unlike the voltage gated and ligangate on channels, which are usually specific and can only move these inorganic ions, gap junctions are non specific."}, {"title": "Gap Junctions.txt", "text": "They allow any molecule to move across or any ion to move across, as long as it's not too large."}, {"title": "Gap Junctions.txt", "text": "So large substances such as proteins and polynucleotides and polysaccharides, these molecules cannot pass across gap junctions."}, {"title": "Gap Junctions.txt", "text": "Now, unlike these voltage gated and ligand gate on channels, which are only open for about a millisecond before being closed or inactivated, these gap junctions can be open anywhere from seconds to minutes."}, {"title": "Gap Junctions.txt", "text": "Now, voltage gated and ligand gate on channels connect the cytoplasm of a cell to the outside extracellular environment."}, {"title": "Gap Junctions.txt", "text": "But we see that these gap junctions actually connect two adjacent cells."}, {"title": "Gap Junctions.txt", "text": "And more specific, they transverse the membrane of these two adjacent cells and they connect the cytoplasm of one cell to the cytoplasm of that contiguous adjacent cell."}, {"title": "Gap Junctions.txt", "text": "So gap junctions transverse two membranes of contiguous cells."}, {"title": "Gap Junctions.txt", "text": "That simply means the cells are very close in proximity, closely packed to one another, and they connect the cytoplasm of one cell to the cytoplasm of the adjacent cell."}, {"title": "Gap Junctions.txt", "text": "And this can be seen in the following diagram."}, {"title": "Gap Junctions.txt", "text": "So this entire structure that transverses the membrane of one cell and the membrane of the adjacent cell, and also transverses this into cellular space."}, {"title": "Gap Junctions.txt", "text": "This is a single gap junction."}, {"title": "Gap Junctions.txt", "text": "So this is the cytoplasm of one cell and this is the cytoplasm of that adjacent cell."}, {"title": "Gap Junctions.txt", "text": "And the length of this gap junction is about 35 angstroms."}, {"title": "Gap Junctions.txt", "text": "And the final aspect, the final difference between the voltage gated and ligan gate channels and the gap junctions is that these iron channels are produced by single type of cell, but gap junctions are actually produced by two cells."}, {"title": "Gap Junctions.txt", "text": "And we'll see why in just a moment."}, {"title": "Gap Junctions.txt", "text": "So let's move on to actually discuss what the structure of this gap junction is."}, {"title": "Gap Junctions.txt", "text": "So notice we have these two individual structures which are connected end to end inside that intercellular space."}, {"title": "Gap Junctions.txt", "text": "So each of these structures is known as a hemichannel or a connection."}, {"title": "Gap Junctions.txt", "text": "And we see that a single gap junction consists of these two hemichannels, also known as connections that are connected end to end to basically form this single gap junction."}, {"title": "Gap Junctions.txt", "text": "Now, if we examine each one of these hemichannels, each one of these hemichannels actually consist of six individual polypeptide chains we call connections."}, {"title": "Gap Junctions.txt", "text": "And these connections are basically formed to form a hexamer, which basically means we have six individual units within that hemichannel."}, {"title": "Gap Junctions.txt", "text": "Now, cell number one produces hemichannel number one, and cell number two produces hemichannel number two, and then they connect them to form that gap junction."}, {"title": "Gap Junctions.txt", "text": "And so that's the final difference between these voltage gated and ligandgate on channels and gap junctions."}, {"title": "Gap Junctions.txt", "text": "Now, what exactly?"}, {"title": "Gap Junctions.txt", "text": "Well, actually, before we examine the functionality of these gap junctions, let's discuss how these gap junctions are actually regulated by ourselves."}, {"title": "Gap Junctions.txt", "text": "Because just like voltage gated and ligan gate on channels have to be regulated for the proper functionality of the cells, these gap junctions too have to be regulated."}, {"title": "Gap Junctions.txt", "text": "And there are four methods by which we can actually close off these gap junctions."}, {"title": "Gap Junctions.txt", "text": "So we can close off these gap junctions by either increasing the concentration of the calcium, increasing the concentration of the h plus ions."}, {"title": "Gap Junctions.txt", "text": "So the same thing as saying lowering the PH number three is there are special hormones that can basically induce the process of phosphorylation of these gap junctions."}, {"title": "Gap Junctions.txt", "text": "And that too can close off the gap junction."}, {"title": "Gap Junctions.txt", "text": "And number four is in some cases, changing the voltage difference can also actually close off these gap junctions."}, {"title": "Gap Junctions.txt", "text": "Now, why would we want to actually close off a gap junction?"}, {"title": "Gap Junctions.txt", "text": "Well, let's suppose we have two cells which are connected by these gap junctions, and one of the cells is damaged in some way and ends up dying."}, {"title": "Gap Junctions.txt", "text": "So to basically prevent a second nearby healthy cell from being damaged, that dying cell will want to close off these gap junctions."}, {"title": "Gap Junctions.txt", "text": "And that's exactly where these different processes come into play to close off that gap junction."}, {"title": "Gap Junctions.txt", "text": "Now, finally, let's move on to the functionality of gap junction."}, {"title": "Gap Junctions.txt", "text": "So there are three important functions that we're going to take a look at function number one, intercellular communication."}, {"title": "Gap Junctions.txt", "text": "Function number two, cell nourishment."}, {"title": "Gap Junctions.txt", "text": "And function number three, embryological development."}, {"title": "Gap Junctions.txt", "text": "So let's focus on function number one, intercellular communication."}, {"title": "Gap Junctions.txt", "text": "This simply means communication between adjacent cells."}, {"title": "Gap Junctions.txt", "text": "So let's take a look at example number one."}, {"title": "Gap Junctions.txt", "text": "Let's take a look at our heart."}, {"title": "Gap Junctions.txt", "text": "So in our heart, we have these specialized muscle cells we call cardiac myocides, or simply cardiac muscle cells."}, {"title": "Gap Junctions.txt", "text": "And these cardiac muscle cells are closely packed, so they are contiguous in nature."}, {"title": "Gap Junctions.txt", "text": "And because of that, many of these cardiac muscle cells are connected by these gap junctions."}, {"title": "Gap Junctions.txt", "text": "So what's the function of these gap junctions?"}, {"title": "Gap Junctions.txt", "text": "Well, basically, when one cell receives an action potential as a result of these gap junctions, the action potential can actually propagate into nearby cardiac myosytes."}, {"title": "Gap Junctions.txt", "text": "And what that does is it allows the creation of a continuous and a forceful contraction of the entire heart."}, {"title": "Gap Junctions.txt", "text": "And that allows the heart to pump all the blood throughout the cardiovascular system."}, {"title": "Gap Junctions.txt", "text": "Now, another example of these intercellular communications via gap junctions is in the muscle cells of the uterus."}, {"title": "Gap Junctions.txt", "text": "So if a woman is about to give birth, so that uterus must contract."}, {"title": "Gap Junctions.txt", "text": "And it's these gap junctions that allows the contraction of that uterus muscle."}, {"title": "Gap Junctions.txt", "text": "Now, another area that uses gap junctions to basically communicate between nearby cells is inside the brain."}, {"title": "Gap Junctions.txt", "text": "So inside the brain, certain types of nerve cells don't actually use neurotransmitters to send action potential from one cell to another."}, {"title": "Gap Junctions.txt", "text": "Instead of using your transmitters, they actually use gap junctions."}, {"title": "Gap Junctions.txt", "text": "So on the presynaptic cell and the post synaptic cell, they're connected by these gap junctions."}, {"title": "Gap Junctions.txt", "text": "And that allows the quick movement of the action potential from one cell, the presynaptic neuron, to the other cell that postsynaptic neuron."}, {"title": "Gap Junctions.txt", "text": "Now let's move on to function number two, cell nourishment."}, {"title": "Gap Junctions.txt", "text": "So every single cell in our body needs things like glucose, amino, amino acids, nucleotides, to actually survive and function correctly."}, {"title": "Gap Junctions.txt", "text": "Now, not all of these cells actually are found next to capillaries."}, {"title": "Gap Junctions.txt", "text": "And that means not all cells in our body can actually directly obtain the nutrients they need from the body."}, {"title": "Gap Junctions.txt", "text": "And that's where these gap, from the capillaries and that's where these gap junctions actually come into play."}, {"title": "Gap Junctions.txt", "text": "Certain cells which are found far away from capillaries to cells in our bone and cells in our eye, for instance, basically depend on gap junctions to receive the proper nutrients such as glucose and nucleotides and amino acids in order to actually survive and function correctly."}, {"title": "Gap Junctions.txt", "text": "And the final function is embryological development."}, {"title": "Gap Junctions.txt", "text": "So things like differentiation and setting up the polarity of cells basically depends on the presence of gap junctions."}, {"title": "Gap Junctions.txt", "text": "And if we block the function of gap junctions, that embryo will not be able to develop into that adult individual."}, {"title": "Gap Junctions.txt", "text": "And so we see that these gap junctions, although they are a category of on channels, they're very different than the voltage gated and ligand gated on channels that we focused on previously."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So let's summarize the process of glycogenesis."}, {"title": "Overview of Gluconeogenesis .txt", "text": "glycogenesis is the synthesis of glycogen molecules from glucose precursors."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So let's suppose we just ingested a meal that is rich in sugar molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so what that means is inside our blood plasma there will be an increase in the glucose levels."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, our liver is responsible for maintaining the proper glucose levels of our of blood."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so what the liver cells do is they begin to uptake some of that glucose into the cytoplasm of that cell."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once the glucose is inside the cell, the liver cell will want to trap that glucose inside the cell and prevent it from actually escaping back into the blood plasma."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so what the liver cells actually do is they phosphorylate the glucose on the 6th position and they use an enzyme known as hexacinase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So hexaginase takes a phosphoryl group from ATP and places it onto carbon six of glucose and that creates glucose six phosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once glucose actually once glucose six phosphate is created, glucose phosphate then undergoes a reaction in which there is a transfer of the phosphoryl group from the six position to the first position of that glucose and we form glucose one phosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, the enzyme that catalyze this step is known as phosphorglucomutase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And what this enzyme does is the following."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Inside the active side of this enzyme is a phosphorylated serine residue."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And that phosphoryl group on that serene residue is initially placed onto carbon one."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And what that generates is an intermediate molecule known as glucose one six bisphosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "In the second step that is not shown here, this blue phosphoryl group is transferred back onto that Serene residue and that regenerates the catalytic enzyme, the phosphoglucomutase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And it also generates the final product, glucose one phosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so this phosphoryl group that's attached onto carbon one of the glucose ultimately comes from this enzyme and the enzyme picks up this phosphoryl group shown in blue."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we form glucose one phosphate, in the next step, the glucose one phosphate needs to be activated because by itself, glucose one phosphate cannot simply be added onto the growing glycogen chain because it's not active enough."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we have to make it much more reactive and higher in energy."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And what we do is we essentially attach a phosphoryl group as well as a uridine molecule onto this section to form the UDP glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So that takes place in this step three."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we take the glucose one phosphate shown here and then we basically reacted with a urine triphosphate in the presence of the enzyme known as UDP glucose pyrophosphorylase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And what this enzyme basically does is it attaches the phosphoryl group and the urine onto this region."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we generate the following molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So this entire purple region came from the urine triphosphate and the pyrophosphate, the remaining Pyrophosphate was essentially kicked off."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So this is the Pyrophosphate that was kicked off from the urine triphosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And the remaining portion of that urine triphosphate basically was attached onto this molecule to form the uriidine diphosphate UDP glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, the purpose of this was to create this high energy bond that is very reactive because as we'll see in just a moment, this is able to actually undergo the reaction which we attach it onto that growing glycogen chain."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, the pyrophosphate that is formed in the presence of water, which is basically found in the cytoplasma baristalis, will undergo a hydrolysis reaction in which this bond will be cleaved and will form two orthophosphate molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, this is the reaction that actually drives the formation of UDP glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "It's because of this reaction, because this is continually being depleted, that this reaction actually takes place in the product favor direction."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So this is an important reaction because it ensures that we continually produce the UDP glucose molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we produce the UDP glucose molecules, the next step is to basically generate a primer molecule."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So remember that a primer molecule is basically a short sequence of glucose nucleotides which are connected by alpha one four glycocytic bonds."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So why do we need a primer molecule?"}, {"title": "Overview of Gluconeogenesis .txt", "text": "Because the enzyme that elongates that glycogen chain, known as glycogen synthase, needs a primer to actually initiate that elongation process."}, {"title": "Overview of Gluconeogenesis .txt", "text": "It simply cannot begin from scratch."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And the enzyme that generates that primer is known as glycogenin."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So it is not shown in the diagram, but basically an enzyme known as glycogenin creates this primer."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so this is the primer that we have here."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So let's say this primer consists of N number of glucose molecules which are all connected by alpha one four glycocitic bonds."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we have not yet created any branching points."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so this is a linear unbranched polymer."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So in the next step, once we generate that primer by using the UDP glucose molecules and the enzyme we call glycogenin."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, glycogen synthase takes the primer and takes the UDP glucose shown here and basically catalyze the formation of that alpha one four glycocytic bond between this glucose here and the terminal glucose molecule of this primer."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And we basically form and extend it."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we extend that primer by one and we also form the UDP, which is basically shown here."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So UDP is urine diphosphate, it contains the uridine and two phosphate groups."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And we're going to use the UDP in the last step, as we'll see in just a moment."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we form that glycogen, that linear unbranched glycogen, we want to actually begin branching that glycogen."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Because remember, branching actually increases the solubility of glycogen within the cytoplasm and it also increases the number of terminal positions on the glycogen."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And that in turn increases the rate by which we can break down and synthesize glycogen molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So in the next step, step six, we have an enzyme we call the glycogen branching enzyme that basically catalyzes the cleavage of alpha one four glycocitic bond and the formation of Alpha one six glycocitic bond."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So let's suppose we have the following hypothetical glycogen molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So let's suppose this molecule here is this molecule that we have right over here."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So what the glycogen branching enzyme does is it basically takes a region of seven glucose residues that contain a terminal position shown here."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we have 123-4567."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So it cleaves the alpha one four glycocytic bond and then it forms an alpha one six glycocity bond."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so we create this branching point."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And notice, as we discussed in a previous lecture, this section has to have at least eleven glucose residues."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we have 1234-5678, 910, eleven."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So this is how glycogen is actually branched."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And once we undergo this entire process, for this process to actually continue taking place, we have to regenerate the UTP molecules, the urine triphosphate that we use up in this particular step, because glycogen will essentially stop taking place if we don't have enough UTP, because we need the UTP to actually generate the UDP glucose, the active form of glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so in the final step, what our cells actually do is they use an ATP molecule, transfer the phosphoral group from ATP onto the UDP that we basically formed in this step here."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we take the UDP, we take an ATP and we transfer that phosphorus loop onto this to basically reform the UTP that now can be used in this step to continually produce the UDP glucose molecules needed to generate that glycogen."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And the enzyme that catalyzed this step is nucleocide difosphokinase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So in this final step, an ATP is used to phosphorylate a UDP and that regenerates that UTP."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So once again, let's very briefly overview this entire process."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we ingest a meal that is rich in sugar molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "The blood level of glucose basically increases."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Our liver wants to maintain that and decrease it back to normal."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So the liver cells uptake the glucose molecules to trap the glucose within the cell and to prevent it from leaving the cell, they use hexacionase and an ATP to form glucose six phosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Next, the glucose six phosphate is transformed into glucose one phosphate by the activity of phosphor glucom Utase."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we form the glucose one phosphate, we want to activate the molecule, make it much more reactive and increase its energy."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so what we do is we use UDP glucose pyrophosphorylase to basically transfer a group from UTP onto the glucose one phosphate and that kicks off a Pyrophosphate, as shown in this diagram."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So we generate the UDP glucose and the Pyrophosphate."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now this reaction isn't really product favored."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And to make it product favored to drive the formation of UDP glucose, the Pyrophosphate is cleaved by water into two orthophosphate molecules."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So Pyrophosphate is hydrolyzed into two orthophosphates and this drives the formation of UDP glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we have a bunch of these UDP glucose molecules, the enzyme we call glycogenin, not shown in this diagram, basically uses the UDP glucose molecules to generate a primer, a short sequence of glucose molecules that are linked by alpha one four glycocitic bonds."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Because glycogen synthase needs that primer to begin the elongation process, to begin extending that glycogen."}, {"title": "Overview of Gluconeogenesis .txt", "text": "So now we take the UDP glucose."}, {"title": "Overview of Gluconeogenesis .txt", "text": "In the presence of the primer, the enzyme glycogen synthase basically increases or attaches this glucose onto that primer."}, {"title": "Overview of Gluconeogenesis .txt", "text": "In the process, we form a UDP molecule."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Now, once we continually add these glucose molecules, eventually we want to actually branch that glycogen."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so that's where step six takes place."}, {"title": "Overview of Gluconeogenesis .txt", "text": "Glycogen branching enzyme is responsible for creating those alpha one six linkages which lead to the branching points."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And for this process to actually continually taking place, we have to take the UDP that we form here and regenerate back that UTP."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And that's where step seven comes into play."}, {"title": "Overview of Gluconeogenesis .txt", "text": "The enzyme nucleotide di nucleoside diphosphokinase uses an ATP to attach it onto the UDP here, and that forms that UTP."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so once we reject generate the supply of UTP, this process can continue taking place."}, {"title": "Overview of Gluconeogenesis .txt", "text": "And so as long as we're forming the UTP glucose molecules, we can continually build that glycogen and extend that glycogen polymer."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So once we amplify a gene of interest, once we produce many identical copies of a single gene, what exactly do we do next?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Well, usually the next process is to take that gene and produce a restriction map for that particular gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now what exactly is a restriction map?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Well, let's suppose that we have the following ruler and this ruler describes as our gene of interest that we amplify."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So this is the double stranded DNA molecule that describes the interest, that describes the gene that we're studying."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So what a restriction map is?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "It's basically a description of all the different locations found on this gene where our restriction enzymes can bind to and cleave that gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So for example, let's suppose this gene has three different restriction sites."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So here, here and here."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And what that means is a type of restriction enzyme can bind onto these three locations and cleave that particular gene and those locations."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So that's what we mean by a restriction map."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now what exactly is the procedure in creating the restriction map?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Well, the restriction map basically involves or creating the restriction map involves a process known as gel electrophoresis."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And this will be the focus of this lecture."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So we're going to focus on the process of gel electrophoresis that is used in the creation of the restriction map for any particular gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So let's suppose we look at diagram A."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "In diagram A, we have the following gene shown in black."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So this is our gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Let's suppose we expose this gene, this gene here, to a specific type of restriction enzyme we're going to call enzyme number one."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now what happens is once we expose the gene to this restriction enzyme, the restriction enzyme cuts or cleaves this gene at two different locations."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So at this location, somewhere here, and in this location somewhere here."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So at the end, once we expose this gene to this enzyme, we get three different DNA fragments."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So we have DNA fragment one, DNA fragment two, and DNA fragment three."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And these fragments all came from this entire gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now once we obtain these fragments, we now expose the fragments to the process of gel electrophoresis."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And what this process does is it ultimately separates these three DNA fragments that came from the gene based on their physical size."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So what exactly is gelatrophresis?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Well, it's basically the process by which we take our fragments."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "We place them into a special type of porous gel and then we allow those fragments to move through the porous of the gel as a result of an electric field that exists within that gel."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So we take the apparatus, we connect the apparatus to a voltage source and that creates an electric potential difference, a voltage difference between the two sides of that electrophoresis setup."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And so what happens is, because we connected to our battery source, one end of that plate will have a negative charge."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So that will be the count node and the other end will have a positive charge that will be the anode."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now remember, DNA contains a negative charge as a result of all those phosphate groups."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And so all these DNA fragments that came from the gene will contain negative charge and they will move from the calcio, the negatively charged side, to the anode, the positively charged side."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So all these fragments will move along the same direction, but they will move at different speeds."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And that's because if we examine the gel inside this setup, that gel is basically a special type of polymer that contains many different pores."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And these pores basically contain a certain size to them."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And so the larger DNA fragments, the larger molecules will find it more difficult to move along these pores, while the smaller fragments will find it easier to move along and through these pores because of their smaller physical size and smaller physical weight."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So in gel electrophoresis, different fragments are separated on the basis of physical size."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "The larger molecules are not able to move as quickly as the smaller ones through the pores of that gel."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now, since DNA fragments are all negatively charged, they all move along the same direction."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "They always move from the cathode, the negatively charged side, to the anode, the positively charged side."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And this voltage difference is created because this entire structure is connected to a battery source."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So this is what gel electrophoresis is."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So the way that we create the restriction map is by exposing this initial gene to many different types of restriction enzymes."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "For example, in case A, we expose the gene to restriction enzyme number one."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And we form three different fragments, as shown, that have these different sizes."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now, in case B, we take that same initial gene, but now we expose it to a different restriction enzyme which cuts at different locations along that gene."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So now, instead of producing these three fragments, we only produce two fragments because this gene only contains one side, one location where this restriction enzyme number two can actually act on."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So now we produce fragment four and fragment five."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And once again, we expose these two fragments."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "We place these two fragments into our gel and now we have the separation based on size."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And we can compare this diagram to this diagram and we can use the information obtained to basically create a restriction map."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So if we examine the following diagram right over here, we see that for this particular case, this fragment is this fragment here."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And notice it is closest to the anode because it is the smallest."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And it is able to move the farthest along and through the porous of the gel."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "This fragment is basically fragment two."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "This fragment is fragment three."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now, what about this case?"}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Well, notice that fragment three is almost the same size as fragment four."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And so these two will correspond to the same exact position, horizontal position, along the following diagram."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now, this is the largest fragment of these five fragments."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "And so it will be found highest farthest up along the following plate."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So we have the largest fragment."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "These two fragments are about the same size."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Then the next fragment and the smallest fragment, fragment number one."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So let's take a marker and let's label these just so we know."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So this is fragment number one, fragment number two, fragment number three, fragment number four and fragment number five."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "So this is what gel electrophoresis is."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "Now, when we're, we'll get into biochemistry, we're going to see that we can use gel electrophoresis not only for DNA molecules, but we can also use for proteins."}, {"title": "Restriction Map and Gel Electrophoresis.txt", "text": "We can basically separate our proteins by their physical size using the same exact process of gel electrophoresis."}, {"title": "Southern and Northern Blotting.txt", "text": "Previously we discussed restriction enzymes and we said we can use these restriction enzymes to cut our DNA molecule into smaller fragments known as restriction fragments."}, {"title": "Southern and Northern Blotting.txt", "text": "Now, once we have these DNA restriction fragments we can basically study these fragments, we can analyze them, we can manipulate them, we can amplify them, make many copies and we can do all sorts of different things with these DNA fragments."}, {"title": "Southern and Northern Blotting.txt", "text": "Now let's suppose we take the DNA molecule, we expose it to our restriction enzymes and we create these many DNA fragments."}, {"title": "Southern and Northern Blotting.txt", "text": "And let's say that one of these fragments contains a specific gene that we want to study."}, {"title": "Southern and Northern Blotting.txt", "text": "The question is how do we identify that specific fragment that is carrying the gene and how do we isolate and separate that fragment to basically study it further?"}, {"title": "Southern and Northern Blotting.txt", "text": "Well, we have to carry out a process known as southern Blotting."}, {"title": "Southern and Northern Blotting.txt", "text": "In southern Blotting we essentially use gel electrophoresis as we'll see in just a moment to basically identify and isolate a specific DNA fragment of interest."}, {"title": "Southern and Northern Blotting.txt", "text": "So let's begin with step number one."}, {"title": "Southern and Northern Blotting.txt", "text": "So we take our double stranded DNA molecule that contains the gene that we want to study."}, {"title": "Southern and Northern Blotting.txt", "text": "Now we know what the sequence of nucleotides within that gene is before we actually carry out that process and we'll see why that's important in step three."}, {"title": "Southern and Northern Blotting.txt", "text": "So we take the DNA, the double stranded DNA molecule, we expose it to specific restriction enzymes so that when they clean that DNA molecule one of these fragments will carry that gene of interest."}, {"title": "Southern and Northern Blotting.txt", "text": "So let's suppose we break it down into five different fragments and these fragments differ in their size."}, {"title": "Southern and Northern Blotting.txt", "text": "So we have the largest fragment of fragment A, we have the smallest fragment of fragment E and the fragment in between these fragments in terms of their size is fragment C. And that's the fragment, let's say, that contains the gene that we want to actually study."}, {"title": "Southern and Northern Blotting.txt", "text": "So fragment C is that DNA fragment, that restriction fragment that we actually want to identify and then separate."}, {"title": "Southern and Northern Blotting.txt", "text": "So let's move on to step two."}, {"title": "Southern and Northern Blotting.txt", "text": "So we take these fragments, we essentially place them into a solution that denatures the double helix structure."}, {"title": "Southern and Northern Blotting.txt", "text": "And so now in our solution we have these single stranded individual DNA molecules and now we take them and place them into a gel electrophoresis seven."}, {"title": "Southern and Northern Blotting.txt", "text": "Now, if the DNA molecule isn't too large we can use the polyacrylamide gel."}, {"title": "Southern and Northern Blotting.txt", "text": "But if the DNA molecule is very large then we have to use a gel that has larger pore size."}, {"title": "Southern and Northern Blotting.txt", "text": "So we normally use anguarose gel."}, {"title": "Southern and Northern Blotting.txt", "text": "So these are the two gels that we can basically use and the one that we use determines or which one we use is determined by the size of that initial DNA molecule."}, {"title": "Southern and Northern Blotting.txt", "text": "Now, so we take our fragments and we place them into the gel electrofreeze setup."}, {"title": "Southern and Northern Blotting.txt", "text": "And now the gel electrophoresis basically separates the DNA fragments based on size."}, {"title": "Southern and Northern Blotting.txt", "text": "So the largest fragments, fragment A, will be all the way at the top because it will experience the greatest resistance, while the smallest fragment, fragment e, will be found all the way at the bottom because it does not experience a large resistive force."}, {"title": "Southern and Northern Blotting.txt", "text": "And once we separate the five fragments based on size, we can then basically transfer that result onto a special polymer sheet that we can use more effectively."}, {"title": "Southern and Northern Blotting.txt", "text": "And usually we use the nitrocellulose polymer sheet."}, {"title": "Southern and Northern Blotting.txt", "text": "Now, once again, it's important to know that within these regions, these are no longer in their double stranded form, they exist as single stranded DNA molecules."}, {"title": "Southern and Northern Blotting.txt", "text": "And that leads us directly into step three."}, {"title": "Southern and Northern Blotting.txt", "text": "So in step two, we essentially separated these fragments based on size."}, {"title": "Southern and Northern Blotting.txt", "text": "The next question is how do we identify which one of these bands contains that gene of interest?"}, {"title": "Southern and Northern Blotting.txt", "text": "So remember in the beginning I said that we have to know what that sequence of nucleotides is in that gene that we want to isolate."}, {"title": "Southern and Northern Blotting.txt", "text": "And so what we do in step three is we build a DNA molecule, a DNA probe that contains a complementary nucleotide sequence that is complementary to that DNA fragment, the gene that we want to isolate found in fragment C. And when we build it, we radioactively label that DNA probe."}, {"title": "Southern and Northern Blotting.txt", "text": "For example, we use radioactively heavy phosphorus atoms."}, {"title": "Southern and Northern Blotting.txt", "text": "And what that will allow us to do is in step four, we're going to be able to use x ray autorediography to basically find exactly where that DNA molecule is."}, {"title": "Southern and Northern Blotting.txt", "text": "So in step three, a specific restriction fragment of interest."}, {"title": "Southern and Northern Blotting.txt", "text": "So this seed can be detected by creating and adding a radioactively labeled complementary DNA strand to that polymer sheet."}, {"title": "Southern and Northern Blotting.txt", "text": "Since it is complementary to the gene of interest, it will hybridize with the fragment of interest."}, {"title": "Southern and Northern Blotting.txt", "text": "So it will basically form a double stranded, form a double stranded helix."}, {"title": "Southern and Northern Blotting.txt", "text": "So, to see exactly what we mean, let's take a look at the following diagram."}, {"title": "Southern and Northern Blotting.txt", "text": "So in this diagram, it is before we added that DNA probe."}, {"title": "Southern and Northern Blotting.txt", "text": "And so if we zoom in on this band, band C, we basically get this double stranded DNA molecule has been denatured."}, {"title": "Southern and Northern Blotting.txt", "text": "And so these two individual single strands exist as single strands."}, {"title": "Southern and Northern Blotting.txt", "text": "Now, when we add that DNA probe that has been radioactively labeled by, let's say, a heavy phosphorous atom, so what will happen is, because the sequence is complementary to this sequence here, the green radioactively labeled DNA probe will hybridize, will form a double helix structure with that single stranded complementary molecule."}, {"title": "Southern and Northern Blotting.txt", "text": "And so now this has been radioactively labeled."}, {"title": "Southern and Northern Blotting.txt", "text": "And notice this DNA probe will not form the same double helix with any of these other bands because the other bands don't have that complementary sequence."}, {"title": "Southern and Northern Blotting.txt", "text": "So this molecule is a single stranded DNA fragment of interest that we want to actually detect."}, {"title": "Southern and Northern Blotting.txt", "text": "And the green molecule is that radioactively labeled DNA probe that contains a nucleotide sequence that is complementary to that restriction fragment above that we essentially want to detect."}, {"title": "Southern and Northern Blotting.txt", "text": "And once we carry out step three, then we can use the process of order radiography and that will allow us to pinpoint exactly where that fragment is."}, {"title": "Southern and Northern Blotting.txt", "text": "And now we know if we go back to this setup, that this band C contains those fragments that we want to isolate."}, {"title": "Southern and Northern Blotting.txt", "text": "And so we can take out the fragments, remove the other unwanted fragments, and now we have a pure solution that contains only the fragment, only that gene that we were actually interested in the first place."}, {"title": "Southern and Northern Blotting.txt", "text": "So this process by which we can actually pinpoint, detect and then isolate that DNA fragment of interest by using our DNA probe is known as southern blotting."}, {"title": "Southern and Northern Blotting.txt", "text": "But we also can repeat the same exact process with RNA molecule."}, {"title": "Southern and Northern Blotting.txt", "text": "So if we have an RNA molecule that we actually want to isolate, we can use an RNA probe or radioactively RNA probe in the same exact process."}, {"title": "Southern and Northern Blotting.txt", "text": "But if we're dealing with RNA, the process is known as north and blotting."}, {"title": "Southern and Northern Blotting.txt", "text": "So in the same analogous way, we can conduct the same steps to separate and locate RNA fragments."}, {"title": "Southern and Northern Blotting.txt", "text": "But instead of using the DNA probe, we use a radioactively labeled RNA probe in this process is known as north and Blotting."}, {"title": "Southern and Northern Blotting.txt", "text": "So in southern blotting we essentially pinpoint, we detect and separate DNA fragments."}, {"title": "Southern and Northern Blotting.txt", "text": "In northern blotting, we detect and separate RNA fragments and in western blotting we basically detect and isolate our protein fragments as we discussed in our lecture on purifying proteins via western blotting process."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Inside our body, we have many different types of exergonic and endergonic reactions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, we know to basically calculate, to determine whether reaction is actually exergonic or endergonic, we have to calculate what the gibsfree energy is of that reaction because ultimately it's the gift's free energy value that tells us whether reaction is spontaneous or non spontaneous."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, the mathematical equation that allows us to actually calculate the magnitude of Gibbs free energy is this equation here."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So the gibsfree energy of that particular reaction under those conditions is equal to the Gibbs free energy under standard conditions when the concentration of products and reactants is equal to one molar plus this entire quantity."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So 2.33 times r t log q, where r is simply the gas constant, t is the temperature in Kelvin and q is the reaction quotient."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And that tells us the ratio of the concentration of products to the reactants."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, what exactly is the meaning of delta g?"}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Well, delta g tells us the amount of free energy that is produced or used up when a chemical reaction takes place under certain conditions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So if a chemical reaction takes place and it releases gets free energy, that reaction will have a negative delta g value."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And such a reaction is said to be spontaneous exergonic."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And so this reaction releases useful energy that can be used to power other processes and reactions inside our cells and inside our body."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, if the delta g is positive, what that means is that particular reaction will be endergonic, non spontaneous, and a positive delta g means we have to input energy for that reaction to actually take place."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And in fact, inside our body, we can use exergonic reactions to produce energy and then that energy can be used to carry out undergonic reactions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, what about when the delta g is zero?"}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Well, when the delta g is zero, that means our reaction has achieved equilibrium and this q value will become a k, the equilibrium constant."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, what about the delta g with this degree symbol?"}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "What's the meaning of this quantity?"}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Well, this describes the free energy value of the reaction under specific conditions called standard state conditions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And this describes conditions when the concentration of the reactors and products is equal to one molar."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, to see what we mean by that, let's take a look at the following graph."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So this energy graph basically contains the y axis, that's the Gibbs free energy."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And the x axis is the reaction progress."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And in this particular example, I used this chemical reaction."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So formic acid associates into the conjugate base and produces the H plus ion."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, let's suppose the concentration of this is one molar, and the concentration of these two products is also one molar."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So when this is the case, we see that when 1 mol of formic acid at a concentration of one molar transforms into 1 mol of conjugate base and 1 mol of H plus ion."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Which are also at a concentration of one molar."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Then we see the Delta G between the product and the reactants is given by 21.3 kilojoules or 21,300 Joules of energy."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, because the energy, the free energy of the products is higher than the free energy of the reactants, that means this reaction is andergonic."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And so we need to input 21.3 kilojoules of energy to actually drive this reaction in the forward direction."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So this reaction, as described here understanding conditions, is andergonic it's non spontaneous, it's reactant favorite."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And this is in accordance with the fact that formic acid is a weak acid and will not associate to a very large extent."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, just because the Delta G degree symbol the Delta G under standard state conditions is positive for these conditions, does not mean the Delta G will be positive under some other conditions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "In fact, by changing the Q value, by changing the concentrations of the reactants and products, we can ultimately transform this endergonic reaction into an exergonic reaction."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And this is a very important concept because it is continually used inside our body."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Our body changes the concentrations of energonic reactions to basically transform them into exergonic reactions."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, if we look at the following equation, this equation tells us exactly that."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So what the equation tells us is if this quantity is positive, then this doesn't necessarily have to be positive."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "If this is positive, but this entire term is more negative than this is positive as a result of this Q value, then a positive quantity plus a negative value that is greater than this in magnitude will give us a Delta G that is negative."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And it's this Delta G, it's the sign of this Delta G, not this one, that ultimately dictates whether reaction is actually product favored or reactant favored."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And to see what we mean by that, let's carry out the following calculation."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So, in this particular case, we know that Delta G standard state condition is equal to 21.3 kilojoules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, the question is what exactly should the Q value be for this Delta G to actually be negative and for our reaction to be spontaneous product favorite."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And the way that we're going to solve this problem is by basically using some type of negative value for this Delta G. So let's suppose Delta G is any negative value for, so let's suppose it's negative five kilojoules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So this quantity is negative five kilojoules and this quantity is positive 21.3 kilojoules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, because the gas constant R is given to us in Joules, so 8.3 114 Joules per kelvin times mole, let's transform these quantities into Joules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So this quantity is equivalent to 21,300 Joules and that's a positive value."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "While this quantity, we said just a moment ago we're going to use negative five kilojoules, or equivalently negative 5000 Joules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, the goal is to ultimately calculate what the Q value has to be, what the ratio of the concentrations of the products to the reactants has to be for the reaction to actually be product favored, for this to be negative 5000 on negative value."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, notice we could have also used negative five joules or negative 1 million joules."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Basically any negative value here works because any negative value means this reaction will be spontaneous under that Q situation, under that concentration of products and reactants."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So if we take this equation now and solve for a log of Q, we get that log of Q is equal to so this term is brought to this side."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So it's this minus this on the top."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And then we divide by this quantity."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So 2.33."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Then the gas constant is 8.3 114 joules per mole times Kelvin."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And the temperature we're going to assume is, let's say 25 degrees Celsius, so equivalently 298 Kelvins."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, if we solve for Q, we get that Q is equal to ten to the power of this ratio."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now this divided by this gives us negative 4.61."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And so if we carry out this calculation, raised ten to the power of negative 4.61, we get about 2.45 times ten to negative five."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "Now, what this means is when the Q value, when this quantity, when the ratio of the concentration of the product and the reactants is equal to 0.245, the reaction, this reaction here will actually be exergonic, it will be spontaneous and it will be product favored."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So what we basically show is even though this reaction is undergodonic under standard conditions, when the concentrations of these are equal, if we change the concentrations around, we can actually transform that endergonic non spontaneous reaction into an exergonic spontaneous reaction, as can be seen in the following example where we use the delta g on negative quantity."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "So ultimately it's the delta g that determines whether our reaction under those concentration conditions and that temperature value is actually spontaneous or not."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "This doesn't necessarily have to be negative or positive."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "It doesn't matter what this is."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "It ultimately matters that this is a negative value to actually dictate spontaneity."}, {"title": "Gibbs Free Energy and Spontaneity.txt", "text": "And this concept is important because in our body, our body can change the concentrations and therefore transform these energonic reactions into exergonic spontaneous reactions, as we'll see when we discuss processes such as the crept cycle, glycolysis and so forth."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Within the developing fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "The organ that is involved in exchanging gas between the mother and the fetus is called the placenta."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, the placenta has other functions as well, but in this lecture we're going to focus primarily on its function in gas exchange."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So let's begin by actually looking at the structure of our placenta."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So this is a diagram of the placement placenta."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So we have the umbilical cord shown here that contains two types of blood vessels."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "We have the umbilical vein shown in red and we have umbilical arteries shown in blue."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the umbilical arteries carry deoxygenated blood that contains carbon dioxide from the organs and tissues of that fetus and to the placenta itself."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And it carries them to these Corianic villi, these extensions of the Coriane known as the corionic villi."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And within the Corianic villi, we have the tiny blood capillaries that belong to the circulatory system of that fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, these entire Corianic villi are found inside a pool of maternal blood."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And that pool of maternal blood essentially oozes out of these maternal blood vessels that are found in close proximity."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So remember, when the placenta was actually developed, the Corian released these digestive enzymes that digested tiny holes inside these maternal blood vessels."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And those holes essentially allow the blood to actually leak out."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the way that the exchange takes place is within the maternal blood."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Within the pool of maternal blood we have oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And oxygen moves down its concentration gradient from the pool of blood and into the capillaries of that fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "At the same time, carbon dioxide is deposited out of the capillaries of that fetus and into the pool of blood and eventually picked up by the maternal blood veins."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And that carries the carbon dioxide to the lungs of that mother and the lungs expel the carbon dioxide to the rest of that environment."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "At the same time, when the lungs inhale, they bring in oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And that oxygen is ultimately brought into this pooling area of that maternal blood."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, when the oxygen is picked up, it is picked up by these blood vessels."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And then the blood vessels connect to the umbilical vein and umbilical vein."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "This blood vessel, shown in red, actually carries the oxygenated and nutrient filled blood to the organs, tissues and structures found within that developing fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So this is how gas exchange actually takes place."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, the question we want to ask in this lecture is what exactly makes the placenta effective and efficient in actually exchanging that oxygen and what allows it to exchange that oxygen, carbon dioxide, in the right direction."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So remember, we want the placenta not only to exchange the gases quickly and efficiently, but we also want to exchange the gasses in the right direction."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So we must make sure that oxygen always travels into that fetus and carbon dioxide is always removed from that fetus and moves into the blood capillaries and the blood system of the mother."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So there are three factors that affect the efficiency of that placenta, and one of them is the type of hemoglobin molecule that is found inside the blood of that fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So recall that oxygen is actually a nonpolar molecule."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And what that means is it cannot readily dissolve in the blood plasma."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so it requires a special type of protein carrier to carry it from point A to point B."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And this type of protein is known as hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, the type of hemoglobin molecule found inside adults is different than the type of hemoglobin that is found inside the fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Before we actually see why this is the case, let's discuss what the difference is between the adult and the fetal hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So, in adults, we know that the hemoglobin consists of four subunits."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Two of these subunits are alpha subunits, and the other two subunits are beta subunits."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So we have alpha one and alpha two that combines with beta one and beta two to form a protein tetrimer that we call the dull hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So this is what it looks like."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "We have alpha one, alpha two shown in green, and we have beta one and beta two shown in orange."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, when we form the adult hemoglobin, the adult hemoglobin actually contains a cavity inside a space that is capable of binding a molecule called two three BPG."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, what exactly is two three BPG?"}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Well, two three BPG is a molecule that is a byproduct of cellular respiration."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So when cell respiration takes place inside the cells of the adult individual, they produce two three BPG."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And two three BPG can actually bind into that cavity into the space that is found in the adult hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, as soon as the binding takes place, when the two three BPG binds into that space inside the adult hemoglobin, it creates a change in the structure of the adult hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And what that does is it decreases the adult hemoglobin's ability to actually bind to oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "It lowers its affinity for oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So when the binding takes place, that adult hemoglobin is much less likely to actually bind oxygen and carry oxygen from point A to point B."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, what about the fetal hemoglobin?"}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Well, just like the delt hemoglobin, the fetal hemoglobin also consists of four subunits."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "It contains alpha one and alpha two, as shown in the following diagram."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "But it doesn't contain beta one and beta two."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Instead, it contains a slightly different two subunits gamma one and gamma two."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And when these four subunits create the tetrimer fetal hemoglobin, notice we no longer have that space inside the hemoglobin that can accommodate the two three BPG."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so, unlike the Dull hemoglobin, the fetal hemoglobin in the presence of two three BPG does not actually bind to two three BPG."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And what that means is if we compare the affinity of these two hemoglobin molecules in the presence of the same concentration of two three BPG, we see that because the fetal hemoglobin doesn't actually bind the two, three BPG, that means its affinity for oxygen will be much higher than the affinity for oxygen of adult hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And if we plot this curve on the x y axis, where the x axis is the partial pressure of oxygen given in millimeters of mercury, and the y axis is the percent saturation of that hemoglobin, we get the following curve."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the blue curve is the curve that describes the adult hemoglobin, while the red curve describes the fetal hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And notice at the same partial pressure, let's say at 40 degrees partial pressure of oxygen, the adult hemoglobin has much less saturation than the fetal hemoglobin does."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And that's because a fetal hemoglobin does not actually bind to two, three BPG."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so it is much more likely to actually attract other oxygen molecules and bind to those oxygen molecules."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So we see that the maternal red blood cells have hemoglobin, the adult hemoglobin that binds oxygen much less readily than the fetal red blood cells that contain the fetal hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And as a result, the oxygen will be much more likely to actually move from the blood of that mother and into the blood of that fetus that contains that fetal hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, aside from this, there are two other factors that also facilitate the function of the placenta, facilitate the gas exchange process."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the movement of oxygen from the mother to the fetus can be facilitated by three factors."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So one of them is higher affinity of fetal hemoglobin for oxygen than the adult hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "The other is the fact that inside the blood of the mother, we have a higher concentration of oxygen than inside these capillaries of that fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so because of this difference in concentration, because the concentration of oxygen is naturally higher inside the blood of that mother than inside the blood of that fetus, oxygen will tend to basically move down its concentration gradient, down its pressure gradient from the mother and to that fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the final fact that that facilitates the diffusion of oxygen across our placenta is something called the double bore effect."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So let's recall what a bore effect is."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So, the bore effect is basically the ability of carbon dioxide to affect the affinity of hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the more carbon dioxide we have in the blood, the less likely that hemoglobin will actually bind onto that oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And conversely, the less CO2 we have in the blood, the more likely our oxygen, our hemoglobin, will actually bind to oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So what exactly do we mean by double bore effect?"}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Well, let's take a look at the following diagram to see what the double bore effect is."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So, let's suppose that this purple line is basically our placental membrane."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And our gas exchange takes place across the placental membrane, which is basically this coryonic membrane shown right here in purple."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So this is the side of the mother."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "This is the side of the fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So what happens is carbon dioxide moves down its concentration gradient from this side from the fetus's side to the mother's side."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, as it moves this way, what happens is the concentration of the carbon, the oxide, begins to increase within the side of the mother."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And by increasing the CO2 concentration, that makes the hemoglobin much more likely to actually release the oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And once oxygen is released, we have the bore effect."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So that is the bore effect."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So as a result of the release of carbon dioxide onto the mother's side we have the bore effect take place on the mother's side."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "The carbon dioxide affects the affinity of hemoglobin, decreases its affinity for hemoglobin, decreases hemoglobin's affinity for oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Oxygen is released, and then it moves into the side of our fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, at the same time that carbon dioxide concentration on the mother's side is increasing the carbon dioxide on the fetus side is decreasing in concentration because this is moving this way."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Now, when we decrease the concentration of carbon dioxide that means less of the CO2 can actually affect that hemoglobin on the side of the fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so we also see a bore effect taking place on this side."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So less CO2 means more of that hemoglobin will be able to buy to more of that oxygen that is coming in."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so this is the double bore effect that takes place not only on the mother's side but also on the side of the fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So these three factors actually facilitate the exchange of gases inside our placenta."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So we have the the ability of that fetal hemoglobin to actually bind to oxygen much more readily than the adult hemoglobin."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "That is factor number one."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "Factor number two is the fact that inside the mother we have a higher amount of oxygen than inside the fetus."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so it moves down its concentration and pressure gradient from the mother's side to the fetus side."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And finally, we also have the double bore effect."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "So the fact that carbon dioxide is being pumped is being expelled into the blood of that mother causes the hemoglobin inside this mother's area to basically decrease its affinity for oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And because of that, more oxygen is expelled, is released, and then the oxygen moves into the capillaries of the Corianic villi."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And as the concentration of carbon dioxide decreases within the capillaries of that fetus we have less CO2 that can affect hemoglobin's ability to bind to oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And so because we have less CO2 we have more of that fetal hemoglobin that will be able to bind to oxygen."}, {"title": "Gas Exchange in Placenta, Fetal Hemoglobin and Double Bohr Effect .txt", "text": "And this is called the double bore effect."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "In the cells of our body."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "We have many different types of biological processes that are catalyzed by enzymes."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And what these enzymes do is they speed up the rates of these biological reactions."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now, because enzymes affect the rates, to actually understand how enzymes work, we have to understand the rates of these enzymecatalyzed reactions."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And in fact, enzyme kinetics is the study of the rates of these enzyme catalyzed reactions that take place inside our body."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now, in the next lecture we're going to begin our study of enzyme kinetics."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But in this lecture we're going to remember some basic information about how to actually represent and express the rates of chemical reactions."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "We're going to remember what the rate law is and what the rate constant is and how enzymes affect these two quantities."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And we're also going to remember what the order of reaction is."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So let's begin with the following hypothetical chemical reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "We have reactants A and B that are being consumed and C and D, the products are being formed."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now because we have a one to one to one to 1 mol ratio, because the coefficients are one to one to one to one and because these are being consumed and these are being produced at the same time these are being consumed."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "These four equations basically describe the rates of these individual reactants."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So as the reaction is progressing from the reactant side to the product side, a is being consumed."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And that's why the rate of A is negative and the rate of A is simply given by the change in the concentration of A with respect to some time interval and likewise B is also being consumed."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So the rate of B is negative and it's given by delta the change in concentration of B with respect to the time and likewise over the same time interval."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "These are the rates of C and D. So the rate of C is the change in C with respect to T and the rate of D is change in D with respect to T. Now, these equations aren't very useful."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "What we actually want to be able to express is the entire rate of that entire equation as a whole."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And this is where the rate law and the rate constant comes into play."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "The rate law basically uses the rate constant as well as the concentrations of reactants to basically express mathematically what the rate of that chemical reaction is as a whole."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So let's suppose we have the following elementary reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So what do we mean by an elementary reaction?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Well, recall from general chemistry, an elementary reaction is a reaction that takes place in a single step."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And the important thing about elementary reactions that you have to remember is in any elementary reaction we can use the coefficient of that reactant to basically determine what the order of that reactant is within that rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So we can use the coefficient in front of the reactant to basically tell us what the exponent value is of that particular reactant in that rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So the rate law of the above elementary chemical reaction is usually described by using the rate law and the rate will depends on the rate constant k and usually depends on the concentration of the reactants."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So in this lecture we're only going to look at elementary reactions."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But you have to remember that if we're dealing with a multistep complicated reaction, then we cannot simply use the coefficients."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "In that case, we have to determine the rate law experimentally."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But if we have a single step reaction, then we can use the coefficients to calculate the rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So in this particular case, going from A to B, a is the reactant and B is the product."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And let's suppose the rate constant is k one and that means the rate law for this reaction is given by so the rate of the four reaction v forward is equal to k one multiplied by the concentration of A to the power of one, because the coefficient here is one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "If this coefficient was two, then this exponent here would be two and so forth."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now, if we go in reverse, then the only thing that changes is this becomes the reactor, this becomes the product."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so we replace the concentration A with concentration B and we replace k one with K minus one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And remember that if this reaction achieves equilibrium, then the rate of the forward will be equal to the rate of the reverse and these two quantities will be equal."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now notice, k one is not necessarily equal to K minus one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "K one is only equal to K minus one if the concentration of A is equal to the concentration of b when equilibrium is actually achieved."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So normally k one is not the same as k minus one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now, what exactly is the meaning of k?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "What exactly is the meaning of the rate constant?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Well, the rate constant is given by the following equation known as the radius equation."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And this Iranius equation describes what the rate constant actually symbolizes."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So the rate constant K is equal to the product of the frequency factor a and e to the power of negative EA divided by RT where r is the gas constant, t is the absolute temperature, EA is our activation energy."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So right away, because the activation energy appears in this arrangeous equation, that means changing the activation energy changes the value of K. And so when an enzyme acts on a chemical reaction, it affects the k value."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And that makes sense because we know that enzymes do not affect the concentrations of reactants or products."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so if enzymes increase the rate of the reaction and they cannot increase the a value or b, that means they have to increase the k value, the rate constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So if we look at the radius equation, we see that if we decrease the value of EA."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So remember enzymes, they stabilize the energy of the transition state, decreasing the energy of the transition state and that decreases the free energy of activation."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so when enzymes decrease the activation energy, EA, they essentially decrease this entire exponent."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And since the exponent is negative, what that means is this entire quantity will increase."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so by decreasing the activation energy our enzyme increases the rate constant and that's precisely what increases the rate of that reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So remember, inside our body the temperature remains constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "The core temperature is about 37 degrees Celsius."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And that means all the reactions taking place inside our body take place at a constant temperature."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So the temperature remains constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And what that means is the enzymes have to affect the EA to actually change the K to increase the rate of that particular reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "What about a Well, A is known as the frequency factor and this basically describes the frequency of collision between the reactants."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Remember, according to the collision theory, for a reaction to actually take place those reactants have to collide with a great enough energy."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now this collision frequency is described by A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And we know if the collisions are more frequent then it's more likely that we're going to produce the products."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so if the frequency of collision increases, the A value increases and the K will also increase."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now, does the enzyme affect A?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Well, remember, the enzyme places the substrate inside the active side and what that does is it creates a microenvironment and it basically decreases the space in which the reactants are colliding."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And if the space is smaller, the collision between the reactants will be much more likely."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so enzymes can also actually increase A because they decrease the space in which the reactants are actually allowed to move."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so if the reactants basically collide more, the A value increases."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So we see that enzymes predominantly affect the EA, but they can also affect A, they can decrease EA and increase A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And in both cases we basically increase the value of K. So enzymes affect the rate constant, they increase the rate constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so that in turn increases the rate of that reaction inside the rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So enzymes affect the rate constant and in turn affect the rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So if we take a look at the following elementary reaction in which we take A and produce B, where K is the rate constant, we see that this is our rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And when an enzyme is added into the mixture, the enzyme will increase K. It will not affect the concentration of A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so to increase V the rate of that reaction, the enzyme must increase the value of K. Now what exactly is the order of the reaction?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So earlier we said that the order of this reaction was one and the order of this reaction was also one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And the same thing was true for this particular case."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So we see that the order of the reaction basically describes the rate of the reaction and how it actually depends on the concentration of those reactants."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So let's begin with the first order reaction that we basically described in this lecture."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So when a reaction rate is directly proportional to the concentration of the reactant, it is set to be first order with respect to that reactant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So in this particular case, because the exponent is one, this is a first order reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And that means the rate law or the rate of that particular reaction depends directly, is directly proportional to the concentration."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So by doubling the concentration of A, we double the rate by quadrupling it, we quadruple the rate, by tripling it, we triple the rate and so forth."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So if we have a direct correlation between the reactant concentration and the rate of the reaction, then that means that reactant is first order with respect to that particular reactant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now to calculate the overall order of that particular reaction we have to sum up all the exponents in that particular chemical rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so because in this particular case we only have one exponent, that means the rate, the order is first."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And in this particular case the order is also first."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But if we for example move on to a second order reaction, let's suppose we have A and B are the two reactants and they react to produce C. And this k value is basically the reaction constant, the rate constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now if A is first order and B is also first order, then this will be our rate law."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So the rate of the reaction v is equal to k, that rate constant multiplied by the concentration of A to the power of one and the concentration of B to the power of one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And the overall order of this reaction is one plus one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So we simply sum up the exponents and that gives us two."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And what that means is by doubling A we double v as long as everything else remains constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Likewise, if we double B while A and K is constant, v will also double."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But if we double A and B while K is constant, we quadruple that v value."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so that's what it means for reaction to actually be 1st 2nd order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now we can also have a slightly different second order reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So in this case we have two reactants."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But what if we have a single reactant?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So let's suppose we have A and A basically converts to form B."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And let's suppose that we have two moles of A, produces 1 mol of B and this is an elementary reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So this is the k value, the rate constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so in this case, the rate law v is equal to k multiplied by the concentration of A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But because this is an elementary reaction and the coefficient is two, what that means is we'll have a coefficient of two on top of that A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So this reaction is second order with respect to K and with respect to A."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And the overall order is also second order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So this reaction and this reaction, they are both second order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "The only difference is we have a single reactant here but we have two reactants here."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "In this particular case if we double A, then we quadruple the velocity because two to the power of two gives us four."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But in this case by doubling A we essentially double v if everything else is kept constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "But if we double A and B and we keep K constant then we quadruple the value of v and finally we can also have 0th order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And in the 0th order basically the concentration of the reactant has no effect on the rate of that reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "So if a reaction is 0th order with respect to some reactant then the rate is independent of that reactant's concentration."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "For instance, if we have A and A is transformed into B and K is the rate constant and we know that A is zero's order, what that basically means is the exponent will be zero."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "This will become one."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And so the rate law is v is equal to K. And notice that changing A, either increasing or decreasing will not affect the value of V. And some enzyme catalyze reactions inside our body are in fact 0th order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And what that means is by changing the concentration of A that will not affect that rate of the reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now we can also have something known as a pseudo first order reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "And a pseudo first order reaction is actually a second order reaction that behaves like it's a first order reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now what's one example of such a reaction?"}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Well, let's suppose is we have a second order reaction as shown, but the concentration of A is very tiny but the concentration of B is very, very high."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant .txt", "text": "Now in this particular case even though it's a second order reaction it will behave like a first order."}, {"title": "Modification of Amino Acids .txt", "text": "Proteins are an extremely diverse group of macromolecules, and that's partially because they consist of 20 different amino acids."}, {"title": "Modification of Amino Acids .txt", "text": "So by arranging the amino acids in some specific sequence, we basically create a particular type of shape for that protein."}, {"title": "Modification of Amino Acids .txt", "text": "And that shape dictates what the function of that protein is."}, {"title": "Modification of Amino Acids .txt", "text": "And so by changing the arrangement of our amino acids, we we can basically create a different protein with a different type of function."}, {"title": "Modification of Amino Acids .txt", "text": "Now, in addition to increase the functionality and the diversity of the functionality of our proteins, we can basically modify the proteins by modifying the amino acids."}, {"title": "Modification of Amino Acids .txt", "text": "And there are five common ways by which our cells modify amino acids, as we'll see in just a moment."}, {"title": "Modification of Amino Acids .txt", "text": "Actually, there are many more ways, but we're going to focus on these five in this lecture."}, {"title": "Modification of Amino Acids .txt", "text": "So we can modify amino acids by adding acetal groups, hydroxyl groups, carboxyl groups, sugar groups, phosphoryl groups, as well as many other different types of groups which we're going to discuss in future lectures."}, {"title": "Modification of Amino Acids .txt", "text": "So in this lecture, let's focus on these five."}, {"title": "Modification of Amino Acids .txt", "text": "So let's begin with the first one."}, {"title": "Modification of Amino Acids .txt", "text": "So the majority of the polypeptides and proteins inside our body are actually modified by the addition of acetyl groups."}, {"title": "Modification of Amino Acids .txt", "text": "And that's because what this does is it tells our cells not to break down and degrade those polypeptide."}, {"title": "Modification of Amino Acids .txt", "text": "So many proteins are acetylated at the terminal amino groups to prevent degradation by our cells."}, {"title": "Modification of Amino Acids .txt", "text": "So if we go to the beginning of our polypeptide, the nitrogen is basically modified by adding this acetal group."}, {"title": "Modification of Amino Acids .txt", "text": "And what that does is it prevents this polypeptide from being broken down."}, {"title": "Modification of Amino Acids .txt", "text": "Now, another way by modifying proteins is by adding on hydroxyl groups."}, {"title": "Modification of Amino Acids .txt", "text": "And one common example is Collagen."}, {"title": "Modification of Amino Acids .txt", "text": "So Collagen is by far the most abundant protein found in our body."}, {"title": "Modification of Amino Acids .txt", "text": "It is found mostly in the extracellular tissue in our connective tissue, such as, for example, bone."}, {"title": "Modification of Amino Acids .txt", "text": "And what Collagen does is it gives our tissue its strength."}, {"title": "Modification of Amino Acids .txt", "text": "So what is the structure of Collagen?"}, {"title": "Modification of Amino Acids .txt", "text": "Well, Collagen has a coronary structure, and one of the most abundant amino acids in Collagen is proline."}, {"title": "Modification of Amino Acids .txt", "text": "Now, what Collagen does is it modifies the structure of proline by adding a hydroxyl group to produce hydroxyproline."}, {"title": "Modification of Amino Acids .txt", "text": "And what that does is it increases the stability of the three dimensional structure of Collagen."}, {"title": "Modification of Amino Acids .txt", "text": "So Collagen, the most abundant protein in our body, contains proline amino acids that contain hydroxyl groups."}, {"title": "Modification of Amino Acids .txt", "text": "These hydroxyl groups, as shown in the following diagram, basically give the Collagen its stability."}, {"title": "Modification of Amino Acids .txt", "text": "Now, what happens if we can't produce these hydroxyproline groups?"}, {"title": "Modification of Amino Acids .txt", "text": "Well, basically, a condition in humans of a disease known as Scurvy is essentially this inability of Collagen to basically produce and modify its own proline molecules in the following way."}, {"title": "Modification of Amino Acids .txt", "text": "So, in Scurvy, the body has a deficiency of vitamin C, and vitamin C is needed to basically modify and convert the proline molecules into hydroxyproline."}, {"title": "Modification of Amino Acids .txt", "text": "And so, because we can't modify these amino acids in this way, the structure of collagen basically is destabilized."}, {"title": "Modification of Amino Acids .txt", "text": "And what that means is it decreases the strength of our tissue."}, {"title": "Modification of Amino Acids .txt", "text": "Now let's move on to carboxyl groups."}, {"title": "Modification of Amino Acids .txt", "text": "So once again, many different types of proteins inside the body can be modified by the addition of carboxyl groups."}, {"title": "Modification of Amino Acids .txt", "text": "And one particular example is a protein and enzyme in the blood clotting cascade we call prothrombin."}, {"title": "Modification of Amino Acids .txt", "text": "So prothrombin is needed to basically stop bleeding."}, {"title": "Modification of Amino Acids .txt", "text": "And if prothrombin can't stop bleeding, then what that means is we're going to get a condition known as hemorrhage."}, {"title": "Modification of Amino Acids .txt", "text": "Now, what happens is in some cases if, for example, our glutamate amino acid in prothrombin cannot be modified by this process of carboxylation, the addition of this carboxyl group, then our prothrombin will essentially not be as active, it will not be able to carry out its function correctly."}, {"title": "Modification of Amino Acids .txt", "text": "And that can lead to the condition we call hemorrhage."}, {"title": "Modification of Amino Acids .txt", "text": "Now, let's move on to addition of sugar group."}, {"title": "Modification of Amino Acids .txt", "text": "So many, many proteins inside our body are modified by adding carbohydrate components."}, {"title": "Modification of Amino Acids .txt", "text": "For example, the proteins that are destined to be in a cell membrane or outside the cell, they're modified in this way."}, {"title": "Modification of Amino Acids .txt", "text": "And the reason we add carbohydrate components is to basically increase the polarity, increase the hydrophilic nature of those proteins, so that they can interact better with other proteins as well as with other hydrophilic molecules."}, {"title": "Modification of Amino Acids .txt", "text": "So, for example, we can have asparagne, the amino acid asparagine be modified by the addition of the sugar component."}, {"title": "Modification of Amino Acids .txt", "text": "And all these different hydroxyl groups basically increases the hydrophilic nature of that protein."}, {"title": "Modification of Amino Acids .txt", "text": "Finally, we can also undergo the process of phosphorylation."}, {"title": "Modification of Amino Acids .txt", "text": "We can add these phosphoryl groups onto our amino acids."}, {"title": "Modification of Amino Acids .txt", "text": "In fact, many different types of cellular processes that take place inside our cells and inside our body use the phosphorylation as a way to turn on and off these different types of cell processes."}, {"title": "Modification of Amino Acids .txt", "text": "For example, epinephrine, a hormone, and a newer transmitter can act on the serene and three anion amino acids by phosphorylating them."}, {"title": "Modification of Amino Acids .txt", "text": "And that can turn on or off many different types of molecules and reactions of processes that exist inside our body."}, {"title": "Modification of Amino Acids .txt", "text": "For example, insulin, which is a molecule that is used to regulate the amount of glucose found inside our body, inside our blood functions via this process."}, {"title": "Modification of Amino Acids .txt", "text": "So we can turn on or off insulin by using these phosphoryl groups."}, {"title": "Modification of Amino Acids .txt", "text": "Now, finally, we can also not only modify the amino acids, but in some cases when we cleave peptides within the proteins, within our polypeptide that can activate or deactivate our protein."}, {"title": "Modification of Amino Acids .txt", "text": "So many, many proteins inside our body are actually synthesized in their inactive form."}, {"title": "Modification of Amino Acids .txt", "text": "And some examples include digestive enzymes, for example, chimotrypsin, we have blood clotting enzymes."}, {"title": "Modification of Amino Acids .txt", "text": "Fibrin, we have hormones, for example, adrenal, corticotropic hormone, ACTH."}, {"title": "Modification of Amino Acids .txt", "text": "All these different types of hormones in our body are synthesized initially in their inactive state and to activate them, some type of enzyme, some type of catalyst basically cleaves a peptide bond."}, {"title": "Modification of Amino Acids .txt", "text": "And once we cleave that bond, we produce the active form of that protein."}, {"title": "Modification of Amino Acids .txt", "text": "So not only can we modify the amino acids of our proteins and thereby modify their functionality, we can also actually cleave specific peptide bonds within many different types of proteins, thereby activating those proteins."}, {"title": "Modification of Amino Acids .txt", "text": "And we'll see that in much more detail when we'll focus on these different types of enzymes and these different types of cellular processes."}, {"title": "Glucose-alanine cycle .txt", "text": "Although our liver is responsible for the majority of the metabolism of amino acids that occurs inside our body, other organs and tissues can also break down amino acids and then use the carbon skeleton byproducts for energy."}, {"title": "Glucose-alanine cycle .txt", "text": "And one example of such a tissue is our muscle tissue."}, {"title": "Glucose-alanine cycle .txt", "text": "So if we're undergoing prolonged exercise or if we're fasting, our skeleton muscle tissue tissue can actually begin to break down branch chain amino acids such as valine, isolucine and leucine."}, {"title": "Glucose-alanine cycle .txt", "text": "And then we form carbon skeleton intermediates, and then those are used for energy purposes."}, {"title": "Glucose-alanine cycle .txt", "text": "But of course, every time we metabolize amino acids, we form nitrogen as a byproduct."}, {"title": "Glucose-alanine cycle .txt", "text": "More specifically, we form ammonium."}, {"title": "Glucose-alanine cycle .txt", "text": "And as this process continually takes place, we build up the amount of ammonia that is present inside our skeleton muscle cells."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, ammonium is toxic, and so what the skeleton muscle cells must do is they must be able to dispose of that ammonium."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, unlike in the liver, and to a smaller extent in the kidney, where we have the urea cycle to basically dispose of that ammonium inside the skeleton muscle cells, we don't actually have a way to dispose of ammonium directly."}, {"title": "Glucose-alanine cycle .txt", "text": "And that's because the urea cycle does not take place inside the muscle."}, {"title": "Glucose-alanine cycle .txt", "text": "And so our body actually has two ways by which it can get rid of this ammonium from our skeletal muscle."}, {"title": "Glucose-alanine cycle .txt", "text": "But ultimately, what the skeleton muscle cell must do is it must be able to transport that ammonium back to the liver, where that ammonium can be fed into the urea cycle."}, {"title": "Glucose-alanine cycle .txt", "text": "And one of these pathways is known as the glucose alanine cycle."}, {"title": "Glucose-alanine cycle .txt", "text": "And this will be the focus of this lecture."}, {"title": "Glucose-alanine cycle .txt", "text": "So let's suppose we are fasting."}, {"title": "Glucose-alanine cycle .txt", "text": "Eventually, we begin to break down the branch chain amino acids into the carbon scale intermediates, and then we form ammonium as a byproduct."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, ammonium must be transformed into some other molecules."}, {"title": "Glucose-alanine cycle .txt", "text": "So we must have some type of carrier molecule that ultimately transports through the blood to the liver."}, {"title": "Glucose-alanine cycle .txt", "text": "So ammonium must be combined with Pyruvate."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, where do we get the Pyruvate from?"}, {"title": "Glucose-alanine cycle .txt", "text": "Well, inside our muscle, we have glycogen storages."}, {"title": "Glucose-alanine cycle .txt", "text": "We break down the glycogen to glucose, and we break down glucose into Pyruvate via glycolysis."}, {"title": "Glucose-alanine cycle .txt", "text": "So we generate ATP."}, {"title": "Glucose-alanine cycle .txt", "text": "That ATP can be used by the cell, and the Pyruvate can also be used to actually combine with ammonium to form glutamate, and then glutamate is transformed into aluminium."}, {"title": "Glucose-alanine cycle .txt", "text": "And actually, this is the reverse pathway that we discussed in the previous lecture."}, {"title": "Glucose-alanine cycle .txt", "text": "So previously we discussed how we can break down alanine into ammonium, but now we see how, under other conditions, we can actually do the reverse."}, {"title": "Glucose-alanine cycle .txt", "text": "We can take the ammonium combined with Pyruvate to ultimately form that alanine, and it's the alanine that is transported out of the cell into our bloodstream and that ultimately is absorbed by hepaticides, our liver cells."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, once the alanine moves into the liver, the alanine basically undergoes this pathway."}, {"title": "Glucose-alanine cycle .txt", "text": "But in reverse."}, {"title": "Glucose-alanine cycle .txt", "text": "So we begin with Alanine."}, {"title": "Glucose-alanine cycle .txt", "text": "Alanine then is formed into glutamate, and then that breaks down into pyruvate and ammonium."}, {"title": "Glucose-alanine cycle .txt", "text": "So ultimately, what happened is the ammonium that we used here or that we formed here, eventually made its way to the liver."}, {"title": "Glucose-alanine cycle .txt", "text": "And it's the liver that uses the urea cycle to basically help our body dispose of this toxic substance."}, {"title": "Glucose-alanine cycle .txt", "text": "Also notice, though, that we form pyruvate and it's in the liver that we undergo gluconeogenesis."}, {"title": "Glucose-alanine cycle .txt", "text": "It's in the liver where we undergo gluconeogenesis."}, {"title": "Glucose-alanine cycle .txt", "text": "And so pyruvate is used to form glucose."}, {"title": "Glucose-alanine cycle .txt", "text": "And the glucose that we essentially used here is then transported back into the skeleton muscle via the bloodstream."}, {"title": "Glucose-alanine cycle .txt", "text": "So ultimately, even though we used a glucose here to form that pyruvate, and we used that to essentially attach that ammonium and then transported via the bloodstream via Alanine, the glucose is ultimately returned back to the skeleton muscle tissue."}, {"title": "Glucose-alanine cycle .txt", "text": "So all that happened here is we ultimately transported this ammonium to our liver."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, this is known as the glucose Allenine cycle."}, {"title": "Glucose-alanine cycle .txt", "text": "We call it glucose Allenine because we utilize a glucose here to form pyruvate, to use it to actually attach that ammonium and form that alanine."}, {"title": "Glucose-alanine cycle .txt", "text": "That's why we call it the glucose Alanine cycle."}, {"title": "Glucose-alanine cycle .txt", "text": "It cycles between glucose and Alanine, but it's also returned back to its source, the skeleton muscle cell."}, {"title": "Glucose-alanine cycle .txt", "text": "But the ammonium is transported into the skeletal, into the liver."}, {"title": "Glucose-alanine cycle .txt", "text": "It's not returned back to the skeleton muscle."}, {"title": "Glucose-alanine cycle .txt", "text": "Now, so the glucose Alanine cycle is one pathway by which we can transport the ammonium from our target tissue, our skeletal muscle tissue, to our liver."}, {"title": "Glucose-alanine cycle .txt", "text": "But there is another method and that utilizes an enzyme known as glutamine synthetase."}, {"title": "Glucose-alanine cycle .txt", "text": "So glutamine synthetase is an ATP driven enzyme."}, {"title": "Glucose-alanine cycle .txt", "text": "It uses ATP to basically attach the ammonium that we formed here onto glutamate to form glutamine."}, {"title": "Glucose-alanine cycle .txt", "text": "And glutamine, just like Alanine, can move into the bloodstream, ultimately move into the hepatocytes, our liver cells, and then the glutamine can be broken down into glutamate releasing ammonium, and the ammonium can be fed into the urea cycle in the same exact way."}, {"title": "Glucose-alanine cycle .txt", "text": "So these are the two pathways, the methods by which, once we form the ammonium inside our skeletal muscle tissue, we can transport that ammonium into the liver, where the liver uses the urea cycle to basically dispose of that toxic substance."}, {"title": "The Genetic Code.txt", "text": "Before we discuss the process of translation in which we synthesize our proteins from RNA molecules we have to discuss a concept known as the genetic code."}, {"title": "The Genetic Code.txt", "text": "Now, as we'll see in just a moment, the genetic code is basically a system that is used by the cells specifically by the ribosomes to translate the language used by the RNA molecules molecules the language that is used by our proteins."}, {"title": "The Genetic Code.txt", "text": "And we'll see what that means in just a moment."}, {"title": "The Genetic Code.txt", "text": "First, let's discuss several other important points."}, {"title": "The Genetic Code.txt", "text": "So the central dogma of molecular genetics is basically a concept that tells us that the flow of genetic information in any cell goes from the DNA molecule to the RNA molecule to the protein."}, {"title": "The Genetic Code.txt", "text": "Now, any given DNA molecule in any given organism consists of genes and genes are basically specific sequences of nucleotides that code for proteins."}, {"title": "The Genetic Code.txt", "text": "Now, even though DNA molecules contain genes DNA molecules themselves are not directly used in protein synthesis."}, {"title": "The Genetic Code.txt", "text": "What happens is our DNA molecules, the genes in DNA molecules are transcribed into RNA molecules."}, {"title": "The Genetic Code.txt", "text": "So we basically transfer the genetic information from our DNA to our RNA and then those RNA molecules are used by ribosomes to basically form our proteins by using the genetic code as we'll see in just a moment."}, {"title": "The Genetic Code.txt", "text": "So it's not the DNA but it's the RNA molecules that is directly involved in the process of translation in the process of protein synthesis."}, {"title": "The Genetic Code.txt", "text": "Now, the entire sequence of DNA of any organism including the genes as well as the non coding regions of our DNA is known as the genome."}, {"title": "The Genetic Code.txt", "text": "And only a small percentage of the genome actually consists of the coding regions of the regions of nucleotides that code for proteins."}, {"title": "The Genetic Code.txt", "text": "And that's exactly why we have to use these RNA molecules because the DNA molecules consist predominantly of non coding regions."}, {"title": "The Genetic Code.txt", "text": "So one reason why we use the process of transcription is to basically only transcribe the genes into our RNA molecules so that we don't have to worry about the non coding regions about the non coding regions that basically do not code for any protein."}, {"title": "The Genetic Code.txt", "text": "Now let's recall what the process of transcription is."}, {"title": "The Genetic Code.txt", "text": "So as we mentioned earlier, the process of transcription is pretty simple and that's because both RNA and DNA molecules are polymers of the same exact units of the same exact molecule known as the nucleotide."}, {"title": "The Genetic Code.txt", "text": "The only difference between the nucleotides of RNA and DNA molecules is that in DNA the sugar is the deoxyribose and in RNA the sugar is the ribose and in RNA the thymine are replaced with the uracil nitrogenous bases."}, {"title": "The Genetic Code.txt", "text": "So let's take a look at the following diagram."}, {"title": "The Genetic Code.txt", "text": "So let's suppose we have the following DNA molecule that we want to use as the template for transcription."}, {"title": "The Genetic Code.txt", "text": "And this DNA molecule is commonly known as the antisense strand or the antisense strand."}, {"title": "The Genetic Code.txt", "text": "So basically the antisense strand consists of our adenine cytosine adenine and thymine nucleotides."}, {"title": "The Genetic Code.txt", "text": "So when transcription takes place our cell transcribes beginning on the three end and ending at the five end, so that we transcribe the new RNA beginning at the five and ending at the three end."}, {"title": "The Genetic Code.txt", "text": "And the method by which we actually transcribe is pretty simple, because the language that is used by RNA and DNA is exactly the same."}, {"title": "The Genetic Code.txt", "text": "That is, both of these molecules use nucleotides."}, {"title": "The Genetic Code.txt", "text": "So when transcribing from DNA to RNA, we synthesize RNA by using the nucleotides that are complementary to the nucleotides on the antisense DNA strands."}, {"title": "The Genetic Code.txt", "text": "So basically, if this is A, then we know this must be you."}, {"title": "The Genetic Code.txt", "text": "If this is cytositosine, this must be guanine."}, {"title": "The Genetic Code.txt", "text": "If this is adenine, this must be uracil."}, {"title": "The Genetic Code.txt", "text": "And if this is thymine, then this must be adenine, and so forth."}, {"title": "The Genetic Code.txt", "text": "So basically, when in the nucleus transcription takes place, the cell has no problem transcribing from our DNA to our RNA, because all it has to do is find the complementary nucleotide."}, {"title": "The Genetic Code.txt", "text": "But during the process of translation, when we synthesize our proteins from RNA molecules, things aren't that simple."}, {"title": "The Genetic Code.txt", "text": "And that's because our mRNA consists of nucleotides."}, {"title": "The Genetic Code.txt", "text": "So the language of RNA is the language of nucleotides, but proteins use the language of amino acids."}, {"title": "The Genetic Code.txt", "text": "And as we know, nucleotides and amino acids are not the same type of molecules."}, {"title": "The Genetic Code.txt", "text": "So the question is, how exactly does the cell know what sequence of nucleotides corresponds to a sequence of amino acids?"}, {"title": "The Genetic Code.txt", "text": "So once again, things become a bit more complicated when we synthesize proteins during the process of translation, which we'll discuss in much more detail in the next several lectures."}, {"title": "The Genetic Code.txt", "text": "So, in translation, the mRNA molecule, which itself is composed of nucleotides, is used as a template to synthesize our proteins that consist of amino acids."}, {"title": "The Genetic Code.txt", "text": "And here lies our problem."}, {"title": "The Genetic Code.txt", "text": "Nucleotides are different from amino acids, so we cannot use this complementary method."}, {"title": "The Genetic Code.txt", "text": "So how exactly does the cell know what sequence of nucleotides corresponds to what sequence of amino acids?"}, {"title": "The Genetic Code.txt", "text": "So what the cell actually does is it translates the language of our nucleotides, our mRNA molecule, to the language of our proteins, our amino acids, by using a system known as the genetic code."}, {"title": "The Genetic Code.txt", "text": "So basically, the ribosomes of the cell use our RNA molecule, use our genetic code to translate the sequence of nucleotides in the mRNA molecule to the sequence of amino acids."}, {"title": "The Genetic Code.txt", "text": "So the genetic code basically is the link between the sequence of nucleotides and our sequence of amino acids."}, {"title": "The Genetic Code.txt", "text": "Now, what exactly does our genetic code actually consist of?"}, {"title": "The Genetic Code.txt", "text": "Well, basically, the genetic code is a list of codons."}, {"title": "The Genetic Code.txt", "text": "And a codon is basically a series of three consecutive nucleotides, where each codon corresponds to specific type of amino acids."}, {"title": "The Genetic Code.txt", "text": "So in the mRNA molecule, a series of three consecutive nucleotides, known as our codon, corresponds to some specific amino acid."}, {"title": "The Genetic Code.txt", "text": "For example, the sequence of nucleotides, our guanine, uracil."}, {"title": "The Genetic Code.txt", "text": "Uracil, corresponds to a specific amino acid known as valine."}, {"title": "The Genetic Code.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "The Genetic Code.txt", "text": "So, let's suppose our ribosomes in the cell take the following mRNA."}, {"title": "The Genetic Code.txt", "text": "And what the ribosomes do is they use our genetic code to basically translate what these codons correspond to."}, {"title": "The Genetic Code.txt", "text": "So the codon guu, the sequence of Guamine uracil uracil, always corresponds to the amino acid valine, while the sequence CCU always corresponds to our amino acid proline."}, {"title": "The Genetic Code.txt", "text": "So we see that our genetic code links our mRNA molecule to our protein, and that's exactly how we synthesize or translate our proteins."}, {"title": "The Genetic Code.txt", "text": "Now, the question you might be wondering is, why is our codon exactly three nucleotides?"}, {"title": "The Genetic Code.txt", "text": "Why isn't the sequence only two nucleotides?"}, {"title": "The Genetic Code.txt", "text": "Well, to answer this question, we can use simple mathematics."}, {"title": "The Genetic Code.txt", "text": "We can use simple combinatorics."}, {"title": "The Genetic Code.txt", "text": "So recall that proteins consist of 20 different amino acids."}, {"title": "The Genetic Code.txt", "text": "So we have 20 different amino acids that our body, as well as other organisms actually use."}, {"title": "The Genetic Code.txt", "text": "So that means if the genetic code actually makes sense, then we better have 20 different unique codons that correspond to 20 different unique amino acids that appear in our body."}, {"title": "The Genetic Code.txt", "text": "But if we use simple math, we see that if we only have two different positions, two different nucleotides in our codon, then the maximum number of different types of codons is 16."}, {"title": "The Genetic Code.txt", "text": "And that's because we have four different possibilities for nucleotides."}, {"title": "The Genetic Code.txt", "text": "And four times four gives us 16."}, {"title": "The Genetic Code.txt", "text": "And 16 is not enough to actually correspond to the 20 different amino acids that exist in nature."}, {"title": "The Genetic Code.txt", "text": "And that's exactly why we have to add one more nucleotide so that we have three consecutive nucleotides in our codon sequence, because four times four times four gives us 64 possibilities."}, {"title": "The Genetic Code.txt", "text": "And that is enough to basically describe the 20 different amino acids that exist in nature."}, {"title": "The Genetic Code.txt", "text": "Now, right away, you should notice that the genetic code contains 64 different codons in that particular genetic code."}, {"title": "The Genetic Code.txt", "text": "So 64 different variations of three letter sequences of nucleotides."}, {"title": "The Genetic Code.txt", "text": "And since there are only 20 different amino acids that exist in nature, that implies that many of the three letter codons correspond to the same exact amino acid."}, {"title": "The Genetic Code.txt", "text": "And this phenomenon, the fact that two or more different codons can correspond to the same exact amino acid, makes our genetic code redundant or degenerate."}, {"title": "The Genetic Code.txt", "text": "So, basically, if we look at the following diagram, it describes what we just mentioned."}, {"title": "The Genetic Code.txt", "text": "So if we take our genetic code, we see that the sequence CC, you or cytosine cytosine yourself, and the sequence Cytosine cytosine cytosine or CCC, these two different sequences, both correspond to the same exact amino acid."}, {"title": "The Genetic Code.txt", "text": "They correspond to our amino acid proline."}, {"title": "The Genetic Code.txt", "text": "Now, I haven't actually listed all the codons that are found in the genetic code, but if you want to, you can look up our genetic code online or in a textbook."}, {"title": "The Genetic Code.txt", "text": "So, once again, as we'll see in the next several lectures, during the process of translation, when we synthesize our proteins from mRNA molecules, we have to have a way to translate the language used by the mRNA to the language that is used by the proteins."}, {"title": "The Genetic Code.txt", "text": "And what the ribosomes do is they use this system known as the genetic code, in which we basically have three letter sequences that are known as codons that correspond to specific amino acids."}, {"title": "The Genetic Code.txt", "text": "And the genetic code is set to be redundant or degenerate, which basically means that two or more different codons can correspond to the same exact amino acid."}, {"title": "The Genetic Code.txt", "text": "And this makes sense because we only have 20 amino acids and we have 64 different combinations for our codons."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "Our wing type gene."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "And we have this gene right here."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "That is our color gene."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "So we have the color gene and we have the wing type gene."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "Okay, this distance here, given in Map units is equal to ten Map units or ten recombination units."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "Now, it's important to remember that Map units do not actually give us a physical distance, but the Map units are correlated."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "They're related to the physical distance."}, {"title": "Gene Mapping, Recombination and Map Units Part II.txt", "text": "And what that means is, the greater the number of Map units, the greater the number of recombination units, the greater the distances between those two particular genes on that given in chromosome."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "The cells of our body depend on signal transduction pathways to carry out different types of cell processes at the right moments in time to basically produce physiological responses to certain types of external stimuli."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, even though these signal transduction pathways are very, very important to the functionality of our cells, these signal transduction pathways must, must be closely maintained and regulated by ourselves."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "In fact, the inability of our cells to regulate and terminate these signal transduction pathways can actually lead to tumor growth and eventually cancer."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so in this lecture, what I'd like to focus on is discuss how different types of abnormalities in a signal transduction pathway can actually lead to cancer."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, before we actually begin our discussion on the abnormality part, let's focus on how normal process takes place and how normally our cells terminate these signal transduction pathways."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And to use an example, we're going to focus on the EGF signal transduction pathway where EGF stands for Epidermal growth factor."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Remember, this is the pathway used by the cells that ultimately stimulates the growth and division of epithelial and epidermal cells."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So let's begin by focusing on how this pathway actually takes place, beginning with the binding of the EGF molecules onto their domains."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we have two EGF molecules bind onto each one of these domains shown in purple."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once the binding takes place, these two monomers associate with one another to form a dimer and that creates conformational changes in these two structures found in a cytoplasm."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now these two structures, and by the way, this is the EGF receptor these two structures actually contain tyrosine protein kinase domains."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once a conformational change takes place upon binding and the dimerization process, a cross phosphorylation takes place and the carboxyl terminal ends of this tail and this tail are phosphorylated by the active sides of these corresponding kinases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once we form these phosphorylated residues, we have an important adaptor protein known as GRB Two that binds onto this section and that calls upon another protein known as SOS."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And what SOS does is it binds an inactive small G protein known as Ras."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "When Ras binds unto this structure, there's a conformational change that takes place in the Ras protein and the GDP Guanosine diphosphate is expelled and the GTP Guanosine triphosphate moves into that pocket."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once GTP binds, that activates that G protein we call Ras."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once Ras is activated, it moves on and activates a protein kinase we call Raff."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once this protein kinase is activated, it goes on to form these to activate other protein kinases we call mex the Max."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Once activated, it goes on to activate other protein kinases we call Hercs."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now these Hercs can actually move into the nucleus of our cell."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we have this double phospholipid bilayer of the nucleus."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "These IRCS go into the cell nucleus and they activate transcription factors."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "These transcription factors then move on and express different types of genes that produce mRNA molecules which then exit the cell and they essentially are used by the ribosomes to produce proteins."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "The proteins are in turn used to basically build up the cytoplasm, build up the cytoskeleton which basically increases the size of the cell and that cell eventually is able to divide."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so in this process, the EGF signal transduction pathway stimulates cell differentiation, cell growth and cell proliferation of two types of cells, epidermal cells and epithelial cells."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, once this pathway actually carries out its specific purpose, how exactly does a normal cell terminate this process?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Well, there are three major methods."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Method number one is the fact that because we have a G protein involved and G proteins have Gtpa's activity, what that means is they have a built in clock that allows it to actually shut itself down following activation."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So sometime after this has been activated into the GTP form, this green structure, the G protein, because it has Gtph activity, it is able to actually take a water molecule from the cytoplasm and hydrolyze the GTP back into GDP."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once it inactivates itself, this can no longer stimulate the rest of the process."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so this pathway essentially shuts down as a result."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So cells can terminate the pathway by using Gtpa's activity of G proteins and that is built in into that molecule."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Number two, these cells can also actually terminate the pathway by using a class of molecules we call phosphatases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So in fact, as soon as this pathway is activated, it also activates many different types of phosphatases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And what phosphatases do is they essentially remove us four groups that were attached by protein kinases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So for instance, we have the Rat, the Mechs, the Irks, and these two structures that act as protein kinases in this particular case."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And what the phosphatases do is they essentially move onto the target proteins and they remove those phosphoryl groups that were placed by all these different protein kinases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "For instance, these phosphatases can remove these phosphoryl groups here and that essentially inactivates this part of the pathway and so it cannot continue and as a result it is shut down."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so anywhere I have an asterisk, that basically means we're dealing with a protein kinase."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so these phosphatases can influence and shut down this protein, these proteins, these proteins and also these two structures here which are actually part of that EGF receptor."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And finally we can terminate the pathway by inactivating that receptor of the pathway."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And actually we already spoke about one way by which we can inactivate is by removing these phosphoryl groups."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Another way is if these two ligands actually dissociate."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "When the two ligands dissociate, the entire diameter basically breaks apart into monomers and in that particular case it is not as active as in this particular case."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so what that means is that will decrease the activity of this signal transduction pathway."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So this is the normal way by which the pathway actually is terminated."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "But what happens in the abnormal case?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "How can an abnormality in each one of these cases, one, two, three, actually lead to the production of tumors and eventually cancer?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So let's focus on number one."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we said our cells can terminate by using these Gtpas activity G proteins."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So this Rasp protein has a certain gene in the DNA that expresses it."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now let's suppose the gene is a normal gene and that means this will be a normal protein."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "But what happens if that gene that encodes for this structure is actually mutated in some way?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And let's suppose we mutate that gene in such a way so that this molecule loses its ability to basically hydrolyze the GTP back into GDP."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so if there's a mutation that takes place in the Ras gene, and the mutation basically destroys the Gtpa's activity of this g protein, then once the protein is activated, it will remain in the on position."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "It will remain active."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And that means it will continually stimulate these processes."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And the signal transduction pathway will continue the process of cell growth, cell division and cell proliferation."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we see that one way by which a signal transduction pathway may malfunction is if a gene encoding for a protein that is part of that pathway is actually mutated."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "For instance, the rat gene that codes for the Ras protein in the EGF pathway is the most commonly mutated gene that leads to tumor growth of epithelial and epidermal cells."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So a mutation in the gene might produce a Raspotee that is incapable of Atpa's activity, which basically means it cannot turn itself off after actually being activated."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So this is essentially the off position and this is the on position."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so if we have a mutation that destroys the Atpa's activity of this structure, it will always remain on and always go on to activate Rap proteins which will contain these processes that essentially lead to self growth and division."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now we see that these types of mutated genes that lead to the production of these cells that have cancer characteristics are known as oncology."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So this is what an oncogene actually is."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now let's move on to two."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So if there is an abnormality in this process, how can that lead to cancer?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we said that phosphatases are these proteins which are used to reverse the effects of protein kinases and that essentially shuts down this process."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, just like any other protein in our chromosomes, in our DNA, we have genes that code for phosphatases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So for any given phosphatase, we have one gene that comes from the father and the other gene that comes from the mother."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So let's suppose we have this homologous pair of chromosomes and this is the gene that let's say comes from the mother."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And this is the gene showed in blue that comes from the father."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we have the pair of alleles that code for that same type of."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So this should be phosphatase, not phosphatase."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Okay?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So let's change that real quick."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "We have phosphatase."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we have these genes that code for phosphatase."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, if these two genes are normal, then there really will be no problem."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "In fact, if one of them is abnormal, the other one is normal."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Usually the cell will be functional and will be able to actually shut down and terminate the process by using phosphatases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And by the way, because the phosphatases turn off the activity of these pathways and that essentially decreases the likelihood that tumor growth will actually take place, these genes that code for phosphatases are also known as tumor suppressing genes."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And the phosphatase themselves are known as tumor suppressing molecules because it's a result of these molecules that tumors do not actually develop."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So phosphatases are called tumor suppressing molecules because they inactivate proteins and enzymes that drive that signal transduction pathway."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And for this reason, we call the genes that code for phosphatases tumor suppressing genes."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, what happens if both of these genes are for some reason inactivate or for some reason mutated or blocked?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So it could be some type of chromosomal abnormality, so a deletion, an insertion, a movement to some other chromosome, and so forth."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So when both of these genes in the allele pair and coding for a specific type of phosphatase that inactivates some specific type of molecule in this process are actually knocked out or destroyed, that may lead to tumor formation because the cell will not be able to correctly terminate that process by using these phosphatases."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we know how abnormality can lead to cancer here as well as here."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "What about this final case?"}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we said that we could actually terminate the pathway by inactivating that receptor protein."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "In this case, it's the EGF receptor."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "Now, in some cases we see that over expression of these tyrosine kinase domains."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So the tyrosine kinase receptors like the EGF receptor here, if the cell actually builds too many of these proteins and inserts too many of these proteins into the membrane of that cell, what that will do is increase the likelihood that the cell will activate the pathway at an inappropriate time."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so this access number, the excess amount of these receptors, the access amount of these receptors in a cell membrane can basically lead to the production of these cancer cells."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So, overexpression of tyrosine kinase receptors can also lead to cancer of the epithelial cells."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "For instance, we have cancers like breast cancers, ovarian cancers, colorectal cancers and so forth."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So any place we have these epithelial cells, this can actually cause this type of cancer."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So, if a cell expresses too many receptors, that access receptors may stimulate growth at inappropriate times."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And actually by studying this specific type of mechanism, we were able to create different types of drugs which act as anticancer, anti tumor agents."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And these drugs are essentially antibodies."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "So we were able to develop these antibodies in a laboratory that actually bind onto these EGF receptors."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And once the antibody binds onto these pockets of the EGF receptor, that can basically inactivate these receptors."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And by inactivating these receptors, that decreases the likelihood that this will lead to producing a cancer cell."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And so one important drug that is basically used to treat individuals who have breast cancer is known as herceptin."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "And herceptin is basically used to bind onto a specific type of EGF like receptor known as her two."}, {"title": "Cancer and Termination of Signal Pathways .txt", "text": "In fact, about 30% of the individuals who have breast cancer have breast cancer as a result of the excess quantity of this her two receptor in the membrane of their epithelial cells."}, {"title": "Introduction to Electrocardiogram .txt", "text": "The human heart is capable of generating electrical signals."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And it uses those electrical signals to create the muscular contraction that is needed to move all that blood through the blood vessels of our body."}, {"title": "Introduction to Electrocardiogram .txt", "text": "In fact, physicians can actually study and analyze the way that the heart of the patient produces electrical signals."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And they can determine different types of abnormalities that might exist within the heart simply by using this tool."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this tool is known as an electrocardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "An electrocardiogram is a graph that describes the electrical signal that is generated by the heart."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, how do we actually obtain the electrocardiogram?"}, {"title": "Introduction to Electrocardiogram .txt", "text": "Well, we basically take special electrodes and we connect the electrodes onto the surface of the skin as special locations on the body."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So six electrodes are usually placed around the heart."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Two electrodes are placed on the arms and two electrodes are placed on the legs."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that creates a closed electric circuit."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And if we connect the wires to a special device, that device can read the electrical signal that is generated by our heart."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we basically create an electrocardiogram that is nothing more than an XY graph, where the X axis is the time and the Y axis is the voltage."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we see that the electrocardiogram is the fluctuations, the change in voltage that is produced by the heart."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And this voltage is used to basically generate that muscular contraction that propels all that blood through the blood vessels of our body."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, in this lecture, we're going to study the normal electrocardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We're not going to discuss any abnormalities that might exist within the heart and that might be described by an abnormal electrocardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we're simply going to focus on the brief details of a normal electrocardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So let's take a look."}, {"title": "Introduction to Electrocardiogram .txt", "text": "By taking a cross section of our heart, we basically expose the four different chambers."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So if we're examining the heart from this angle, we have the right side and the left side."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this is the right side of the heart, the left side of the heart, the right atrium, right ventricle, the left atrium and our left ventricle."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So let's begin by looking at the different sections of the lecture cardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we have a wave known as the P wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have an upside down Q wave, an upside down S wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have this r wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We also have a T and a U wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, we also have points on the actual curve."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we have the points shown in blue."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have point P and point R, and we have point S and point T. So let's discuss what each one of these segments and waves actually represents."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Let's begin with wave P or the P wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So let's recall where the heart actually begins, where it generates that electrical signal."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So within the right atrium, within the upper wall of the right atrium, we have a collection of specialized cells that collectively are called the sinoatrial node, or simply the SA node."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this is where the SA node is located."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And the essay note contains cells where the membrane of those cells depolarize."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that creates an electrical potential difference."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that's exactly why we have an increase in the voltage taking place within this portion."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So when the SA node generates that electrical signal, the action potential, it increases the voltage, it makes it more positive."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And our electrical signal then propagates through these conduction channels shown in purple."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And these conduction channels extend through the right atrium and through the left atrium."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, when the voltage reaches its maximum, so at the peak of this wave, at the peak of the P wave, that is when these two atriums begin to contract simultaneously."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this ventricle, this atrium and this atrium begin to contract."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And as they begin to contract, they cause these two valves, the tricuspid and the Bicuspid valve, to basically open."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And as they open, the blood begins to rush into the right ventricle and into our left ventricle."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, at the same time that our two atrium begins to contract, that signal eventually reaches another specialized section known as the AV node, or the atrial ventricular node."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And this note is located in the interatrial septum of the heart in the wall separating our two atrium."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, when the signal arrives at the AV node, the AV node, what it does is it delays that signal by about zero of a second."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And what that does is it gives the atria enough time to fully contract and move all that blood into the fully relaxed ventricles."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So we see along our P waves, our atria begins to contract at the tip while the ventricles are actually fully relaxed."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now let's move on to our PR segment."}, {"title": "Introduction to Electrocardiogram .txt", "text": "This PR segment basically has no voltage difference."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have a zero voltage difference."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that's why we have a slope that has a zero line that has a zero slope."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that's because within this section, what happens is our AV note essentially sends that electrical signal through the bundle of his and through our perkinji fibers."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And within this segment, no contraction actually takes place."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So once the AV node delays the signal, it depolarizes and sends the electrical signal through the bundle of his and our PerkinsI fibers that essentially permeate through the walls of our two ventricles, as shown by these purple fibers within this diagram, this does not actually cause any contraction."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now let's move on to this segment, the QRS segment, which is commonly known as the QRS complex."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And this complex actually consists of three individual waves."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have the Q wave, the R wave, and the S wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, the Q wave and the Swave are known as the downward deflection waves because they actually decrease our voltage."}, {"title": "Introduction to Electrocardiogram .txt", "text": "They make it more negative."}, {"title": "Introduction to Electrocardiogram .txt", "text": "But the R is known as our right side up, or the upward deflection wave because it increases the voltage, it makes it more positive now, what exactly takes place within the QRS?"}, {"title": "Introduction to Electrocardiogram .txt", "text": "So here we have the electrical signal that permeated through the entire walls of our right and left ventricle."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And now what begins to happen as soon as we reach the maximum point of the R way, this voltage here contraction of these ventricles begins to take place."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And as the ventricles begin to contract, there is an increase in hydrostatic pressure."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that forces these two valve, the tricuspid and the biconspid valve, to close."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And when they shut close, that's exactly what causes that first sound that we hear when we listen to our heart via a stethoscope."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So if we listen to our heart, we hear the love dub love dub sound."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And the love is caused by the closure of these two valves during the QRS complex."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, this is when the ventricles actually begin to contract."}, {"title": "Introduction to Electrocardiogram .txt", "text": "These valves closed and the right and left atrium are now relaxing."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, the question is why exactly is the voltage difference here so high?"}, {"title": "Introduction to Electrocardiogram .txt", "text": "Well, that's because this section of the heart, the ventricles, contain the thickest layer of myocardium."}, {"title": "Introduction to Electrocardiogram .txt", "text": "They have the thickest layer of muscle cell."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And so that means a much higher voltage difference is needed to cause the contraction of all these muscles found within our right and left ventricle."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that's exactly why this peak is such a high peak."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now let's move on to the st segment."}, {"title": "Introduction to Electrocardiogram .txt", "text": "What exactly takes place within our st segment?"}, {"title": "Introduction to Electrocardiogram .txt", "text": "So within the st segment, that contraction increases that hydrostatic pressure."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And what that causes is these two semi lunar valves, our pulmonary semi lunar valve and our aortic semilunar valve, to basically open up."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And as those valves open up, all that blood flows from the ventricles into our arteries."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So the left ventricle sends that oxygenated blood into the order, while the right ventricle sends our deoxynated blood into the pulmonary arteries and eventually into our lungs."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So within the st segment, all of the cells within the ventricles have been depolarized, and repolarization of those cells basically begin."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, the semi lunar valves, both of them, actually open up and our blood begins to eject into these blood vessels."}, {"title": "Introduction to Electrocardiogram .txt", "text": "This takes place in this flat region, the st segment, where the voltage is basically flat."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now let's move on to our T wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And then let's take a look at the U wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, what exactly happens within our T wave?"}, {"title": "Introduction to Electrocardiogram .txt", "text": "So within a T wave, we also have a slight increase in voltage."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And what happens here is repolarization begins or repolarization continues."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So repolarization begins in the st segment, but it continues and takes place fully within our T wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this is when the cells of the ventricle repolarized."}, {"title": "Introduction to Electrocardiogram .txt", "text": "During this stage, these ventricles essentially empty out all that blood into our blood vessels."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And because the hydrostatic pressure now decreases within our ventricles, these two semi lunar valves close."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And when they shut close, that is the second sound that we normally hear in our lub dub."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So lub is when our bicuspid and tricuspid valves close, but the dub takes place when our two semi lunar valves close."}, {"title": "Introduction to Electrocardiogram .txt", "text": "We have the pulmonary and the aortic semi lunar valve."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So the QRS complex is when our bicuspid and tricuspid valves close, but the T wave is when these two valves right here actually close."}, {"title": "Introduction to Electrocardiogram .txt", "text": "Now, what about this last wave we call the U wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So the U wave is usually a very small peaked wave that follows our T wave."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And what we believe the U wave actually describes is the repolarization of all the cells found within the wall separating our two ventricles."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So this wall is known as our interventricular wall."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And what the uWave is believed to describe is the repolarization of all the cells found within this particular segment."}, {"title": "Introduction to Electrocardiogram .txt", "text": "So these are some of the segments and waves that one would normally find on a normal cardiogram."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And this is exactly what they describe."}, {"title": "Introduction to Electrocardiogram .txt", "text": "They describe the propagation, the movement of our electrical signal as we have a change in voltage."}, {"title": "Introduction to Electrocardiogram .txt", "text": "And that ultimately creates that contraction of our hearts."}, {"title": "Formation of DNA Double Helix .txt", "text": "In your study of biochemistry you're going to come across many different types of biological reactions that take place inside our body and inside our cells."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, for every one of these biological reactions, in order to be able to determine what the pathway of the reaction is and what the final structure of the final biomolecule is in that particular process is, we have to consider the many different types of factors that can influence the reaction pathway and the structure of that final product molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, so far we discussed three of these important factors."}, {"title": "Formation of DNA Double Helix .txt", "text": "We discussed how intermolecular bonds can influence the final structure of that biological molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "We discussed hydrogen bonds."}, {"title": "Formation of DNA Double Helix .txt", "text": "We examined London dispersion forces, also sometimes known as vandalbal forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "And we also discussed the hydrophobic interactions and the hydrophobic effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now we also discussed how the solvent in which the reaction is in can influence the pathway of that reaction and the final structure of that molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "For example, we said that the majority of the reactions that take place in nature and specifically in our body take place in water."}, {"title": "Formation of DNA Double Helix .txt", "text": "So water is the universal natural solvent and the properties of water can influence the reaction pathway as we'll see in just a moment."}, {"title": "Formation of DNA Double Helix .txt", "text": "We also spoke about thermodynamics and how in any reaction we always have to remember that that reaction has to obey the laws of thermodynamics."}, {"title": "Formation of DNA Double Helix .txt", "text": "So it has to obey the first law of thermodynamics that basically states that energy is never created, energy is never destroyed."}, {"title": "Formation of DNA Double Helix .txt", "text": "Energy can only be transformed from one form to another."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the total amount of energy in our universe is always constant."}, {"title": "Formation of DNA Double Helix .txt", "text": "We also have to remember the second law of thermodynamics which basically describes the fact that in any real biological process the change in entropy of the universe is always positive, it always increases."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we also have to consider the temperature and the conditions under which a reaction is taking place because under certain conditions a reaction might be spontaneous but under other conditions the reaction might not be spontaneous."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so we have to consider the gifts free energy of our reaction."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, another factor that we haven't yet focused on is the PH of a solution."}, {"title": "Formation of DNA Double Helix .txt", "text": "So in the next several lectures we're going to discuss how the PH of a solution can also influence the pathway of the reaction and the final structure of that biological molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "So to demonstrate how these factors can influence a particular biological reaction let's take a look at a common reaction the formation of a double helix of DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "So inside every nucleus of every cell in our body we have DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, the DNA doesn't exist as a single strand."}, {"title": "Formation of DNA Double Helix .txt", "text": "It exists as a double helix."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, from basic biology we know that a double helix consists of these two single strands of DNA that run in an antipowerall direction opposite with respect to one another."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, on the outside of the DNA we have the phosphate groups and we have the carbon backbone as well as the deoxyribosugars."}, {"title": "Formation of DNA Double Helix .txt", "text": "And on the inside of that DNA double helix, we have the basis that pair with each other."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the question is how do intermolecular bonds, how does the reaction solvent and how does thermodynamics basically influence this reaction, the formation of the double helix of DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "So let's begin with the intermolecular interaction."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the question is how exactly do these intermolecular interactions drive the formation of the double helix?"}, {"title": "Formation of DNA Double Helix .txt", "text": "So let's take a look at the following diagram that basically describes a portion of our double helix."}, {"title": "Formation of DNA Double Helix .txt", "text": "So this is the deoxyribo sugar, and for simplification purposes, I've omitted the hydroxyl group."}, {"title": "Formation of DNA Double Helix .txt", "text": "So no hydroxyl groups are found on these sugar molecules."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we have the sugar that is attached to our phosphate."}, {"title": "Formation of DNA Double Helix .txt", "text": "And the sugar and phosphate is basically on the outside of that DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "So this is the outside portion of the DNA that interacts with the solvent."}, {"title": "Formation of DNA Double Helix .txt", "text": "In this case, water."}, {"title": "Formation of DNA Double Helix .txt", "text": "Why water?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Well, because in the nucleus we have water that predominates and that's why it acts as a solvent."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now on the inside of the DNA we have these bases."}, {"title": "Formation of DNA Double Helix .txt", "text": "The question is why exactly does this interaction actually take place?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Why is it favorable from the inter molecular perspective, from the intermolecular interaction perspective?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Well, number one is on the inside of the DNA molecule we have these bases that are able to form hydrogen bonds."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we have one base that interacts with a complementary base on the other single strand molecule and that forms our hydrogen bond."}, {"title": "Formation of DNA Double Helix .txt", "text": "So in this case, this is hydrogen bonding and this is also hydrogen bonding."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we can say hydrogen bonding and this is also hydrogen bonding or simply age bonding."}, {"title": "Formation of DNA Double Helix .txt", "text": "Okay?"}, {"title": "Formation of DNA Double Helix .txt", "text": "So a base on one DNA strand interacts with via hydrogen bonds with a complementary base on the other DNA molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so when these single strand molecules approach one another, these hydrogen bonds that are formed, that is a stabilizing effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now what about the second type of interaction, the London Dispersion forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "So notice that these base pairs are essentially parallel with respect to one another."}, {"title": "Formation of DNA Double Helix .txt", "text": "So they lie along the same exact plane."}, {"title": "Formation of DNA Double Helix .txt", "text": "So they're essentially stacked on top of one another."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now remember, when they are stacked on top of one another, there are instantaneous dipole moments that exist within our bases."}, {"title": "Formation of DNA Double Helix .txt", "text": "And those instantaneous dipole moments will interact with one another via the London dispersion forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "So not only do we have hydrogen bonding between the complementary adjacent bases, but we have the Vanderbilt forces, these London dispersion forces, between our bases stacked on top of one another."}, {"title": "Formation of DNA Double Helix .txt", "text": "So these are H bonds, but these Brown bonds are essentially our London forces, the London Dispersion forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we have these two important types of intermolecular bonds that play a role in forming our DNA double helix."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now not only that, but because the bases are essentially non polar, notice what happened."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the entire DNA molecule is swimming around in the solvent, in water, inside the nucleus of the cell."}, {"title": "Formation of DNA Double Helix .txt", "text": "And water is a polar molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "So what that means is these bases which are predominantly non polar, will not once interact with that polar water solvent."}, {"title": "Formation of DNA Double Helix .txt", "text": "And what this double helix structure ensures is that all these non polar bases are found inside the structure of the double helix and away from the polar water molecules."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so that is known as the hydrophobic effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "And these base cells will interact via the hydrophobic interactions and that will be a stabilizing effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we see that we have hydrogen bonds, we have London dispersion forces and we have the hydrophobic effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "That basically ensures that the double helix is a favorable structure."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now the only type of nonfavorable interaction is basically the interaction between the phosphate groups."}, {"title": "Formation of DNA Double Helix .txt", "text": "So notice that this phosphate group has a negative charge, this phosphate group also has a negative charge."}, {"title": "Formation of DNA Double Helix .txt", "text": "And when we have two light charges in close proximity, they will create a repulsive force."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so the only type of electric force, the only type of intermolecular force that tends to separate these single strands are these negative charges on these adjacent phosphate groups."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the negatively charged phosphate groups lead to electric repulsive forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now normally under room temperature or in body temperature, at body temperature, these attractive forces overpower these repulsive forces."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so that's exactly why the double helix structure remains."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now let's move on to the reaction solvent."}, {"title": "Formation of DNA Double Helix .txt", "text": "How exactly do the properties of water, the solvent found in the nucleus, affect the structure of that DNA molecule?"}, {"title": "Formation of DNA Double Helix .txt", "text": "How does it lead to a double helix formation?"}, {"title": "Formation of DNA Double Helix .txt", "text": "So basically, outside this DNA molecule are a bunch of water molecules."}, {"title": "Formation of DNA Double Helix .txt", "text": "So this is a water molecule, this is a water molecule and so forth."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now this is the oxygen and these are the age groups."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we know that the age groups, because of the polarity of water, the age groups will be partially positive and our oxygen groups will be partially negative."}, {"title": "Formation of DNA Double Helix .txt", "text": "So what that means is these polar water molecules will orient themselves in such a way as to interact with the phosphate groups that are pointing to the outside on the double helix DNA molecule and that will be a stabilizing interaction."}, {"title": "Formation of DNA Double Helix .txt", "text": "So once again we see that not only do we have hydrogen bonds that exist between the bases, but we also have these hydrogen bonds that exist between our water molecules and these phosphate groups."}, {"title": "Formation of DNA Double Helix .txt", "text": "And that will be a very stabilizing effect."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so we see that the fact that water is the solvent, the properties of water that acts as a solvent in the formation of the DNA molecule actually favorably leads to the formation of that double helix DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "And finally let's discuss how the thermodynamics of this reaction is also favorable."}, {"title": "Formation of DNA Double Helix .txt", "text": "So let's suppose that this is our system and everything outside this box, everything outside our system are the surroundings."}, {"title": "Formation of DNA Double Helix .txt", "text": "And let's suppose that the temperature at which our reaction takes place is either room temperature or we can also say it's a body temperature."}, {"title": "Formation of DNA Double Helix .txt", "text": "So it's either 25 degrees Celsius or a body temperature 37 degrees Celsius."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, before the reaction takes place, we have these single strands of DNA."}, {"title": "Formation of DNA Double Helix .txt", "text": "So we have three of these blue strands and three of these complementary red strands."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, when this reaction takes place, what do we form?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Well, we form three of these DNA molecules that are in their double helix form."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, what can we say about the entropy of this system and this system after the reaction?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Well, before the reaction took place, the entropy of the system was greater than the entropy of the system after the reaction."}, {"title": "Formation of DNA Double Helix .txt", "text": "Why?"}, {"title": "Formation of DNA Double Helix .txt", "text": "Well, because in this case, we have much more order in our system as in this case."}, {"title": "Formation of DNA Double Helix .txt", "text": "So actually, in this reaction, the entropy of this system decreases."}, {"title": "Formation of DNA Double Helix .txt", "text": "It becomes negative."}, {"title": "Formation of DNA Double Helix .txt", "text": "So the Delta S of our system is negative."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, we know, according to thermodynamics this is only possible if this reaction releases enough energy to compensate for that decrease in entropy."}, {"title": "Formation of DNA Double Helix .txt", "text": "And this is exactly what happens at room temperature or at body temperature inside our cells."}, {"title": "Formation of DNA Double Helix .txt", "text": "This reaction is actually spontaneous because even though the entropy of the system decreases, there's so much heat, so much energy released into the surroundings that that increases the entropy of the surroundings by a greater amount than the decrease of the entropy of the system."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so what that means is the change in entropy of the Universe is positive."}, {"title": "Formation of DNA Double Helix .txt", "text": "Because if this is greater than this, then this is a positive value."}, {"title": "Formation of DNA Double Helix .txt", "text": "For example, if, let's say, this is negative ten, but this is positive 20, that means this value will be a positive value."}, {"title": "Formation of DNA Double Helix .txt", "text": "And whenever our delta S of the Universe is a positive value, that means at that particular temperature, the Delta G that gives free energy will be a negative value."}, {"title": "Formation of DNA Double Helix .txt", "text": "And so our reaction will be spontaneous, it will be favorable, and the product molecule will be formed."}, {"title": "Formation of DNA Double Helix .txt", "text": "And in this case, that double helix DNA molecule will, in fact, form."}, {"title": "Formation of DNA Double Helix .txt", "text": "So this is basically what we have to do, what we have to think about every time we examine a reaction in biochemistry."}, {"title": "Formation of DNA Double Helix .txt", "text": "We have to think about how these different types of factors will influence that reaction pathway and the final structure of that final molecule."}, {"title": "Formation of DNA Double Helix .txt", "text": "Now, what we haven't discussed yet is how the PH influences our reaction."}, {"title": "Formation of DNA Double Helix .txt", "text": "And we'll focus on that in the next several lectures."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So when we want to understand the way that a chemical reaction takes place, we usually study the thermodynamics and the kinetics of that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that involves studying things like Gibbs free energy which involves enthalpy and entropy, as well as studying things like activation energy of that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, because enzymes act on chemical reactions, if we are are to actually understand how enzymes behave and act on those chemical reactions, we also have to study the GIBS free energy and the activation energy of that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So let's begin by discussing gifts free energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Then we'll look at activation energy and we'll finish off with how the enzyme actually affects these two quantities."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So let's begin by supposing that we have the following hypothetical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So we have reactants being transformed into products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, we're going to assume that the reaction has not reached equilibrium."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And what that basically means is the reaction can either have a negative gives free energy or a positive Gibbs free energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So what is gives free energy?"}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Well, the gives free energy, loosely speaking, describes how much energy can be used in that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So let's suppose we have the following graph."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So the y axis is the energy value and the x axis is the reaction progress."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So these are the reactants here and the energy value of the reactant is somewhere here."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, the products have a free energy value that is equal to somewhere here."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And notice that the products have a lower free energy than the reactants."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, to calculate mathematically the gives free energy of this reaction, all we have to do is take the free energy of the products and subtract the free energy of the reactants."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that gives us the gives free energy given by Delta G. So this quantity here is how much energy is going to be released in this reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And it's basically how much energy we can use in some process."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, for this particular case, this reaction describes an exergonic reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And exergonic reactions always have a negative Delta G. That means energy is released in this reaction and the reaction is said to be spontaneous."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So a chemical reaction is said to be exergonic and spontaneous if the Delta G is negative."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And one example of a spontaneous reaction in nature is combustion."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So combustion reactions are examples of exergonic reactions where the Delta G value is negative."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, what about the opposite?"}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Well, if we read this reaction going backwards, if this is the reactant and this is the product that if we subtract a high free energy from a low free energy, we're going to get a positive Delta G. And a positive Delta G means the reaction is endergonic and non spontaneous."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that means it will not take place unless we input a certain amount of energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And one example of an endorganic reaction that is not spontaneous is the synthesis of ATP molecules inside our body."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So to synthesize ATP, we have to actually input energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And the ATP molecules, when they break down, that is an exergonic reaction and energy is released."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And every time we break down ATP molecules inside our body, energy is released."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And we can use that energy to basically power different types of processes that take place inside our body that require those ATP molecules."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So on the other hand, a chemical reaction is said to be endergonic and non spontaneous if a delta g is positive."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And ATP synthesis is an example of such an endergonic reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So we can see that if we know what the gives free energy value is of some particular reaction, we know whether or not that reaction is actually spontaneous."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, another important fact that you have to know about this quantity gives free energy is gives free energy only depends on the energy, the free energy value of the product and the free energy value of the reactants."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So if we know what the free energy of the product is and the free energy of the reactants, all we have to do is subtract the two to find that gives free energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So the pathway that we take when we go from the reactant to the products does not actually determine, does not change what the Gibbs free energy is."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "It doesn't matter if we take pathway one, two or three when we go from the reactants to products, gives free energy will not actually change."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So if we, for example, compare a reaction that has an enzyme and that same reaction that is uncatalyzed does not have an enzyme, the Gibbs free energy in those two reactions will be exactly the same."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So a catalyzed and an uncatalyzed reaction will have the same exact Gibbs free energy value."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that leads us to a very important point."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Enzymes, when they act on chemical reactions, they do not affect the Gibbs free energy value."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "They do not change the energy of the reactants, nor they actually change the energy of the products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that's exactly why the difference, namely the delta g that gives free energy will remain exactly the same when an enzyme is used or when an enzyme is not used."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, the final thing I'd like to mention about Gibbs free energy is what happens if Gibbs free energy is equal to zero?"}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Well, if Gibbs free energy is zero, then no energy is being produced in that reaction that actually can be used in any useful way."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "In fact, when Gibbs free energy is zero, that reaction is said to have reached equilibrium."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And at that moment in time, the rate of the four reaction is equal to the rate of the reverse reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So if the Gibbs free energy is zero, the reaction has achieved equilibrium and is said to be neither spontaneous nor non spontaneous."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "In such a case, the rate of the four reaction going from reactants to products is equal to the rate of the reverse reaction going from products back to reactants."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now let's move on to Activation energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So what exactly is the activation energy?"}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Well, any reaction has some activation energy and this is simply the amount of energy that we have to input for the reaction to take place to convert the reactants to the products or in reverse."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now let's suppose we go from reactants to products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "In this case, our activation energy is simply this quantity here."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "It's the difference between the energy of the molecule found on this topmost portion of the hill and the energy of that reacting."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "This is the GIBS free energy given by Delta G with the symbol on top or simply Delta E A, where the A stands for activation."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now this topmost apex of the hill describes the energy of the transition state of this chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And if you, if you recall from organic chemistry, the transition state is not something that exists for a very long time and that's because it has a very high energy value."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "As can be seen by the following diagram, this apex has the highest energy value in that reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that's precisely why the transition state does not exist for a very long time."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And in fact, because it doesn't exist for a very long time, it's unstable."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And we can't actually study how the transition state looks like."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "We can't isolate it and we can't examine it because it quickly converts into the products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So the activation energy, delta G with that symbol describes the amount of energy that must be supplied to any reaction in order to actually get it going."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now the activation energy describes how quickly a reaction actually takes place."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So a reaction can be spontaneous, it can have a negative delta G value, but it can take place very, very slowly."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And if a reaction takes place very slowly, what that means is it has a very high activation energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So activation energy is not the same thing as Gibbs free energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "GIBS free energy basically describes the difference between the energy of the reactants and the products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "But activation energy describes how quickly a reaction actually takes place."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So Gibbs free energy talks about where that equilibrium will be achieved while Activation energy talks about how quickly that equilibrium will actually be achieved."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And so once again, as we'll see in more detail in a future lecture, the apex of this curve describes the energy of the transition state."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "Now, what exactly does the enzyme do and how does the enzyme affect the activation energy?"}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So we said previously that the enzyme does not change the Gibbs free energy of the reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "It has no effect on the energy of the reactants and the products."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And so their difference, the Delta G is exactly the same."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "It remains unchanged when the enzyme acts on that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "But the enzyme does have an effect on the activation energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "In fact, what the enzyme typically does is it actually lowers the energy of that transition state."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And by lowering the energy of the transition state, it makes this mountain smaller."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And so this height will be smaller, and the delta g that gives the activation energy of that reaction will become smaller."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And if we decrease the activation energy by essentially stabilizing that transition state, we will speed up the reaction, because ultimately, it's the activation energy, it's the energy barrier that determines the kinetics, the speed, and the rate of that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So enzymes do not affect the equilibrium."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "They have no effect on the Gibbs free energy of that reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "The free energy of the reactants and the free energy of the products remains unchanged in any catalyzed reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "However, what the enzymes do is they stabilize the transition state, lower its energy, they lower the energy of that transition state, and so they decrease the activation energy, and that speeds up that chemical reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "So, once again, enzymes, when they act on chemical reactions, they do not change the Gibbs free energy."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "And that means they do not increase or decrease how much product is formed at the end of that reaction."}, {"title": "Enzymes\u2019 Effect on Activation Energy and Free Energy .txt", "text": "But they basically allow equilibrium to be achieved quicker by increasing the rate, by decreasing that activation energy."}, {"title": "Summary of Gene Mutations .txt", "text": "In the past two lectures, we discussed the concept of a gene mutation, and we examined the different types of gene mutations that exist in nature."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, let's actually summarize our results, and let's begin by looking at the following flowchart."}, {"title": "Summary of Gene Mutations .txt", "text": "So, this flowchart basically describes the many different types of mutations that can arise in nature."}, {"title": "Summary of Gene Mutations .txt", "text": "And it also tells tells us the reasons for our gene mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, a gene mutation is basically a change in the nucleotide sequence on the DNA that is not a result of genetic recombination."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, basically, there are two reasons for a gene mutation in the first place."}, {"title": "Summary of Gene Mutations .txt", "text": "So one of these reasons is a result of an error that might take place in one of the many processes that take place in the body."}, {"title": "Summary of Gene Mutations .txt", "text": "For example, one process in which an error can basically lead to a g mutation is DNA replication."}, {"title": "Summary of Gene Mutations .txt", "text": "So, during DNA replication, our DNA polymerase can basically make a mistake and incorrectly base pair a certain nucleotide pair, and that will create our gene mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "So, these types of natural g mutations that take place as a result of one of the many natural processes that exist in the cell is known as a spontaneous mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, on the other hand, a gene mutation can also take place as a result of one or more physical or chemical agents known as mutagens."}, {"title": "Summary of Gene Mutations .txt", "text": "So these are basically outside physical or chemical forces that can basically induce our g mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "And one example is UV radiation."}, {"title": "Summary of Gene Mutations .txt", "text": "So, UV radiation is an outside physical agent that can basically cause harm and create a gene mutation in DNA."}, {"title": "Summary of Gene Mutations .txt", "text": "So we have induced mutations or spontaneous mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "So we have two reasons for our mutations to arise."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, once we form the mutation, there are two categories of mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "We have insertion and deletions, as well as point mutations, which are also known as base pair mutations or base pair substitutions."}, {"title": "Summary of Gene Mutations .txt", "text": "And let's begin by discussing insertion deletions."}, {"title": "Summary of Gene Mutations .txt", "text": "So, to insert something or to delete something means we're basically either placing nucleotides into the DNA or we're removing nucleotides from that DNA sequence."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, an insertion or deletion of a number of nucleotides that is not a multiple of three, that is not a multiple of the codons that exist in the genetic code will cause the reading frame to shift, which will change the amino acid sequence of the polypeptide chain."}, {"title": "Summary of Gene Mutations .txt", "text": "And this is known as a frame shift mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "So insertion deletions can form frame shift mutations in which the entire reading frame, the entire mRNA sequence, is shifted."}, {"title": "Summary of Gene Mutations .txt", "text": "And that means that completely new codons will be read by our ribosomes, and a completely new sequence of amino acids will be produced."}, {"title": "Summary of Gene Mutations .txt", "text": "And this usually leads to non functional proteins."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, let's take a look at the other type of insertion deletion, known as a non frame shift mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "So, on the other hand, an insertion or deletion of nucleotides that is a multiple of three will simply insert or remove a number of amino acids equaling to the number of new codons that are added or removed."}, {"title": "Summary of Gene Mutations .txt", "text": "And this is known as a non frame shift mutation because the reading frame is not actually shifted and because the majority of the amino acid in the sequence is actually unchanged."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, let's move on to the second category known as point mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "So, a point mutation, also known as a base pair mutation or a base pair substitution, is basically a change of a single nucleotide on that DNA template."}, {"title": "Summary of Gene Mutations .txt", "text": "So, if the point mutation does not actually change the amino acid that is produced, and in this case, it is known as a silent mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, a silent mutation can either arise on the non coding region of the DNA or on the coding region of the DNA."}, {"title": "Summary of Gene Mutations .txt", "text": "And the reason a silent mutation can arise on the coding region of the DNA is because our genetic code is degenerate."}, {"title": "Summary of Gene Mutations .txt", "text": "And that means more than one codon can basically code for the same exact amino acid."}, {"title": "Summary of Gene Mutations .txt", "text": "So, if we have a point mutation that causes that forms a new codon, and that new codon still codes for the same exact amino acid, then we know that this is a point mutation because the same exact amino acid sequence will form."}, {"title": "Summary of Gene Mutations .txt", "text": "On the other hand, a point mutation that changes the codon and the amino acid that is produced is known as a miscense mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "So, we have two types of point mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "They can either be silent, or they can be miss sensed."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, actually, all point mutations are also non frame shift mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "So let's put that in parentheses."}, {"title": "Summary of Gene Mutations .txt", "text": "So, non frame shift."}, {"title": "Summary of Gene Mutations .txt", "text": "So, all point mutations are non frameshift mutations, while insertion deletions can either be frame shift or non frame shift."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, the final type of mutation that I want to briefly discuss is a nonsense mutation."}, {"title": "Summary of Gene Mutations .txt", "text": "So, a nonsense mutation can arise if as a result of insertion deletions or point mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "So, both of these categories of mutations contain nonsense mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "So, a nonsense mutation is a mutation when we basically change a codon that codes for an amino acid into a codon that is a stop codon, that terminates our polypeptide chain, and this basically terminates the polypeptide chain prematurely."}, {"title": "Summary of Gene Mutations .txt", "text": "And this causes or creates a non functional protein."}, {"title": "Summary of Gene Mutations .txt", "text": "So, basically, this concludes our discussion on genetic mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "We have two different types of categories."}, {"title": "Summary of Gene Mutations .txt", "text": "We have insertion deletions and point mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "Now, insertion deletions can cause frame shift or non frameshift mutations, but point mutations themselves are always is non frameshift mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "And there are two types."}, {"title": "Summary of Gene Mutations .txt", "text": "We have solid mutations as well as midstance mutations."}, {"title": "Summary of Gene Mutations .txt", "text": "And both of these categories can contain nonsense mutations."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "Value for our tyrosine will be five five."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And once again, as that PH value, the PH value of five five, all these charges will exactly cancel out."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And so if we place our amino acid on this line here, it will not move in this direction, nor will it move in this direction."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "Now, by the way, what happens if I take this molecule and place it, let's say somewhere here, where at this location, when it is to the right of the pi value, this molecule will tend to want to move back in this direction."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And that's because anywhere in this region, this molecule will have a net negative charge."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And so, because this negative charge will cause it to move this way, it will gravitate towards our pi value."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And likewise, if we take this same tyrosine and place it within this region, in this region, it will have a net negative charge."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And so, as a result of that electric field, it will gravitate and move towards this pi line."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "So if we place this here, it will move this way."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "If we place this here, it will move in the other direction."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And the same thing is true for all these other cases."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "For example, Glycine."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "If we take Glycine and place it here, it will have a net positive charge."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "So it will move this way until it reaches that point."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "And if we take Glycine and place it here, it will move this way until it reaches that pi value of five."}, {"title": "Isoelectric Focusing and Isoelectric Point (Part II) .txt", "text": "Now, in the next lecture, we're going to take a look at how to actually determine what the pi value is of proteins of polypeptide that consists of two or more amino acids."}, {"title": "Specificity of Serine Proteases.txt", "text": "Chymatrypsin is a serum protease and it has the ability to catalyze the cleavage of peptide bonds on the carboxyl end of large hydrophobic nonpolar amino acids."}, {"title": "Specificity of Serine Proteases.txt", "text": "For instance, chymatrypsin, Cleaves at the carboxyl end of methionine, phenylalline, tyrosine, as well as Tryptophan."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, as we discussed previously, it's the presence of of the catalytic triad inside the active side of Chimetrypsin that actually gives it the power of catalysis, gives it the ability to actually cleave those peptide bonds."}, {"title": "Specificity of Serine Proteases.txt", "text": "So remember, the catalytic triad is basically this collection of three individual residues aspartate HistoGene and Serene, which work together to basically promote the cleavage of those peptide bonds."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, the question still remains what exactly gives Chimotrypsin its specificity?"}, {"title": "Specificity of Serine Proteases.txt", "text": "What gives Chimotrypsin the ability to only Cleave on the carboxyl end of specific amino acids, those amino acids that contain bulky hydrophobic side chain groups?"}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, to answer this question, we actually have to study the shape of the active side, the structure of that enzyme."}, {"title": "Specificity of Serine Proteases.txt", "text": "If we examine the active side of that enzyme, we're going to find something called the S one pocket."}, {"title": "Specificity of Serine Proteases.txt", "text": "And the S One pocket in China trypsin is basically that region to which that side chain group will actually move into."}, {"title": "Specificity of Serine Proteases.txt", "text": "And if we examine the shape and structure of the S One pocket, we're going to find that it's relatively long, so relatively deep and mostly hydrophobic, so non polar."}, {"title": "Specificity of Serine Proteases.txt", "text": "And because of that structure of the S one pocket, only those amino acids that contain side chain groups that are long, nonpolar, do not have any charges, will actually be able to fit into that pocket, into the active side, without creating too much electric repulsion."}, {"title": "Specificity of Serine Proteases.txt", "text": "So amino acids such as methionine, phenyl, aline, tyrosine and Tryptophan."}, {"title": "Specificity of Serine Proteases.txt", "text": "So once again, it's the catalytic triad in the active side."}, {"title": "Specificity of Serine Proteases.txt", "text": "It's the presence of these three individual amino acids that give climate Trypsin its catalytic power, the ability to actually catalyze the cleavage of those peptide bonds."}, {"title": "Specificity of Serine Proteases.txt", "text": "But it's this long and narrow shape and the fact that it's mostly hydrophobic, it's the shape of the S one pocket that actually gives chymetrypsin its specific nature, its specificity to Cleave only on the carboxyl end of specific side chain groups."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, as we discussed in our study of proteases, we basically said there are many different types of proteases that exist inside our body and inside nature."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, so far, we focused on Serene proteases and we use Chimetrypsin as the prototypical seren protease."}, {"title": "Specificity of Serine Proteases.txt", "text": "But of course, in our body, in our digestive system, for example, we have many other examples of seren proteases."}, {"title": "Specificity of Serine Proteases.txt", "text": "The question is, what is the mechanism that these other seren proteases actually use to cleave peptide bonds?"}, {"title": "Specificity of Serine Proteases.txt", "text": "Well, it turns out other crises also use this same catalytic triad."}, {"title": "Specificity of Serine Proteases.txt", "text": "And what that means is they also carry out the catalysis process by using the same exact mechanism, namely covalent catalysis and acid based catalysis and two examples of other cum proteases inside our digestive system that also contain the same catalytic triad is Trypsin as well as elastase."}, {"title": "Specificity of Serine Proteases.txt", "text": "So Chimotrypsin is not the only serum protease that utilizes this catalytic triad."}, {"title": "Specificity of Serine Proteases.txt", "text": "In fact, Trypsin and Elastase are two other serum proteases found in our digestive system that use this same exact catalytic triad and therefore the same exact mechanism of catalysis that we spoke about in the previous lecture."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, the question is, why do we have different types of C and proteases inside our body?"}, {"title": "Specificity of Serine Proteases.txt", "text": "And the question is, what exactly differentiates Trypsin elastics and Chimera Trypsin if they have the same exact catalytic triad?"}, {"title": "Specificity of Serine Proteases.txt", "text": "Well, remember, it's the catalytic triad that gives the enzyme its catalytic power, that gives the protease the ability to cleave those peptide bonds."}, {"title": "Specificity of Serine Proteases.txt", "text": "But it's the shape of that active side, the s one pocket that determines the specificity of that protease, the type of peptide bond it actually breaks."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so the difference between Chima, Trips and Trypsin and Elastase is not in the type of catalytic triad used, but it's in the shape of that particular s one pocket."}, {"title": "Specificity of Serine Proteases.txt", "text": "The structure of that s one pocket, as we'll see in just a moment, as a result of a slight variation in the s one pocket of Trypsin and Elastase, we see that these other CM proteases cleave other amino acids."}, {"title": "Specificity of Serine Proteases.txt", "text": "So although Trypsin elastics use the same mechanism, so covalent catalysis and acid based catalysis, which we spoke about in the previous lecture, they differ in their specificity."}, {"title": "Specificity of Serine Proteases.txt", "text": "And that has to do to the fact that there is a slight structural difference in the s one pocket in Trypsin as well as elastics."}, {"title": "Specificity of Serine Proteases.txt", "text": "And let's see what these differences are and what they result in."}, {"title": "Specificity of Serine Proteases.txt", "text": "So let's begin with trypsin."}, {"title": "Specificity of Serine Proteases.txt", "text": "So Trypsin catalyzes the cleavage of peptide bonds on the carboxyl end of Lysine and Arginine."}, {"title": "Specificity of Serine Proteases.txt", "text": "And if you recall, Lysine and Arginine both contain positive charges on their sidechain groups."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, the question is, why is this true?"}, {"title": "Specificity of Serine Proteases.txt", "text": "So Trypsin uses the same exact catalytic triad that climate Trypsin uses."}, {"title": "Specificity of Serine Proteases.txt", "text": "But what gives this Trypsin the difference in specificity?"}, {"title": "Specificity of Serine Proteases.txt", "text": "Well, if we examine the s one pocket of Trypsin at the bottom of that s one pocket, we're going to see a residue that we don't see in the s one pocket of Chimetrypsin at the bottom of the Trips."}, {"title": "Specificity of Serine Proteases.txt", "text": "In s one pocket, we have a negatively charged side chain that came from the aspartate that we see in Trypsin and we don't see in Chimetrypsin."}, {"title": "Specificity of Serine Proteases.txt", "text": "So as a result of the negatively charged side chain of Aspartade 189 that is found at the bottom of the s one Trypsin pocket, we see that this Trypsin only Cleaves at the carboxyl end of those amino acids which are long and contain a positive charge at the end."}, {"title": "Specificity of Serine Proteases.txt", "text": "And these happen to be Lysine and Arginine."}, {"title": "Specificity of Serine Proteases.txt", "text": "So if we examine the following hypothetical polypeptide, we have glycine this one here."}, {"title": "Specificity of Serine Proteases.txt", "text": "We have Lysine this one here."}, {"title": "Specificity of Serine Proteases.txt", "text": "We have glycine this one."}, {"title": "Specificity of Serine Proteases.txt", "text": "We have Arginine this one and we have glycine, this one."}, {"title": "Specificity of Serine Proteases.txt", "text": "Now, the only ones that contain positive charges are these two amino acids."}, {"title": "Specificity of Serine Proteases.txt", "text": "And only these amino acids will be able to actually fit into the pocket of Trypsin, and at the end will be able to actually interact in a stabilizing manner."}, {"title": "Specificity of Serine Proteases.txt", "text": "So the positive charges of these two side chain groups will interact with the negative charges of this aspartate 189 and that will create a stabilizing effect, it will neutralize the net charge in that space and that will create a very stable effect."}, {"title": "Specificity of Serine Proteases.txt", "text": "So at the bottom of the active cytotrypsin is an aspartate residue and the negative charge of the aspartate side chain group will stabilize those amino acids that contain side chain groups with positive charges, namely the Lysine and the arginine."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so the only bonds that Trypson will be able to cleave are this bond and this bond here."}, {"title": "Specificity of Serine Proteases.txt", "text": "So at the carboxyl end of Lysine and arginine, so we see that a very tiny variation in the structure of the s one pocket in Trypsin gives Trypsin a different specificity than that of chimetrypsin."}, {"title": "Specificity of Serine Proteases.txt", "text": "And finally, let's move on to elastics."}, {"title": "Specificity of Serine Proteases.txt", "text": "So, if we examine the s one pocket of Elastanes, we'll see the presence of two additional Valene and valine, if you recall, are these small or valine molecules, have these small, relatively small hydrophobic chains."}, {"title": "Specificity of Serine Proteases.txt", "text": "And notice where these two valleys are positions, they're positioned opposite of each other and they essentially play the role of blocking the majority of the bottom portion of that s one pocket."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so what that means is when the side chain group of the amino acid moves into the s one pocket, it cannot actually occupy this space here because this blocks, as a result of the stair kindle of the hydrophobic properties of these side chain groups."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so only those amino acids that have relatively small side chain groups and which are nonpolar so uncharged, will be able to fit into this pocket."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so we see that Elastase cleaves peptide bonds on the carboxyl end of small hydrophobic amino acids such as glycine, vallene, Alanine, Valine, Alanine Leucine and Isolucine, as well as serene."}, {"title": "Specificity of Serine Proteases.txt", "text": "So if we have this hypothetical polypeptide chain, we have glycine, lysine, Alanine, phenylalanine, glycine."}, {"title": "Specificity of Serine Proteases.txt", "text": "So the only ones which have a small hydrophobic side chain are glycine Alamine, as well as glycine at the end."}, {"title": "Specificity of Serine Proteases.txt", "text": "So the only two peptide bonds that are going to be cleaved are this peptide bond."}, {"title": "Specificity of Serine Proteases.txt", "text": "So on the carboxyl end of glycine, as well as this one on the carboxyl end of Alanine."}, {"title": "Specificity of Serine Proteases.txt", "text": "So Lysine and Phenylalanine are not small ones, this one has a large long one and it's positively charged."}, {"title": "Specificity of Serine Proteases.txt", "text": "Although this one is non polar hydrophobic, it's too large to actually fit into this pocket because these two valleyses block the majority of that pocket."}, {"title": "Specificity of Serine Proteases.txt", "text": "And even though this is a glycine, there's no bond on the carboxyl side."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so nothing will be cleaved on this side by elastase and so we see that two Vallene residues found in the S One pocket of Elastase block off the majority of the pocket in Elastase."}, {"title": "Specificity of Serine Proteases.txt", "text": "And this allows Elastase to only cleave small hydrophobic residues."}, {"title": "Specificity of Serine Proteases.txt", "text": "And so we see that the majority of the seagram protease is found inside our body."}, {"title": "Specificity of Serine Proteases.txt", "text": "For instance, chimetrypsin trypsin as well as Elastase."}, {"title": "Specificity of Serine Proteases.txt", "text": "Although they use the same catalytic triad to basically catalyze the cleavage of the peptide bonds, they actually differ in the types of amino acids that they cleave."}, {"title": "Specificity of Serine Proteases.txt", "text": "Types of peptide bonds that they cleave."}, {"title": "Specificity of Serine Proteases.txt", "text": "As a result of these structural differences and shapes in the S one pockets of their active site, it's."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "The lipid bilare membrane is not a static structure."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So it is not rigid in nature."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "On the contrary, it's very much a fluidlike structure."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "In fact, the viscosity of the membrane is very much like olive oil."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It's about 100 times more viscous than water."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, the question is, why is this the case?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Well, because of phenomenon known as lateral diffusion."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And what that means is the molecules that constitute the phospholipids and in many cases, the proteins that constitute the membrane are actually in a constant state of horizontal lateral emotion."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And to visualize the lateral diffusion of these lipid molecules or proteins within our cell membrane, we can basically use a technique, a process known as fluorescence recovery after photo bleaching, which basically is also known as FRAP."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So what we basically do is we take the membrane and we attach these fluorescent molecules onto the membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And what these fluorescent markers will basically help us do is help us visualize the movement of these molecules, the lipids and the proteins within our membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So that's step one."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So at a time of zero, the membrane is labeled with fluorescent molecules."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, let's suppose at time of T one, what we basically do is we choose a certain area, a certain region of that particular membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Let's suppose the area is about 3 squared."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And what we do is we direct electromagnetic radiation and electromagnetic pulse."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "For example, a high intensity laser pulse."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "We direct it exactly at that 3 \u03bcm squared area."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And what that does is it basically bleaches that area."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It destroys those fluorescent molecules."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And now, if we examine those molecules, they will not essentially display that color."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So at a time of T one, a region of the membrane is bleached with electromagnetic with an electromagnetic pulse, which destroys those fluorescent molecules in that region."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So all these molecules here are basically the unbleeached molecules, the ones that weren't destroyed by the electromagnetic radiation."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "But these molecules have been bleached."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "They have been destroyed."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "The fluorescent markers have been destroyed."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, what exactly are we going to see?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Well, if there was no movement and if the membrane was in fact a rigid and a static structure, then that means this area will remain bleached."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "But what happened is, because there is a lateral movement of these molecules, eventually these bleached molecules will disperse throughout that membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And what that means is, because these unbleached molecules will replace the bleached molecules in this area, that will recover the fluorescence in that particular area."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So over time, the lateral movement of the lipids will disperse the non fluorescent, the bleached molecules."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "This will return that fluorescence to that initially bleached area."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So initially, this is what we see once we bleach it, we see this purple spots, let's say it's purple."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And then over time, this purple spot disappears because these bleached purple molecules essentially move away."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And so the fluorescence actually is recovered."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And this can be summarized in the following graph."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So the y axis is the intensity, the fluorescent intensity."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "The x axis is the time, let's say, given in seconds."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And this is basically what the curve describes."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So this straight line is part A before we actually Bleached."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "This is the point at which we bleach."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And notice that at that particular section, we no longer see that same type of color, but over time, we see that the color basically returns because of lateral diffusion along that membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So this graph demonstrates the recovery of fluorescence in that Bleached area."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It confirms the existence of this phenomenon we call lateral diffusion."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, the question is, what determines the rate at which that area actually recovers its fluorescence?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So what determines the slope of this particular line?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Because the slope is ultimately the rate of recovery of fluorescence."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Well, basically, it's the speed at which these molecules can actually move along that membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So the higher the speed, the greater the likelihood that the molecules will move away."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And so the higher the recovery rate is."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So it turns out that phospholipids in general can move at a rate of about 1 \u03bcm squared per second."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So that basically means every single second, that phospholipid can move 1 \u03bcm along that membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So, once again, these phospholipids generally move with a uniform constant value at a rate of about 1 \u03bcm squared per second."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, what about proteins?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Well, unlike these phospholipids, which basically move at a relatively uniform rate of 1 \u03bcm squared per second, proteins basically vary in the rate of movement."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Some are immobile, they move very slowly, while others basically move very quickly and so are mobile."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, what determines the mobility of these proteins?"}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Well, basically, it's the functionality of that protein is the protein attached onto some other component, onto some other structure."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, for instance, if we look at Rhodopsin, which is basically a photopigment that is found in the retina cells of our body, rhodopsin's functionality depends on its ability to move quickly along the membrane."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And so proteins, membrane proteins such as Rhodopsin can actually move at a relatively high rate, which is about the rate of half this quantity."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Here, on the other hand, other proteins, because their functionality depends that they basically remain in that single position."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "In these cases, proteins are relatively mobile."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And one example is fibronectin."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So Fibronectin is basically a peripheral glycoprotein that is actually attached onto a transmembrane protein known as Integrin, or Integrin."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "Now, fibronistin is not only anchored onto the Integrin, but the fibronectin is actually itself anchored onto the collagen fibers found in the extracellular matrix."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "On top of that, the Integrin is actually also attached onto the actin filaments that are found inside the cytoplasma, inside the cytoskelet and the cytoplasm."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So, because of all these anchoring positions and attachment points, fibro nectin doesn't actually move."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It moves very slowly."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It's essentially immobile."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "So we conclude that the cell membrane is not a static rigid structure."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "It's very fluid like."}, {"title": "Lateral Diffusion of Lipids and Proteins .txt", "text": "And that's because of the lateral motion, lateral diffusion of not only those fossil lipids, but also also the proteins that exist inside the membrane of that particular structure."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Following the discovery of the structure of DNA the next question was how exactly does DNA replication actually take place inside the cells of our body?"}, {"title": "Meselson and Stahl Experiment .txt", "text": "And initially there are three hypotheses that were proposed so we had the conservative hypothesis, we had the semiconservative hypothesis and we had dispersive hypothesis and only one of these became the true hypothesis the hypothesis that described the way that cells actually replicate inside our cells."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So in 1958, two individuals, one by the name of Matthew Methleton and the other one by the name of Franklin Stahl, conduct an experiment that became known as the methylsen and style experiment."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And what this showed was that the semiconserved replication hypothesis correctly described the way that DNA molecules actually replicated."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, before we discuss what the experiment looked like, let's actually take a look at what this hypothesis tells us."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So based on the semiconserve replication of DNA we have our DNA molecule the original DNA molecule that consists of this double helix that contains two individual strands of DNA that we're going to call the parent strands or the parental strands so we have parental strand number one and it's complementary parental strand number two shown in blue."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, before replication begins, we have to separate our DNA molecule."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so we separate the two individual strands of DNA and once we separate them, each one of these blue strands, the original parenthal strands, act as a template to synthesize the complementary new strand we're going to call the daughter strand that is shown in green."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And following the replication process, this will be the distribution, the arrangement of the parent strand and the daughter strand."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So in each one of these two DNA molecules, one of these strands will be conserved, it will be that original parental strand and the other one will be the complementary newly synthesized daughter strand."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so we have this semiconservative process in which we have 50% of that original parental strand and 50% of that newly synthesized daughter strand."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And these two DNA molecules are essentially identical, assuming that process was mitosis."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, let's actually discuss what this experiment consisted and how it showed that the semiconservative replication process was correct."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So what they did initially was they wanted to grow these special bacterial E. Coli cells that contain labeled DNA molecules."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So radioactively labeled DNA molecules."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And the way that they did that is they took a medium that was very high, very rich in isotopic nitrogen atoms."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So m 15."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, remember, the normal nitrogen atom contains an atomic mass of 14, and that's because it contains seven protons and seven neutrons in the nucleus."}, {"title": "Meselson and Stahl Experiment .txt", "text": "But in the case of this heavy isotopic nitrogen atom, we have eight neutrons and seven protons."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so eight plus seven gives us an atomic mass of 15."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So initially, E. Coli bacterial cells were grown in a medium rich in heavy nitrogen and 15, as shown in the following diagram."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And this was done to basically produce E. Coli cells that have incorporated this isotopic N 15 into their DNA."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And now the DNA is radioactively labeled and contains the heavier nitrogen atoms."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now once we form these E. Coli cells that contain the heavy DNA molecules, these ecology cells are then transferred into a beaker into a flask that contains the regular nitrogen N 14 isotope."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so now when these E. Coli cells are going to reproduce via mitosis, they're going to incorporate the N 14 isotope into the newly synthesized DNA molecules."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And what we want to answer is what will be the distribution of the N 14 and N 15 isotopes following several cycles of replication."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And based on this, we can basically determine if the semiconservative process actually works."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So this experiment has three important points."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Number one is the original parental strands contain the N 15 isotopes and that's because they were initially grown in the N 15 rich medium b is or .2 is replicated daughter strands because now the medium is changed to the N 14."}, {"title": "Meselson and Stahl Experiment .txt", "text": "The replicated daughter strands will contain N 14 isotopes because as these daughter cells are synthesized we're going to take the nitrogen to synthesize the nitrogenous bases and sugars and so forth from this median that contains the M 14."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So the newly synthesized strands will contain the regular N 14 isotope."}, {"title": "Meselson and Stahl Experiment .txt", "text": "But the other ones, the original will contain that labeled N 15 isotope."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, why did we want to use N 15 and N 14?"}, {"title": "Meselson and Stahl Experiment .txt", "text": "Well, because they have a difference in mass the DNA molecules, the old ones and the new ones will also different mass and we can separate them via the process of centrifugation which separates bimass by size and by density."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So the DNA with different densities can be separated by centrifugation."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So what we basically do is we allow these cells, the equalized cells, to replicate, to divide and replicate and we extract the DNA."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Then we centrifuge that DNA and we analyze our DNA."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So what they obtained was the following three photographs."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So each of these photographs basically describes the band that correlates to the DNA molecules that were extracted."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So if we take out our DNA molecule from our equalized cell that has not yet divided, then what we'll see is a single band that describes a single type of DNA molecule."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, by the way, as we go this way from left to right along the x axis, we increase in density."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so if this is our test tube, this way it's towards the bottom of that test tube and this way it's towards the top of that test tube."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so if the band appears lower that means the DNA molecule that is described by that band has a higher density because the farther we go to the right along the x axis, the more dense our molecule is."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so initially what our initial sample showed was we had a single band."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now this single band basically described a single type of DNA molecule in which both of those strands consisted of that isotopic N 15 atom."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So this describes the N 15 DNA molecule and so this is what we see."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So one of these strands consists of the N 15 and the other strand also consists of the N 15."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And that's because the initial equalize cells that we took out from this beaker consisted of these radioactively labeled DNA molecules."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So before replication occurred, all cells had heavy DNA and this was represented by a single band along the following diagram."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, following one replication, when we extract the DNA from the first generation cells that came from those initial equalized cells, this is the band that we found."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And notice we also had a single band just like in this case."}, {"title": "Meselson and Stahl Experiment .txt", "text": "But this band was shifted to the left along this diagram, along the photograph."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And what this basically means is we have a single type of DNA molecule because we have that single band but it is lighter, less dense than in this particular case because it is found farther to the left along the x axis."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And that essentially confirmed the fact that after one generation, after one cycle we form one type of DNA molecule that consists of one radioactively labeled strand and one newly synthesized strand that contains the lighter N 14 isotopes."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so this is what we saw."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So one of these was N 15 and the other one was N 14 because it was synthesized using the nitrogen atoms that had an atomic mass of 14 and not 15."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And because of their lighter nature they're going to be less dense and so they're going to appear farther to the left along that x axis."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, what do they see after a second cycle of division?"}, {"title": "Meselson and Stahl Experiment .txt", "text": "So following a second division, a second replication, once we extract the DNA molecules from those cells, this is what we saw."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now we saw two individual bands and noticed that these two bands are separated."}, {"title": "Meselson and Stahl Experiment .txt", "text": "What that means is one band describes a lighter DNA molecule and the other one describes a heavier DNA molecule."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Also notice that this second band is along the same, I guess, y direction, y axis as this band here."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And that means these two bands here have the same exact heaviness have the same exact density while this band, the second band, is found farther to the left along the x axis and so it is slightly lighter."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, what exactly does that actually describe?"}, {"title": "Meselson and Stahl Experiment .txt", "text": "Well, once again, it confirms the semiconservative replication process."}, {"title": "Meselson and Stahl Experiment .txt", "text": "What that means is each one of these strands here separated."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Now, when the N 15 strand is separated, the purple one, we use the N 14 isotopes."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so we basically form this molecule right over here."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And likewise, when these two separate and when we use this purple N 15 band, what happens is we essentially form this molecule here."}, {"title": "Meselson and Stahl Experiment .txt", "text": "But when these two separate and instead we use the brown strand here and the brown strand here because we have the N 14 in our mixture and the N 14 will be used to synthesize that."}, {"title": "Meselson and Stahl Experiment .txt", "text": "Dodostran these are the DNA molecules that we're going to form and they're going to consist purely of these N 14 atoms."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And because N 14 is lighter and less dense than the N 15 this will be this band right here."}, {"title": "Meselson and Stahl Experiment .txt", "text": "So this is purely N 14 while this band here is the N 14 N 15 because it consists of a combination."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And likewise this band describes the N 14 and 15 DNA molecule in which half of it is that original parent strand and the other half is that newly synthesized N 14 lida strand."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so because these two individuals following these experiments obtained these photographs, these density distributions, they were able to basically show that the semiconservative process confirms these diagrams."}, {"title": "Meselson and Stahl Experiment .txt", "text": "And so as a result, we believe that it's the semiconservative replication process that actually correctly describes the way that DNA molecules replicate inside our cells."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Although glycolysis is a very important process, glycolysis itself is not a perfect process."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And what that means is there's a very important step that is missing in glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And actually, because this step is missing, glycolysis all by itself will not be able to continue for a very long time."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So what step is missing from glycolysis?"}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Well, let's run that."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Remember step six of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So what happened in step six?"}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Well, in step six of glycolys, that's the beginning of stage three."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "We essentially take a molecule we call gap."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So glyceroaldehyde three phosphate and we oxidize it into a molecule we call 13 BPG one three bisphosphoglyceride."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And the enzyme that catalyzes this reaction is known as gap dehydrogenase."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, for gap dehydrogenase to actually function, it must be able to use a coenzyme we call nicotine amide adenine Dinucleotide in its oxidized form, namely NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And if it can't use NAD plus, if for some reason the NAD plus is not available in a cell, this process will essentially stop."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "An entire process of glycolysis will come to stop."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, the problem with step six and the remaining steps of glycolysis is once the cell uses up NAD plus and transforms it into NADH, that NAD plus is not actually regenerated."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So in the process of glycolysis, we use up NAD plus molecules to form the nadhs."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And those NAD pluses are not actually regenerated at the end of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And because our cells have a limited supply of the NAD plus molecules, and by the way, the NAD plus molecules actually are derivatives of niacin, which is vitamin B three."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so because our cells have a limited supply of the NAD plus, this process of glycolysis will eventually come to a stop when that cell runs out of that limited supply of nicotine amyde adenine Dinucleotide."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so for this not to actually take place, something else must be done after glycolysis takes place."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So something must be done to regenerate that coenzyme the NAD plus that is necessary for the activity of gap dehydrogenase that basically catalyzes step six of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So once again, in step six of glycolysis, NAD plus nicotine amide adenine dinucleotide in the oxidized form, this is the molecule that comes from niacin, vitamin B three."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Basically, this molecule acts as a coenzyme and helps gap dehydrogenates to transform the gap molecule glyceroaldehyde three phosphate into one three bisphospho bisphosphoglycerate."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And in this process, we see that NAD plus was used up and it was never actually regenerated in the remaining steps of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so this means that glycolysis basically depends on NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And when the concentration of NAD plus basically runs out, the process of glycolysis will come to a stop and the cell will no longer be able to actually produce those ATP molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And the way that our cells fix the problem is by taking the Peruvate molecule and actually using that Peruvate molecule, metabolizing it to regenerate those NAD plus molecules so in order for Glycolysis to proceed over and over and over, the NAD plus must be regenerated."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so the cell regenerates the NAD plus by breaking down, metabolizing those pyruvate molecules produced at the end of Glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, there are two major pathways."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "We have an aerobic pathway and an anaerobic pathway."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, in aerobic, that simply means we're going to use oxygen."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And in this particular case, the pyruvate molecules travel into the mitochondria and there they're broken down into acetylcoenzyme A."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And that molecule goes into the citric acid cycle and that uses the electron transport chain to basically regenerate those NAD plus molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "But we'll focus on that process in a future lecture."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "In this lecture, I'd like to focus on the anaerobic process."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "The anaerobic process takes place in the absence of oxygen."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And our own cells and many other cells in nature use this specific type of process that we call fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, there are many different examples of fermentation processes."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "But the most common fermentation processes are those that produce lactate or ethanol from the pyruvate molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So these are known as ethanol fermentation or alcoholic fermentation or in the case of producing lactate which is actually the conjugate base of lactic acid."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "This is known as lactic acid fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So let's focus on ethanol fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So basically, yeast cells and several other bacterial cells utilize this process of fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So alcoholic fermentation to basically reform those NAD plus coenzyme molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And what happens is the pyruvate molecules ultimately are transformed into the ethanol molecule of this process actually takes place in two steps."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "The first step is a decarboxylation process and the enzyme that catalyzes this process is known as pyruvate decarboxylase."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so we begin with our pyruvate molecule and in the presence of an H plus ion as well as an important coenzyme known as thymine pyrophosphate, which actually is a thymine vitamin derivative."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So thiamine is vitamin B one."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So in the presence of this coenzyme, what will happen is this bond will be broken."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "This H plus will basically create a bond here while this carbon dioxide molecule shown in blue will be released into the environment in the gas form."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So we have this CO2 molecule in the gas form and we have this molecule basically this entire structure plus this H. And this is known as acetyl aldehyde."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, this is the first step."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And in the second step, this is when we actually produce that ethanol."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So in the first step, we have the decarboxylation reaction catalyzed by pyruvate decarboxylase the coenzyme Thiamine pyrophosphate, which is a Thiamine derivative."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So Thiamine vitamin is the vitamin B one."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "It assists in this process which transforms the pyruvate into acetal aldehyde as well as releasing this CO2 molecule shown here."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, what about step two?"}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Well, in step two we have a different enzyme and this enzyme is known as alcohol dehydrogenase."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, like any dehydrogenase, alcohol dehydrogenase will essentially catalyze the transfer of a Hydride group from that NADH onto this acetolaldehyde."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, if we examine the active side of the alcohol dehydrogenase we're going to see a zinc ion."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And what that zinc ion does?"}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Well, first of all, it interacts with the active side of that enzyme."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So it actually binds with residues on that active side."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "To be more specific, it binds with with 216 residues and one histidine residue."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And once it binds it's able to actually interact with this substrate molecule."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "It polarizes this bond, weakens the bond and that's exactly what allows the Hydride to actually attack this carbon here and then allowing the H to go into this oxygen."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so ultimately we form ethanol and we regenerate that NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now of course, because we form two Pyruvate molecules that means we have to multiply these two steps by two."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And once we multiply these two steps by two and then we sum up all the processes, the ten processes of glycolysis and we sum these as well, this is the net equation that we get."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And because we essentially regenerate that NAD plus, the NAD plus will cancel from both sides of the equation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So that does not appear in this equation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so the net equation of glycolysis following fermentation, specifically ethanol fermentation, this is our net equation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So a glucose goes in."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "We use two ATP, two orthophosphates two H plus ions and that produces two ethanol molecules, two ATP molecules, two H so molecules and two carbon dioxide molecules that came from this process."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So we multiply that by two and that's where that actually comes from."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And notice the NAD pluses and Nadhs are canceled out because they are regenerated in this step."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now what about lactic acid fermentation?"}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So lactic acid fermentation is used by many prokaryotic cells so bacterial cells that we're going to discuss in just a moment as well as many eukaryotic cells."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "In fact, the cells of our body also use under some circumstances, lactic acid fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "For instance, when we're exercising strenuously the skeletal muscles at some point will not be able to get enough oxygen and at that moment in time they have to switch to the process of lactic acid fermentation because that allows them to continually generate those ATP molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so that's exactly what allows the buildup of lactate."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So lactic acid in our body and that eventually causes fatigue."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So many prokaryotic and eukaryotic organisms undergo lactic acid fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "In fact, when the two supply runs low in our cells they use this process to regenerate the NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And this process is a single step process that essentially consists of a well, not a single step process but it's more complicated than that."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "But we can think of it as being one step in the sense that here we have two steps but here we have one step."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So essentially this process is catalyzed by an enzyme known as lactate dehydrogenase."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And again, just like this dehydrogenase and the dehydrogenase that was used in step six of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "This dehydrogenase, like any dehydrogenase, will essentially catalyze the movement, the transfer of a Hydride group from one molecule to another."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "In this case it's from this NADH onto this pyruvate molecule."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so ultimately what happens is the Hydride from this essentially goes on, attacks this carbon and then the H is picked up by the oxygen and so we form this lactate."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now if an H is picked up by this, that is what we call lactic acid."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So lactate is the conjugate base of lactic acid."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So we see that the lactate dehydrogenase catalyze the transfer of the hydrad group and so ultimately we regenerate that NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And again we have to multiply this by two because we have two pyruvate molecules coming in from the process of glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And again, if we sum up all those reactions in glycolysis and this reaction, this is the net equation that we get."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And notice it's slightly different than this equation here because here we produce carbon dioxide, but here we don't have carbon dioxide and we also don't have the two H plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So here it becomes glucose plus two ADP plus two ortho phosphates produces two lactate, two ATP and two water molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And as I mentioned just a moment ago, during strain use exercise, our skeletal muscle cells may not receive an adequate supply of oxygen and these cells will begin to undergo lactic acid fermentation to generate those ATP molecules quickly and effectively."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And in that case, there's a build up of lactate so lactic acid and that causes fatigue."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Now, our own cells are not the only cells that utilize lactic acid lactic acid fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Many bacterial cells that infect our body and many other organisms utilize lactic acid fermentation."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "For instance, three important bacterial cells that utilize lactic acid fermentation to basically generate ATP are the following."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So we have Closetridium tetani, closetium botulinum and Closetridium per fringes."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So Closetridium tetani is that bacteriosat that causes tetanus in humans, also known as lockjaw."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "We have Clostridium botulinum, which is actually the most toxic bacteria in the world."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And interestingly, this is the same bacteria that is used for the plastic surgery we call botox."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So this is the same exact bacteria that is used to make us supposedly prettier."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And then we have the Clostridium preferring."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And by the way, this also causes botulism in humans."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so Clostridium, so Clostridium, there should be an odd there."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Clostridium so Clostridium preferrings is the disease, is that bacteria that causes gangrene when we have wounds or some types of cuts."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So these can be very, very dangerous bacteria."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And these three types of bacterial cells essentially are obligate anaerobes."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And what that means is they cannot survive in the presence of oxygen and they only utilize fermentation to produce their ATP molecules."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So the takeaway lesson from this lecture is the fact that glycolysis by itself is not a perfect process."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And if it's left alone, then it will eventually end because it will run out of that supply of the coenzyme NAD plus."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "And so to regenerate that NAD plus and to make sure that the NAD plus is continually used and glycolysis is continually taking place in producing ATP molecules in our cells, we have to metabolize the Pyruvate under aerobic conditions."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "That's when the citric acid takes a citric acid cycle takes place."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "Under anaerobic conditions, we have lactate fermentation or lactic acid fermentation, ethanol, fermentations, and also many other examples of fermentation processes that we're not going to discuss in this lecture."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "So in the next lecture, we're basically going to discuss how glucose molecules are not the only molecules that can undergo glycolysis."}, {"title": "Ethanol and Lactic Acid Fermentation .txt", "text": "We have many other examples of sugars that can also enter the cycle of glycolysis, not as glucose molecules, but as something else."}, {"title": "Isozymes .txt", "text": "In order to ensure that all the different types of enzymes of our body carry out their function at the proper location and at the proper time, our body must be able to continuously monitor and regulate the activity of enzymes."}, {"title": "Isozymes .txt", "text": "And so far we discussed three different mechanisms that our body uses to regulate the activity of enzymes."}, {"title": "Isozymes .txt", "text": "So we discussed allosteric regulation, we discussed covalent modification and proteolytic activation."}, {"title": "Isozymes .txt", "text": "Now, we're going to discuss yet another mechanism that our body uses."}, {"title": "Isozymes .txt", "text": "And this mechanism involves using different forms of the same type of enzyme to carry out a single specific type of reaction that basically takes place at different locations and different times in our body."}, {"title": "Isozymes .txt", "text": "And these different forms of the same type of enzyme are known as isozymes or ISO enzymes."}, {"title": "Isozymes .txt", "text": "So isozymes generally allow our body to regulate the same type of biochemical reaction that takes place at different locations and sometimes at different times."}, {"title": "Isozymes .txt", "text": "Now, before we actually look at a specific example of ISO enzymes, let's generalize what we know about isozymes or ISO enzymes."}, {"title": "Isozymes .txt", "text": "So once again, isozymes are these different forms of the same type of enzyme and these isozymes come from different genes."}, {"title": "Isozymes .txt", "text": "And what that means is they're going to have different amino acid sequences and different threedimensional structures, but they will catalyze the same type of biochemical reaction."}, {"title": "Isozymes .txt", "text": "So we see that ISMES arise from different genes, they have different sequences of amino acids and what that means is they will generally have different biochemical properties."}, {"title": "Isozymes .txt", "text": "And this is exactly what allows us to actually separate or purify mixtures of isozymes."}, {"title": "Isozymes .txt", "text": "Now, not only that, but Icimes also generally have different enzyme kinetics."}, {"title": "Isozymes .txt", "text": "So they differ in the Km value, the mechanism constant in a turnover number Kcat, and they also differ in things like the V max, the maximum velocity at which the enzyme operates."}, {"title": "Isozymes .txt", "text": "And isozymes are also typically regulated by different types of regulatory molecules, different types of allosteric effectors."}, {"title": "Isozymes .txt", "text": "So, inside our body we have many different types of cells."}, {"title": "Isozymes .txt", "text": "And these different types of cells basically exist under slightly different conditions."}, {"title": "Isozymes .txt", "text": "Yet all these different types of cells have to carry out identical types of reactions."}, {"title": "Isozymes .txt", "text": "For instance, to see what we mean, let's imagine we have a cardiac muscle cell and a skeleton muscle cell."}, {"title": "Isozymes .txt", "text": "So we have two different types of cells that are found at two different types of locations."}, {"title": "Isozymes .txt", "text": "So cardiac muscle cells found in the heart and skeleton muscle cell is basically found around the bone."}, {"title": "Isozymes .txt", "text": "Now, cardiac muscle cells are found in a rich oxygen environment, but it's the skeleton muscle cell that is found usually in a lower oxygen environment."}, {"title": "Isozymes .txt", "text": "But both of these different types of cells found under different conditions must carry out the same type of biochemical process, namely let's say glycolysis."}, {"title": "Isozymes .txt", "text": "So they both have to be able to metabolize glycolysis glucose in the process of glycolysis."}, {"title": "Isozymes .txt", "text": "And in fact, skeleton muscle cells and cardiac muscle cells actually use ISMES in the process of glycolysis."}, {"title": "Isozymes .txt", "text": "So remember a specific type of enzyme that we spoke of previously."}, {"title": "Isozymes .txt", "text": "So we discussed lactate dehydrogenase and we said that lactate dehydrogenase is an enzyme that is basically involved in glucose metabolism."}, {"title": "Isozymes .txt", "text": "And more specifically, what it does is it transforms pyruvate into lactic acid, it reduces pyruvate into lactic acid and that at the same time oxidizes NADH into NAD plus."}, {"title": "Isozymes .txt", "text": "And what that allows us to do is it allows us to regenerate NAD plus."}, {"title": "Isozymes .txt", "text": "And so that means we can basically restart another cycle of glycolysis."}, {"title": "Isozymes .txt", "text": "So we see that lactate dehydrogenase catalyzes the reduction of pyruvate into lactic acid at the same time and oxidizes NADH into NAD plus."}, {"title": "Isozymes .txt", "text": "Now, if we examine the quadrantary structure of lactate dehydrogenase LDH, we're going to see that it consists of four individual polypeptide chains."}, {"title": "Isozymes .txt", "text": "And inside our body, in the human body, we have two types of these polypeptide chains that can constitute lactate dehydrogenase."}, {"title": "Isozymes .txt", "text": "So humans have two isozymic chains for lactate dehydrogenase."}, {"title": "Isozymes .txt", "text": "We have the H ISome chain and we have the misozyme chain."}, {"title": "Isozymes .txt", "text": "And it's the H isime chain that is expressed predominantly in high concentration in the cardiac muscle cell."}, {"title": "Isozymes .txt", "text": "And it's the mike chain that is expressed in high concentration predominantly in the skeletal muscle cell."}, {"title": "Isozymes .txt", "text": "So if we examine the lactate dehydrogenase in skeletal muscle cells, we're basically going to find a quaternary structure that consists of these four individual chains, where these four individual chains are all the Mi design chains."}, {"title": "Isozymes .txt", "text": "So each one of these red chains is basically that Mi design chain."}, {"title": "Isozymes .txt", "text": "On the other hand, if we study the cardiac muscle cells, we're going to see the coronary structure of the LDH basically consists of four individual H I design chains and these are shown in purple."}, {"title": "Isozymes .txt", "text": "So this lactate dehydrogenase, which is basically denoted with H four, where H means we have the H ISome and four means we have four of these individual A chains."}, {"title": "Isozymes .txt", "text": "So we have this lactate dehydrogenase is made up of four A chains and it's found in cardiac muscle cells, while the M four, which basically consists of these four individual M isotime chains, makes up the LDH that predominates in skeletal muscle cells."}, {"title": "Isozymes .txt", "text": "So we see that it's this molecule, the M four, that operates at a maximum efficiency inside skeleton muscle cells where we typically have a lower oxygen concentration."}, {"title": "Isozymes .txt", "text": "But it's this purple H four LDH molecule that predominates in cardiac muscle cell which operates at a maximum efficiency when there's a high concentration of oxygen, as we typically find in the heart, in the cardiac muscle cell."}, {"title": "Isozymes .txt", "text": "So these are what isoenzymes are."}, {"title": "Isozymes .txt", "text": "So isozymes or isoenzymes are these multiple different forms of the same type of enzyme that catalyzes the same type of biochemical reaction that takes place at different locations and ore at different times."}, {"title": "Isozymes .txt", "text": "Now let's see how we can apply this to our body, to the field of medicine."}, {"title": "Isozymes .txt", "text": "So remember, that a heart attack, also known as a myocardial infraction is basically the condition by which we have a partial blockage of the blood flow to the heart of our body."}, {"title": "Isozymes .txt", "text": "For instance, previously we discussed that if we block if we create some type of embolism inside the coronary artery of our heart, that will lead to a heart attack."}, {"title": "Isozymes .txt", "text": "Now, if there's a partial blockage of blood flow to the heart, that will cause damage inside the cardiac muscle of the heart."}, {"title": "Isozymes .txt", "text": "And if the cardiac muscle cell is damaged, it will begin releasing its internal components, and that includes releasing the H four LDH molecule."}, {"title": "Isozymes .txt", "text": "Now, as the cardiac muscle is damaged, releasing the H four LDH into the blood will increase the relative concentration of this molecule inside of the blood."}, {"title": "Isozymes .txt", "text": "And this molecule is typically not found in a specific high concentration inside our blood."}, {"title": "Isozymes .txt", "text": "So physicians can basically test for the presence of elevated H four concentration in the blood."}, {"title": "Isozymes .txt", "text": "And this can basically help them show or help them discover the fact that this individual has experienced a myocardial infraction or a heart attack."}, {"title": "Isozymes .txt", "text": "So we see that not only can our body control and regulate enzyme activity by using these three different types of mechanisms, it can also use is and isozymes."}, {"title": "Isozymes .txt", "text": "Are these different forms of the same type of enzyme that carries out a specific type of biochemical process that takes place at different locations and at different times."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So let's take a small section of the membrane that we typically find in closing the cells of our body."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "This is what we're going to get."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So let's say this is the outside, this is the inside."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And because we have a bilayer membrane, we have two layers."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Let's call this the outer leaflet that points towards the outside."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "This the inner leaflet that point towards the side of plasma."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, if we take take a line and we draw a line that separates the membrane in half, like so, we'll see that this side is not the same as this side."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "These two leaflets are not identical."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And that implies that the plasma membrane is asymmetric."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So the two leaflets, the two sides of the membrane are structurally and functionally not the same."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, what factors contribute to the asymmetry of the plasma membrane?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we have to consider three things."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Number one is there is a difference in the composition of the proteins and lipids and carbohydrates found on the two sides of the membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So for instance, in this particular case, we have glycolipids and glycoproteins on this side that we don't find on the other side."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And likewise, we have the peripheral protein that we find on this side and don't find on the other side."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Number two is we have asymmetry because of the difference in the positioning and the orientation of proteins."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "For instance, if we look at this transmembrane protein, this is oriented in such a way so that this side only contains the peripheral component protein and not this side."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And number three is there is asymmetry as a result of a difference in the enzymatic activities of the two sides."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Basically, those reactions that take place on this side of the membrane don't take place on this side and vice versa."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "For instance, if a protein needs to use ATP molecules, the ATP molecules are only found in the cytoplasm."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so that protein component can only interact with the ATP from the cytoplasmic side of the membrane, as we'll discuss in more detail in just a moment."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, why is asymmetry so prevalent?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So every single plasma membrane basically is asymmetric."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Why?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Well, asymmetry is actually crucial for the proper functioning of that membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So to see what we mean to demonstrate, let's study the ATP or the sodium potassium ATP pump found in every single cell of our body."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So this is what it basically looks like."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And what it is is it's this pump that utilizes ATP molecules to create an electrochemical gradient and it pumps the sodium ions to the outside and the potassium ions to the inside."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, because it uses ATP molecules, ATP molecules are only found in the cytoplasm."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And what that means is this protein has to be positioned in the proper orientation so that the proper side can actually interact with the ATP molecule."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And this has to be positioned in the proper orientation because we want to move the sodium this way and the potassium this way, and not in the opposite direction."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so we see that the proper positioning of this protein within the membrane determines its functionality."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And this cell as a whole must be able to actually use the ATP and pump these in the proper directionality to basically establish that electrochemical gradient."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so we see that asymmetry is very important to the functionality of the cell membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, when we synthesize these proteins in the ribosomes of our cell, these proteins as well as lipids actually are placed into the membrane in an asymmetric fashion."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we essentially place these proteins asymmetrically."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so we create this asymmetry in the membrane as a result of the difference in the composition and the positioning and orientation of the proteins."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "But the question is, how is this asymmetry?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "How is this asymmetric nature of the membrane actually retained?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "How is it preserved over time?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So what exactly prevents, for instance, these two proteins from actually oring themselves and flipping to the other side?"}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Well, basically, when we discussed flip flopping, or also known as transverse diffusion, we said that proteins cannot actually rotate from one leaflet to the other leaflet, and that's because when they rotate, that is energetically unfavorable, because the proteins contain extensive hydrophilic."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So polar regions, when they rotate, that means the polar regions must interact with the hydrophobic core of the membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And that is too energetically unfavorable."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "The energy is very high for that reaction and it doesn't actually take place."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so we see that proteins do not flip flop."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "They cannot rotate or move from one leaflet to the opposing leaflet."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so we see that this is precisely what prevents the asymmetry from being lost."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So the membrane asymmetry is preserved over long periods of time, because membrane proteins do not actually rotate from one side of the membrane to the other side of the membrane, because this is too energetically unfavorable."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, in addition, what also retains or preserves the asymmetry of the membrane is the fact that membranes are always constructed from preexisting membranes, and those preexisting membranes are always asymmetric."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So, in the same way that to actually create a cell, we have to begin with a cell, to create a membrane, we have to begin with the membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So when we're building our cell membrane, we build it by essentially expanding the preexisting membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And that preexisting membrane basically was asymmetric to begin with."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we see that, in addition, asymmetry is also preserved because membranes always arise and grow and extend from preexisting membranes, which are asymmetric to begin with."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, in our discussion here, we said that the difference in the composition of not only the proteins but also the lipids basically gives this membrane the property of asymmetry."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So now let's move on from proteins to lipids."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we know that just like proteins are synthesized and eventually placed into the membrane in an asymmetric fashion, lipids are also synthesized and inserting to the membrane asymmetrically."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "However, the thing about lipids is, so fossil lipids is they can actually flip flop, they can actually rotate."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so what that implies is, unlike the absolute configuration, unlike the absolute asymmetry of the proteins in the membrane that basically do not change because they cannot flip flop, the asymmetry of the membrane due to the lipids does in fact change over time."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "It is not absolute because these lipids can actually rotate, can actually flip flop from one leaflet to the other."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we see that however, lipids such as fossil lipids can actually flip flop and therefore the asymmetry of the fossil lipids in that membrane does not remain absolute, it changes over time."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "However, we know that flip flopping of fossil lipids actually takes place very, very slowly because it is also energetically unfavorable."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "In fact, certain lipids, such as Glycolipids that contain very large components that are polar, cannot actually rotate because of those polar interactions, because these polar interactions will be unstabilized when they interact with that core hydrophobic region."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "And so, just like proteins, glycolipids cannot actually flip flop or rotate."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "Now, nevertheless, we see that lipids such as glycolipids and spingolipids can and do lead to asymmetry of the membrane."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So basically, because the flip flopping process takes place so long, takes place not so long, but takes place so slow, and because certain lipids, like Glycolipids can have actually rotate, we see that lipids also, just like proteins, actually contribute to the asymmetric nature of membranes."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "In fact, if we study the membranes of red blood cells, we'll see that the outside layer of the red blood cell membrane consists of these two lipids."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So, these two lipids are found in high proportion on the outside of the membrane, while the inside contains these two lipids in high proportion."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we find fingomyeline and phosphatel choline on the outside, and these two are found predominantly on the inside."}, {"title": "Asymmetry of Cell Membrane .txt", "text": "So we see that it's not only the proteins, but also the lipids that basically give rise to the asymmetric nature of the phospholipid bilayer membrane."}, {"title": "Introduction to DNA.txt", "text": "DNA, which stands for deoxyribonucleic acid, is a very important biological molecule whose function is to store the genetic information that is found within the cell."}, {"title": "Introduction to DNA.txt", "text": "So the cell, including eukaryotic and prokaryotic cells, can use the DNA molecules to synthesize proteins and enzymes that are necessary for the cell survival."}, {"title": "Introduction to DNA.txt", "text": "And in fact, whenever our cell or organism reproduces, each individual cell must replicate the DNA molecule and pass it down to the offspring."}, {"title": "Introduction to DNA.txt", "text": "Now, what exactly is the composition of DNA?"}, {"title": "Introduction to DNA.txt", "text": "So, in the same way that proteins consist of individual units known as amino acids, DNA molecules are also polymers, meaning they consist of individual subunits known as nucleotides."}, {"title": "Introduction to DNA.txt", "text": "And any given nucleotide consists of three parts."}, {"title": "Introduction to DNA.txt", "text": "So we have a deoxyribo sugar, which is a five member sugar."}, {"title": "Introduction to DNA.txt", "text": "We have a nitrogenous base and we also have our phosphate group."}, {"title": "Introduction to DNA.txt", "text": "Now, what exactly is the structure or arrangement of these three different types of sections or groups within our nucleotide?"}, {"title": "Introduction to DNA.txt", "text": "So this is one example of a nucleotide."}, {"title": "Introduction to DNA.txt", "text": "We have our base, the nitrogenous base, attached to our center sugar, which is also attached to our phosphate group."}, {"title": "Introduction to DNA.txt", "text": "Now, there are four different types of nitrogenous bases."}, {"title": "Introduction to DNA.txt", "text": "We have adenine, guanine, cytosine and thymine."}, {"title": "Introduction to DNA.txt", "text": "Now, adenine and guanine, or simply A and g are two types of nitrogenous bases that consist of two rings."}, {"title": "Introduction to DNA.txt", "text": "And these types of nitrogenous bases that consist of two rings are known as purines."}, {"title": "Introduction to DNA.txt", "text": "And notice thymine and cytosine or TNC consist of only a single ring structure."}, {"title": "Introduction to DNA.txt", "text": "And these types of nitrogenous bases are known as pyrimidines."}, {"title": "Introduction to DNA.txt", "text": "So let's look at the arrangement of our nucleotide and how the nucleotides bond to one another."}, {"title": "Introduction to DNA.txt", "text": "So remember, in a protein we have amino acids that bond to one another via covalent bonds known as dipeptide or peptide bonds."}, {"title": "Introduction to DNA.txt", "text": "In the case of DNA, the individual subunits known as nucleotides bond to one another via bond, known as a phosphol diaster bond."}, {"title": "Introduction to DNA.txt", "text": "So let's take a look at the following molecules."}, {"title": "Introduction to DNA.txt", "text": "So we have one nucleotide and a second nucleotide."}, {"title": "Introduction to DNA.txt", "text": "And notice that these two nucleotides bond to one another via the phosphol diaster bond."}, {"title": "Introduction to DNA.txt", "text": "So we have the phosphorus atom and we also have the two aster bonds shown here."}, {"title": "Introduction to DNA.txt", "text": "And that's exactly why it's called a phosphodia ester bond."}, {"title": "Introduction to DNA.txt", "text": "Now, notice that the bonding takes place between the third carbon of one sugar and the fifth carbon of the second sugar."}, {"title": "Introduction to DNA.txt", "text": "And that's exactly why this is called a three to five bond."}, {"title": "Introduction to DNA.txt", "text": "So this is our phosphol diester bond."}, {"title": "Introduction to DNA.txt", "text": "So notice that because there are four different types of nitrogenous bases, that means there are four different types of nucleotides."}, {"title": "Introduction to DNA.txt", "text": "And it is very common to call our nucleotide by the type of nitrogenous base that it contains."}, {"title": "Introduction to DNA.txt", "text": "So for example, because this nucleotide contains the guanine nitrogenous base, we simply call the nucleotide the guanine."}, {"title": "Introduction to DNA.txt", "text": "And because this contains the adenine nitrogenous base, this nucleotide can be called simply the adenine nucleotide."}, {"title": "Introduction to DNA.txt", "text": "So we have one nucleotide bonds to a second nucleotide via this phosphodia ester bond."}, {"title": "Introduction to DNA.txt", "text": "Now, DNA in cells, specifically in human cells, doesn't actually exist as a single strand of DNA."}, {"title": "Introduction to DNA.txt", "text": "In fact, two strands of DNA that are complementary to one another actually bind to form a double stranded DNA."}, {"title": "Introduction to DNA.txt", "text": "And that double stranded DNA forms a coil that we call the double helix."}, {"title": "Introduction to DNA.txt", "text": "And the two single stranded DNAs bond to one another via a special type of dipole dipole bond known as hydrogen bonds."}, {"title": "Introduction to DNA.txt", "text": "So the thing that holds our two strands of DNA together to form our double helix are hydrogen bondings or hydrogen bonds between adjacent or opposite nucleotide, specifically our nitrogenous basis."}, {"title": "Introduction to DNA.txt", "text": "So we have this nucleotide, which is right next to this nucleotide, and the bonding takes place between our adjacent or complementary nitrogenous bases."}, {"title": "Introduction to DNA.txt", "text": "So guanine always forms hydrogen bonds with cytosine, while our Adamine always forms hydrogen bonds with arithymine."}, {"title": "Introduction to DNA.txt", "text": "And notice in the case of guanine and cytosine, we have three hydrogen bonds."}, {"title": "Introduction to DNA.txt", "text": "And in the case of adenine and thymine, we only have two of these hydrogen bonds."}, {"title": "Introduction to DNA.txt", "text": "So that means the guanine cytosine pair forms a more stable attraction than our adenine, thymine."}, {"title": "Introduction to DNA.txt", "text": "So if a given DNA molecule contains more guanine cytosine pairs, that means the bonding between our two single stranded DNA molecules is stronger."}, {"title": "Introduction to DNA.txt", "text": "Now, one other important thing that we have to mention about the double helix is the directionality of our single stranded DNA."}, {"title": "Introduction to DNA.txt", "text": "So let's take a look at this single stranded DNA that only consists of two nucleotides."}, {"title": "Introduction to DNA.txt", "text": "So we have the guanine and the anine."}, {"title": "Introduction to DNA.txt", "text": "Notice that the guanine begins on our five carbon and it goes down to our three carbon, while the second single stranded DNA begins with the third carbon and goes down to the fifth carbon."}, {"title": "Introduction to DNA.txt", "text": "And this type of opposite or reverse arrangement is known as antiparallel."}, {"title": "Introduction to DNA.txt", "text": "That is, the two single stranded DNA, this one and this one run in the parallel direction, but they run in the opposite direction, meaning that this goes from the five to the three carbon and this runs from the three to the five carbon."}, {"title": "Introduction to DNA.txt", "text": "So once again, we have our notice that if the first strand runs in the five three direction, then the complementary strand must run in the reverse three to five direction."}, {"title": "Introduction to DNA.txt", "text": "And this type of arrangement is known as antiparallel."}, {"title": "Introduction to DNA.txt", "text": "And the reason the two DNA molecules run antiparallel is to ensure that the bonding between our nitrogenous bases is exactly right, so that we create strong bonds between our two DNA molecules and so that our double stranded DNA molecule basically doesn't unzip itself spontaneously."}, {"title": "Introduction to DNA.txt", "text": "So this is a slightly better description of our DNA molecule because this shows our double helix structure."}, {"title": "Introduction to DNA.txt", "text": "So we have the blue and our purple strand."}, {"title": "Introduction to DNA.txt", "text": "So the blue one begins at the five end and goes all the way to the three N, while the pink begins at the three N and goes all the way to the five end."}, {"title": "Introduction to DNA.txt", "text": "And this is what we mean by the antiparallel directionality, where one of our single stranded DNA runs from the five to three, while the other one runs from the three to five."}, {"title": "Introduction to DNA.txt", "text": "Now, one other thing that we have to notice is that the sugar as well as the phosphate within our double stranded DNA points outside of that DNA while inside that double stranded DNA double helix structure, we have our nitrogenous basis."}, {"title": "Introduction to DNA.txt", "text": "So that is shown by the following diagram."}, {"title": "Introduction to DNA.txt", "text": "So this line basically represents the sugar and the phosphate, while these squares represent our nitrogenous bases."}, {"title": "Introduction to DNA.txt", "text": "And our nitrogenous bases are basically protected and are found inside our double stranded DNA molecule."}, {"title": "Introduction to DNA.txt", "text": "And that means our bonds can form and those bonds are not disrupted by any type of outside force that is found on the outside of that double stranded DNA molecule."}, {"title": "Introduction to DNA.txt", "text": "Of course, if we, for example, increase the temperature, eventually a temperature will be reached where these bonds will break, regardless of the fact that our nitrogenous bases are found inside that DNA molecule."}, {"title": "Introduction to DNA.txt", "text": "So once again, DNA is basically a polymer molecule that contains nucleotides."}, {"title": "Introduction to DNA.txt", "text": "And any given nucleotide consists of three sections."}, {"title": "Introduction to DNA.txt", "text": "We have the sugar, the nitrogenous base and our phosphate group."}, {"title": "Introduction to DNA.txt", "text": "And there are four different types of nitrogenous bases."}, {"title": "Introduction to DNA.txt", "text": "The purines are adenine and guanine, while our perimeterines are thymine and cytosine."}, {"title": "Introduction to DNA.txt", "text": "Now, the way that our two antiparall singlestranded DNA bonds together is via hydrogen bonds between our adjacent nitrogenous bases."}, {"title": "Introduction to DNA.txt", "text": "So guanine nitrogenous base always forms bonds with cytotine while adenine always forms bonds with thymine."}, {"title": "Introduction to DNA.txt", "text": "And notice that the way our individual nucleotides in any single stranded DNA form our bonds is via these special types of bonds known as phosphodiester bonds."}, {"title": "Generation of Action Potential.txt", "text": "So, now that we discussed voltagegated and ligandgated ion channels, let's see how we can combine these two channels to basically generate an action potential along the membrane of a neuron."}, {"title": "Generation of Action Potential.txt", "text": "And let's begin with the following diagram."}, {"title": "Generation of Action Potential.txt", "text": "So, in this diagram, we actually have two neurons."}, {"title": "Generation of Action Potential.txt", "text": "This is known as the presynaptic neuron, and this is known as the postsynaptic neuron."}, {"title": "Generation of Action Potential.txt", "text": "And so the question is, how can we actually generate an action potential on this membrane of the post synaptic nerve cell?"}, {"title": "Generation of Action Potential.txt", "text": "And to begin, let's actually look at this axon terminal of the presynaptic nerve cell."}, {"title": "Generation of Action Potential.txt", "text": "So along the axon HALOCK of this presynaptic nerve cell, an action potential is generated."}, {"title": "Generation of Action Potential.txt", "text": "And that action potential propagates all the way to the axon terminal of this cell."}, {"title": "Generation of Action Potential.txt", "text": "And once at the axon terminal, it basically stimulates the release of hundreds of these vesicles that carry acetylcholine molecules."}, {"title": "Generation of Action Potential.txt", "text": "So these vesicles containing acetylcholine are released into this area known as the synaptic cleft, and it travels along that synaptic cleft, and these acetylcholine ultimately end up binding onto special ligand gated I channels we call acetylcholine receptors, which are these protein membranes shown here."}, {"title": "Generation of Action Potential.txt", "text": "Now, when they bind, they cause the opening of these ligand gated ion channels."}, {"title": "Generation of Action Potential.txt", "text": "And the thing about these ligangated ion channels is they're nonspecific."}, {"title": "Generation of Action Potential.txt", "text": "And what that means is they will allow the movement of not only the sodium ions down their electrochemical gradient, but also allow the movement of these potassium down their electrochemical gradient."}, {"title": "Generation of Action Potential.txt", "text": "And so we know that we have many more potassium molecules on the inside than on the outside."}, {"title": "Generation of Action Potential.txt", "text": "And so these potassium molecules sorry, these potassium mines will move spontaneously in this direction, while at the same time, because we have many more sodium on the outside than the inside, these sodium ions will move spontaneously into the cell."}, {"title": "Generation of Action Potential.txt", "text": "And as they move along their electrochemical gradient, they will cause an increase in the voltage difference across the cell membrane."}, {"title": "Generation of Action Potential.txt", "text": "So remember, for a neuron, the resting membrane potential is around negative 70 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "And so as a result of this, the voltage will actually begin to increase."}, {"title": "Generation of Action Potential.txt", "text": "Now, if the voltage increases to about negative 40 millivolts, this voltage is known as the threshold voltage."}, {"title": "Generation of Action Potential.txt", "text": "Why?"}, {"title": "Generation of Action Potential.txt", "text": "Well, because this is the voltage that is needed to activate the voltage gated on channels."}, {"title": "Generation of Action Potential.txt", "text": "And this includes not only the sodium, but also the potassium voltage gated on channels."}, {"title": "Generation of Action Potential.txt", "text": "So as the voltage increases from the resting membrane potential of about negative 70 millivolts to about negative 40 millivolts, the voltage gated sodium channels begin to open, and they open very quickly."}, {"title": "Generation of Action Potential.txt", "text": "And this is what initiates the action potential."}, {"title": "Generation of Action Potential.txt", "text": "And the value of negative 70 millivolts is known as the threshold value."}, {"title": "Generation of Action Potential.txt", "text": "So as soon as we reach this threshold value, that will initiate that action potential."}, {"title": "Generation of Action Potential.txt", "text": "If that value is not reached when this movement takes place, the no action potential is actually generated."}, {"title": "Generation of Action Potential.txt", "text": "So we have to reach that value."}, {"title": "Generation of Action Potential.txt", "text": "So let's assume that value is in fact, reached."}, {"title": "Generation of Action Potential.txt", "text": "So once we reach this value, we have a very rapid opening of these sodium voltage gated on channels."}, {"title": "Generation of Action Potential.txt", "text": "So let's take a look at the following diagram."}, {"title": "Generation of Action Potential.txt", "text": "So, when the membrane is at a resting memory potential of negative 70 millivolts, this structure is basically in its closed form."}, {"title": "Generation of Action Potential.txt", "text": "And this is the voltage gated sodium ion channel."}, {"title": "Generation of Action Potential.txt", "text": "Now, what happens when we go from this voltage difference to this voltage difference?"}, {"title": "Generation of Action Potential.txt", "text": "These paddle domains essentially orient themselves upward."}, {"title": "Generation of Action Potential.txt", "text": "And as they move from this orientation to this orientation, that opens, that widens that pore on this side of the membrane."}, {"title": "Generation of Action Potential.txt", "text": "And as soon as that pore widens, that creates the open state."}, {"title": "Generation of Action Potential.txt", "text": "And the sodium ions can basically move down their electrochemical gradient from a high outside concentration to a low inside concentration."}, {"title": "Generation of Action Potential.txt", "text": "So basically, this area is known as the depolarization period."}, {"title": "Generation of Action Potential.txt", "text": "And what that means is, because of the rapid opening of many of these voltage gated sodium ion channels, we have a rapid influx of these sodium ions into the cell."}, {"title": "Generation of Action Potential.txt", "text": "And so many of these positively charged sodium ions move into the cell."}, {"title": "Generation of Action Potential.txt", "text": "And that makes the inside of the cell positive with respect to the outside."}, {"title": "Generation of Action Potential.txt", "text": "And that's exactly why we increase the value to about positive 30 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "Now, notice it increases, but we don't actually get to the positive 60 millivolt value, which is what the sodium voltage is at equilibrium."}, {"title": "Generation of Action Potential.txt", "text": "And that's because as we begin to approach this value, some of these actually become inactivated."}, {"title": "Generation of Action Potential.txt", "text": "So remember, about a millisecond after we actually open these channels, they begin to close as a result of the occlusion, as a result of the blocking action of this chain."}, {"title": "Generation of Action Potential.txt", "text": "So, based on the ball and chain model, we know that this ball will basically move into that pore and that will block and inactivate the movement of these ions."}, {"title": "Generation of Action Potential.txt", "text": "And so that's exactly what happens in this region at the peak of this graph."}, {"title": "Generation of Action Potential.txt", "text": "Now, at the same exact time."}, {"title": "Generation of Action Potential.txt", "text": "Oh, and by the way, if we go back to this section here."}, {"title": "Generation of Action Potential.txt", "text": "So here I said that we have the opening of these voltage gated sodium channels, but the voltage gated sodium channels are not the only ones to open."}, {"title": "Generation of Action Potential.txt", "text": "We also have the opening of the potassium voltage gated on channels."}, {"title": "Generation of Action Potential.txt", "text": "But these potassium voltage gate on channels are very, very slow to open."}, {"title": "Generation of Action Potential.txt", "text": "On the contrary, the sodium voltage gated on channels open up very, very quickly."}, {"title": "Generation of Action Potential.txt", "text": "And so that's exactly why we have this deep polarization period, a rapid increase to a positive value of that potential."}, {"title": "Generation of Action Potential.txt", "text": "So the opening of the voltage gated sodium channels leads to a rapid rise in the membrane potential."}, {"title": "Generation of Action Potential.txt", "text": "Now, although the voltage gated potassium channels are slow to open, they too begin to open."}, {"title": "Generation of Action Potential.txt", "text": "But they open very slowly."}, {"title": "Generation of Action Potential.txt", "text": "But after about one millisecond of the opening of these sodium voltage gate on channels, they begin to close as a result of the inactivation of this ball."}, {"title": "Generation of Action Potential.txt", "text": "So this ball domain enters this section and it blocks that pore as shown in this particular diagram."}, {"title": "Generation of Action Potential.txt", "text": "And so now the sodium ion channels, the sodium ions can no longer move into the cell at the same moment in time."}, {"title": "Generation of Action Potential.txt", "text": "So in this region, we have the quickening of the opening process of these potassium voltage gated on channels, and so they begin to open up."}, {"title": "Generation of Action Potential.txt", "text": "So essentially the same exact thing happens as in this particular case."}, {"title": "Generation of Action Potential.txt", "text": "These paddle domains basically begin to orient themselves as a result of that depolarization of the membrane."}, {"title": "Generation of Action Potential.txt", "text": "And so, when this orients upward, that opens and winds the port at the bottom."}, {"title": "Generation of Action Potential.txt", "text": "And that allows the movement of these potassium odds down their electrochemical gradient."}, {"title": "Generation of Action Potential.txt", "text": "And unlike in this case, the electrochemical gradient basically tells us that these potassium mons will move from the inside to the outside of the south."}, {"title": "Generation of Action Potential.txt", "text": "And this takes place here."}, {"title": "Generation of Action Potential.txt", "text": "So basically, what we see happening is the sodium ions can no longer flow into that cell, while at the same time, these potassium ions begin to flow out of the cell."}, {"title": "Generation of Action Potential.txt", "text": "And what that means is the positive charge inside the cell will begin to decrease."}, {"title": "Generation of Action Potential.txt", "text": "And so that means we'll see a drop in that voltage difference between the membrane."}, {"title": "Generation of Action Potential.txt", "text": "And so, because of that, this is known as the repolarization period."}, {"title": "Generation of Action Potential.txt", "text": "So it tries to repolarize and return that voltage to its resting membrane potential of about negative 70 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "But let's see what happens."}, {"title": "Generation of Action Potential.txt", "text": "Notice that it actually drops below the negative 70 millivolts value."}, {"title": "Generation of Action Potential.txt", "text": "And that's because many of these voltage gated potassium ions actually open."}, {"title": "Generation of Action Potential.txt", "text": "And so we have this outflux of these potassium ions out of the cell, and that causes a hyperpolarization period."}, {"title": "Generation of Action Potential.txt", "text": "So hyperpolarization basically means it drops the value below that resting memory potential to a value of about negative 80 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "So the inactivation of the sodium channels and at the same time, the opening of those potassium voltage gated on channels causes the outflux of positive charge out of that cell."}, {"title": "Generation of Action Potential.txt", "text": "And so this rapid drop causes hyperpolarization such that the membrane potential drops below the resting potential of negative 70 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "Now, after about two milliseconds from where everything essentially begun, what begins to happen is as a result of this drop in voltage, these voltage gated potassium ions will begin to close and some of them will also become inactivated in the same method that we discussed here."}, {"title": "Generation of Action Potential.txt", "text": "So the ball will basically enter that port section that will close that channel and will prevent the movement of these potassium potassium ions."}, {"title": "Generation of Action Potential.txt", "text": "And so what happens is, as both of these are closed and inactivated, we'll see that eventually that voltage difference will approach that resting membrane potential."}, {"title": "Generation of Action Potential.txt", "text": "In fact, the sodium potassium Atph pump actually is also used to help return this voltage to its original resting membrane potential."}, {"title": "Generation of Action Potential.txt", "text": "And that happens around this section."}, {"title": "Generation of Action Potential.txt", "text": "So, once again, let's summarize how these two types of ion channels, the voltage gated ion channels and the ligand gated ion channels actually work together."}, {"title": "Generation of Action Potential.txt", "text": "And let's take a look at this diagram."}, {"title": "Generation of Action Potential.txt", "text": "So, in this section, we basically have the action of that acetylcholine receptor."}, {"title": "Generation of Action Potential.txt", "text": "So as it is opened up as a result of the binding of that ligand, the acetylcholine, it causes an increase in that voltage value."}, {"title": "Generation of Action Potential.txt", "text": "And eventually, if that voltage reaches the threshold voltage, it causes the rapid opening of the voltage gated sodium ion channels."}, {"title": "Generation of Action Potential.txt", "text": "At the same time, it causes a slow opening of those potassium voltage gated ion channels."}, {"title": "Generation of Action Potential.txt", "text": "And so, because we have the rapid opening of these voltage gated sodium ion channels, these sodium ions move into the cell and that makes the inside positive with respect to the outside."}, {"title": "Generation of Action Potential.txt", "text": "And that's why it shoots up."}, {"title": "Generation of Action Potential.txt", "text": "And this is known as the depolarization period, because we change the charge values on that cell membrane."}, {"title": "Generation of Action Potential.txt", "text": "So before, during the resting memory potential, the inside was negative, the outside was positive, and now it essentially reverses."}, {"title": "Generation of Action Potential.txt", "text": "So the inside becomes positive, the outside becomes negative."}, {"title": "Generation of Action Potential.txt", "text": "And that's where we're in this period here."}, {"title": "Generation of Action Potential.txt", "text": "So it reaches a peak of about positive 30 millivolts and it never actually reaches this value here."}, {"title": "Generation of Action Potential.txt", "text": "And that's because now these become inactivated."}, {"title": "Generation of Action Potential.txt", "text": "So as a result of this ball, it basically goes into that pore and then inactivates that protein."}, {"title": "Generation of Action Potential.txt", "text": "And it basically prevents the movement of those ions across the cell membrane."}, {"title": "Generation of Action Potential.txt", "text": "And that happens here."}, {"title": "Generation of Action Potential.txt", "text": "At the same exact time, those voltage gated potassium ions that were slow to open, now open up much, much quicker."}, {"title": "Generation of Action Potential.txt", "text": "And so, because we have the closure of these and the opening of the potassium voltage gate on challenge, now the positive charge begins to move out of the cell."}, {"title": "Generation of Action Potential.txt", "text": "And this is known as repolarization, because as the charge moves out, the inside of the membrane will once again become negatively charged."}, {"title": "Generation of Action Potential.txt", "text": "And so, because we have the inactivation of these potassium of these sodium voltage gate channels and the activation of these potassium voltage gate on channels, it actually goes below that negative 70 millivolt value."}, {"title": "Generation of Action Potential.txt", "text": "And this is known as the hyperpolarization period."}, {"title": "Generation of Action Potential.txt", "text": "And eventually there will be a closure and in some cases, an inactivation of these potassium voltage gate on channels."}, {"title": "Generation of Action Potential.txt", "text": "And so that will basically help return that voltage difference back to normal."}, {"title": "Generation of Action Potential.txt", "text": "Of course, with the help of that sodium potassium Atpace pump, eventually that resting membrane potential is returned back to normal to value of negative 70 millivolts."}, {"title": "Generation of Action Potential.txt", "text": "And at that moment in time, these are basically returned back to this stage and this stage and that cycle can basically repeat itself once again."}, {"title": "Generation of Action Potential.txt", "text": "So this is how these two online channels work together to basically generate that action potential."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "In our introduction to Proteolytic cleavage, we mentioned that digestive enzymes are examples of enzymes found inside our body which are activated proteolytically."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so this is what I'd like to focus on in this lecture."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And I'd like to begin by focusing on a specific digestive enzyme found inside our body known as Chimetrypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, actually, we already spoke about Chimotrypsin in detail when we discuss proteases."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And we said that Chimotrypsin is actually an example of a serene protease that breaks peptide bonds on the carboxyl side of specific amino acids, those amino acids that contain bulky hydrophobic aromatic side chains."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, Chimetrypsin is initially synthesized in a Zymogen form in the inactive form."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And the Zymogen form of China trypsin is known as Chimotrypcinogen."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And Chimitripcinogen is a single polypeptide chain that consists of 245 individual amino acids."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, the Chimitripcinogen is not fully functional."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "In fact, it's not functional at all."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And that's because the active side and the oxyanion whole of this particular Zymogen is not yet formed."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "It's not in the proper confirmation to be able to actually fit this substrate molecule."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So what has to happen is this Chimotrypcinogen has to actually be activated proteolytically."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And we'll see how that happens in just a moment."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "First, let's actually discuss where the Chimotrypcinogen is formed."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So if we study the pancreas of our body, in the pancreas, we're going to find these special cells, exercise cells known as acinor cells."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And it's the asinr cells of the pancreas which are responsible for forming this Chimetrypcinogen, as well as other digestive zymogens."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And all these Xiaomogens are essentially stored in membrane bound organelles, in membrane bound granules shown in green."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so all these granules that contain the zymogens basically accumulate on the apex side of these asinr cells."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And when the cell is stimulated by some type of hormone or some type of action potential, these granules basically exit the cell via exocytosis and they release all these zymogens into the duct."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And then the duct basically empties out into a larger duct which eventually empties out into the pancreatic duct."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And it's the pancreatic duct that connects directly to the initial portion of the small intestine we call the duodenum."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And once these zymogens are inside the intestine, they only begin to cleave those proteins when the Xiaomogens are activated into their fully functional form."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So the question is, how exactly is Chimotryptynogen actually activated proteolytically?"}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Well, as it turns out, interestingly enough, it's actually another active digestive enzyme known as trypsin, another protease that is responsible for activating Chimotrypcinogen into its active form, Chimotrypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So let's take a look at how that actually takes place by looking at the following diagram."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So, in part A, we basically have that inactive Zymogen, the Chimotrypcinogen."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And notice it consists of 145 individual amino acids."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So this is not functional because its active side does not have the correct orientation."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And the oxyanion hole that is used to basically stabilize the tetrahedral intermediate is not formed."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so what must happen is to actually activate the enzyme activity of this molecule, trypsin and active form another digestive enzyme basically must cleave at a single peptide bond this inactive chymatrypcinogen."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so what it does is it cleaves the peptide bond between the 15th and the 16th amino acid."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, the 15th amino acid is arginine and the 16th amino acid is isolucine."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So the bond holding these two amino acids is cleaved by Trypsin and this activates this Zymogen to form something we call pychiamitrypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, Pi chymatrypsin is not yet a fully functional enzyme."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "What Pi Chimetrypsin does is it goes on to other Pi Chimetrypsin molecules and it cleaves those molecules at several sites."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And what it does is it ultimately removes two dipeptides from this molecule."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So it removes a dipeptide from this region to basically remove two amino acids."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "That's why we go from 15 to 13 and we also cleave in this section and we remove a dipeptide."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so that's why we have two amino acids missing in this section."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so once we form these three individual chains these three individual chains are held together by disulfide bonds."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And now the active side takes the proper confirmation and the oxyanine hole that is used to stabilize that tetrahedral intermediate takes on that perfect form so that once the active side is formed it can actually fit that substrate intermediate."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And once the reaction takes place the tetrahedral intermediate can be stabilized by that fully formed oxyanion hole."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So once again, we see that Trypsin cleaves the peptide between the peptide bond between the arginine 15 and the isolucine 16 producing this active pie Chimetrypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, this active Pychiamatripsin goes on, reacts with another pikmatripsin and that removes two dipeptides to produce a total of three individual chains."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And these three chains, which are held together by disulfide bonds basically constitute that fully functional, fully active Chimotrypsin molecule we call Alpha Chimetrypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, what's so different between the active Alpha Chimetrypsin and the inactive Chimetrypsinogen?"}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Well, as it turns out, the active side and the oxyanine hole are not formed correctly in this Zymogen form."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And what that proteolytic cleavage does is it allows for a localized conformational change to basically take place within this region."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And as a result of that localized conformational change that basically creates the proper confirmation of the active side and also creates that oxynine hole that is needed to stabilize the tetrahedral intermediate that is formed in that proteolytic reaction that climate Trypsin actually carries out."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So we see that proteolytic activation of Chimotrypsinogen causes a local conformational change that allows the active side and the oxygenine hole to actually form."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So we conclude that by proteolytically cleaving this inactive Chimotrypcinogen so the entire structure of this Chimetrypsin doesn't actually change too much."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "But because of a small localized change in this section of that enzyme that creates a perfect active that can fit the substrate molecule and also creates the oxygen hole that will be used by the Chimetrypsin to basically stabilize and decrease that transition state that is formed in that proteolytic reaction that is carried out that is carried out by the digestive enzyme climate trypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, this is only one of the many different types of digestive enzymes that exist inside our body."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And the reason we have these different digestive enzymes is because each digestive enzyme has a slightly different specificity."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And we need all these different enzymes to be able to cleave all the different peptide bonds that are found within the proteins that we actually ingest."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And the interesting thing about the trypsin molecule that we discussed earlier, trypsin doesn't only activate the chinatriptcinogen, it also activates many other zymogens."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And so in a way, we can imagine that trypsin is actually the master activator which is responsible for actually activating the majority of the xiaogens found inside our body."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Now, the question is what activates the trypsin itself?"}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Well, the cells of our body basically produce a special type of enzyme known as anterappeptidase."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So it's the anteripeptidase that is produced by our body that actually activates trypsin from tryptinogen."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Remember, tryptogen is the xiaomogen, the inactive form of trypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And when anteripeptidase basically proteolytically cleaves a bond in trypsin, the entire structure of the trips, ingen or not trypsin tryptogen, the entire structure of the trypsinogen changes and that creates the proper confirmation of the active side that now allows that trips and to basically carry out its activity."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And what trypsin does is it activates not only for other different xiaomages, but it also activates itself."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Trypsin, once activated, basically goes on to nearby tryptogen molecules and activates them to produce trypsin."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So this is an amplification effect."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And trypsin can also go on to activate proelastates into elastics climate trypsynogen into chimetrypsin, which we spoke about just a moment ago."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "Prolipase, which activates lipase and lipase is used to basically break down the lipids that we ingest into our body and finally procarboxy peptidase into carboxy peptidase."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So we see that tryptin is the master activator that proteolytically activates the majority of the digestive enzymes, including itself."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And Trypton itself is activated by interate peptidase."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "And it's the collective activity, the collective action of all these enzymes found inside our small intestine and the stomach that allows us to actually break down all different types of peptide bonds and all different types of proteins that we ingest into our body."}, {"title": "Proteolytic Activation of Digestive Enzymes .txt", "text": "So we see that enzymes can be controlled not only allosterically and not only via covalent modification methods, but also via proteolytic activation by using the technique we call proteolytic cleavage."}, {"title": "Lymphatic System .txt", "text": "The Lymphatic system is a network of specialized vessels that plays two important roles."}, {"title": "Lymphatic System .txt", "text": "Firstly, it protects our body from different pathogenic infections and filters our blood from pathogenic agents that can essentially cause harm to our body and the cells of our body."}, {"title": "Lymphatic System .txt", "text": "And secondly, the Lymphatic system also maintains fluid homeostates."}, {"title": "Lymphatic System .txt", "text": "Specifically, what it does is it prevents the buildup of fluid from taking place inside the tissues of our body."}, {"title": "Lymphatic System .txt", "text": "Now, to see exactly what we mean by that, let's take a look at the following diagram."}, {"title": "Lymphatic System .txt", "text": "This diagram describes the cells of some particular tissue and the cells are shown in brown."}, {"title": "Lymphatic System .txt", "text": "It also describes the capillary system that is found within our tissue."}, {"title": "Lymphatic System .txt", "text": "And wherever we have a capillary system, we also have a Lymph system."}, {"title": "Lymphatic System .txt", "text": "And the vessel of the Lymph system is shown in green."}, {"title": "Lymphatic System .txt", "text": "So basically, we have the arterial, the blood vessel shown in red, that brings the oxygenated and the nutrient filled blood to the capillary of our blood vessel system."}, {"title": "Lymphatic System .txt", "text": "And within the capillary, we have exchange between nutrients and wastes taking place."}, {"title": "Lymphatic System .txt", "text": "And then the Venuel is the blood vessel that carries the deoxygenated blood that contains the waste products back to the heart."}, {"title": "Lymphatic System .txt", "text": "So let's recall how the exchange of nutrients and waste products takes place within our capillary."}, {"title": "Lymphatic System .txt", "text": "So, if we examine the arterial side of the capillary, on the arterial side, we have a higher hydrostatic pressure than osmotic pressure."}, {"title": "Lymphatic System .txt", "text": "And that's exactly why that hydrostatic pressure is able to force the blood plasma that contains the nutrients and our oxygen from the capillary and into the surrounding tissue space."}, {"title": "Lymphatic System .txt", "text": "And the surrounding tissue space is known as the interstitial tissue."}, {"title": "Lymphatic System .txt", "text": "So what happens is when the blood plasma leaves the capillaries and enters this cell tissue area, that brings the nutrients, such as glucose and fats and amino acids and oxygen to the cells of that surrounding tissue."}, {"title": "Lymphatic System .txt", "text": "And at the same time as that fluid travels along the tissue space, along the interstitial tissue, it picks up those waste products that are secreted by the cell, such as carbon dioxide and ammonia."}, {"title": "Lymphatic System .txt", "text": "And once the fluid is on the Venuel side, on this side of the capillary, because the zmotic pressure is now greater than the hydrostatic pressure, the blood rushes back into the capillary of our body."}, {"title": "Lymphatic System .txt", "text": "And now the deoxygenated blood that contains the waste products travels along the Venuel, then to the veins and finally into the heart of our body."}, {"title": "Lymphatic System .txt", "text": "Now, it turns out that osmotic pressure on the Venuel side is not that much higher than the hydrostatic pressure."}, {"title": "Lymphatic System .txt", "text": "And what that means is not all of that blood plasma that left the capillary actually returns back into that capillary on the Venuel side."}, {"title": "Lymphatic System .txt", "text": "In fact, about 10% of that fluid that left the capillary and entered our tissue will remain in that interstitial space, in the space surrounding our capillary."}, {"title": "Lymphatic System .txt", "text": "The question is, what happens to this 10% fluid if this 10% fluid is not removed in any way, there will be a build up of pressure as a result of the build up of fluid inside that tissue."}, {"title": "Lymphatic System .txt", "text": "And that will lead to swelling, the process of edema."}, {"title": "Lymphatic System .txt", "text": "And that can lead to very serious medical conditions and medical complications."}, {"title": "Lymphatic System .txt", "text": "So to prevent this from happening, what our body does, and specifically what the lymphatic system does, is it drains and removes that fluid into the system of vessels we call lymph vessels or lymphatic vessels."}, {"title": "Lymphatic System .txt", "text": "These lymph vessels essentially connect with larger lymph vessels known as lymphanes."}, {"title": "Lymphatic System .txt", "text": "And along the lymph vessels we have these regions known as lymph nodes."}, {"title": "Lymphatic System .txt", "text": "And we'll talk about them in just a moment."}, {"title": "Lymphatic System .txt", "text": "And these lymph nodes essentially filter our lymph from different types of pathogenic agents."}, {"title": "Lymphatic System .txt", "text": "And eventually that lymph is returned back into our blood system via specific types of veins, as we'll see in just a moment."}, {"title": "Lymphatic System .txt", "text": "And the reason we want to return our lymph back into our blood is because we want to ensure that the same volume of blood remains in our cardiovascular system."}, {"title": "Lymphatic System .txt", "text": "So once again, the question is what happens to the 10% fluid that remains in the tissue space?"}, {"title": "Lymphatic System .txt", "text": "If it remains in the tissue space, it will lead to a continual buildup, the process of swelling, the process of edema."}, {"title": "Lymphatic System .txt", "text": "And to prevent this from happening, our body uses lymph vessels, shown in green, to drain this fluid out of the interstitial space."}, {"title": "Lymphatic System .txt", "text": "Now, the fluid, which is now known as lymph, travels along these venues, along these vessels and eventually connects with these larger vessels we call lymph veins."}, {"title": "Lymphatic System .txt", "text": "And eventually the lymph veins reconnect with the blood vessels and the fluid is returned back into our blood circulation through the thoracic duct and the right lymphatic duct that bolt contains that bolt connects with special types of veins."}, {"title": "Lymphatic System .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Lymphatic System .txt", "text": "So we have two important types of ducts the thoracic duct as well as our right lymphatic duct."}, {"title": "Lymphatic System .txt", "text": "The thoracic duct essentially collects the lymph from the lower right part of the body, from the GI system and from the left side of the body, the entire left side of the body."}, {"title": "Lymphatic System .txt", "text": "And it connects with our circulation system via the left subclavian vein."}, {"title": "Lymphatic System .txt", "text": "So this is the bronchiocephalic vein, this is the right subclavian vein and this is the left subclavian vein."}, {"title": "Lymphatic System .txt", "text": "Remember, the subclavian veins carries the deoxynated blood from the arm portion and into the vena cava which brings that blood to the right atrium of our body."}, {"title": "Lymphatic System .txt", "text": "And along the right subclavian vein, we have a connection between that vein and the right lymphatic duct."}, {"title": "Lymphatic System .txt", "text": "While along this left subclavian vein we have a connection between this thoracic duct and the left subclavian vein."}, {"title": "Lymphatic System .txt", "text": "So the lymph, once we actually filter that lymph, it returns back into the vein system, bare body and back into the cardiovascular system."}, {"title": "Lymphatic System .txt", "text": "So we see that the Rice lymphatic dust collects the lymph from the right side of the head, the necks and the chest and empties into the right subclavian vein."}, {"title": "Lymphatic System .txt", "text": "Now, previously we mentioned that one of the other functions of the lymphatic system is to filter our blood, to filter our lymph that travels along these lymph vessels."}, {"title": "Lymphatic System .txt", "text": "And this filtering process takes place in lymph nodes."}, {"title": "Lymphatic System .txt", "text": "So along many parts of our lymphatic system are small masses of tissue called lymph nodes."}, {"title": "Lymphatic System .txt", "text": "So this is one lymph node, a second lymph node, a third lymph node."}, {"title": "Lymphatic System .txt", "text": "And we have many of these lymph nodes along different regions of our body."}, {"title": "Lymphatic System .txt", "text": "Now, within these lymph nodes, we have cavities, we have sinuses."}, {"title": "Lymphatic System .txt", "text": "And within these cavities, we have specialized types of leukocides wide blood cells."}, {"title": "Lymphatic System .txt", "text": "Now, when dendritic cells found in the tissue pick up pathogenic antigens, they carry these pathogenic antigens into our lymph nodes."}, {"title": "Lymphatic System .txt", "text": "And inside the lymph nodes, we have plasma cells that produce antibodies against these antigens."}, {"title": "Lymphatic System .txt", "text": "And these antibodies basically leave the lymph nodes along the other side and eventually, they are dumped into our vein system."}, {"title": "Lymphatic System .txt", "text": "And that's how antibodies end up in the cardiovascular system, in the blood vessels of our body."}, {"title": "Lymphatic System .txt", "text": "Now, within these lymph nodes, we also have other wide blood cells, such as macrophages that can engulf any type of pathogenic agent that might be present inside our lymph system."}, {"title": "Lymphatic System .txt", "text": "And in this manner, our lymphatic system not only drains our tissue and prevents the build up of fluid inside the tissue, but it also filters our blood."}, {"title": "Lymphatic System .txt", "text": "It basically eats up and digests different types of pathogens that are found inside our blood inside these specialized masses of tissue we call lymph nodes."}, {"title": "Lymphatic System .txt", "text": "Now, the final portion that I'd like to focus on is how that fluid actually gets into these lymph vessels in the first place and how the limb travels along our limb vessels."}, {"title": "Lymphatic System .txt", "text": "So let's take a look at the following diagram."}, {"title": "Lymphatic System .txt", "text": "So this is a small portion of our lymph vessel."}, {"title": "Lymphatic System .txt", "text": "Now, notice along the lymph vessel, we have these endothelial cells."}, {"title": "Lymphatic System .txt", "text": "So the walls of the lymph vessels consist of endothelial cells that overlap slightly."}, {"title": "Lymphatic System .txt", "text": "And at the portions where they overlap, these overlapping portions act as one way doors."}, {"title": "Lymphatic System .txt", "text": "And when there is a fluid build up inside the tissue, that fluid pressure pushes on these overlapping sections, these one way doors."}, {"title": "Lymphatic System .txt", "text": "And that opens these endothelial cells and allows fluid to actually flow into the endothelial cell."}, {"title": "Lymphatic System .txt", "text": "So for example, let's imagine that we have a build up of pressure here."}, {"title": "Lymphatic System .txt", "text": "And so the fluid pushes against the overlapping portion and the fluid moves into this cavity, this region of our lymph vessel."}, {"title": "Lymphatic System .txt", "text": "Now, as the fluid builds up in the lymph vessel, it pushes back onto this side, the other side of our endothelial cell."}, {"title": "Lymphatic System .txt", "text": "And because these endothelial cells open only one way and not the other way, when our hydrostatic pressure pushes on our cells this way, the fluid cannot escape back because these overlapping regions between the cells only open this way and not the other way."}, {"title": "Lymphatic System .txt", "text": "And we also have a system of one way valves found along the lymph vessel."}, {"title": "Lymphatic System .txt", "text": "So that means these valves also open one way and not the other way."}, {"title": "Lymphatic System .txt", "text": "So when there is a build up of pressure here, it closes these overlapping regions so that fluid cannot exit that lymph node."}, {"title": "Lymphatic System .txt", "text": "It pushes against a valve that opens up and that allows the movement of lymph along our vessel as shown in the following diagram."}, {"title": "Lymphatic System .txt", "text": "And if there is a decrease in pressure and it basically wants to move back, it cannot move back because when the fluid tries to move back it forces these valves to actually close."}, {"title": "Lymphatic System .txt", "text": "And that means we do not have a backflow of lymph inside our lymph system in the same way that we do not have a back flow inside our veins."}, {"title": "Lymphatic System .txt", "text": "Remember, the veins also contain this valve system that prevents the movement of our lymph back down that lymph vessel."}, {"title": "Lymphatic System .txt", "text": "So the walls of the lymph vessels consist of endothelial cells that overlap slightly when there is a build up of fluid in the interstitial tissue, in the tissue space, that creates fluid pressure that pushes on the cells, this opens up those overlapping regions, forces the fluid into that lymph vessel."}, {"title": "Lymphatic System .txt", "text": "Now, inside the lymph vessel we have a system of one wave valves."}, {"title": "Lymphatic System .txt", "text": "These valves, as well as the overlapping portion of the endothelial cells open only in one direction and not the other."}, {"title": "Lymphatic System .txt", "text": "And this keeps the lymph inside that lymph vessel and it keeps it moving along one direction."}, {"title": "Lymphatic System .txt", "text": "Now, in the same way that our veins are situated next to our skeletal muscle and the contraction of our skeletal muscle promotes the movement of blood inside the veins in the same exact way the contraction of skeletal muscle pushes against our lymph vessels and that promotes the movement of lymph inside our lymphatic system."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So let's continue our discussion on glycoproteins, the process of protein glycosylation."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So when we modify proteins by adding carbohydrates to them we basically change their properties and modify their functions to basically give them the ability to carry out a certain type of process."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So inside our body we have many different types of glycoproteins and generally speaking, glycoproteins have a wide range of function."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So what I'd like to do in this lecture is focus on several important glycoproteins that exist inside our body and see how by adding the sugar component onto the protein, we give the protein the ability to carry out some specific type of process."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now at the end of the lecture I'd also like to discuss an example of a disease known as the eye cell disease that exists in humans that basically demonstrates the importance of protein glycosylation."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So let's begin by discussing a category of glycoproteins known as mucins."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now mucins, as we'll see in just a moment, are the major constituents, the major components of the mucus membranes that exist inside our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So the mucous membranes can be found in the nasal cavity, in our air passageways, the bronchioles and so forth."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now mucints are basically these heavily glycosylated proteins that are produced and released by the epithelial tissue, the epithelial cells of our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now heavily glycosylated basically means there are many oligosaccharides, many sugar molecules found attached onto these proteins."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "The reason, the question is why?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, if we examine the protein sequence, the amino acid sequence of the protein will find a high density, a high number of serene and three ending residues."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And it's these two residues that are basically needed to produce the old glycocytic bonds between the protein and the sugar molecule."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So because mucins contain a high number of threeanine and steam residues, they are heavily glycosylated with the old glycositic linkages."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, although most mucins are actually produced by the cells and released into the extracellular matrix, some of these mucins actually remain attached onto the cell membrane."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And this is what is shown in this diagram."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So we have the cell membrane, we have this hydrophobic section of the protein Children Brown and this is the rest of that protein."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And these are basically the ligosaccharides."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And we have many of these oligosaccharides as shown."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So what exactly is a function of mucins?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, because mucins are part of the mucus membrane and the mucus membrane basically acts to lubricate and protect our body from pathogenic agents."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "What that means is these individual mucins have to be able to carry out that specific function."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now how exactly does it carry out the function of lubrication?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, basically these red oligosaccharides contain modified sugar molecules that contain negative charges and these negative charges attract water molecules which are polar molecules."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so as a result of those charges we're basically going to have many of these water molecules which are basically going to surround this entire mucin molecule."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And as a result that basically gives the addition of these sugar molecules, gives the mucins, these proteins, the ability to actually absorb water."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And that's exactly what gives the mucous membranes the ability to lubricate those epithelial cells."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "On top of that, these carbohydrates are very sticky and they can basically trap pathogenic and infectious agents."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so that means the mucints that form the mucus barriers basically have the ability to lubricate and protect epithelial tissue."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, let's move on to the second type of glycoprotein that we'll find inside our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And this is known as erythropoietin, or EPO."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, urethropoietin is a glycoprotein, and the protein component basically consists of an amino acid sequence of 165 amino acids."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And four of these amino acids are actually glycosylated."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So three of these amino acids are asparaging amino acids, and that means we have the N glycocitic bonds, and one of these amino acids is the Serene amino acid, and that means we have the O glycocitic bond."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so this brown section, which actually looks like a bunny, this brown section is the protein component of erythropolietin."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And these are these four oligosaccharides, which are bound onto these four different amino acids."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Three of them are asparagus, three of them are asparagine, and one of them is the serene."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, what exactly is the function of erythropletin?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, erythropletin is basically a glycoprotein that is produced by special cells found inside our kidneys."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And these glycoproteins are released into the blood plasma and they act as hormones."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "They basically bind on suspension precursor cells and they stimulate the cells to basically produce erythrocytes, red blood cells."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, the reason we essentially add these sugar molecules onto the protein component is to basically increase the stability of erythropleton within the blood plasma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And this decreases the likelihood that the kidneys are going to remove this hormone from the blood plasma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So glycosylation of Erythropolietin helps to stabilize this structure in the blood plasma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And what that means is it decreases the likelihood of the kidneys are going to remove this protein, the glycoprotein, from the blood plasma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "That means this glycoprotein can basically stimulate the production of red blood cells."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, urethraplatin is not the only glycoprotein that act as a hormone inside our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "We have many other examples of glycoproteins that act as hormones."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "For instance, we have the thyroid stimulating hormone that is a glycoprotein."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "We have the human coriane gunitosropin that also acts as a hormone and is a glycoprotein."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "We have the leezing hormone and the follicle stimulating hormone, which are also examples of glycoproteins that act as hormones."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, let's move on to tissue factor and antibodies."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So we're not going to go into detail into these two glycoproteins because we actually focus on them in detail previously."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So tissue factor is a glycoprotein that is basically exposed when the blood vessels in our cardiovascular system experience some type of trauma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And these glycoproteins, the tissue factor, is found on the membrane of epithelial cells and once the tissue factor, the glycoprotein, is exposed, it initiates the extrinsic pathway of the blood clotting cascade."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "It basically initiates the formation of blood clots, the coagulation process."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, antibodies are also glycoproteins, which basically are found floating within our blood plasma."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And we have many different types of antibodies."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So what these immunoglobulins do is basically they bind onto pathogenic or infectious antigens and they initiate some type of immune defense or response that ultimately kills off that infecting agent."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So it protects our body from these different types of infectious agents."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So we see that glycoproteins have a wide range of functionality."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So some glycoproteins basically absorb water and act as lubricants and also protect our body from infectious agents."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And antibodies also carry out the function of protecting our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "We see that others play a role in the blood clotting cascade and basically creating these blood clots and initiating the coagulation process."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Other glycoproteins act as hormones and we have many, many other examples of glycoproteins."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, the final thing I'd like to discuss in this lecture is this disease we call the eye cell disease, also known as Mucolipidosis II, which is basically a liposomal storage disease."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So what exactly does that mean?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, inside our normal cells we basically have an organelle known as a lysosome."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And inside the lysosome we have these digestive enzymes, these hydrolytic enzymes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And what they do is they basically recycle and break down the different types of byproducts which are produced inside the cells."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So they break down things like large carbohydrates and glycosaminoglycans and glycolipids."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And all this takes place inside the lysosomes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, these hydrolytic enzymes, under normal conditions are produced inside the Er, then modified inside the Golgi apparatus, and then they end up inside the lysosome."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So how this process takes place is in the following way."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So the ribosomes found on the rough Er basically synthesize these hydrolytic enzymes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And once synthesized, they are basically modified in some way by adding the endgycoacetic linkages."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And then those hydrolytic enzymes are transferred into this membraneous sac known as the Golgi apparatus."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And as they move within the Golgaparatus, a special enzyme known as phosphotransphrase basically adds up a sporal group onto the mano sugar found on the hydrolytic enzyme and that produces the manos six phosphate."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, the special thing about this modified sugar molecule found on the hydrolytic enzymes is that it is the marker."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "It basically dictates exactly where the hydrolytic enzyme will actually end up."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So it's the mano six phosphate that acts as the marker that basically is used to direct the hydrolytic enzymes to the lysosomes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so normally, if this process takes place correctly and the hydrolytic enzymes are actually properly phosphorylated via this process, only then will they actually end up in the lysosomes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And only then will the lysosomes actually be able to carry out their process."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Now, what happens in individuals that have the eye cell disease?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "Well, in individuals with the eye cell disease, this phosphate transferase cannot actually create the mano six phosphate."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So what happens is, when the hydrolytic enzymes end up inside the Golgi apparatus, that mano sugar remains unmodified."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so what that means is the protein Glycosylation process does not take place correctly."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And because we have the unmodified mannose, because we don't have the mano six phosphate, those hydrolytic enzymes do not actually know that they should go into the lysosome."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so what happens in individual with the eye cell diseases?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "These hydrolytic enzyme, hydrolytic enzymes basically end up being transported out of the cell."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And so in individuals with the eye cell disease will have a high concentration of these hydrolytic enzymes in our blood plasma, and the lysosomes are going to be deficient in these hydrolytic enzymes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And what happens if we don't have the hydrolytic enzymes inside the lysosomes?"}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "That means we're going to have an accumulation of all these different types of byproducts inside the lysosomes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So things like glyco, lipids and large carbohydrates and glycosaminoglycans will not be able to be broken down because of the absence of these hydrolytic enzymes."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "And that can lead to many, many negative problems inside our cells and inside our body."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So we see that the process of Protein Glycosylation is very important because it doesn't only modify the functionality of proteins, it also actually tells the proteins where to actually go."}, {"title": "Functions of Glycoproteins and I-Cell Disease .txt", "text": "So, as in this particular case, so we see that the mano six phosphate is the marker that is used to basically direct these digestive enzymes, the hydrolytic enzymes, to their correct location, to the lysosomes of the cell."}, {"title": "Major Arteries of Circulation System .txt", "text": "So let's quickly take a look at some of the major arteries found within our circulatory system and let's begin within the left ventricle of the heart."}, {"title": "Major Arteries of Circulation System .txt", "text": "So when the left ventricle of the heart contracts, it pumps all that blood into the largest artery of the body known as our aorter."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now we have different segments of the aorta and the segment of the aorta that actually extends from the left ventricle and moves upward is known as our ascending an order."}, {"title": "Major Arteries of Circulation System .txt", "text": "And this is shown in red as it travels right over to this location here."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now at the beginning portion of our ascending A order, we have branching taking place and we form two smaller arteries given by one A."}, {"title": "Major Arteries of Circulation System .txt", "text": "So these arteries right here are the left and the right coronary arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "And these bring oxygenated and nutrient filled blood to the cells of our heart."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now if we follow the ascending A order, eventually we get to this arch."}, {"title": "Major Arteries of Circulation System .txt", "text": "And this arch is commonly known as our aortic arch."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now, Aortic arch contains three important branching points."}, {"title": "Major Arteries of Circulation System .txt", "text": "We have one on the left side, one on the right side and one in the middle."}, {"title": "Major Arteries of Circulation System .txt", "text": "So we have the left side of the body and the right side of the body."}, {"title": "Major Arteries of Circulation System .txt", "text": "So let's begin with our leftmost branch labeled as two A."}, {"title": "Major Arteries of Circulation System .txt", "text": "This is known as our left subclavian artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now if we follow the left subclavian artery, it extends all the way to the left shoulder, the left arm and the left hand."}, {"title": "Major Arteries of Circulation System .txt", "text": "So the left subclavian artery brings oxygen to these parts of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now at this particular intersection point, we see that the left subclavian artery actually branches."}, {"title": "Major Arteries of Circulation System .txt", "text": "So it branches and informs this artery, known as the left vertebral artery, that goes to our head portion of the body."}, {"title": "Major Arteries of Circulation System .txt", "text": "It also extends many times, it permeates many times within our shoulder and arm portion as shown."}, {"title": "Major Arteries of Circulation System .txt", "text": "And that is to ensure that all the blood gets to the cells of our left shoulder and our left arm."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now what about the middle branching point on the arch?"}, {"title": "Major Arteries of Circulation System .txt", "text": "This right here labeled as two B, is known as our left common carotid artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "And this artery brings our oxygenated blood filled with nutrients to the head of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "For example, the thyroid and a parathyroid glands."}, {"title": "Major Arteries of Circulation System .txt", "text": "These organs receive blood from this common carotid artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now what about the final branching point given by two C?"}, {"title": "Major Arteries of Circulation System .txt", "text": "This is called the branchiocephalic artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now the bronchiocephalic artery travels a short distance before it actually branches itself."}, {"title": "Major Arteries of Circulation System .txt", "text": "And it branches at this particular location."}, {"title": "Major Arteries of Circulation System .txt", "text": "At this location it forms two important arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "This artery is known as our right common carotid artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "So this one is the right common carotid artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "So just like we have a left common carotid artery, we also have a right common carotid artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now this other one, this one right here that essentially extends, continues and extends all the way into the right arm is known as the right subclavian artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "So just like we have a left subclavian artery, we also have a right subclavian arteries that extends into the right shoulder and into the right arm and the right hand of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now in the same way that we have this splitting taking place and we form our left vertebral artery, we also form the right vertebral arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "So this is the right vertebral artery right here."}, {"title": "Major Arteries of Circulation System .txt", "text": "So we have symmetry taking place."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now the subclavian artery, the common carotid artery, this vertebral artery all bring our oxygenated and nutrient filled blood to the organs and tissues found in the upper portion of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "In the head portion, the neck region, the shoulders, as well as our arms and the coronary arteries bring our blood to the heart of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now let's continue onwards."}, {"title": "Major Arteries of Circulation System .txt", "text": "So we have the ascending portion of the aorter."}, {"title": "Major Arteries of Circulation System .txt", "text": "We also have this aortic arch."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now when the arch circles backwards, it then basically extends in the back of the heart and all the way to our pelvic portion of the body."}, {"title": "Major Arteries of Circulation System .txt", "text": "So remember, this chest portion of the body is known as our thoracic region."}, {"title": "Major Arteries of Circulation System .txt", "text": "And this is the abdomen portion."}, {"title": "Major Arteries of Circulation System .txt", "text": "This is our abdominal region."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now as our order actually extends downward, we call that portion the descending an order."}, {"title": "Major Arteries of Circulation System .txt", "text": "And we can break down the descending an order into two regions."}, {"title": "Major Arteries of Circulation System .txt", "text": "We have the thoracic descending an order and we have the abdominal descending an order."}, {"title": "Major Arteries of Circulation System .txt", "text": "And basically the order extends and branches many times as we go down our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "And these branches form smaller arteries, eventually form arterios and then capillaries."}, {"title": "Major Arteries of Circulation System .txt", "text": "And these capillaries are found within the organs and tissues found within the thoracic and within the abdomen portion of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now eventually when we get down to our pelvic region, the descending an order and more specifically our abdominal descending order actually splits."}, {"title": "Major Arteries of Circulation System .txt", "text": "And this splitting takes place in the following region."}, {"title": "Major Arteries of Circulation System .txt", "text": "So these two arteries are called the common iliac arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "So we have a left common iliac artery and a right common iliac artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "And as they extend down they split many more times."}, {"title": "Major Arteries of Circulation System .txt", "text": "For example, they split in the following location."}, {"title": "Major Arteries of Circulation System .txt", "text": "And when they split here they become the external and the internal iliac arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "So these here are the external iliac arteries and these smaller ones are the internal iliac arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "And these common iliac arteries deliver oxygenated and nutrient filled blood to the leg portion of our body, to our right and our left leg."}, {"title": "Major Arteries of Circulation System .txt", "text": "So these are some of the major arteries that are found within our arterial circulation system."}, {"title": "Major Arteries of Circulation System .txt", "text": "Now of course we have many more arteries that we haven't actually shown."}, {"title": "Major Arteries of Circulation System .txt", "text": "For example, we have our pulmonary arteries."}, {"title": "Major Arteries of Circulation System .txt", "text": "So our right ventricle, when it actually contracts, it forces all that deoxygenated blood into the pulmonary trunk."}, {"title": "Major Arteries of Circulation System .txt", "text": "And the pulmonary trunk, this section here extends into our left and our right pulmonary artery."}, {"title": "Major Arteries of Circulation System .txt", "text": "And those arteries carry deoxygenated blood to the left lung and the right lung of our body."}, {"title": "Major Arteries of Circulation System .txt", "text": "And that is where we actually oxygenate our blood."}, {"title": "Major Arteries of Circulation System .txt", "text": "And the blood eventually returns via the pulmonary veins to the left atrium, where then it moves into the left ventricle and it continues over and creates that same cycle that we spoke about."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "The next two amino acids that we're going to focus on will be the aromatic amino acids phenolalamine and tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And we're going to look at how our liver cells can metabolize these two amino acids, ultimately forming acetylacetate and fumarate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, acetoacitate can be used by hepatocytes to form ketone bodies, while fumerate can be be used to form glucose."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And that's exactly why these two amino acids, phenylalanine and tyrosine, are known as glucogenic and ketonic amino acids, because we can use them to ultimately form both glucose and ketone bodies."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So let's begin by examining step one."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And actually what step one shows us is we can transform phenylalanine directly into tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And this is precisely how our cells can synthesize tyrosine by beginning with phenylalanine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, the enzyme that catalyzes step one is phenylalanine hydroxylase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And this enzyme is part of a category of enzymes we call mixed function oxygenases."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So this is a mixed function oxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And what that means is it uses a diatomic oxygen."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "It takes one of the oxygen atoms within this diatomic molecule, places it on this, reactant the phenylalanine, and this basically forms the tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And this oxygen is shown here."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, the other oxygen atom goes to form water, and that's exactly why water is released here."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So phenylalanine hydroxylase is a mixed function oxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, in order for the phenolaline hydroxylase to be able to catalyze this step, it has to use the reducing power of an electron carrier molecule we call tetrahydrobiopterin."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, tetrahydrobiopterin is actually not a vitamin because our cells can synthesize this molecule."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And to synthesize this molecule, we basically begin with dihydrobiopterin."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So in the presence of NADPH and an H plus ion, the enzyme Dihydrophobate reductase basically takes the dihydrobiopterine and transfers the reducing power from NADPH onto this molecule to give us tetrahydrobiopterin."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And then this mixed function oxygenates, this enzyme, phenylaline hydroxylase, uses the reducing power of tetrahydrobiopterin to basically form tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And of course, we also use up the reducing power of this molecule to form Quinnode dihydrobiopterin."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, to regenerate back the tetrahydrobiopterin so that it can be used again in this reaction, we use an enzyme called dihydropyridine reductase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And this enzyme takes the reducing power of NADPH, transfers it onto this molecule to form back the tetrahydrobiopter."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so that again, we can use the reducing power of this molecule to undergo this first step."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So again, in the first step, we utilize a phenylalamine, a diatomic water molecule."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "We use NADPH to basically give us this."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And by using the reducing power of this molecule, we transform the phenylalanine into tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So one of the oxygen atoms goes on to this ring of the phenomealine, and the other one is used to form a water molecule."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, once we form tyrosine, what happens next?"}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Well, next we basically have to use an amino transferase to transfer the alpha amino group from tyrosine onto an alpha keto acid."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so we have the enzyme tyrosine amino transferase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And just like any immunransferase, this one has to use PLP."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So, periodoxylphostate, we transfer this alpha aminogroup from the tyrosine onto an alpha ketoglutrate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, the alpha ketoglutrate, upon receiving that amino group, we form glutamate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Upon removing the alpha amino group from tyrosine, we form this alpha keto acid, the p hydroxy phenyl pyruvate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, once we form this molecule, the next step is to use a dioxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And unlike an oxygenase, where one of the oxygen atoms was used to form water, and the other oxygen atom went onto the phenolalanine to form the tyrosine, an enzyme that we call dioxygenase uses a diatomic water, a diatomic oxygen, and it uses both atoms of that diatomic oxygen to attach it onto that substrate molecule."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So in this step, we basically want to remove this carbon dioxide, and we want to use both of the oxygen atoms and attach them onto this substrate to basically form an intermediate we call homogenesate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So the enzyme that catalyze this step is p hydroxy phenyl, Pyruvate dioxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so ultimately, we attach an oxygen here onto this carbon, and the other oxygen goes onto this ring here."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So now we have two oxygen atoms here, two oxygen atoms here, and this carbon dioxide group was basically removed as carbon dioxide."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, in the next step, we want to use, yet again, a dioxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So now we use homogeneousate one two dioxygenase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Again, we use a diatomic water, a diatomic oxygen."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "One of the oxygen is basically attached onto this carbon."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "The other oxygen is attached onto this carbon."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So ultimately, we break this sigma bonded pi bond."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Within this ring, we attached oxygen here and here to form this intermediate formal acetyl acetate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "Now, in the next step, we basically want to isomerize."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So we want to transform this CIS group into a TransGroup."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So we have the cyst double bond here, but we want to form a trans double bond, as shown here."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So the enzyme that catalyze this step is an isomerase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So we have malleal acetoacetate isomerase, which uses the activity of glutathione to basically form this molecule, the four funeral acetylacetate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And the final step in this reaction, in which we ultimately want to cleave this Sigma bond here by using essentially a water molecule, this is catalyzed by fumarol acetylacetase."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so ultimately, we form a fumerate, because once we cleave this bond, the oxygen essentially attaches onto this carbon and this becomes a ch three."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so we form acetoacetate and fumerate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And now this can be used to form a ketone body, and this can be used to form our glucose."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So we see that inside our cells, we can transform phenylalanine into tyrosine."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And so ultimately, we can basically form tyrosine within this step."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And both and tyrosine, by following these series of steps, can be transformed into these carbon skeletons, acetylacetate and fumerate."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "And these can ultimately be used to form fuel molecules."}, {"title": "Metabolism of phenylalanine and tyrosine.txt", "text": "So either ketone bodies in this case or glucose molecules in this case."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "Away the electrons this way, and that will form a partial positive charge here and a partial negative charge on this one."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "And that will also create an instantaneous dipole moment that points in the following general direction."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "And so what that means is these instantaneous partial charges will attract each other as a result of an electric force forest."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "And that is what a London dispersion forest is."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "Now, London dispersion forces are the weakest because these exist only for a moment in time."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "So at one moment they exist, and another moment they don't exist, and a third moment, they exist once again."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "And so that's why they're the weakest types."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "But once again, if we have many of these molecules in close proximity, Vanderwald forces, lunaspersion forces begin to play a very substantial role in holding the molecule together, as we'll see in the structure of DNA."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "So London dispersion forces are forces that exist because these electrons fluctuate over time."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "So the electron density around atoms is not static, but rather fluctuates with time."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "The asymmetric distribution of one molecule, as shown here, can cause the electron density of a nearby molecule here to basically change in accordance with the law of repulsion."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "So we have these electrons repelling these electrons, creating a partial positive charge here, and these can interact a moment in time."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "And this is what we mean by an instantaneous interaction, which is another way of saying London dispersion forces."}, {"title": "Intramolecular and Intermolecular Forces (Part II).txt", "text": "So these are the two types of intermolecular forces that you should be familiar with in your study of biochemistry."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "In fact, a two step process is followed."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "And in this twostep process, an important intermediate known as the oxalo acetate molecule is used."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So gluconeogenesis bypasses step ten V, a two step reaction pathway that involves the oxalo acetate intermediate."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "And if we sum up those two steps, this is a reaction reaction that we're basically going to get."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So Pyruvate plus ATP plus GTP plus the water molecule gives us that pet molecule that we want, the ADP, GDP, an orthophosphate and two H plus ions."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "And this makes this reaction an exergonic reaction, unlike this reaction that would be an endorganic reaction."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "Now, by the same exact reasoning, steps three and one are also bypassed by using this step and this step respectfully."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So in each one of these steps, we basically use a simple hydrolysis reaction and we'll talk about the details of that in the next lecture."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So we see that step three is bypassed via an exergolic hydrolysis of fructose one, six bisphosphate into a fructose six phosphate."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So this is hydrolyzed by water and the activity of a special enzyme to produce the fructose six phosphate and the orthophosphate."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "And step one is bypassed by another hydrolysis reaction that is basically catalyzed by a different enzyme to form that glucose molecule."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So once again, again, glucomune genesis is not simply the reverse of glycolysis, although there are steps that are exactly the same."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "So in fact, there are seven steps that are the same, the other steps are not the same."}, {"title": "Introduction to Gluconeogenesis Part II .txt", "text": "And the reasoning is because gluconeogenesis, if it simply follows the reverse steps of glycolysis, it would be a very endergonic reaction."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Inside the alveoli of our lungs, we have a special type of substance known as the pulmonary surfactant that consists of phospholipids and proteins."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And what the pulmonary surfactant does is it decreases the surface tension of the fluid found inside the alveoli of our lungs."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that decreases the pressure that is needed to actually actually inflate those alveoli during the process of inhalation."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So it decreases the pressure needed to expand or inflate the alveoli when we actually inhale, when we breathe in, it also prevents the alveoli from actually collapsing onto themselves when we actually exhale."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So overall, what the surfactant in the alveoli of the lungs does is it makes the process of breathing much more efficient and much more easy to carry out."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now the question is why and how does the surfactant actually carry out these two functions?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Well, to answer this question, we have to begin by answering question number one and question number two, if we understand these two questions."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And the answer to these two questions will have no problem actually understanding how the surfactant in the alveoli actually works."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So let's begin with question number one."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "An individual droplet of water placed on the tabletop will basically form a spherical shape as shown in diagram A."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "If we then add a tiny drop of detergent using some type of pipette onto that droplet of water, that droplet of water will basically break and collapse its spherical shape and will flatten out and spread out along the surface of the table as shown in diagram B."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "The question is, why does this actually take place?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "How does our detergent actually break and cause the water droplet to actually collapse its shape?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So let's begin with diagram A."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And let's actually answer why the water actually forms that spherical shape in the first place."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So if we examine inside that water droplet, if we get down to the microscopic level, we'll see that the individual water molecules are actually forming relatively strong intermolecular bonds known as hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So water can form many hydrogen bonds with adjacent water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, because hydrogen bonding is stabilizing, that means the water will tend to create a shape that will maximize the number of hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And it turns out that this spherical shape has the highest volume to surface area ratio and it creates an optimal arrangement of molecules that creates a maximum amount of hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that's exactly why the water forms that spherical shape in the first place."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So pure water has a high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, in diagram B, when we take our pipette that contains our detergent and we release a small amount onto the water, that water breaks its spherical shape, it collapses and spreads out."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "It flattens out along the surface of the table."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "The question is why?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Well, what exactly is a detergent?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "A detergent is basically some type of oil that contains hydrophobic non polar sections and hydrophilic polar sections."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And when we add our detergent to the water."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "The polar section of our detergent will try to interact with the water and that will break the intermolecular bonds between water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And the non polar will try to orient itself as far away from the water and that will also break intermolecular bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So by adding our detergent that contains hydrophobic and hydrophilic regions, we essentially break many of those inter molecular bonds that are needed to create the spherical shape."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that's exactly why our water essentially collapses and spreads out along the surface of our table."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now let's move on to question number two."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So pure water, as I mentioned earlier, has a relatively high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So in diagram A before we added our detergent, we had a relatively high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now when we add our detergent, we decrease the surface tension of that liquid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "The question is why?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Well, to begin, let's actually define what surface tension is."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So surface tension basically means that the molecules found on the surface of the liquid remain on the surface and they're able to bond very well with adjacent liquid molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "In the case of water, it's adjacent water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And so when we try to apply a force onto the surface of that liquid, because of these relatively strong intermolecular bonds, and because the molecules on the surface don't actually move too much, those molecules are able to actually stand their ground when a force is applied onto that surface."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So surface tension means that it is relatively difficult to break the bonds that exist on the surface of that liquid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And this implies that the bonds on the surface of our water are strong and the water molecules on the surface don't actually move too much and so they can stand their ground when a force is applied on them."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So if we zoom in on the surface of the water in diagram A, we basically get the following picture."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So let's compare the water molecules found deep inside that droplet and the water molecules found on the surface."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So deep inside our water droplet, these molecules can easily move around."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that's because if they move from one location to a different location, it doesn't matter where they are within the water droplet, anywhere they are, they still are surrounded by cage of other water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that always creates intermolecular bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So beneath the surface of the water, the molecules can move around freely because by doing so, they are not losing any hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So in this location, the water molecule creates 123456 of these bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now when it moves somewhere else, it will create those same six bonds because it is always surrounded by water."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now let's take a look on the surface."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "On the surface of our water, there is a change of phase."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "We have air that is right above our surface."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And what that means is these water molecules on the surface will have a limited number of hydrogen bonds because they cannot actually bond with the air molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "They can only bond with the adjacent water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And so if we take a look at this particular water molecule, we only have one, two, three of these hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, whenever our water molecule moves or rotates from the surface, it will lose those hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "But it doesn't want to lose those hydrogen bonds because hydrogen bonds are stabilizing."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So because on the surface we have this air phase and because the molecules cannot interact with the air molecules, that means the water molecules on the surface will be constrained to that location."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "They will not be able to move as freely as the molecules inside our water because by moving or rotating on the surface they lose those precious hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And we only have a limited number of hydrogen bonds on the surface."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So on the surface of the water, the water molecules are more restricted."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "That is because they cannot interact well with the air molecules above."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And even the smallest rotational movement can cause them to lose those limited number of hydrogen bonds that they have in the first place."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And because these water molecules remain in their location, they don't move, they stand their ground."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "When we apply a force, those molecules still don't want to move."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "They don't want to break those bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And so that's exactly why it has a high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Because when we apply force, those surface molecules will apply force back."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that's what surface tension is."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So when we add our detergent, that decreases the surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Why?"}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Well, what we basically do when we add our detergent into our liquid is we replace the surface water molecules with our detergent molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So this is the arrangement that we basically have."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So what happens is, on the surface, instead of having the water molecules, we now have our detergent molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And these hydrophilic polar heads shown in blue will orient and interact with the water molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "But the hydrophobic tails, the non polar green tails will basically orient away from the water molecules and to the air."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So we essentially replace our water molecules on the surface with these hydrophobic hydrophilic detergent molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And now all these water molecules are found inside the liquid and they can easily move about because as we said earlier, once the water molecules are deep inside our liquid beneath the surface, they can move about freely because by moving about, they're not losing any net amount of hydrogen bonds."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So adding detergent molecules will cause them to align along the surface so that their polar sections point inward towards the water, as shown in this diagram."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And their non polar green tails, hydrophobic tails, point towards the air."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, the water molecules near the surface now feel much more comfortable because they can interact with the polar heads of our detergent."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And this means when we apply a force onto the surface of that liquid because these water molecules feel much more comfortable they're not constrained anymore and they can move around freely."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "When we apply a force, they will have no problem moving around that force."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that's exactly why the surface tension drops."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So this means that the water molecules can rotate and move much more freely than before."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And this lowers their ability to withstand any force because once we apply force, they simply move around that force and so our surface tension drops."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So by adding a detergent, a molecule that contains hydrophobic and hydrophilic properties into our water, into our liquid, we decrease our surface tension as a result of this concept."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And this is exactly what happens inside the alveoli of our lungs."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So within the lungs are microscopic balloon like structures called alveoli."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, they resemble balloons in that we actually have to apply a certain pressure to inflate them."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "But when we release that pressure, when the pressure is removed, the elasticity of our balloons causes them to actually deflate and return back to their original shape."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So let's take a look at the following microscopic sections."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So, this is our bronchiol."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And the bronchiol eventually connects to this space."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And around this space, we have many of these alveoli."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So if we zoom in on a single alveolis, we basically get the following diagram."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So, inside this region, we have air, we have carbon dioxide and we have oxygen."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, this purple section is the wall of the alveola of the alveola."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So it's the alveolar wall."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And now within the wall, within the inside portion of the wall, between the wall and the air, we have this layer of fluid we call the alveolar fluid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And this is a polar fluid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Just like this water is a polar fluid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So we have this layer of fluid known as the alveolar fluid that is polar."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, this, because it's polar, it basically has a high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So just like water has a high surface tension, this fluid also has a high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, what that means is because the fluid has a high surface tension, when we actually apply pressure, when we breathe inside these alveoli, we actually need to breathe, we need to create a high pressure to expand them, to inflate them because of the high surface tension of our fluid."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And that means without any type of detergent, without any type of surfactant, which is basically a detergent inside the alveoli, we have to apply a high pressure to inflate our alveoli found within our lungs."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So what the pulmonary surfactant does is it basically decreases the surface tension of the fluid and it makes it much easier for us to actually breathe in and apply a smaller pressure to inflate those balloon like structures, our alveoli."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So pulmonary surfactant is a substance that resembles our detergent because it consists of about 90% of phospholipids and it also contains about 10% protein."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So that means it contains polar hydrophilic and nonpolar hydrophobic regions."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So these tiny molecules shown here are basically our surfactant molecules."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So we have the non polar hydrophobic tail and the polar hydrophilic head."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So in the same way that we discussed here, the head of the surfactant, the head of the surfactant basically interacts with the surface of our fluid, but the tail points away towards our air found within this cavity."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So the wall of the alveolus is lined with the polar fluid that contains a high surface tension."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "This means that because of the high surface tension, we require a relatively high pressure to expand and inflate those balloon like structures when we basically inhale our air."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, by mixing the surfactant into that fluid, and by the way, the surfactant is produced by specialized type of cell inside the lungs known as the alveolar type two cells."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "By mixing the surfactant, which is our detergent with the fluid, we decrease the surface tension as a result of what we discussed earlier."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And by decreasing the surface tension, we make it much easier for ourselves to actually inflate those alveoli."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So we decrease the pressure that is needed to expand the alveoli during the process of inhalation."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "Now, what it also does is it basically decreases the recoil ability of our alveoli."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "And what that means is when we exhale, when the air basically leaves the alveoli, these alveoli don't actually collapse onto themselves because if they collapse, that means we're going to need a much greater pressure to actually inflate them back to their original position."}, {"title": "Surfactant in Alveoli and Surface Tension.txt", "text": "So this surfactant also prevents the alveoli from collapsing onto themselves during the process of exhalation."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Let's begin with the same exact spermatogonium, the same exact precursor cell."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Once again, we're not considering the autosomes."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "We're only looking at the sex chromosome."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So we have replication taking place."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "We produce these two identical cystochromatids."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "These two?"}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Identical cystochromatids and let's assume that nondisjunction does not take place during my Ptosis during meiosis one so during meiosis one, we have the normal segregation process taking place so these fibers are able to extend they form connections with these chromosome pairs and they move apart to form the following two cells."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So cell number one and cell number two that are normal now in anaphase of meiosis two."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So anaphase two of meiosis."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Now, we have nondisjunction take."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Place in both of these cells."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Now, of course, we can have nondisjunction taking place in one of these two cells, but let's assume that nondisjunction takes place in both of these cells."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "What will happen is so we have one fiber forms a connection, the other one doesn't."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "One fiber forms a connection, the other one doesn't."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And so when we have the segregation process take place, this entire pair of cystochromatids moves to one cell."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So we form."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Sperm cell number one."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "The other one doesn't get anything."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So we form sperm cell number two and the same thing happens here."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "This entire pair of identical cytochromatids moves into sperm cell number one."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And the other one basically gets nothing."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So just like in this case, we have sperm cell two and sperm cell four that have nothing but sperm cell one, in this case contains two identical X chromosomes."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "In here, we have two identical Y chromosomes."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And so now, if we study the same exact picture as we discussed in this particular diagram, if we take, let's say, sperm cell number one and we combine it with a normal X cell, what we're going to get?"}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Is an individual that has three X chromosomes."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So this will be replaced with an X chromosome."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "We combine and so we'll form a Zygote that has anapply that will contain axxx genotype arrangement."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So an X and X and an X."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Likewise, if we take this sperm cell and combine it with the normal XL, we're going to have an arrangement of XYY."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And finally, if either one of these two sperm cells for or combines with a normal xcel, we're going to have an EXO condition, just like we had in this particular case."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And once again, and I have to emphasize this, Meiosis, one or two can experience nondisjunction."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "So we have two places where nondisjunction can."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "Take place in Meiosis."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And if it takes place in Meiosis, then all the somatic cells within that particular individual will contain this anemployed condition."}, {"title": "Aneuploidy and Nondisjunction (Part II) .txt", "text": "And that's why it's much more dangerous if Unemployed takes place if Non Junction takes place in Meiosis than if it takes place in Mitosis."}, {"title": "Properties of Water and Hydrophobic Effect Part II.txt", "text": "Around the nonpolar substance and allows them to actually form those stabilizing hydrogen bonds."}, {"title": "Properties of Water and Hydrophobic Effect Part II.txt", "text": "Now, the interactions between the nonpolar molecules and water are called hydrophobic interaction and this effect is known as the hydrophobic effect."}, {"title": "Properties of Water and Hydrophobic Effect Part II.txt", "text": "So as we discuss the many different tops, the many different topics, the many different topics in biochemistry we have to keep this effective mind because the hydrophobic effect and these properties of water determine many important properties of many important reactions that exist in biochemistry."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "The proteins found inside our body consist of 20 different amino acids."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And seven of these 20 different amino acids have readily ionizable side chain groups."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And what that means is the side chains can basically lose or gain an age atom at a specific PH value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And so for a specific amino acid that is ionizable at certain PH values, the side chain will have a charge."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "But at other PH values, the side chain will be neutral."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, to see exactly what we mean by this, let's take a look at the following two examples."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So these are the two out of the seven ionizable amino acids."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We have cysteine, and we have lysine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, for the case of cysteine, the side chain group that is ionizable is the following group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So notice the sulfur atom contains an h atom."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "But when the PH value reaches the PKA value of the side chain group, namely 8.3, what that means is this will begin to lose our h atom."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And at the PH value of 8.3, exactly half of the cysteine amino acids will exist in this form, and the other half will exist in this form with a negative charge on that sulfur."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, if we go above 8.3, then this group will predominate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If we go below 8.3, this group will predominate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, for the case of Lysine, the end of the side chain group that is ionizable is this group shown here."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the same exact thing is true for this particular group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "At this PH value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "When the PH is equal to the PKA of this group of 10.8, then half of them will exist in this form."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "The other half will exist in this form."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If we go below a PH of 10.8, this group will predominate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If we go above a PH of 10.8, this is the group that will predominate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And the same thing is true for the other five readily ionizable amino acids."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, since proteins consist of different combinations of these readily ionizable amino acids, what that means is they will have different net charge values at some specific PH value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "For example, they will have different net charges at the physiological PH of around seven."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, what it also means is that every protein will have a unique PH value at which the overall net charge on that protein, on that polypeptide, will be zero."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And this will be the case."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "At a specific PH value, all the charges on all our amino acids on that protein will exactly cancel one another out."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "The net charge will be zero."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And this specific point is a property of that protein because the protein is unique."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "It consists of a specific combination of these amino acids."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "In fact, the PH value at which the protein has a net charge of zero is given a special name."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "It's called the isoelectric point, or simply pi."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So every protein contains this isoelectric point."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, some proteins, if they consist of the same exact combination of ionizable amino acids, they will have the same isoelectric point."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "But usually proteins have different values, isoelectric point values, because they have different combinations of these ionizable amino acids."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And because this is another property of proteins that is unique to most proteins, we can use this property to basically purify our protein."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So if we have a mixture of different types of proteins, we can separate and isolate specific proteins from that mixture by using a method known as the isoelectric focusing method."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the isoelectric focusing technique is basically a method that we can use to purify and mixture proteins by using a specific property of the protein we call the isoelectric points."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's take a look at the following diagram, which basically describes the setup of isoelectric focusing."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So in the setup, we basically create a special type of gel, and we create a PH gradient along that gel."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's suppose we take a gel."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We take the gel, we place the gel into a special apparatus, and we create a PH gradient."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "What that means is on one side, let's say on the left side of our gel, we're going to have a low PH acidic environment."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "On the other end, on the right side, we're going to have a high PH, a basic environment."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, we're also going to connect both ends of that gel to a voltage source."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We're going to create an electric potential difference between the two sides, and that will create an electric field."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And we'll see why that's important."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Just a moment."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So once we set up this apparatus, what we do next is we take our mixture of proteins and we essentially place it into our gel."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, what will begin to happen?"}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Well, what will begin to happen is the proteins will begin to migrate, they will begin to move."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Why?"}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Well, because the proteins will have a net charge."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And whenever they have a net charge, they will move within an electric field as a result of the interaction between the electric field and the charge, the net charge on that protein."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So, for instance, if we take a protein that contains a net positive charge and we place it into our field, it will begin to move towards the negative end."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And if we take a protein that contains a net negative charge, it will begin to move away from this end and towards this positively charged end."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, the proteins will continue moving along our gel until they reach the PH value at which the overall charge is zero."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And when the overall charge is zero, because there is no net charge, those proteins will no longer move along that electric field."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So when the protein reaches its specific isoelectric point, the pi value, it will be, it will stop moving within that gel."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And so if we, for example, have a mixture of three proteins that each have their own unique ISO electric point value, and we place them into our mixture, they will separate until they will separate, and they will stop moving when they reach their pi value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So for protein one, the pi value is acidic, or relatively acidic."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "For protein three, the pi value is relatively basic."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And for protein two, it's somewhere in the middle, so it's essentially neutral."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So once again, in isoelectric focusing, a gel with a PH gradient is created."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "The two ends are connected to a voltage source, a battery, and the proteins are placed into our gel."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, each protein will move due to the presence of an electric field as a result of that battery source."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And so when they reach their pi value, the isoelectric point, they will stop moving because the net charge at the pi value of the protein is zero."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, of course, this method is not very useful if these three proteins have the same combination, have the same number of these ionizable amino acids, because what that means is these three proteins will have the same exact value for the isoelectric point."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So they have to have a different isoelric point value for this technique to actually be useful in separating our proteins."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, the question is, how exactly do you determine what your pi value is for a specific polypeptide?"}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, before we determine what the pi value of specific proteins is, let's ask the following question."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "How do you determine what the pi value is of a single amino acid?"}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's take a look at the following four cases."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "There are four cases that we basically have to remember."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So case number one, let's suppose that the amino acid is not ionizable."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If that's the case, if the side chain is not ionizable, then to find the pi value of that particular amino acid, to find the isoelectric point, we simply sum up and we take the average of the PKA values of the terminal alpha amino group and the terminal carboxyl amino group and the terminal carboxyl group of that particular amino acid."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Remember, every single amino acid contains an a terminal alpha carboxyl group and a terminal alpha amino group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And those two groups are also capable of losing and gaining h atoms at specific PH values."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So if the side chain is non ionizable, then the isoelectric point of that amino acid is the average of the PKA values of the terminal alpha amino group and the terminal alpha carboxyl group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So one example of a nonionisable amino acid is glycine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Another example is valine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We have Alanine leucine, isolucine and so forth."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's take a look at glycine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So glycine contains the h atom sidechain group, and that means it is not ionizable."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, at some specific temperature value, the PKA of this particular alpha amino group is 8.0."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And for this particular alpha carboxyl group, let's say it's 3.1 at that same temperature condition."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So in this particular case, all we have to do to find the pi value of this amino acid is simply take the sum of these, divide by two and we get the average."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we have eight plus 3.1, which is 11.1."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We divide that by two, we get 5.55."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the pi value for glycine is 5.55, assuming these are our PKA values."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now these PKA values might change if we change the conditions under which this amino acid is in."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So in your textbook, or maybe your teacher might give you different PKA values."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And that's because the temperature conditions or other conditions under which that amino acid exists in are different."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's move on to the second case."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If the side chain is ionizable and that ionizable side chain is acidic, then to find a pi value of that amino acid, we simply take the average of the PKA values of the terminal alpha carboxyl group and that side chain."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So to see what we mean, let's take an example."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Let's look at an ionized blamino acid that is acidic."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we have two cases."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We have aspartate and we have glutamate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's take a look at aspartate."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "For aspartate, this is our side chain group, and the PKA value of Aspartate is 4.1."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, this PKA value is the same as above."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "It's 3.1."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So notice they both have negative charges."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And that makes sense, because if both of these groups give the same type of charge, then to basically cancel out the positive charge, we have to average these two negative charges."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And so we average these two PK values."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So 4.1 plus 3.1, that gives us 7.2."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We divide that by two, that gives us 3.6."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So what that means is at a PH of 3.6, these two negative charges from these two groups will exactly cancel out this positive charge found on this terminal alpha amino group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And so at this particular PH value, this will have a net charge of zero."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now let's move on to case number three."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Let's suppose we have an ionizable amino acid, but it is basic."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So that means there are three different amino acids that fit this category."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we have Lysine, we have arginine and we have HistoGene."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now in this particular case, what we have to do is we basically take the sum of the PKA value of that side chain group and the PKA value of the alpha amino group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "We divide that by two, we get the average, and that is our isoelectric point."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So let's take a look at lysine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So Lysine contains this side chain group, and the PK value of Lysine is around 10.8."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Now, the PK value of this alpha terminal group, alpha amino terminal group is eight."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So notice once again, in this case we have two negative charges on two different groups."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "In this case, we have two positive charges on two different groups."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So now, instead of summing this and dividing by two, we summon this, divide that by two."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we get 10.8 plus eight."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "That's 18.8."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Divided by two gives us 9.4."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the pi, the isoelectric point for this amino acid, which is basically Lysine, is equal to 9.8."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So at a PH of 9.8, these two charges will exactly cancel out this negative charge that is found on the alpha carboxyl group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And finally, let's move on to case four."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So, if we have an ionizable side chain group, but it is neither basic nor acidic, so we're basically dealing with two cases."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And these two cases are 15 and tyrosine."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "If the amino acids are 15 or tyrosine, to calculate our pi value, we have to determine what the middle PKA value is out of the three different PKA values."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And then we take that middle value and we basically sum it with the terminal alpha carboxyl PK value and we divide that by two."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So to see what we mean, let's take a look at the following example."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So, this is our tyrosine amino acid."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So, tyrosine has an ionizable side chain group, but it is neither basic nor acidic."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the side chain group is this female group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So the PK value of this is 10.9."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So in this particular case, because it is ionizable but neither basic nor acidic, what that means is out of these three PKA values, we have to find a middle PKA value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we have 10.93.1 and eight."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So Diaz is our middle PK value."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "And then we average this value and the PK value for the alpha carboxyl terminal group."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So we take 3.1, we added to eight, we get 11.1."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "Divide that by two, we get 5.55."}, {"title": "Isoelectric Focusing and Isoelectric Point .txt", "text": "So in this particular case, if the PK values are shown, then the PIV."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So previously we discussed how the skeleton muscle cells are able to use different types of allosteric effectors and allosteric activators to basically regulate the activity of glycogen breakdown."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So we said that in skeleton muscle cells we have the enzyme known as glycogen phosphorylase that can be regulated."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And that in turn regulates the breakdown of glycogen."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Now, in liver cells, things are slightly different, and that's because liver cells have a different function than of skeletal muscle cells."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So in liver cells that's our goal is to actually regulate the concentration of glucose inside our blood."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So our liver is responsible for regulating the concentration of glucose in the blood."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And what that means is liver cells can actually mobilize glycogen by breaking down to glucose, but they don't actually use that glucose to form ATP."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Instead, they can release that glucose into the blood to basically increase the concentration of glucose in the blood when the blood glucose levels drop below normal."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Now, how exactly is glycogen breakdown controlled in the liver?"}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So in the liver, we also regulate the breakdown of glycogen by regulating the allosteric enzyme we call glycogen phosphorylase."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "But the glycogen phosphorase inside liver cells is slightly different than the phosphorase that we find inside skeletal muscle cells."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So essentially, the liver phosphorase is an isozyme version of the muscle phosphorase."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "They're pretty much the same molecule with some minor differences."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And one important minor difference between liver phosphorylase and muscle phosphorase is that liver phosphorylase is actually sensitive to glucose molecules."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Glucose is an allosteric effector."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "More specifically, it's an allosteric inhibitor of phosphorase."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So let's take a look at the following diagram."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So, this diagram describes the fully active r state of phosphorace A found in the liver, and the T state, inactive state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Office Fourlase A of the liver."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So essentially, when glucose molecules bind into a specific allosteric regulating side shown here and here, what we have is a transition from the R state, the fully active state, where the activity of the enzyme is high, to the inactive state, the T state, where the activity of the enzyme is low."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Now, we can have two different situations."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "We can basically have a situation in which the blood glucose levels are low, or we can have a situation where the glucose blood level is high."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So let's suppose we have a high blood glucose level, and this happens after we ingest some type of carbohydrate rich meal."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So when blood glucose levels are high, what happens is glucose will act as an allosteric inhibitor."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "It will bind onto special regulatory sites, allosteric sites."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And once they bind, they will create a conformational change in the structure of this phosphoralase A of the liver."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And it will basically shift the equilibrium toward the T state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "In the T state, the enzyme is not active, it has low activity, and so it will not break down glycogen into glucose."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And that makes sense because after we ingest the meal rich in sugar molecules."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "We don't want to produce and release any more glucose molecules into the blood."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Now, what about when we have low blood glucose levels?"}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Well, when we have low blood glucose levels, we're essentially going from this T state to this r state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So when we have very low concentration of glucose in the blood, these glucose molecules will essentially remove themselves."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And once they remove themselves, a conformational change takes place that shifts the equilibrium toward the r state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And in the rstate the enzyme is fully active and it will bite to glycogen and begin breaking down glycogen into glucose and then the glucose will be removed into the blood plasma."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "Now remember, in skeleton muscle cells we have phosphorase A and phosphorace B."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "In liver cells we also have phosphorase A and phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "But unlike phosphorase A, the liver phosphorase B is not actually sensitive to glucose molecules."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "In addition, when we discuss skeleton muscle cells, we saw that in skeleton muscle cells, amp adenosine monophosphate is an allosteric activator of phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "But in liver cells, the phosphorase B of liver cells does not respond to amp molecules."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And this is primarily because unlike in skeleton muscle cells, liver cells do not actually experience a change in the energy charge of the cell."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So we see that the energy charge inside liver cells remains relatively constant."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And what that means is amp molecules do not actually affect phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So to summarize, let's take a look at the following two diagrams."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "So if we have low blood glucose levels, what will begin to happen is these glucose will essentially depart from these regulatory sites and that will shift the equilibrium toward the r state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "It will activate phosphorase A of the liver and that will initiate glycogen breakdown."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "The glucose molecules will be released into the blood and that will increase the levels of blood, the level of blood glucose back to normal."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "On the other hand, if we have high glucose levels in the blood, like after eating a carbohydrate rich meal, what happens is the glucose molecules will enter these liver cells, they will bind to these special regulatory sites and that will essentially inactivate the molecule by shifting structure into the ten state."}, {"title": "Regulating Glycogen Breakdown in Liver .txt", "text": "And that will stop the breakdown of glycogen and that will stop the release of glucose molecules into the blood plasma of our body."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "In the previous lecture, we focused on step one of the citric acid cycle, and we saw that in step one, we basically take an acetyl group and attach it onto an oxalo acetate molecule to form a six carbon intermediate known as the citrate molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And so in this lecture, I'd like to focus on what happens next."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So we're going to focus on steps two, three, and four of the citric acid cycle."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And so so let's begin with step number two."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, the entire point of step number two is basically to take the citrate molecule and to prepare it for oxidative decarboxylation that will take place in step three and step four of the citric acid cycle."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So in these two steps, we're basically going to produce carbon dioxide molecules, and we're going to abstract those high energy electrons that we're going to use on the electron transport chain."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "But before steps three and four take place, we have to prepare the citrate molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And the way that we prepare that citrate molecule is by actually changing the position of this hydroxyl group."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So citrate and isocytrate are actually isomers."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "They have the same exact molecular formula, but they differ in the position of this hydroxyl group."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "On the citrate, the hydroxyl is attached onto this carbon."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Let's call it carbon three."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And on this molecule, the hydroxyl is instead attached onto this carbon here."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And we see that to go from this reaction to this product, we have to go through an intermediate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And so this step two is actually a two step process."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So in process one of step two, we have a dehydration reaction."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Well, because we want to basically remove this hydroxyl group."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And in addition, we remove this H to form the water molecule and form the double bond between this carbon and this carbon here."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And once we form this double bond, this water molecule that comes in in step two will basically undergo a hydration reaction."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "The water will act as a nucleophile, and instead of attacking this carbon, it will attack this carbon."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Because if the water molecule attacked this carbon, we would have simply reformed the citrate molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "But if the water attacks this carbon, which is basically less hindered because it contains a smaller group on this side compared to this large group here, the water molecule is able to actually attack from this side because of less hindrance."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And so once it attacks that side, we form the isocitrate molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So the entire point of this step is to basically prepare the citrate molecule for oxidative decorboxylation that takes place in step three as well as step four."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, this double bonded intermediate molecule is known as cisaconitate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And because of this cysticonitate, the enzyme that catalyzes step two is known as aconitase."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So once again, once citrate is formed in step one of the citric acid cycle, it must be transformed into its isomeric form, isocitrate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this reaction, we basically transfer a hydroxyl group from the third carbon onto the adjacent carbon shown here."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And what this process does, once again, is it prepares the molecule for a decarboxylation reaction that we'll talk about in the next step."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, the enzyme that catalyzes this step is known as a connotase."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this aconitase actually contains an iron sulfur component."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And that's why this molecule, the connotase enzyme, is known as an iron sulfur enzyme."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "An iron sulfur protein now actually contains a ratio of four iron to four sulfur inorganic sulfide atoms."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this complex is found on the active side, and it binds not the hydroxyl onto the carboxylate ion group of the citrate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And that holds the citrate molecules within the active side and allows the catalysis to actually take place."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So, once again, step two is a two step process."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So we have this dehydration and hydration that is catalyzed by the connotase, which is an iron sulfur protein because it uses the iron sulfur complex to carry out these two reactions."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, once we form the isocitrate molecule, now this six carbon molecule is ready to undergo the first oxidative decorboxylation step of the citric acid cycle."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this is what happens in step three."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So once the isocitrate is formed, it is ready to undergo the first oxidative decorboxylation step."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this reaction is catalyzed by isocytrate dehydrogenase."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Why dehydrogenase?"}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Well, remember, a dehydrogenase is an enzyme that basically abstracts those electrons attached onto the H ion to basically form that reduced NADH molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So in this particular case, in the same exact way that we have a two step process here, we also have a two step process here."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And in the first step of step three, we take the isocytrade and we reacted with the nicotine amide adenine dinucleotide in the oxidized form."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And so in this process, the NAD plus is actually reduced into the NADH, and the isocitrate molecule is oxidized to form the oxylosuxanate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And we also release this H plus ion."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So the first reaction involves abstraction of a pair of high energy electrons to form the NADH."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this high energy intermediate known as oxalosuxnate and oxylosuxanate is unstable because it is a beto keto acid."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So remember from organic chemistry that beta keto acids are generally unstable molecules."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, the NADH that we produced will be used by the electron transport chain, as we'll discuss in a future lecture."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So now let's move on to step two of this process that takes place in step three."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So in the next step, we take that oxylosuxtonate and bivactivity of the same enzyme, isocitrate dehydrogenase."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "We mix it with an H plus ion, and we basically form a molecule known as alpha ketonoglutrate."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So the highly unstable oxylosuxanate can now undergo a decarboxylation reaction."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So this was the oxidation reduction reaction, and this is the decarboxylation step."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And actually, as we'll discuss in much more detail in a future lecture, this essentially is the step, the formation of the alpha ketoglutter rate is the step that actually determines the rate at which the citric acid cycle actually takes place."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So this is a very important step."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And if we sum up these two steps, these two reactions of step three, this is the net reaction that we're going to get."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Notice that the oxylosuxanate molecules don't appear any of the sides because they cancel out."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So if we sum up this reaction with this reaction, this cancels out, and so does this, as well as the H plus here and H plus here."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So this is the net reaction that we get on the reactant side, the isocytrate that we produce in step two and the NAD plus that acts as the carrier and picks up those two electrons that we abstract from the isocytrate, we form the NADH."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "The carbon dioxide molecule is removed from the isocytrate, and we form this alpha ketoglutrate molecule."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now let's move on to step four."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "In step four, once again, we have another oxidative decarboxylation step."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "We're going to remove yet another carbon dioxide in the process abstracting the pair of high energy electrons to basically form the reduced NADH molecule, which eventually will be used by the electron transport chain to generate those high energy adenosine triphosphate molecules."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And in this step, we actually use the coenzyme A, the same coenzyme A that we use in Pyruvate decarboxylation."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So the next step is a second oxidative decarboxylation reaction of the citric acid cycle."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "This step involves the conversion of the alpha ketoglutrate into the succinil coenzy, and this is what the reaction looks like."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So this is the net reaction."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "On the reactant side, we have the product of step three, the alpha key to glutrate in the presence of the mad plus."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "We need this because this acts as the carrier to actually abstract those electrons."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And we have the Co enzyme, the coenzyme A COA."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And on the product side, we essentially attach we remove this component that produces the carbon dioxide, and we attach the coenzyme a onto this bond to form the high energy thio ester bond."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And this is the bond that will be broken in the steps to come as we'll discuss in the next several electrodes."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Now, this succinct coenzyme A basically is the product of step four."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And the enzyme that catalyzes step four is known as alpha ketoglu rate because this is a substrate molecule that binds into the enzyme dehydrogenase complex."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And in fact, this complex is very similar to the complex that catalyze step one of the citric acid cycle."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "How is it similar?"}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "Well, this complex, just like that complex, also consists of three different types of enzymes, and it also uses many different types of Cofactors."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So we have the E one enzyme that is known as alpha ketoglutrade dehydrogenase, that uses the TPP."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So thiamine pyrophosphate cofactor we have the E two known as dihydrolypoil succinct transferase that uses the lipoic acid derivative."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And we have E three, dihydroly pool dehydrogenase that uses the fad."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "So this large complex, the alpha ketoglutrate dehydrogenate complex, consists of these three enzymes, and it uses different types of coenzymes to carry out the steps of step four."}, {"title": "Step 2-4 of Citric Acid Cycle .txt", "text": "And if you want to learn more about out the mechanism of this particular step, go back and watch my lecture on step one, because these two steps are actually very similar to one another."}, {"title": "Types of Blood Vessels .txt", "text": "Blood vessels are the conduits of our cardiovascular system."}, {"title": "Types of Blood Vessels .txt", "text": "And what that means is they create a network of pipes inside our body that allows the movement of our blood."}, {"title": "Types of Blood Vessels .txt", "text": "And that's important because blood carries not only nutrients, electrolytes, minerals and vitamins, but it also carries hormones, waste products and different types of cells to different parts of our body."}, {"title": "Types of Blood Vessels .txt", "text": "Now blood vessels come in three different types."}, {"title": "Types of Blood Vessels .txt", "text": "We have arteries and we have veins and we also have capillary."}, {"title": "Types of Blood Vessels .txt", "text": "So let's begin by focusing on our artery."}, {"title": "Types of Blood Vessels .txt", "text": "Now arteries vary in size."}, {"title": "Types of Blood Vessels .txt", "text": "The largest artery of our body is our aorter and the smallest one is something called an arterial and we also have different sizes in between."}, {"title": "Types of Blood Vessels .txt", "text": "Now by definition an arteries a blood vessel that always carries blood away from the heart and to the cells, the tissues and organs of our body."}, {"title": "Types of Blood Vessels .txt", "text": "And most of the time our arteries carry blood that contains oxygen."}, {"title": "Types of Blood Vessels .txt", "text": "So oxygenated blood."}, {"title": "Types of Blood Vessels .txt", "text": "But sometimes, as in the case of the left and the right pulmonary artery, these actually carry deoxygenated blood away from the heart and specifically to the left and the right lung."}, {"title": "Types of Blood Vessels .txt", "text": "Now what about the structure?"}, {"title": "Types of Blood Vessels .txt", "text": "What about the anatomy of our artery?"}, {"title": "Types of Blood Vessels .txt", "text": "So let's take a cross section of the artery."}, {"title": "Types of Blood Vessels .txt", "text": "We basically get the following diagram and notice that the artery consists of three different layers."}, {"title": "Types of Blood Vessels .txt", "text": "We have the innermost layer, the tunica intima where tunica means layer and intimate means inner."}, {"title": "Types of Blood Vessels .txt", "text": "We have the mid layer, the tunica media and we have the outer layer, the tunica extrema."}, {"title": "Types of Blood Vessels .txt", "text": "Now what exactly is the function of each one of these layers?"}, {"title": "Types of Blood Vessels .txt", "text": "Well notice this inside portion is the lumen."}, {"title": "Types of Blood Vessels .txt", "text": "It's the internal cavity of the blood vessel and this is where the blood actually flows."}, {"title": "Types of Blood Vessels .txt", "text": "And so the tunica intima is actually in direct contact with the blood plasma."}, {"title": "Types of Blood Vessels .txt", "text": "And so what that means is it contains a layer of endothelial cells that are responsible for absorbing the nutrients that the blood vessels actually need to function correctly and efficiently."}, {"title": "Types of Blood Vessels .txt", "text": "Now within the tunica intima we also have a network of protein elastin fibers and this basically gives the ability, gives our blood vessel the ability to actually be flexible, so have the ability to basically expand and stretch back."}, {"title": "Types of Blood Vessels .txt", "text": "Now the middle layer, this red layer is our tunica media and this is where the smooth muscle of the blood vessel is actually found."}, {"title": "Types of Blood Vessels .txt", "text": "And in arteries, the tunica media is a thick layer."}, {"title": "Types of Blood Vessels .txt", "text": "So arteries contain a thick layer of smooth muscle and we'll see why that's important in just a moment."}, {"title": "Types of Blood Vessels .txt", "text": "Now the outer layer is our tunica extrema and this basically contains our collagen fibers."}, {"title": "Types of Blood Vessels .txt", "text": "And collagen fibers give the blood vessels its strength."}, {"title": "Types of Blood Vessels .txt", "text": "And these collagen fibers also anchor the blood vessel along the organs found surrounding our blood vessel."}, {"title": "Types of Blood Vessels .txt", "text": "Now what are some properties of our arteries and how exactly does blood actually flow through the arteries?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, as a result of a thick layer of smooth muscle that makes the artery not only elastic and stretchy, but it also gives it very high recoil capabilities."}, {"title": "Types of Blood Vessels .txt", "text": "So what that basically means is as the blood actually flows through our blood vessel, through the artery, the artery slightly expands as a result of that increase in blood flow."}, {"title": "Types of Blood Vessels .txt", "text": "But because it has a thick layer of smooth muscle, you can think of this as being a rubber band."}, {"title": "Types of Blood Vessels .txt", "text": "When you stretch the rubber band, it wants to return back to place."}, {"title": "Types of Blood Vessels .txt", "text": "And in the same way, because of this thick layer of smooth muscle, when you stretch the artery, it wants to return back into place."}, {"title": "Types of Blood Vessels .txt", "text": "So it expands, but it quickly recoils, returns to place."}, {"title": "Types of Blood Vessels .txt", "text": "And this is exactly how the blood actually flows through our arteries."}, {"title": "Types of Blood Vessels .txt", "text": "Now, recall that smooth muscle is innervated by our autonomic nervous system."}, {"title": "Types of Blood Vessels .txt", "text": "So it's the autonomic nervous system that actually controls the dilation and the contraction of our arteries."}, {"title": "Types of Blood Vessels .txt", "text": "So the autonomic nervous system can basically control the blood pressure and the blood flow through our arteries."}, {"title": "Types of Blood Vessels .txt", "text": "And that's important in our body."}, {"title": "Types of Blood Vessels .txt", "text": "Now, finally, it also has a high resistance to blood flow because as soon as that blood enters our artery, it wants to recoil back into place."}, {"title": "Types of Blood Vessels .txt", "text": "And so that creates a high resistance."}, {"title": "Types of Blood Vessels .txt", "text": "And that's exactly why the ventricles of our heart have to create such a strong force, such a high hydrostatic pressure to move all that blood through these arteries that have a relatively high resistance."}, {"title": "Types of Blood Vessels .txt", "text": "So when the ventricles contract, they fill our blood vessels, they fill the arteries."}, {"title": "Types of Blood Vessels .txt", "text": "And as a result of the elastic nature of these blood vessels, it causes them to actually recoil."}, {"title": "Types of Blood Vessels .txt", "text": "And when they recoil, that is exactly what moves that blood through the rest of our arteries."}, {"title": "Types of Blood Vessels .txt", "text": "So this is how blood flows inside the artery."}, {"title": "Types of Blood Vessels .txt", "text": "Now, what about our veins?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, just like arteries come in different sizes, veins also come in different sizes."}, {"title": "Types of Blood Vessels .txt", "text": "The smallest vein is called a Venuel and the largest vein in our body is called the vena cava."}, {"title": "Types of Blood Vessels .txt", "text": "We have two, we have the inferior and the superior vena cava."}, {"title": "Types of Blood Vessels .txt", "text": "Now, if our arteries actually carry blood away from the heart, then the veins always carry blood to the heart and away from the cells, the tissues and organs of our body."}, {"title": "Types of Blood Vessels .txt", "text": "Most of the time, veins carry deoxygenated blood, but sometimes in the case of the left and the right pulmonary vein, they actually carry oxygenated blood to the left atrium of our heart."}, {"title": "Types of Blood Vessels .txt", "text": "Now, what about the structure?"}, {"title": "Types of Blood Vessels .txt", "text": "What about the anatomy of the vein?"}, {"title": "Types of Blood Vessels .txt", "text": "So as it turns out, veins also have these same three layers."}, {"title": "Types of Blood Vessels .txt", "text": "They have the tunica intima, the tunica media and the tunica extrema."}, {"title": "Types of Blood Vessels .txt", "text": "However, veins have a much thinner, they have a relatively thin tunica media layer and that's because they have very few smooth muscles."}, {"title": "Types of Blood Vessels .txt", "text": "So this layer here inside veins is relatively thick."}, {"title": "Types of Blood Vessels .txt", "text": "So that's exactly why, unlike our arteries, the veins are not very elastic."}, {"title": "Types of Blood Vessels .txt", "text": "In fact, we can assume they're inelastic."}, {"title": "Types of Blood Vessels .txt", "text": "And that means they do not recoil the same way that our arteries recoil."}, {"title": "Types of Blood Vessels .txt", "text": "And that's exactly why when the blood flows through our vein, when it expands, it remains in that shape because it doesn't have all of that smooth muscle to recoil it back into place."}, {"title": "Types of Blood Vessels .txt", "text": "So that's exactly why, unlike the arteries, these don't actually have such a high resistance, and they can expand and carry much more blood, much more volume of blood than our arteries."}, {"title": "Types of Blood Vessels .txt", "text": "In fact, the veins together carry about 60% to 65% of the total volume of blood."}, {"title": "Types of Blood Vessels .txt", "text": "The rest is carried by the capillaries, and a small portion is carried by our arteries or a relatively small portion."}, {"title": "Types of Blood Vessels .txt", "text": "Now, arteries actually have it pretty easy because when arteries expand from the heart and they travel to the bottom of the body, they are moving with the force of gravity so in the same direction that the force of gravity actually acts."}, {"title": "Types of Blood Vessels .txt", "text": "However, when those venues and veins leave the capillaries in the bottom portion of our body, they have to move up to the harm and against the force of gravity."}, {"title": "Types of Blood Vessels .txt", "text": "The question is, what exactly allows the veins to move that blood against the force of gravity?"}, {"title": "Types of Blood Vessels .txt", "text": "And what keeps that blood from actually flowing back down those veins?"}, {"title": "Types of Blood Vessels .txt", "text": "Remember, veins do not actually have a thick layer of smooth muscles."}, {"title": "Types of Blood Vessels .txt", "text": "So what allows that blood to move through our veins?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, as it turns out, next to our veins are skeletal muscle."}, {"title": "Types of Blood Vessels .txt", "text": "And we can actually voluntarily control our skeletal muscle."}, {"title": "Types of Blood Vessels .txt", "text": "And that's exactly why when we move, when we run, when we swim, anytime we move our legs, that helps the movement of the blood inside our veins."}, {"title": "Types of Blood Vessels .txt", "text": "That's one thing that assists the movement of our blood inside our vein."}, {"title": "Types of Blood Vessels .txt", "text": "Now, what about the problem of that blood going back down the vein as a result of the force of gravity?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, as it turns out, unlike the arteries, veins actually contain a system of valves."}, {"title": "Types of Blood Vessels .txt", "text": "They have a system of one way of valves that prevents the backflow of blood inside the vein."}, {"title": "Types of Blood Vessels .txt", "text": "So, to see what we mean, let's take a look at the following diagram."}, {"title": "Types of Blood Vessels .txt", "text": "So, this is a simplified diagram of the vein."}, {"title": "Types of Blood Vessels .txt", "text": "So, we basically have our blood that is moving against the force of gravity."}, {"title": "Types of Blood Vessels .txt", "text": "So the question is, what exactly prevents the blood from actually stopping and going back down?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, we have these one way valves in place."}, {"title": "Types of Blood Vessels .txt", "text": "So they open up one way when that blood basically creates the pressure and acts against that valve."}, {"title": "Types of Blood Vessels .txt", "text": "But if that valve decides or if that blood decides to basically turn around and go back down, what basically stops it is the fact that these valves only open one way."}, {"title": "Types of Blood Vessels .txt", "text": "As soon as that blood hits these portions of the valve, the valves will close as a result of that pressure, the force due to that blood."}, {"title": "Types of Blood Vessels .txt", "text": "So that's exactly what prevents that blood from flowing back down our veins."}, {"title": "Types of Blood Vessels .txt", "text": "With the force of gravity."}, {"title": "Types of Blood Vessels .txt", "text": "So we see that even though the veins have the same exact three layers as our arteries, the veins have a much thinner tunica media."}, {"title": "Types of Blood Vessels .txt", "text": "And they also have this system of one wave valves in place to prevent the movement of our blood back down our vein as a result of the force of gravity."}, {"title": "Types of Blood Vessels .txt", "text": "Now, what about the third type of blood vessel, our capillaries?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, capillaries are actually very, very tiny blood vessels."}, {"title": "Types of Blood Vessels .txt", "text": "They're the smallest blood vessels found inside our body, and in fact, they're only a single layer thick."}, {"title": "Types of Blood Vessels .txt", "text": "So they have a single cell layer, as we'll see in just a moment."}, {"title": "Types of Blood Vessels .txt", "text": "Now, why is that important?"}, {"title": "Types of Blood Vessels .txt", "text": "Well, it turns out that capillaries are specialized blood vessels where we have the exchange of nutrients and waste products taking place between the cells, the tissues, and the organs of our body."}, {"title": "Types of Blood Vessels .txt", "text": "And these capillaries actually connect the tiny arterials to our tiny venue."}, {"title": "Types of Blood Vessels .txt", "text": "So, capillaries are very tiny blood vessels that are one cell layer thick."}, {"title": "Types of Blood Vessels .txt", "text": "They contain a single layer of endothelial cells that is responsible for absorbing and secreting the nutrients and the waste products between the lumen of the capillary and the cells, the tissues found in close proximity to those capillaries."}, {"title": "Types of Blood Vessels .txt", "text": "So arterioles connect to the venues via these capillaries."}, {"title": "Types of Blood Vessels .txt", "text": "Now, hydrostatic pressure forces the cells of our body."}, {"title": "Types of Blood Vessels .txt", "text": "And as blood travels, hydrostatic pressure for I'm sorry, capillaries run close to the cells of our body."}, {"title": "Types of Blood Vessels .txt", "text": "And when the blood travels through the lumen of the capillary, hydrostatic pressure basically forces the nutrients and our waste products to move back and forth between the lumen and the cells fan around that capillary."}, {"title": "Types of Blood Vessels .txt", "text": "Now, there are actually four ways by which the nutrients and waste products can be exchanged by the capillary."}, {"title": "Types of Blood Vessels .txt", "text": "So let's discuss these four ways quickly."}, {"title": "Types of Blood Vessels .txt", "text": "So, this is the cross section of the capillary."}, {"title": "Types of Blood Vessels .txt", "text": "This is the lumen of the capillary."}, {"title": "Types of Blood Vessels .txt", "text": "And these are two cells that basically are found that create that capillary wall."}, {"title": "Types of Blood Vessels .txt", "text": "In the first place, we have these endothelial cells."}, {"title": "Types of Blood Vessels .txt", "text": "Now, notice between these cells, we have two types of holes."}, {"title": "Types of Blood Vessels .txt", "text": "We have a hole known as the intracellular cleft, and we also have a fenestration."}, {"title": "Types of Blood Vessels .txt", "text": "And these two holes basically allow the movement of nutrients from one side to another side."}, {"title": "Types of Blood Vessels .txt", "text": "So as the blood flows, that hydrostatic pressure pushes on our capillary."}, {"title": "Types of Blood Vessels .txt", "text": "That expands the holes and allows the movement of things across our wall of the capillary."}, {"title": "Types of Blood Vessels .txt", "text": "So the first way is via the federations."}, {"title": "Types of Blood Vessels .txt", "text": "The second way is via the space between the cells the intercellular collects."}, {"title": "Types of Blood Vessels .txt", "text": "Now, another method by which things actually are transported is via the cell membrane of these endothelial cells."}, {"title": "Types of Blood Vessels .txt", "text": "So notice we have the nucleus showed in purple."}, {"title": "Types of Blood Vessels .txt", "text": "We have the cell membrane, and just like anything else can travel across any other cell membrane, these cells can also actually transport things across the cell membrane."}, {"title": "Types of Blood Vessels .txt", "text": "Now, the final method by which we can exchange nutrients and waste products is via the process of pinocytosis."}, {"title": "Types of Blood Vessels .txt", "text": "So this is simply when some type of molecule approaches the membrane of the cell, the cell essentially invaginates, and it takes in that nutrients into our body and it creates a vesicle inside the cytoplasm that contains that nutrient."}, {"title": "Types of Blood Vessels .txt", "text": "So these are the four ways by which there can be an exchange of nutrients and waste products inside the capillary, between the lumen of the capillary and the surrounding cells, tissues and organs of our body."}, {"title": "Types of Blood Vessels .txt", "text": "So these are the three different blood vessels found inside our body."}, {"title": "Types of Blood Vessels .txt", "text": "Arteries are very elastic."}, {"title": "Types of Blood Vessels .txt", "text": "They have a high resistance, and they can recoil as a result of that thick layer of smooth muscle found in a tunica media."}, {"title": "Types of Blood Vessels .txt", "text": "And they always carry blood away from the heart."}, {"title": "Types of Blood Vessels .txt", "text": "Veins always carry blood to the heart."}, {"title": "Types of Blood Vessels .txt", "text": "And unlike arteries, they have a thin layer of tunica media, a thin, smooth muscle layer, and that makes them inelastic."}, {"title": "Types of Blood Vessels .txt", "text": "They cannot recoil, and they can easily expand to carry more blood."}, {"title": "Types of Blood Vessels .txt", "text": "And unlike these arteries, they actually have this valve system in place to basically prevent the movement of our blood back down that blood vessel."}, {"title": "RNA and DNA Viruses .txt", "text": "Viruses are small infectious agents that can basically infect living cells and take over the processes that take place within that cell."}, {"title": "RNA and DNA Viruses .txt", "text": "Now, there are many different types of viruses that exist in nature and one way by which we can classify our viruses is based on the nucleic acid that is found within our virus."}, {"title": "RNA and DNA Viruses .txt", "text": "Now there are two major categories, categories of viruses."}, {"title": "RNA and DNA Viruses .txt", "text": "We have DNA viruses which contain single or double stranded DNA and we also have RNA viruses that contain single or double stranded RNA molecules."}, {"title": "RNA and DNA Viruses .txt", "text": "Now let's begin by discussing DNA viruses."}, {"title": "RNA and DNA Viruses .txt", "text": "Now although single stranded DNA viruses do exist and one example is the Inovirus that infects bacterial cells, the more common type of DNA virus is the one that contains the double stranded DNA."}, {"title": "RNA and DNA Viruses .txt", "text": "Now basically what the DNA virus does is it infects that cell by essentially injecting our nucleic acid the single or double stranded DNA molecule inside that cell."}, {"title": "RNA and DNA Viruses .txt", "text": "And that DNA basically ends up in the nucleus of our cell."}, {"title": "RNA and DNA Viruses .txt", "text": "Now once in the nucleus of that cell, it can basically use the infected host cells machinery."}, {"title": "RNA and DNA Viruses .txt", "text": "It can use the infected host cells polymerase enzymes to basically transcribe as well as replicate the DNA molecules."}, {"title": "RNA and DNA Viruses .txt", "text": "So transcription of DNA into RNA and then into mRNA can take place."}, {"title": "RNA and DNA Viruses .txt", "text": "And then that viral mRNA can be used to produce our proteins by using the cell's ribosomes in the cytoplasm of that cell."}, {"title": "RNA and DNA Viruses .txt", "text": "So basically, the viral DNA utilizes the cell's polymerase enzymes to replicate the viral DNA within the nucleus and then it can also be used to basically transcribe into mRNA and the mRNA can be used to form the proteins needed for the survival of Araviruses."}, {"title": "RNA and DNA Viruses .txt", "text": "And one such example of a double stranded DNA that follows this pathway are adenoviruses."}, {"title": "RNA and DNA Viruses .txt", "text": "Now, some DNA, and these are much less common, but some DNA actually carry their own polymerase enzymes."}, {"title": "RNA and DNA Viruses .txt", "text": "And that means the DNA doesn't actually have to go into the nucleus."}, {"title": "RNA and DNA Viruses .txt", "text": "It can stay in the cytoplasm of that whole cell and it can replicate and transcribe inside that cytoplasm to form the viral proteins that are needed for the survival of our virus."}, {"title": "RNA and DNA Viruses .txt", "text": "And one example of such a DNA virus is the pox virus."}, {"title": "RNA and DNA Viruses .txt", "text": "Now let's move on to the RNA virus."}, {"title": "RNA and DNA Viruses .txt", "text": "So we saw that the double stranded DNA viruses are much more common than single stranded DNA virus."}, {"title": "RNA and DNA Viruses .txt", "text": "For RNA viruses it's the opposite."}, {"title": "RNA and DNA Viruses .txt", "text": "So although we do have some examples of double stranded RNA viruses, the single stranded RNA viruses are much more common."}, {"title": "RNA and DNA Viruses .txt", "text": "So RNA viruses basically inject their RNA molecules, the RNA nucleic acids into the cynoplasm of that whole cell."}, {"title": "RNA and DNA Viruses .txt", "text": "And once inside the cytoplasm, the RNA can be used to synthesize the proteins or the RNA can be used to basically transcribe into mRNA and then that viral mRNA can be used to form the proteins needed for the virus to actually survive."}, {"title": "RNA and DNA Viruses .txt", "text": "Now a special category of RNA viruses include something called a retrovirus."}, {"title": "RNA and DNA Viruses .txt", "text": "So these viral agents."}, {"title": "RNA and DNA Viruses .txt", "text": "These RNA viruses contain a protein enzyme known as reverse transcriptase."}, {"title": "RNA and DNA Viruses .txt", "text": "And what reverse transcriptase basically does is once the RNA is inside the cytoplasm of the cell the reverse transcriptase basically transcribes our RNA into DNA which is in the opposite direction of normal transcription."}, {"title": "RNA and DNA Viruses .txt", "text": "And then once that viral DNA is synthesized it can go into the nucleus of that cell and in the nucleus of the cell it can be incorporated or integrated with the cell's own DNA genome."}, {"title": "RNA and DNA Viruses .txt", "text": "Now when the cell replicates its DNA and divides it passes down the viral DNA portion to the offspring cells."}, {"title": "RNA and DNA Viruses .txt", "text": "And one common example of an RNA virus known as the retrovirus that in fact humans is known as HIV or human immunodeficiency virus."}, {"title": "RNA and DNA Viruses .txt", "text": "Now the next type of category within RNA viruses that we're going to discuss are plus strand RNA and minus strand RNA also known as positive strand RNA and negative strand RNA viruses."}, {"title": "RNA and DNA Viruses .txt", "text": "Now what exactly is the plus strand or the positive strand RNA virus?"}, {"title": "RNA and DNA Viruses .txt", "text": "So these are the viruses that contain the RNA molecules that serve directly as the mRNA."}, {"title": "RNA and DNA Viruses .txt", "text": "So once our plus stranded RNA virus inject the RNA into the cytoplasm that same RNA is used to translate into proteins to synthesize those proteins."}, {"title": "RNA and DNA Viruses .txt", "text": "However, in minus trend RNA viruses the viral RNA that is injected into the cytoplasm must first be transcribed must first be modified into the mRNA before it can actually be used to synthesize our protein."}, {"title": "RNA and DNA Viruses .txt", "text": "So this is the major difference between plus transit RNA virus and minus trans RNA virus."}, {"title": "RNA and DNA Viruses .txt", "text": "So let's basically go over the summary of the differences between DNA viruses and RNA virus."}, {"title": "RNA and DNA Viruses .txt", "text": "Three major differences basically exist."}, {"title": "RNA and DNA Viruses .txt", "text": "So DNA viruses are predominantly in the double stranded form."}, {"title": "RNA and DNA Viruses .txt", "text": "They have double stranded DNA while RNA viruses predominantly comes in the single stranded RNA form."}, {"title": "RNA and DNA Viruses .txt", "text": "Now DNA replication occurs in the nucleus while RNA transcription replication takes place within the cytoplasm of our cell."}, {"title": "RNA and DNA Viruses .txt", "text": "And finally DNA viruses must first transcribe DNA into RNA before the proteins can actually be synthesized."}, {"title": "RNA and DNA Viruses .txt", "text": "However, for RNA viruses they basically contain the RNA that can be used pretty much directly to synthesize our protein."}, {"title": "RNA and DNA Viruses .txt", "text": "So we see our RNA viruses basically bypass the DNA to RNA transcription process."}, {"title": "RNA and DNA Viruses .txt", "text": "They can use that RNA to basically translate to synthesize our proteins."}, {"title": "RNA and DNA Viruses .txt", "text": "And these are the major differences between DNA and RNA viruses."}, {"title": "RNA and DNA Viruses .txt", "text": "And once again within the RNA viruses we have the plus strand RNA and the minus trans RNA virus."}, {"title": "RNA and DNA Viruses .txt", "text": "Plus transa is used directly as the mRNA to synthesize the proteins."}, {"title": "RNA and DNA Viruses .txt", "text": "The minus trans RNA means that RNA must first be transcribed into mRNA to actually synthesize those proteins."}, {"title": "RNA and DNA Viruses .txt", "text": "And a special type of RNA virus also known as the retrovirus exists."}, {"title": "RNA and DNA Viruses .txt", "text": "Retroviruses contain these special enzymeatic proteins known as reverse transcriptase that can basically transcribe the RNA into the DNA which then can be incorporated into the genome of that cell which can be passed down to the offspring cells during replication and division of that cell."}, {"title": "RNA Transcription.txt", "text": "Although DNA contains the genetic information that is used by the cell to synthesize the many different proteins that are used by the cell the DNA molecule itself is not directly involved in protein synthesis."}, {"title": "RNA Transcription.txt", "text": "In fact, what the cell does is it uses an intermediate molecule known as RNA which is involved directly in protein synthesis."}, {"title": "RNA Transcription.txt", "text": "And as we discussed in the previous lecture there are three types of RNA molecules and each type of RNA molecule serves its own unique purpose in protein synthesis."}, {"title": "RNA Transcription.txt", "text": "Now, we see that the DNA is basically first transcribed into our RNA so we undergo the process of transcription in which we synthesize RNA from DNA and then the RNA molecule is directly involved in the process of protein synthesis."}, {"title": "RNA Transcription.txt", "text": "So in a way we can imagine that the process of transcription is the passing down of the genetic information from the DNA molecule to the RNA molecule."}, {"title": "RNA Transcription.txt", "text": "Now the question is why can't we use our DNA molecule to directly synthesize our proteins?"}, {"title": "RNA Transcription.txt", "text": "Why do we have to use these intermediate RNA molecules?"}, {"title": "RNA Transcription.txt", "text": "Well, the answer is pretty simple."}, {"title": "RNA Transcription.txt", "text": "So the advantage of using RNA in that cell is to basically make sure that we do not damage or hurt our DNA in any way."}, {"title": "RNA Transcription.txt", "text": "So we want to ensure that the DNA is not mutated because the DNA is essential for the survival of the cell as well as of the offspring."}, {"title": "RNA Transcription.txt", "text": "So during reproduction it's the DNA that is passed down and not the RNA."}, {"title": "RNA Transcription.txt", "text": "And so that means we have to make sure that the DNA is not damaged."}, {"title": "RNA Transcription.txt", "text": "And by using these RNA molecules we ensure that the DNA basically decreases the opportunity to damage itself."}, {"title": "RNA Transcription.txt", "text": "So we see that because our RNA is not passed down to the offspring our cells have no problem recycling or breaking down the damage or mutated RNA molecules."}, {"title": "RNA Transcription.txt", "text": "So we see that transcription is the process by which we pass down the genetic information from our DNA molecule to our RNA molecule."}, {"title": "RNA Transcription.txt", "text": "And because DNA are only found in two locations in the nucleus and the mitochondria we see that the process of transcribing our DNA to RNA only takes place either in the nucleus or in our mitochondria."}, {"title": "RNA Transcription.txt", "text": "Now, the process of transcription can be broken down into three stages."}, {"title": "RNA Transcription.txt", "text": "We have initiation, we have elongation and we also have termination."}, {"title": "RNA Transcription.txt", "text": "So let's begin by discussing what initiation is."}, {"title": "RNA Transcription.txt", "text": "Now, just like in the process of DNA replication the first step in our transcription process is to actually locate is to find that initiation point."}, {"title": "RNA Transcription.txt", "text": "That basically is the location where we unwind our double stranded DNA molecule."}, {"title": "RNA Transcription.txt", "text": "Now, a group of proteins known as initiation factors basically move along our double stranded DNA molecule until it reaches a special location a special region on the DNA known as the promoter region."}, {"title": "RNA Transcription.txt", "text": "Now, what the promoter region is it's basically a special sequence of DNA nucleotides that signals the RNA polymerase to actually join the protein complex and begin the synthesis of our RNA strand."}, {"title": "RNA Transcription.txt", "text": "Now the promoter region usually does not vary too much from one organism to another organism."}, {"title": "RNA Transcription.txt", "text": "In fact, the most common type of sequence that appears in our promoter region is known as the consensus sequence."}, {"title": "RNA Transcription.txt", "text": "And we'll talk much more about the consensus sequence and this promoter region when we'll get into the field of biochemistry."}, {"title": "RNA Transcription.txt", "text": "So let's discuss what we just said by looking at the following diagram."}, {"title": "RNA Transcription.txt", "text": "So basically this is our double stranded DNA."}, {"title": "RNA Transcription.txt", "text": "So this is the three end."}, {"title": "RNA Transcription.txt", "text": "This is the five end of the single strand shown above and this is the five and this is the three end of the single stranded DNA molecule shown below and they're connected via hydrogen bonds between our nitrogenous bases."}, {"title": "RNA Transcription.txt", "text": "Now this is our RNA polymerase as well as our initiation factors."}, {"title": "RNA Transcription.txt", "text": "And as the initiation factors move across eventually they come across a region, a sequence of DNA nucleotides known as the promoter region that basically signals our RNA polymerase to begin unwinding and to begin the synthesis process."}, {"title": "RNA Transcription.txt", "text": "So when this reaches this region basically the RNA polymerase combines with this initiation factor with these proteins and it's the RNA polymerase itself that actually unwinds these two molecules, unwinds the two single stranded DNA molecules and creates a bubble that is known as the transcription bubble and we'll discuss that in detail in just a moment."}, {"title": "RNA Transcription.txt", "text": "So basically one important difference between DNA polymerase and RNA polymerase is that DNA polymerase itself cannot actually unwind the double helix of our DNA but the RNA molecule, the RNA polymerase can in fact itself unwind our molecule."}, {"title": "RNA Transcription.txt", "text": "Recall that in our discussion on DNA replication a special type of enzyme known as DNA helicase actually has to unwind the double helix."}, {"title": "RNA Transcription.txt", "text": "But in this case the RNA polymerase itself can actually unwind our double helix."}, {"title": "RNA Transcription.txt", "text": "So this concludes our discussion of initiation."}, {"title": "RNA Transcription.txt", "text": "Let's move on to the process of elongation."}, {"title": "RNA Transcription.txt", "text": "So elongation is basically the process where our RNA polymerase actually synthesizes the RNA molecule."}, {"title": "RNA Transcription.txt", "text": "So once RNA polymerase unwinds the DNA it creates a bubble that is commonly known as our transcription bubble that is shown in the following diagram."}, {"title": "RNA Transcription.txt", "text": "So basically what the transcription bubble is it's a region where our two single strands of DNA have been separated and are now exposed."}, {"title": "RNA Transcription.txt", "text": "Now notice only one of these DNA strands is actually used to synthesize our RNA molecule."}, {"title": "RNA Transcription.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "RNA Transcription.txt", "text": "So we can imagine that our initiation factors, these proteins are moving across our DNA."}, {"title": "RNA Transcription.txt", "text": "Eventually they reach our promoter region and then the RNA polymerase joins and it unwinds our double stranded molecule, our double helix and it creates this transcription bubble."}, {"title": "RNA Transcription.txt", "text": "And now as our RNA polymerase moves across this upper strand which runs from the three to the five direction it uses this strand to basically synthesize our RNA molecule."}, {"title": "RNA Transcription.txt", "text": "So it uses this trend because just like DNA polymerase RNA polymerase can only read our DNA strand beginning at the three N and ending at the five end."}, {"title": "RNA Transcription.txt", "text": "So it synthesizes our RNA beginning at the five end and ending at the three end as shown in a following diagram."}, {"title": "RNA Transcription.txt", "text": "So this green strand is in fact our RNA strand."}, {"title": "RNA Transcription.txt", "text": "Now the DNA strand that is used to actually synthesize the RNA strand is known as the template strand or more commonly the antisense strand."}, {"title": "RNA Transcription.txt", "text": "Now the other DNA strand is called the sense strand or the coating strand."}, {"title": "RNA Transcription.txt", "text": "And basically the nucleotides found on this trend are almost exactly the same as the nucleotides found on the RNA strand."}, {"title": "RNA Transcription.txt", "text": "The only difference is the thymines are replaced with uracil on the RNA because remember in RNA the thymines are replaced by the uracil."}, {"title": "RNA Transcription.txt", "text": "So basically the reason this is called an antisense because this has a complementary nucleotide sequence to this strand here."}, {"title": "RNA Transcription.txt", "text": "So this three to five strand is known as the antisense strand and our RNA polymerase uses the antisense strand to basically direct the synthesis of our RNA molecule and the other strand is known as the sens strand or the coating strand."}, {"title": "RNA Transcription.txt", "text": "So once again notice that just like DNA polymerase RNA polymerase can only read the DNA strand in the three to five direction and it can synthesize the RNA strand shown in green in the five to three direction."}, {"title": "RNA Transcription.txt", "text": "Now another important distinction that must be known between DNA polymerase and RNA polymerase is the following."}, {"title": "RNA Transcription.txt", "text": "DNA polymerase has the ability to basically correct any mismatches that are made with our base pairs."}, {"title": "RNA Transcription.txt", "text": "However, RNA does not have this proofreading mechanism and that means many more errors are actually formed during the process of transcription than the process of replication."}, {"title": "RNA Transcription.txt", "text": "And that makes sense because during replication we have to replicate our DNA precisely to pass it down to our offspring."}, {"title": "RNA Transcription.txt", "text": "Now the other thing that I want to mention about RNA polymerase is the following."}, {"title": "RNA Transcription.txt", "text": "In prokaryotic organisms there's only one RNA polymerase while in eukaryotic organisms there are three different types of RNA polymerases and each one of these RNA polymerases is used to synthesize the three different types of RNA molecules our messenger RNA, the transfer RNA and the ribosomal RNA."}, {"title": "RNA Transcription.txt", "text": "Now what about the process of termination?"}, {"title": "RNA Transcription.txt", "text": "So just like there is a sequence of nucleotides that initiates the process of transcription there is also a sequence of nucleotides of DNA nucleotides found on the double stranded DNA that also signal the process of termination."}, {"title": "RNA Transcription.txt", "text": "So the process by which our transcription basically stops and the sequence of DNA of DNA nucleotides is known as the termination sequence."}, {"title": "RNA Transcription.txt", "text": "Now when the RNA polymerase basically reaches this termination sequence certain types of specialized proteins may assist in the process of termination."}, {"title": "RNA Transcription.txt", "text": "For example in prokaryotic organisms a special type of protein known as the Rofactor binds to our RNA and helps the RNA to dissociate from our DNA molecule and that basically terminates the process of transcription."}, {"title": "RNA Transcription.txt", "text": "So once again transcription transcription is the process by which we basically transfer the genetic information from DNA to RNA."}, {"title": "RNA Transcription.txt", "text": "And there are three stages of transcription."}, {"title": "RNA Transcription.txt", "text": "We have initiation, we have elongation, and we have termination."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Glucokinase is not a fact that it's not inhibited by that molecule."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And that does two important things."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So let's see what this actually does."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So let's suppose inside our blood, we have a very high level of glucose."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, if we have a very high level of glucose, that glucose is toxic if it remains at that high level."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And it's the job of the liver cells to uptake all that glucose to maintain the proper level."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And so the fact that inside the liver cells, we not only have that hexagoninas, but in addition, we also have that glucokinase, both of these two is will basically work together to take in as many glucose molecules as possible and to transform those glucose molecules, for instance, into glycogen, so that all those glucose molecules can be removed from the blood."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So we see that when blood glucose levels are high, the glucokinates make sure that the liver cells transform that glucose into glycogen and fatty acids and other building blocks, so that all those glucose molecules are removed from the blood."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, that's the first important reason why we have gluco kinase in liver cells and we don't have in muscle cells, because muscle cells, the function of muscle cells is to simply move our, create voluntary motion."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "But liver cells have a much more diverse biochemical role."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, the other reason, well, what happens when the blood glucose level is low?"}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So let's suppose we're essentially starving."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So we haven't eaten for, let's say, a week, and we essentially want to eat."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "We need to eat to actually survive."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, let's suppose we see a sandwich on a table, okay?"}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And to get to that sandwich, what has to happen?"}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Well, the skeleton muscle cells actually will allow us to move to that table and grab that sandwich."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And it's the brain cells in our nervous system that essentially will tell those skeleton muscles to make our way to that table so that we can actually eat that sandwich and survive."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So what I'm basically saying is, under certain circumstances, when the blood glucose level is low, the fact that in liver cells we have the glucokinase basically means the glucokinase will be much less likely to bind to that glucose than the hexokinases found in the brain cells and the muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And so, when the blood glucose level is low, the low affinity of the glucokinase for glucose, remember, glucokinase is 50 times less likely to bind to glucose than hexaginase is found in other cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So muscle cells and brain cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And so that basically ensures that the hexokinases of the brain and the muscle cells get that glucose first, because under these conditions of, let's say, starvation, the liver function isn't as important as the muscle function and the brain function that will allow us to actually get to that food source and ingest those carbohydrates, those sugar molecules."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So these are the two important reasons for why we have the glucokinase in these liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And finally, let's move on to pyruvate kinase."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So pyruvate kinase is responsible for catalyzing the final step of glycolysis and that means the transformation of phosphorino Pyruvate into Pyruvate and ATP."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So this is our step."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So we begin with glucose that is eventually transformed to fructose one six bisphosphate this molecule here, so many more steps take place."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Then we have PEPSO phosphate, enochyruvate and the pyruvate kinase transforms this molecule into Pyruvate and ATP."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, the same exact alosteric molecules that we spoke about in our discussion of skeleton muscle cells also are applied to these pyruvic kinases found in liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So essentially, if we have high concentrations of ATP, the ATP creates a negative feedback loop that binds until Pyruvate kinase and diminishes its activity, inhibits its activity in the same way that ATP inhibits the phosphor fructokinase."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, because Pyruvate also forms, let's say, building blocks such as amino acids."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "If we have because Pyruvate forms alanine, if we have high amounts of alanine, that will also create a negative feedback loop which will go on and essentially diminish the activity, inhibit the activity of pyruvate kinase."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "But if we have low levels of glucose, low levels of ATP inside our cells, then the fructose one six bisphosphosphate will go on to create a positive feedback loop and stimulate activity of pyruvate kinase."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So this is the same exact mechanism that is used by pyruvate kinases found in skeleton muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "But again, we have a very important difference in skeleton muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "We actually have an isozyme of pyruvate kinase known as M isozyme, where M you can think of stands for muscle, while inside our liver cells we have the L isozyme for the pyruvate kinase."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So essentially, inside the liver cells, we have both l and misozymes."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "But it's the l isozyme in the liver cells that predominates."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And so unlike the misozyme we find in muscle cells, the lizosign is actually controlled by another process and that process is for sporulation."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So, this is the li design that we typically find in liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And it exists in two different states in a phosphorylated state and in a state where it's not phosphorylated."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, when we phosphorylate that alpyruvate kinase in liver cells that deactivates the molecule, it decreases its ability to actually catalyze the reaction."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Now, why would we want this extra mode of regulation in our liver cells?"}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "Because again, the liver cells under, let's say, starvation conditions don't actually need that glucose as much as, for example, brain cells do."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And so what that means is if we have very low amounts of glucose in the blood, our pyruvate kinases will be disabled via this phosphorylation, and that will make sure that the glucose molecules are not uptaken by the liver cells and they actually reach the brain cells and the muscle cells, the cells that actually need them more than the liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So we see that the liver pyruvate kinase is the l isosome, in contrast to the misozyme that we find in muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So the Lysosome predominates in liver cells, the Lpyruvate kinase responds to the same allosteric effects."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So as we discussed a moment ago, ATP alanine and a fructose 116 bisphosphate."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "But in l isozymes, they also respond to covalent modification via the process of phosphorylation."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So when the blood glucose levels are low, the phosphorylation process of this l is I, basically makes that molecule much less active."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And this means more important tissue cells."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "So brain cells and muscle cells can actually obtain that glucose before the liver cells actually do."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "And once again, to go back to our example of where we're essentially starving, we haven't eaten for weeks."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "We can get that sandwich because of this, because our body is able to actually regulate which cells of the body get that glucose first, so that the skeleton muscle cells, our cardiac muscle cells and the brain cells can allow us to actually get that food product."}, {"title": "Regulation of Glycolysis in Liver Cells Part II .txt", "text": "We can ingest that food product and then that glucose can be distributed to the liver cells of our body."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "NAD plus and Fad plus are two molecules that are essential for the synthesis of ATP during cellular respiration."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So NAD plus is known as nicotinemide adenine Dinucleotide, and Fad plus is known as Flavin adenine Dinucleotide."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And both of these molecules are cofactors."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "That means they are non protein molecules that assist enzymes involved in cellular respiration."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, what exactly is the purpose of these two molecules?"}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Well, basically, they accept the high energy electrons that come from fuel sources that we ingest into our bodies, including sugars and fatty acids."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So NAD plus and Fad plus molecules accept electrons and they carry these high energy electrons until the electron transport chain found in the inner mitochondrial membrane."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And the electron transport chain uses these high energy electrons to synthesize ATP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So we see that although NAD plus and Fad plus molecules are not a direct source of energy, they are used to actually form the energy molecules that are used by the cell, namely adenosine triphosphate or ATP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, when these electron carrier molecules accept our electrons, they are reduced."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So the fully reduced form of NAD plus is NADH, and the fully reduced form of Sad plus is Fadh too."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So we see that our electrons, the high energy electrons, are accompanied by hydrogen ions."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So that means when our NAD plus accepts those two electrons, it also accepts a single h plus ion to form the reduced version of our Nicotinemide adenine Dinucleotide."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And when Fad plus accepts those two electrons, it accepts not one, but two h ions to form the reduced version of Flavin adenine Dinucleotide, our Fadh two."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, in which processes do we actually form our NADH and how is it exactly used to synthesize our ATP molecules?"}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Well, NADH molecules are formed in glycolysis, which takes place in the cytoplasm of the cell."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And NADH molecules are also formed in pyruvate decarboxylation and in the citric acid cycle, also known as the crept cycle, which takes place in the mitochondrial matrix."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, once we form our NADH molecules, those NADH molecules then travel to the electron transport chain."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, the electron transport chain is found in the inner phospholipid bilayer membrane of the mitochondria that is shown on the board."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So we have the mitochondrial matrix, we have the inner membrane, the intermembrane space, and our outer mitochondrial membrane that is not shown, which is found somewhere here."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, basically, the electron transport chain is a series of four protein complexes, protein complex one, two, three and four, as well as a protein complex known as ATP synthase."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So when we synthesize NADH, it basically goes on to protein complex number one, also known as NADH dehydronates."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And this complex basically accepts our electrons from the NADH and it oxidizes it back into the NAD plus."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And those two electrons are then carried from complex one to complex three and two, complex four."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And in the process, as the electrons move, we basically pump h plus ions into the intermembrane space from the mitochondrial matrix and this establishes an electrochemical gradient."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And then the ATP synthase enzyme basically uses our H plus ions uses our electrochemical gradient to synthesize our ATP molecule."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So because we have a higher concentration of H plus ions in the intermembrane space these H plus ions will move down their electrochemical gradient from the intermembrane space to the mitochondrial matrix."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And this movement down the electrochemical gradient that was established by protein complex one, three and four synthesizes our ATP molecules from ADP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So adenosine diphosphate and our adenosine triphosphates."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, we see that for our NADH molecules that are formed inside the mitochondrial matrix and this includes the nadhs formed in pyruvate decarboxylation and the citric acid cycle."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "For every one NADH molecule formed we form three ATP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So when we oxidize one NADH on complex number one we form three ATPs."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, for one NADH that is formed in glycolysis which takes place in the cytoplasm of the cell a net of two ATP molecules are produced."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And that's because a single ATP must be used to actually transport that NADH from the location weglisis takes place the cytoplasm into the mitochondrial matrix where our electron transport chain is found."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, what about our Fadh two?"}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Well, Fadh two is not formed in glycolysis and it's not formed in pyruvate decarboxylation."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "It's only formed in the citric acid cycle."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "In fact, our Fadh two is formed directly in protein complex number two known as succinate oxidoreductase that is found on the electron transport chain."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So we synthesize Fadh two inside protein complex number one and then we oxidize it back into Fad plus in the process releasing those electrons."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "As the electrons travel through protein complex three and four we once again pump our H plus ions in this case only two, in this case, four."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And as we pump them, we create our electrochemical gradient that is used by ATP synthase to synthesize our ATP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Now, unlike NADH, our fadh two only Synthesizes two ATP per a single fadh two."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And the reason for that is because our Fadh two begins on protein complex two but the NADH begins on protein complex number one to the left."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And NADH basically pumps four more protons than Fadh two because NADH begins earlier, before Fadh two."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So for a single Fadh two that is synthesized during the citric acid cycle when we actually utilize and oxidize the Fadh two and two Fad we produce only two ATP molecules."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "But for the case of NADH that is formed within the mitochondrial matrix we form three ATPs per one NADH."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So we conclude that NAD plus and Fad plus molecules are cofactor molecules that assist the enzymes involved in cellular respiration."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "Specifically, they assist the enzymes involved in the electron transport chain."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So via the process of oxidative phosphorylation we basically synthesize our ATP molecules by moving these electrons across the electron transport chain and creating this electrochemical gradient."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "It's the electrochemical gradient that is used to drive the synthesis of ATP by this enzyme known as ATP synthase."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And we know that for a single NADH produced in glycolysis, we form two ATPs for a single NADH produced in the mitochondrial matrix."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "So in either one of these two processes, we form three ATPs."}, {"title": "NAD+ and FAD+ Cofactors .txt", "text": "And for a single fadh two produced in our citric acid cycle, which takes place in the mitochondrial membrane, we produce a net of two ATP molecules."}, {"title": "Cell Nucleus.txt", "text": "Every single eukaryotic cell contains the nucleus."}, {"title": "Cell Nucleus.txt", "text": "The nucleus is a membrane enclosed organelle that contains, stores, protects and expresses most of the genetic information that is found in our cell, the DNA, the deoxyribonucleic acid."}, {"title": "Cell Nucleus.txt", "text": "The reason I say most and not all is because actually a small portion, a small portion of the DNA is found in the mitochondria, which is another membrane enclosed organelle found in our body."}, {"title": "Cell Nucleus.txt", "text": "And we'll discuss that when we look at the mitochondria in its structure."}, {"title": "Cell Nucleus.txt", "text": "In this lecture, we're going to focus on the structure and the composition of the nucleus, of the eukaryotic cell."}, {"title": "Cell Nucleus.txt", "text": "So let's begin by discussing the envelope, the region that basically encloses our nucleus."}, {"title": "Cell Nucleus.txt", "text": "This is known as the nuclear membrane or the nuclear envelope."}, {"title": "Cell Nucleus.txt", "text": "So, just like the entire eukaryotic cell contains our cell membrane, the nucleus contains a membrane known as the nuclear membrane."}, {"title": "Cell Nucleus.txt", "text": "And the nuclear membrane, just like the actual cell membrane, also consists of a lipid bilayer."}, {"title": "Cell Nucleus.txt", "text": "So we have an inner as well as an outer region of the membrane that basically looks something like this."}, {"title": "Cell Nucleus.txt", "text": "So we have the outer membrane region that consists of the hydrophilic heads and the hydrophobic tails."}, {"title": "Cell Nucleus.txt", "text": "And we have the inner membrane region that also consists of our hydrophilic heads and the hydrophobic tails."}, {"title": "Cell Nucleus.txt", "text": "And the space, the fluid space between these two regions, the outer and the inner membrane, is known as the perinuclear space."}, {"title": "Cell Nucleus.txt", "text": "Now, throughout the entire nuclear envelope, throughout the entire nuclear membrane, we have very tiny holes known as nuclear pores that basically allow materials to move into the nucleus as well as outside the nucleus."}, {"title": "Cell Nucleus.txt", "text": "And we'll discuss exactly what the nuclear pore is in just a moment."}, {"title": "Cell Nucleus.txt", "text": "Now, the outer membrane is actually physically connected to the membrane of the rough endoplasmic reticulum."}, {"title": "Cell Nucleus.txt", "text": "And this is important because when we synthesize our RNA, ribosomal RNA, we have to have a quick way to transport our rRNA from the nucleus to our endoplasmic reticulum."}, {"title": "Cell Nucleus.txt", "text": "And that's why they are connected."}, {"title": "Cell Nucleus.txt", "text": "So the inner membrane, so this is the outer membrane that is found on the side of our cytoplasm."}, {"title": "Cell Nucleus.txt", "text": "But the inner membrane is found on the side of the fluid found inside our nucleus."}, {"title": "Cell Nucleus.txt", "text": "And the fluid inside the nucleus is known as the nucleoplasm."}, {"title": "Cell Nucleus.txt", "text": "So the nucleoplasm is the fluid inside the nucleus."}, {"title": "Cell Nucleus.txt", "text": "The cytoplasm is this entire region found between the cell membrane and our nuclear membrane."}, {"title": "Cell Nucleus.txt", "text": "Now, the inner membrane is also covered by a network of proteins known as intermediate filaments that extend throughout the entire nucleus, as shown by these extensions here."}, {"title": "Cell Nucleus.txt", "text": "Now, these network, or this network of extensions of intermediate filaments found inside the nucleus is known as the nuclear lamina."}, {"title": "Cell Nucleus.txt", "text": "And the nuclear lantima basically plays the role of stabilizing the structure of the nucleus as a whole and they are also involved in gene expression."}, {"title": "Cell Nucleus.txt", "text": "Now let's return to what a nuclear pores."}, {"title": "Cell Nucleus.txt", "text": "Earlier we said that the entire nuclear membrane contains these holes known as nuclear pores."}, {"title": "Cell Nucleus.txt", "text": "But what exactly is a nuclear pore?"}, {"title": "Cell Nucleus.txt", "text": "Well, a nuclear pore is not exactly an empty hold."}, {"title": "Cell Nucleus.txt", "text": "Nuclear pores are actually protein complexes that extend throughout the entire nuclear membrane."}, {"title": "Cell Nucleus.txt", "text": "And these protein complexes help transport biomolecules such as RNA, ribosomal units, ribosomal proteins, as well as polymerase between our nucleoplasm and our cytosol, the cytoplasm, this region here of our eukaryotic cell."}, {"title": "Cell Nucleus.txt", "text": "Now, a polymerase is basically a type of enzyme, a type of protein that plays an important role when we translate, replicate or when we transcribe our DNA molecules."}, {"title": "Cell Nucleus.txt", "text": "And we'll discuss that when we discuss replication, translation as well as transcription."}, {"title": "Cell Nucleus.txt", "text": "Now, let's move on to a region of the nucleus known as the nucleolus."}, {"title": "Cell Nucleus.txt", "text": "So at the heart of any nucleus of any eukaryotic cell is a region known as the nucleolus."}, {"title": "Cell Nucleus.txt", "text": "And it takes up about 25% of space found inside that nucleus."}, {"title": "Cell Nucleus.txt", "text": "Now, this is a very important section because within this section we have RNA molecules and proteins that are responsible for synthesizing our RNA or ribosomal RNA that is needed to create ribosomes found within the endoplasmic reticulum as well as inside our cytosol of the cell."}, {"title": "Cell Nucleus.txt", "text": "Finally, let's discuss the composition of DNA inside the nucleus."}, {"title": "Cell Nucleus.txt", "text": "So earlier we said the entire purpose of the nucleus is to store, protect and express our genetic information, the DNA, the deoxyribonucleic acid."}, {"title": "Cell Nucleus.txt", "text": "Now, the problem is the linear version of DNA is extremely long."}, {"title": "Cell Nucleus.txt", "text": "In fact, if we take a single DNA molecule found inside the human cell and we extend it in a linear fashion, it will be over 5ft long and that's extremely long."}, {"title": "Cell Nucleus.txt", "text": "So actually, what happens inside the nucleus is we take our linear DNA and we wind it around special proteins known as histones."}, {"title": "Cell Nucleus.txt", "text": "And then we basically take the histones, we connect those histones and we coil them further to create a structure known as the chromatin, which is a very, very condensed version of our linear DNA."}, {"title": "Cell Nucleus.txt", "text": "So inside the nucleus, the linear DNA is wound around special structural proteins called histones, combining eight histones forms, a structure known as the nucleosome."}, {"title": "Cell Nucleus.txt", "text": "And these nucleosomes can be wrapped into coils and super coils of complexes of protein DNA, RNA called chromatin."}, {"title": "Cell Nucleus.txt", "text": "Now, when the DNA is not actually being used, when we are not transcribing our DNA molecule, it exists in this condensed super coiled form."}, {"title": "Cell Nucleus.txt", "text": "However, to actually read and express, to actually transcribe our DNA molecule, we have to uncoil that section of the DNA."}, {"title": "Cell Nucleus.txt", "text": "And at any given time in the nucleus of our cell, only a small percentage of the DNA is actually, actually unwound."}, {"title": "Cell Nucleus.txt", "text": "It exists mostly predominantly in the condensed and super coiled chromatin stage."}, {"title": "Enzyme Regulation .txt", "text": "So far in our discussion on enzymes, we focused on the kinetics of enzymes and then we discussed the mechanisms that enzymes actually use to catalyze the different types of biochemical reactions or processes that take place inside our body."}, {"title": "Enzyme Regulation .txt", "text": "The next question is the next topic we're going to basically study is enzyme regulation."}, {"title": "Enzyme Regulation .txt", "text": "So how exactly do the cells inside our body actually monitor, regulate and control the activity and the functionality of all the different types of enzymes?"}, {"title": "Enzyme Regulation .txt", "text": "So, as we'll discuss in this lecture, there are five major mechanisms of control."}, {"title": "Enzyme Regulation .txt", "text": "One is called allosteric control."}, {"title": "Enzyme Regulation .txt", "text": "And we actually spoke about this in detail when we discussed the hemoglobin molecule."}, {"title": "Enzyme Regulation .txt", "text": "The second type of mechanism of regulation is reversible covalent modification."}, {"title": "Enzyme Regulation .txt", "text": "The third type is known as proteolytic cleavage or proteolytic activation."}, {"title": "Enzyme Regulation .txt", "text": "The fourth control method is enzyme concentration."}, {"title": "Enzyme Regulation .txt", "text": "So actually regulating how much enzyme we produce inside the cell."}, {"title": "Enzyme Regulation .txt", "text": "And finally something called ISO enzymes or isozymes."}, {"title": "Enzyme Regulation .txt", "text": "So let's begin by focusing on allosteric control."}, {"title": "Enzyme Regulation .txt", "text": "So many of the enzymes produced inside our cells actually contain these regions."}, {"title": "Enzyme Regulation .txt", "text": "These sites we call allosteric sites."}, {"title": "Enzyme Regulation .txt", "text": "And these allosteric sites are different than the active sites found on the enzyme that binds onto the substrate molecule."}, {"title": "Enzyme Regulation .txt", "text": "So we have special types of signal molecules, regulation molecules found inside our body that can bind onto these allosteric sites found on allosteric enzymes."}, {"title": "Enzyme Regulation .txt", "text": "And by binding they can create some type of change and that can actually alter the activity, the functionality of the enzyme."}, {"title": "Enzyme Regulation .txt", "text": "Now, allosteric enzymes and allosteric proteins basically observe something called Cooperativity."}, {"title": "Enzyme Regulation .txt", "text": "And we spoke about Cooperativity in detail when we discussed hemoglobin."}, {"title": "Enzyme Regulation .txt", "text": "So we basically said that an allosteric protein or an allosteric enzyme will observe Cooperativity."}, {"title": "Enzyme Regulation .txt", "text": "And what that means is the binding of a molecule onto a side on that enzyme or protein will affect the affinity of the other sides for that same molecule."}, {"title": "Enzyme Regulation .txt", "text": "And again, we focused on this when we discuss hemoglobin."}, {"title": "Enzyme Regulation .txt", "text": "Now, the enzyme that we're going to focus on in the next several lectures that basically is controlled Alisterically is aspartate transcurbamylase."}, {"title": "Enzyme Regulation .txt", "text": "And we'll see exactly how this is done in the next several lectures."}, {"title": "Enzyme Regulation .txt", "text": "Now let's move on to the second regulation mechanism, reversible covalent modification."}, {"title": "Enzyme Regulation .txt", "text": "So the activity of many enzymes is basically controlled and regulated by creating some type of covalent bond, some type of covalent modification on that particular enzyme."}, {"title": "Enzyme Regulation .txt", "text": "And the most common type of modification that we create is the addition of a phosphoryl group by using an ATP molecule."}, {"title": "Enzyme Regulation .txt", "text": "So one example of covalent modification is the attachment of a phosphoryl group onto the enzyme."}, {"title": "Enzyme Regulation .txt", "text": "And as we discussed previously, when we discussed the kinase molecule, so NMP kinase inside our body, we have many different types of protein kinases which are used to basically catalyze the transfer of a phosphoryl group from our ATP molecule onto that particular enzyme."}, {"title": "Enzyme Regulation .txt", "text": "And by transferring that phosphoryl group, that can basically activate or inactivate the activity of that enzyme."}, {"title": "Enzyme Regulation .txt", "text": "Now the reverse process."}, {"title": "Enzyme Regulation .txt", "text": "The removal of that phosphoryl group from that enzyme is catalyzed by a different enzyme known as protein Phosphotase."}, {"title": "Enzyme Regulation .txt", "text": "And we'll discuss this protein in much more detail in a future lecture."}, {"title": "Enzyme Regulation .txt", "text": "So we essentially have the enzyme and the ATP molecule."}, {"title": "Enzyme Regulation .txt", "text": "We use protein kinase to transfer a single phosphoryl from this ATP onto the enzyme to produce this complex here."}, {"title": "Enzyme Regulation .txt", "text": "And this can either activate or usually inactivate the activity of that enzyme."}, {"title": "Enzyme Regulation .txt", "text": "And we also produce that ADP molecule."}, {"title": "Enzyme Regulation .txt", "text": "And if we want to go in reverse, if we want to remove that P and add that P onto that ADP to reform the ATP and that active enzyme or in some cases inactive enzyme, we use protein phosphatase and we'll discuss these proteins in detail in future electrodes."}, {"title": "Enzyme Regulation .txt", "text": "Now, the third mechanism of control is proteolytic activation or proteolytic cleavage."}, {"title": "Enzyme Regulation .txt", "text": "Now, many enzymes produced by the cells of our body are produced in their inactive form."}, {"title": "Enzyme Regulation .txt", "text": "So the precursor inactive form of an enzyme is called a zymogen or sometimes a proenzyme."}, {"title": "Enzyme Regulation .txt", "text": "Now, in order to activate these zymogens, these pro enzymes, special molecules called proteases, which we spoke about previously, are basically used to cleave s special sites and that is what activates these polypeptides, these zymogens."}, {"title": "Enzyme Regulation .txt", "text": "And once activated, they can basically carry out their functionality until they are inhibited by some type of inhibitor, usually an irreversible inhibitor."}, {"title": "Enzyme Regulation .txt", "text": "And two examples of groups of enzymes which utilize this type of regulation method are digestive enzymes such as chimitrypsin trypsin, as well as pepsin, as well as all the different types of enzymes involved in a blood clotting cascade."}, {"title": "Enzyme Regulation .txt", "text": "And we'll discuss this in detail in future electra."}, {"title": "Enzyme Regulation .txt", "text": "So we have the zymogen that the cell produces, that's the inactive enzyme, the pro enzyme and then some type of protease cleaves the zymogen at some specific location."}, {"title": "Enzyme Regulation .txt", "text": "Let's suppose at this position here."}, {"title": "Enzyme Regulation .txt", "text": "And that creates the active form of the enzyme."}, {"title": "Enzyme Regulation .txt", "text": "So this piece is the active form and then this itself can be inhibited by using some type of irreversible inhibitor that binds onto some side found on that active form and that inhibits the activity of that enzyme."}, {"title": "Enzyme Regulation .txt", "text": "Now, the fourth type of mechanism of regulation is actually regulating the amount of the enzyme that is present in the cell."}, {"title": "Enzyme Regulation .txt", "text": "And usually, as we'll discuss eventually this type of regulation is monitored on the level of transcription."}, {"title": "Enzyme Regulation .txt", "text": "So if we control the amount of transcription that takes place on a particular gene of interest that codes for some type of enzyme, we can ultimately control how much of that enzyme is produced inside that cell and in turn control the activity and the functionality level of that particular enzyme."}, {"title": "Enzyme Regulation .txt", "text": "Now, the final regulation method is basically something called an isoenzyme or isozyme."}, {"title": "Enzyme Regulation .txt", "text": "So what exactly is an isoenzyme?"}, {"title": "Enzyme Regulation .txt", "text": "Well, an isoenzyme or isoenzymes, to be more correct, are these enzymes that differ in their sequence of amino acids and so they differ in the structure."}, {"title": "Enzyme Regulation .txt", "text": "They are three dimensional structure but they are actually used to carry out the same type of reaction."}, {"title": "Enzyme Regulation .txt", "text": "So ISO enzymes are basically multiple forms of the same type of enzyme that carries out the same type of function."}, {"title": "Enzyme Regulation .txt", "text": "So ISO enzymes are enzymes that differ in their amino acid sequence and three dimensional structure, but which catalyze the same type of reaction inside our body."}, {"title": "Enzyme Regulation .txt", "text": "So these enzymes allow for the fine tuning of many metabolic processes."}, {"title": "Enzyme Regulation .txt", "text": "Now, isoenzymes are usually not only different in their three dimensional structure and their amino acid sequence, but they can also differ in the enzyme kinetics that they basically exhibit."}, {"title": "Enzyme Regulation .txt", "text": "So things like the V max, the maximum velocity of the enzyme, as well as the Km value, the mechanics constant, these things can basically differ depending on which isoenzyme we're actually looking at."}, {"title": "Enzyme Regulation .txt", "text": "And on top of that, these isoenzymes are usually controlled by different types of regulatory molecules."}, {"title": "Enzyme Regulation .txt", "text": "Now, one example of an isoenzyme found inside our body is lactate dehydrogenase LDH."}, {"title": "Enzyme Regulation .txt", "text": "And this is basically the molecule that is used in the process of anaerobic cellular respiration."}, {"title": "Enzyme Regulation .txt", "text": "So we have two types of isoenzymes for lactate dehydrogenase."}, {"title": "Enzyme Regulation .txt", "text": "One of them is found predominantly in the cardiac muscle cell and the other one is found in a skeletal muscle cell."}, {"title": "Enzyme Regulation .txt", "text": "And we'll discuss what their function is and what their difference is in more detail in the next several lectures."}, {"title": "Enzyme Regulation .txt", "text": "So these are the five different types of methods by which our cells can regulate the activity and the functionality of all the different types of enzymes that exist inside our body."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Previously, we defined what a gene mutation was."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We said that a gene mutation is basically a change in the nucleotide sequence of our DNA molecule other than genetic recombination."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And we said that there are two types of gene mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We have point mutations, which are also known as base pair substitutions or base pair mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And this was, of course, focus of the previous lecture."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "In this lecture, we're going to focus on frameshift mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, frameshift mutations are a result of insertions or deletions that take place on our DNA molecule."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now let's define what an insertion and what a deletion is."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "An insertion basically refers to the insertion of a nucleotide base pair or several nucleotide base pairs at some given location on our DNA molecule, while a deletion is the removal of a nucleotide pair or several nucleotide pairs at some given position on our DNA molecule."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, as we'll see in just a moment, an insertion or a deletion may or may not shift the reading frame of our mRNA molecule."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, what exactly is the reading frame?"}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Well, the reading frame is the sequence of nucleotides."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "It's the sequence of codons that is read by the ribosome during the process of translation when we synthesize our polypeptide chain."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's take a look at an example of an insertion that causes the shift of our reading frame."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And as we'll see in just a moment, this is known as a frame shift mutation."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's begin by looking at our DNA antisense strand that is used during the process of transcription."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's suppose this is our DNA strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The five end is here."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The three end is here."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we have gcgagtag is the nucleotide sequence on our DNA antisense strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, when we actually transcribe our DNA molecule, our RNA polymerase reads beginning on the three end and going towards the five end."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So that means when we synthesize the mRNA, we have to look going this way."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The complement to G is C. The complement to A is U."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The complement to T is a the complement to C is G. The complement to G is C. The complement to A is U."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The complement to G is C, the complement to C is G. And finally, our complement to G is C. So basically this is the five end of the mRNA and this is the three end of the mRNA that is produced during the process of transcription when we transcribe this DNA antisense strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, once we actually synthesize the mRNA molecule, we're going to use this mRNA molecule and the ribosomes are going to translate the code, the nucleotide sequence into the amino acid sequence."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And the ribosome will use the genetic code which consists of the 64 codons."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So our cua corresponds to the amino acid leucine, the sequence GCU corresponds to the amino acid alanine, and the sequence CGC corresponds to our amino acid arginine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's suppose as a result of some type of outside factor."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We have an insertion taking place."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we have a mutation known as insertion."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So basically, let's suppose between the 7th and the 8th nucleotide on the DNA antisense strand, we insert our cytosine nucleotide."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So now our DNA strand consists of ten nucleotides and not nine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we have the mutated DNA antisense strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We have GCG AG, where this is a cytosine that has been inserted between the 7th and the 8th DNA nucleotide."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's see what kind of polypeptide sequence of amino acids we're actually going to form."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So when this molecule is transcribed, we form this mutated mRNA molecule."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The reason it's mutated is because it contains this guanine between the second and the third amino and the third nucleotide."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So the G becomes a C, the complement of A is our U, the C becomes a G, the T becomes an A, C becomes A-G-G becomes a C, the A becomes a U and so forth."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So this is a five end, this is our three end."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, when our ribosome reads this mutated mRNA strain, it will use the genetic code."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But now, because we have a shift in the reading frame, what will happen is the codons will change."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So the first codon in this case is Cua."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "The first codon in this case is Cu g. But because Cua and Cu g basically code for the same exact amino acid, leucine, the first amino acid is not changed."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But look what happens to the next."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Because we insert this single nucleotide into our sequence, it shifts all the other nucleotides and that changes the codons that are read by the ribosome."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So in this case, the second codon was GCU."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "In this case, because we had a shift in the reading frame, the second codon is AGC, which is different than GCU."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Then this one is CGC."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But in this case, the third codon is UCG."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now CUG still codes for Leucine, but AGC codes for Serene and UCG codes for Serene once again."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So these two codons code for the same exact amino acid."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And notice that this, or this for that matter, is different than the sequence given here."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We have serene and theory and we have Alanine and Arginine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we see that the insertion of the cytosine nucleotide between the 7th and the 8th DNA nucleotide causes a shift in the mRNA reading frame."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And this in turn changes the codons that are read by the ribosome."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And this changes the sequence of amino acids that are produced on the polypeptide chain."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And this result usually leads or produces a nonfunctional protein."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we see that any deletion or insertion of a nucleotide that is not a multiple of three nucleotides will cause such a mutation, such a shift in the frame."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And such a mutation is commonly known as a frame shift mutation."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we see that a frame shift mutation is caused when we have either an insertion or a deletion of a nucleotide or nucleotides that are not a multiple of three."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But what exactly happens if the insertion or deletion occurs in a multiple of three?"}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's suppose, let's consider what happens when we insert a three nucleotide sequence into this DNA antisense strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Let's see what the end result will be."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So let's begin with this DNA anti strand once again."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we have the GCG agtag, five to three DNA Antistrand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "If we transcribe this, we produce this same mRNA."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And when we translate the mRNA, we produce once again the leucine alanine arginine nucleotide amino acid sequence."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, instead of inserting a single nucleotide, which is not a multiple of three, let's suppose we insert a multiple of three."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we insert exactly three nucleotides, the CAG nucleotide between our 123456 and the 7th nucleotide on the DNA strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we basically enter the sequence CAG."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now when we transcribe this mutated mr. DNA antistan strand we produce."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So the g becomes a c, the A becomes a u, the T becomes an a, the g becomes a c, the a becomes a u, our c becomes A-G-C becomes a g, the g becomes a c, the a becomes a u, the GCG becomes a CGC."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So this is our mutated mRNA strand."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And when we actually use the ribosome and the genetic code to translate this mutated mRNA strand, we produce the following result."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So the cua is the leucine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So that doesn't change."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But now that we insert this three nucleotide sequence, this sequence CUG corresponds to the amino acid leucine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now next we go on to GCU, which is the alanine MCGC, which is our arginine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now notice what happened."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "There's a big difference between this result and this result."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So because in this case, we had a frame shift mutation because we only inserted a single nucleotide that shifted the reading frame and that changed all the amino acids that were produced after our mutation."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But in this case, what we essentially do, we do not actually shift the reading frame."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "What we do is we simply insert a single amino acid in this case."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But all the amino acids that are produced after the inserted amino acid are exactly the same as before."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So we have leucine, alanine and arginine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And we have leucine, alanine and arginine."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So basically the only difference between the polypeptide chain produced in the non mutated case and in a mutated case is our single amino acid that is found between the second and third amino acid."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "All the other amino acids and their position are exactly the same or is exactly the same."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So whenever an insertion or a deletion takes place in multiples of three, this does not lead to a shift in the reading frame."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And such mutations are known as non frame shift mutations because all the amino acids that would be produced if there was no mutation are still produced."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And this usually leads to either a fully functional protein or a partially functional protein."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And if we compare to the frameship mutation, that usually leads to a non functional protein."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So, basically, insertions or deletions do cause frame shift mutations, but not always."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Sometimes they can cause non frameshift mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "And those basically mean that we do not shift the reading frame of the mRNA molecule, the reading frame that is used by our ribosome."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "What we basically do is we insert or we delete one or more amino acids, but all the other amino acids basically remain exactly the same."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "So, to conclude, we have two main types of mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "We have point mutations, which are basically mutations on a single nucleotide, and these are also known as base pair substitutions or base pair mutations."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "Now, we also have frameshift mutations, and frame shift mutations are caused by insertions or deletions."}, {"title": "Insertion, Deletions and Frameshift Mutations.txt", "text": "But even though insertions and deletions cause frameshift mutations, sometimes they can also cause non frameship mutations."}, {"title": "Aquaporins .txt", "text": "To finish off my discussion on membrane channels I'd like to focus on yet another category of channels we call aquaporeans."}, {"title": "Aquaporins .txt", "text": "So for quite some time, we believed that the only way water molecules can actually make their way across the membrane from one side to the other side of a membrane is by actually diffusing through that membrane."}, {"title": "Aquaporins .txt", "text": "So this process is known as symptoms diffusion."}, {"title": "Aquaporins .txt", "text": "Now, we weren't actually wrong to think that because the membrane is, in fact permeable to water, and because of the small size of these water molecules, because of the fact that water molecules don't actually have a full charge, and because we have so many of these water molecules colliding with the membrane, these water molecules will, in fact, cross that membrane via the process of simple diffusion."}, {"title": "Aquaporins .txt", "text": "Now, in 1992, things actually changed because in 1992 we basically discovered accidentally a special type of channel phantom membranes known as aquaporeans."}, {"title": "Aquaporins .txt", "text": "And we realized that these aquaporeans are channels that selectively funnel allow the movement of these water molecules across the membrane."}, {"title": "Aquaporins .txt", "text": "And the rates at which the water molecules moves through these aquaporeans are much higher than the rates at which the water molecules actually diffuse through that phospholipid bilayer membrane."}, {"title": "Aquaporins .txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Aquaporins .txt", "text": "So basically, there are certain instances inside our body and inside the bodies of other organisms when these cells must be able to actually quickly and effectively move the water molecule from one side to the other side."}, {"title": "Aquaporins .txt", "text": "And that's when these aquaphones are actually used."}, {"title": "Aquaporins .txt", "text": "Now, it's important to note that aquaporns are not actually ion channels."}, {"title": "Aquaporins .txt", "text": "What that means is they don't actually allow the movement of molecules that contain charge or ions."}, {"title": "Aquaporins .txt", "text": "They only allow the movement of water molecules."}, {"title": "Aquaporins .txt", "text": "So they're water channels that allow the movement of molecules, water molecules down their concentration gradient when the cell requires it."}, {"title": "Aquaporins .txt", "text": "So from a high to a low concentration."}, {"title": "Aquaporins .txt", "text": "So when would our cells of the body need to basically take the water and move it to the other side of the cell membrane very quickly?"}, {"title": "Aquaporins .txt", "text": "Well, one example is when we produce tears."}, {"title": "Aquaporins .txt", "text": "So tear production basically involves being able to release the water very, very quickly."}, {"title": "Aquaporins .txt", "text": "And the same thing is true for producing saliva."}, {"title": "Aquaporins .txt", "text": "And so those cells of our body actually use aquaphorns to release the water as quickly as possible."}, {"title": "Aquaporins .txt", "text": "And the rates at which that takes place the water travels through these aquaporeans are much higher than the rates at which the water actually moves through that membrane."}, {"title": "Aquaporins .txt", "text": "Another example are red blood cells."}, {"title": "Aquaporins .txt", "text": "So red blood cells actually contain a high concentration of aquaporeans in their membrane."}, {"title": "Aquaporins .txt", "text": "And that's because red blood cells, as they travel through the capillaries must be able to actually control and regulate the volume inside the red blood cell and the pressure inside that red blood cell."}, {"title": "Aquaporins .txt", "text": "So the hydrostatic and the osmotic pressure."}, {"title": "Aquaporins .txt", "text": "Another location where we find aquaporeans abundantly are the cells of the kidneys."}, {"title": "Aquaporins .txt", "text": "Why?"}, {"title": "Aquaporins .txt", "text": "Well, because the kidneys basically produce the urine."}, {"title": "Aquaporins .txt", "text": "They produce the filter that eventually becomes the urine."}, {"title": "Aquaporins .txt", "text": "And one important function of the kidneys is to basically reabsorb as much water as possible."}, {"title": "Aquaporins .txt", "text": "And this must take place very quickly."}, {"title": "Aquaporins .txt", "text": "In fact, if we examine the cells found within or next to the lumen of the collecting duct, we'll see that these cells express a high concentration of these aquaporean channels."}, {"title": "Aquaporins .txt", "text": "And these aquaphorn channels are used to basically reabsorb as much water as possible back into the capillary."}, {"title": "Aquaporins .txt", "text": "So the water moves from the high concentration to the low concentration."}, {"title": "Aquaporins .txt", "text": "And again, just like any channel, these aquaphorns don't actually use energy ATP molecules."}, {"title": "Aquaporins .txt", "text": "Remember, only membrane pumps actually use energy."}, {"title": "Aquaporins .txt", "text": "Channels like aquaphorns don't actually use ATP."}, {"title": "Aquaporins .txt", "text": "Now, what exactly is the structure of an aquaphorn?"}, {"title": "Aquaporins .txt", "text": "Well, aquaporeans basically consist of six membrane spanning alpha helices and the inner region of these helices, the inner region of that aquaporen actually contains this relatively narrow passageway that is lined with hydrophilic amino acids."}, {"title": "Aquaporins .txt", "text": "Why hydrophilic?"}, {"title": "Aquaporins .txt", "text": "Well, because these hydrophilic amino acids within that narrow passageway of the aquaphorn must be able to interact in a stabilizing fashion with those water molecules because water is, in fact, a polar molecule."}, {"title": "Aquaporins .txt", "text": "On top of that, at the center of that narrow passageway are these amino acids that contain positive charges."}, {"title": "Aquaporins .txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Aquaporins .txt", "text": "So this is what a crosssection of the aquaporin would actually look like."}, {"title": "Aquaporins .txt", "text": "So we have the cell membrane."}, {"title": "Aquaporins .txt", "text": "We have a high concentration of water here."}, {"title": "Aquaporins .txt", "text": "We have a low concentration of water here."}, {"title": "Aquaporins .txt", "text": "So, for instance, we can imagine that this is the lumen of the collecting duct and this is the inside portion of this particular cell."}, {"title": "Aquaporins .txt", "text": "So we have this aquaporne."}, {"title": "Aquaporins .txt", "text": "So we basically have this internal passageway shown here."}, {"title": "Aquaporins .txt", "text": "And these water molecules basically pass along that hydrophilic narrow passageway in a single file."}, {"title": "Aquaporins .txt", "text": "So this passageway is so narrow that they can only make their way across in a single file."}, {"title": "Aquaporins .txt", "text": "And so essentially, this one bumps this one as a result of electrostatic repulsion it, propels it to move this way, and that process continues."}, {"title": "Aquaporins .txt", "text": "And this is so effective and so efficient that 1 million of these water molecules move along this channel every single second."}, {"title": "Aquaporins .txt", "text": "Now, what about these positive charges?"}, {"title": "Aquaporins .txt", "text": "So basically, as a result of the presence of these positive charges at the center of that passageway, ions, for instance, hydronium ions or protons, will not be able to make their way across this channel."}, {"title": "Aquaporins .txt", "text": "And that's important because if these channels somehow were able to actually allow the movement of H plus ions, what that would do is it would disrupt the hydrogen ion gradients within our cells."}, {"title": "Aquaporins .txt", "text": "And those gradients are important because as we'll see in a future lecture, we use these proton gradients to actually create ATP molecules."}, {"title": "Aquaporins .txt", "text": "So we see that ions such as H plus ions will not be able to pass across due to the presence of the positive charges in that passageway at the center of that passageway, as shown here."}, {"title": "Aquaporins .txt", "text": "This means that aquaphorns will not actually disrupt gradients such as the proton gradients that exist inside our cells which are used to produce things like ATP molecules."}, {"title": "Aquaporins .txt", "text": "So we conclude that aquaphorians are not ion channels, but they are channels."}, {"title": "Aquaporins .txt", "text": "They are selective channels that allow the movement."}, {"title": "Aquaporins .txt", "text": "So quick movement of these water molecules across the cell when the time arises, for instance, in red blood cells in the cells found that create the tears and the saliva in the cells of the kidneys and so forth."}, {"title": "Aquaporins .txt", "text": "And these aquapons are not exclusive to eukaryotic cells."}, {"title": "Aquaporins .txt", "text": "Many prokaryotic cells, such as bacterial cells also express and use aquaporeans."}, {"title": "Carbonic Anhyrdase.txt", "text": "Anytime we ingest macromolecules, for instance, proteins, carbohydrates or lipids, we have to break these macromolecules down into their individual form."}, {"title": "Carbonic Anhyrdase.txt", "text": "So we break them down into the amino acids, the individual sugar monomers glucose molecules and into fatty acids."}, {"title": "Carbonic Anhyrdase.txt", "text": "And ultimately, these three different types of molecules, amino acids, glucose molecules and fatty acids are brought into the cell and inside the cell, the cell metabolizes breaks them down into ATP molecules via process known as aerobic cellular respiration."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, these ATP molecules are used as energy molecules to carry out different types of processes and reactions that take place inside the cells."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, the problem with aerobic cellular respiration is it produces a waste byproduct, namely carbon dioxide."}, {"title": "Carbonic Anhyrdase.txt", "text": "And carbon dioxide cannot actually be used by the cell in any useful manner."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so all these trillions of cells which use these food particles to metabolize them into ATP produce these CO2 molecules and they essentially take these CO2 molecules and dump them into the blood plasma."}, {"title": "Carbonic Anhyrdase.txt", "text": "Why?"}, {"title": "Carbonic Anhyrdase.txt", "text": "Well, because as the blood plasma circulates through our blood vessels, through our cardiovascular system, eventually the CO2 molecules will end up in the alveoli of the lungs."}, {"title": "Carbonic Anhyrdase.txt", "text": "And it's the function, it's the responsibility of these alveoli to basically expel all that CO2 to the outside environment out of our body."}, {"title": "Carbonic Anhyrdase.txt", "text": "And then the plants and trees can basically use the CO2 to produce the sugar molecules and then we can eat the sugar molecules and that process basically continues."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, the problem with this is when all these trillions of metabolizing cells dump CO2 into our blood plasma, the CO2 molecules themselves are non polar."}, {"title": "Carbonic Anhyrdase.txt", "text": "But the blood plasma, which consists predominantly of water molecules, is polar."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so the CO2 in its CO2 nonpolar form cannot actually dissolve inside the red blood plasma."}, {"title": "Carbonic Anhyrdase.txt", "text": "Inside the blood plasma."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so what happens is the CO2 tramples into the red blood cell."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, once inside the red blood cell, we have the same problem again because the cytoplasm of the red blood cell consists predominantly of water."}, {"title": "Carbonic Anhyrdase.txt", "text": "So just like the blood plasma, the cytoplasm inside the red blood cell is also polar."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so the carbon dioxide cannot actually be stored inside the cytoplasm of the red blood cells in its CO2 form."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so what ultimately has to happen is the cell has to carry out this particular reaction in which we transform the non polar CO2 molecule into its polar form, bicarbonate ion."}, {"title": "Carbonic Anhyrdase.txt", "text": "And because this contains a full negative charge, it can easily dissolve inside the cytoplasm of the red blood cell and also inside the blood plasma of our body."}, {"title": "Carbonic Anhyrdase.txt", "text": "So the problem with this reaction is so if we study the rate of this reaction in its uncatalyzed form at a PH of seven, at body temperature of, let's say, 37 degrees Celsius, we'll see that the rate of the reaction isn't that great."}, {"title": "Carbonic Anhyrdase.txt", "text": "In fact, the rate is nowhere close to what it should be to actually be able to meet the demands of all the trillions of metabolizing cells found inside our body."}, {"title": "Carbonic Anhyrdase.txt", "text": "So to basically increase the rate to a high enough value so that it can keep up with the demands of our body, what the red blood cells have is they have this enzyme we call carbonic anhydrase, too."}, {"title": "Carbonic Anhyrdase.txt", "text": "So inside our body, we have at least seven types of carbonic and hydraase enzymes."}, {"title": "Carbonic Anhyrdase.txt", "text": "But the one that is found inside the red blood cells is known as carbonic and hydrase two."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, what we want to discuss in this lecture is the active side of this carbonic and hydrate two."}, {"title": "Carbonic Anhyrdase.txt", "text": "And we want to discuss the mechanism that this molecule actually uses to promote and catalyze this reaction."}, {"title": "Carbonic Anhyrdase.txt", "text": "And what this reaction ultimately does is it hydrates the carbon dioxide."}, {"title": "Carbonic Anhyrdase.txt", "text": "So water adds onto the carbon dioxide, and that ultimately produces the carbonic acid, which dissociates into bicarbonate ion and the H plus ion."}, {"title": "Carbonic Anhyrdase.txt", "text": "So let's begin by taking a look at the active side of carbonic and hydrase II."}, {"title": "Carbonic Anhyrdase.txt", "text": "So, in our discussion on the mechanisms of enzymes, we said that one mechanism that enzymes use is known as metal ion catalysis."}, {"title": "Carbonic Anhyrdase.txt", "text": "And in metal ion catalysis, the active side of the enzyme uses some type of metal ion to basically form a strong nucleophile."}, {"title": "Carbonic Anhyrdase.txt", "text": "And that's exactly what we do in the active side of carbonic and hydrase, too."}, {"title": "Carbonic Anhyrdase.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Carbonic Anhyrdase.txt", "text": "So, inside the active side of carbonic and hydrase two and all of these carbonic and hydrates, we have a zinc metal atom."}, {"title": "Carbonic Anhyrdase.txt", "text": "And anytime any biological system uses a zinc atom in nature, the zinc atom always contains an oxidation state of positive two."}, {"title": "Carbonic Anhyrdase.txt", "text": "So it has a net charge of positive two."}, {"title": "Carbonic Anhyrdase.txt", "text": "And what that means is we have four different groups which are bound to that zinc atom."}, {"title": "Carbonic Anhyrdase.txt", "text": "So this is a zinc atom."}, {"title": "Carbonic Anhyrdase.txt", "text": "It has a charge of positive two, and it is bound to four different groups."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, three of these groups are these ring structures that are part of the side chains of histetine residue."}, {"title": "Carbonic Anhyrdase.txt", "text": "So we have historine residue one, two, and three, and they're bound to the zinc, as shown."}, {"title": "Carbonic Anhyrdase.txt", "text": "And the final group is a water molecule."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this is the same water molecule that will react with the carbon dioxide to ultimately produce the bicarbonate."}, {"title": "Carbonic Anhyrdase.txt", "text": "So the first question is, what is the role that zinc actually plays?"}, {"title": "Carbonic Anhyrdase.txt", "text": "So, what zinc actually does is by reacting with the water, it transforms water into a much better nuclear file."}, {"title": "Carbonic Anhyrdase.txt", "text": "And because water will be a much better nuclear file as a result of this interaction, it will be able to react with the carbon dioxide at a much higher rate and so will produce these bicarbonate ions, as we'll see in just a moment, at a much higher rate."}, {"title": "Carbonic Anhyrdase.txt", "text": "So, to see what we mean, let's compare the PKA values of these two reactions."}, {"title": "Carbonic Anhyrdase.txt", "text": "So, remember, the lower the PKA value, the better the acid."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, if we take just plain water and we allow water to dissociate into H plus ions and these hydroxide ions, the PTA value is 15.7."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this is a very high value."}, {"title": "Carbonic Anhyrdase.txt", "text": "And what that or a relatively high value."}, {"title": "Carbonic Anhyrdase.txt", "text": "And what that means is this will not be a good enough acid."}, {"title": "Carbonic Anhyrdase.txt", "text": "And if it's not a good enough acid, it will not be very likely to produce this hydroxide ion."}, {"title": "Carbonic Anhyrdase.txt", "text": "And as we'll see in just a moment, it's the hydroxide ion that will be much more likely to act as a nucleophile and attack the carbon dioxide than the water."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, what this binding does is because of this association, this reaction, the dissociation of that H plus ion to form the hydroxide and the H plus greatly increases."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so the PKA value decreases."}, {"title": "Carbonic Anhyrdase.txt", "text": "So because of this interaction between the zinc atom and the water, we basically decrease the PTA value of this reaction."}, {"title": "Carbonic Anhyrdase.txt", "text": "And by decreasing the PTA value, we essentially make it much more likely that the water will dissociate and produce that hydroxide."}, {"title": "Carbonic Anhyrdase.txt", "text": "And it's the hydroxide that will be more likely to actually react with the carbon of the carbon dioxide."}, {"title": "Carbonic Anhyrdase.txt", "text": "So based on experimental data, we see that the binding of the zinc atom to water lowers the PKA value of water from 15.7 to 7.0."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this makes water much more likely to give up its hydrogen ion and become a hydroxide ion."}, {"title": "Carbonic Anhyrdase.txt", "text": "And why is that useful?"}, {"title": "Carbonic Anhyrdase.txt", "text": "Well, it's useful because hydroxide ions are very, very potent nucleophiles."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so what that means is, once we form that hydroxide, it'll be much more likely to actually attack the carbon of that carbon dioxide to ultimately form that bicarbonate ion."}, {"title": "Carbonic Anhyrdase.txt", "text": "And to see what we mean, let's take a look at this reaction mechanism that takes place inside the active side of carbonic and hydrates."}, {"title": "Carbonic Anhyrdase.txt", "text": "So in the first step, we essentially form this complex that consists of the water molecule bound onto that zinc."}, {"title": "Carbonic Anhyrdase.txt", "text": "So what happens is the oxygen of this water contains a partial negative charge because, remember, it's more electronegative than either one of these H atoms."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so because of that partially negative charge on the oxygen it will be attracted to the positive two charge on the zinc."}, {"title": "Carbonic Anhyrdase.txt", "text": "And that will form this bond, as shown here."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, what that means is, because this oxygen is interacting with the zinc, the interaction between the oxygen and either one of these H atoms will not be as strong."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so the hydrogen, one of these hydrogens will basically be much more likely to dissociate from that oxygen."}, {"title": "Carbonic Anhyrdase.txt", "text": "So water bind onto the metal zinc atom."}, {"title": "Carbonic Anhyrdase.txt", "text": "The partially negative charge of oxygen is attracted to the positive charge of the zinc."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this decreases the ability of water to actually hold on to one of those H plus ions."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this is precisely what facilitates this process the dissociation of the H from this oxygen to basically form this molecule here."}, {"title": "Carbonic Anhyrdase.txt", "text": "And this is because the PTA value is lowered from 15.7 to 7.0."}, {"title": "Carbonic Anhyrdase.txt", "text": "So this is very likely to actually take place."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, once this takes place, now there's room for the carbon dioxide to basically enter the active side, the pocket of that enzyme."}, {"title": "Carbonic Anhyrdase.txt", "text": "So this transforms a weak nuclear file into a very powerful nuclear file."}, {"title": "Carbonic Anhyrdase.txt", "text": "So, once again, as the H plus ion basically leaves the oxygen we transform the water molecule, a poured nuclear file, into a good nuclear file, a strong nuclear file that hydroxide."}, {"title": "Carbonic Anhyrdase.txt", "text": "And now the carbon dioxide basically enters the active side."}, {"title": "Carbonic Anhyrdase.txt", "text": "Now, as the carbon dioxide enters the active side what happens is the oxygen of that hydroxide attached to the zinc acts as a nuclear file attached the carbon of that carbon dioxide and that displaces one of the pip bonds between carbon and oxygen."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so now, in the next step, we have a full negative charge on one of the oxygens and that will be partially stabilized by the zinc, by the positive charge coming from that zinc."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so we have this interaction, shown in orange that is stabilizing this structure here."}, {"title": "Carbonic Anhyrdase.txt", "text": "So in this step, we see the highly nucleophilic oxygen attacks the carbon of the carbon dioxide forming this bicarbonate intermediate shown here."}, {"title": "Carbonic Anhyrdase.txt", "text": "And once we form this intermediate because of the instability of this intermediate and because we'll see another water molecule moving into the active side that water molecule will essentially displace this entire molecule."}, {"title": "Carbonic Anhyrdase.txt", "text": "And that water molecule will attach onto the zinc displacing and replacing this bicarbonate and that will kick off that bicarbonate."}, {"title": "Carbonic Anhyrdase.txt", "text": "And we'll go right back to this stage here."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so this reaction basically cycles back and forth and it takes place very quickly."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so every time this takes place, we produce a bicarbonate."}, {"title": "Carbonic Anhyrdase.txt", "text": "So we transform our carbon dioxide into the bicarbonate which then dissolves into the cytoplasm inside our blood cells and into the blood plasma inside our cardiovascular system."}, {"title": "Carbonic Anhyrdase.txt", "text": "So we see that the proteases we discussed previously were basically examples of Covalent catalysis and acid based catalysis."}, {"title": "Carbonic Anhyrdase.txt", "text": "And in some cases, in the case of metalloproteases, they used the metal ion catalysis."}, {"title": "Carbonic Anhyrdase.txt", "text": "But in the case of carbonic and hydrates these are examples of molecules which always use a metal atom, namely the zinc atom."}, {"title": "Carbonic Anhyrdase.txt", "text": "And so these carbonic anhydrases basically use the mechanism we know as metal ion catalysis."}, {"title": "Carbonic Anhyrdase.txt", "text": "They use the metal ion to basically create a much better nuclear file out of the water."}, {"title": "Carbonic Anhyrdase.txt", "text": "And that allows the hydroxide, the better nuclear file to then attack the carbon of that carbon dioxide to ultimately produce that bicarbonate and ion."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So once glucose undergoes glycolysis in the cytoplasm and produces the pyruvate molecules in the presence of oxygen, those pyruvate molecules will migrate into the matrix of the mitochondria and they will move across the membranes of the mitochondria via special type of membrane protein we call pyruvate translocase."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, what will happen to that pyruvate as soon as it moves moves into the matrix of the mitochondria?"}, {"title": "Pyruvate Decarboxylation .txt", "text": "Well, it will not actually enter that citric acid cycle."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Before it can enter the citric acid cycle, the pyruvate molecule must be prepared for that citric acid cycle."}, {"title": "Pyruvate Decarboxylation .txt", "text": "It must be activated."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And that's why a process known as pyruvate decarboxylation actually takes place, pyruvate carboxylation, which is catalyzed by a large protein complex known as pyruvate dehydrogenase complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "This entire process, it releases the carbon dioxide molecule and attaches a two carbon component of the pyruvate onto a special molecule, a carrier molecule known as coenzyme A, or COA."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And we formed the CETO coenzyme A complex, and this activates the two carbon fuel source of that pyruvate so that now we can actually transfer this component into the citric acid cycle."}, {"title": "Pyruvate Decarboxylation .txt", "text": "In the process."}, {"title": "Pyruvate Decarboxylation .txt", "text": "We also actually abstract two electrons from the pyruvate."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And those two electrons are picked up by the nicotine and nicotine amide adenine dinucleotide molecule to form NADH."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so this is the net process that we call pyruvate carboxylation."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this irreversible reaction prepares the pyruvate for the citric acid cycle."}, {"title": "Pyruvate Decarboxylation .txt", "text": "It releases the carbon dioxide and abstracts a pair of high energy electrons that are carried by the NAD that are incent, that are ultimately used by the electron transport chain to actually generate ATP molecules, as we'll discuss in a future lecture."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, although this net reaction looks simple, it's not actually that simple."}, {"title": "Pyruvate Decarboxylation .txt", "text": "It involves different types of enzymes and also involves different types of steps."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And actually, we have four steps in pyruvate carboxylation, and three steps are actually required to form that acetyl coenzyme A complex, as we'll see in just a moment."}, {"title": "Pyruvate Decarboxylation .txt", "text": "But before we look at the details of these four steps, let's actually discuss what components we find in the pyruvate dehydrogenase complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this complex actually consists of three different enzymes and also uses five different Co enzymes."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So let's begin by focusing on the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So enzyme number one, known as E one, is Pyruvate dehydrogenase."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And this enzyme actually catalyzes the first step, the decarboxylation step, and the second step, an oxidation reduction step."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, the other enzyme, the second enzyme, E two, is known as dihydrolipolitan acetytolase."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And what this does is it actually transfers that acetyl group that was formed in the first two steps onto the coenzyme A to form this complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And in the final step, which is actually catalyzed by E three, dihydrolipole dehydrogenase."}, {"title": "Pyruvate Decarboxylation .txt", "text": "This actually reforms the oxidized version of lipoamide, which is basically a coenzyme that is used in this process."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And what it also does is it generates the NADH molecule."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So what about the five Co enzymes that are used by this protein complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Well, we have thymine pyrophosphate TPP, which is basically used in step one."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And this is actually a prosthetic group that is attached onto pyruvate dehydrogenase, and we'll see what it's used for in just a moment."}, {"title": "Pyruvate Decarboxylation .txt", "text": "We also have a derivative of lipoic acid known as lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And we'll talk about what that does in just a moment."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And then we have the coenzyme A, which basically acts as the carrier molecule for the CETL group."}, {"title": "Pyruvate Decarboxylation .txt", "text": "The two carbon component that is removed from the pyruvate, the fad flavin adenineucleotide, is used to pick up the two electrons."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And then those two electrons are transferred onto the NAD plus nicotine adenine dinucleotide to form the NADH in the final step, as we'll see in a moment."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So let's begin by summarizing the first three steps of this reaction."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Why the first three?"}, {"title": "Pyruvate Decarboxylation .txt", "text": "Well, because the first three are basically used to form that acetyl coenzyme A complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So in the first step, we have a decrypt oxylation reaction taking place in which this entire component, not including these two electrons in this bond, is basically removed because we want to form the carbon dioxide and we form this intermediate."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, remember, decorboxylation reactions like the one shown here are generally exergonic reactions."}, {"title": "Pyruvate Decarboxylation .txt", "text": "They release energy, and that free energy that is released in the decarboxylation process is used to power the other reactions that are endergonic in this particular process."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So once we form this intermediate, the two electrons are then abstracted."}, {"title": "Pyruvate Decarboxylation .txt", "text": "They're used to actually reduce the molecule, as we'll see in just a moment."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And that allows us to form this intermediate."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And now we can couple this intermediate with coenzyme A to form this acetyl coenzyme A complex."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And in the final step, we generate the NADH and we regenerate a coenzyme, the lipopemi, that we mentioned just a moment ago."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So let's see exactly what that means."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Let's begin with step number one."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So, step number one is catalyzed by pyruvate dehydrogenase and it contains a prosthetic group we call Thyamine, pyrophosphate TPP."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And this enzyme, the E one enzyme of this pyruvate dehydrogenate complex, uses this prosthetic group to actually attach onto that pyruvate molecule and at the same time remove a carbon dioxide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, this step is not actually a single step."}, {"title": "Pyruvate Decarboxylation .txt", "text": "It contains individual steps."}, {"title": "Pyruvate Decarboxylation .txt", "text": "But I didn't have space to basically draw the steps out."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this is what happens."}, {"title": "Pyruvate Decarboxylation .txt", "text": "We have the pyruvate and the TPP, and this is actually attached onto the enzyme, the pyruvate dehydrogenase."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And what happens is this entire component here is essentially removed."}, {"title": "Pyruvate Decarboxylation .txt", "text": "In addition, we have to input two H plus ions."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Why?"}, {"title": "Pyruvate Decarboxylation .txt", "text": "Well, because one of them is used to basically form a hydroxyl group, and the other one is attached onto this carbon here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so once the bond forms between this carbon of the TPP and this carbon here, this is what we form."}, {"title": "Pyruvate Decarboxylation .txt", "text": "The complex is known as hydroxy ethyl."}, {"title": "Pyruvate Decarboxylation .txt", "text": "TPP complex or simply hydroxy ethyl TPP."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And we also generate that carbon dioxide that we have right here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, once we form the hydroxy ethyl TPP, this same enzyme, Pyruvate dehydrogenase, also catalyzes the next step, an oxidation reduction step."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, what basically happens is this molecule here is oxidized."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this is the oxidizing agent while this structure is reduced."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this will act as the reducing agent."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And what will happen is electrons will be taken away from this acetyl group here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Or it's not actually in acetyl form just yet, but this purple region actually will abstract."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Two electrons will give the electrons onto this component."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And in the final step, those electrons that we give to the lipoamide will be taken away and given to the mad plus."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So in the second step, we have another important coenzyme lipoic acid, actually a derivative of lipoic acid known as lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so this is what lipoamide looks like."}, {"title": "Pyruvate Decarboxylation .txt", "text": "It is also attached onto the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "In fact, it's attached onto the serine residue of the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this entire structure, which is not shown, is actually attached onto the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so we take the hydroethyl TPP complex, it reacts with the lipoamide structure, and we form this complex known as acetolipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And we also regenerate the TPP that we begin with."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Remember, these coenzymes have to be regenerated."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So we begin with TPP and we regenerate that TPP so that in the next cycle, this same molecule can be reused by another pyruvate decarboxylation step."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, let's focus on the cetolipide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So essentially what happens is we break the bond and these two electrons take an H atom, as shown here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And now this is the Cecil group that is ready to be transferred onto the coenzyme A because ultimately, we take this acetyl group off of that pyruvate."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this is the same group that we essentially have here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And this group is now transferred onto the coenzyme A via the third step that is catalyzed by Dihydrolipol transacetilase e two."}, {"title": "Pyruvate Decarboxylation .txt", "text": "This is the enzyme that catalyzes the transfer of that activated acetyl group onto this molecule here, the coenzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, once this process takes place and this obtains so the coenzyme may obtain this structure, we form dihydrolipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And this is not the same structure that we begin with here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Notice that in step three, we don't actually regenerate the lipo amide that we used in step two."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Unlike in this case, where in step one we used TPP and we regenerated TPP here, we began with lipoamide and we ended up with dying hydro lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So even though in step three we actually formed the acetyl coenzyme a structure, we essentially are able to transfer that to carbon acetyl group from the pyruvate and onto that carrier coenzyme a molecule."}, {"title": "Pyruvate Decarboxylation .txt", "text": "We did not regenerate the lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And that's where the final enzyme comes into play."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Dihydrolipole dehydrogenase reforms the oxidized version of lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Because remember this step, we actually reduced this structure because two electrons from this molecule were abstracted and given to the lipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so, in the final step, we not only regenerate the lipoamide coenzyme that can be then used to restart another cycle of pyruvate carboxylation, but we also oxidize this molecule, the dihydrolipoamide."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Take away those two electrons and give those two electrons ultimately onto that NAD to form the NADH that can ultimately be used by the electron transport chain on the inner membrane of the mitochondria."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So, in the final step, we have the Flavon adenine dinucleotide, which is actually attached onto the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "This is used to actually oxidize this molecule."}, {"title": "Pyruvate Decarboxylation .txt", "text": "What it does is it removes this age along with one electron and this age along with one electron, and we form fadh two."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And we finally reform this lipo amide essentially one electron here, one electron here, reform that sigma bond that existed between these sulfur groups here."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So we reform that lipo amide coenzyme that now can be used to restart this process of pyruvate decarboxylation with another pyruvate molecule, because, remember, we have two pyruvate molecules coming from a single glucose molecule."}, {"title": "Pyruvate Decarboxylation .txt", "text": "But we're not done here, because this fadh two."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And the next step is used to actually transfer those two electrons onto the NAD."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And so we have two electrons, and a single H atom goes onto the NAD to form NADH."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And the other remaining h ion no longer contains electrons."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So it's simply H ion, and we form the H plus as well as the fad."}, {"title": "Pyruvate Decarboxylation .txt", "text": "Now, this step is interesting because it's unlike other steps that take place inside our body, because usually it's the NAD that is used to transfer electrons onto the Sad, but in this case, it's in reverse."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And the reason is because the fad is actually activated by attaching itself onto the enzyme."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And because of that activity, because of being activated in that form, it actually does the opposite."}, {"title": "Pyruvate Decarboxylation .txt", "text": "In this case, it is used to actually give those electrons onto the NAD, as well as that h that carries those electrons to form the reduced nicotine mi adenine dinucleotide molecule that will be used by the electron transport chain to actually generate those ATP molecules."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So, if we sum up all these three reactions, four reactions, I should say this is basically what we get."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So, even though this net equation might seem simple, it actually consists of four different steps."}, {"title": "Pyruvate Decarboxylation .txt", "text": "In three steps, we form that acetocoenzyme A."}, {"title": "Pyruvate Decarboxylation .txt", "text": "But the final step is needed to not only regenerate that Lipomi coenzyme, but also generate that NADH as well as that H ion."}, {"title": "Pyruvate Decarboxylation .txt", "text": "So this is a step that by which we essentially prepare that pyruvate molecule."}, {"title": "Pyruvate Decarboxylation .txt", "text": "We abstract not only electrons, but the Cetil group from the pyruvate, attach it onto the coenzyme A, and that activates this acetyl group, makes it very reactive."}, {"title": "Pyruvate Decarboxylation .txt", "text": "And now we can basically take this acetyl and give it to the citric acid cycle."}, {"title": "Fatty Acid Synthesis .txt", "text": "So now let's actually take a look at the individual steps that help us generate fatty acid molecules."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now as we look at all these different steps, keep in mind that all of them take place in the cytoplasm of our cell."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now let's briefly recall what happened in the previous several lectures."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we said that the building blocks of fatty acid molecules are acetyl coenzyme A molecules and we build these acetyl coenzyme A molecules in a matrix of the mitochondria."}, {"title": "Fatty Acid Synthesis .txt", "text": "So to actually use acetyl coenzyme A to synthesize fatty acid molecules, we have to transport those acetyl coenzyme A molecules from the matrix of the mitochondria into the cytoplasm of that cell."}, {"title": "Fatty Acid Synthesis .txt", "text": "So let's assume that actually took place."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we have the fecal coenzyme A molecule and it's found in the cytoplasm of that cell."}, {"title": "Fatty Acid Synthesis .txt", "text": "What happens next?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, if the conditions are right for fatty acid synthesis, that is, if we have high levels of Sutrade and high levels of ATP, then that will promote the process of fatty acid synthesis."}, {"title": "Fatty Acid Synthesis .txt", "text": "And what that means is we're going to commit the CETL Co enzyme A molecule, to actually undergoing fatty acid synthesis."}, {"title": "Fatty Acid Synthesis .txt", "text": "And this is the step that commits the CETL Co enzyme A to helping form that fatty acid chain."}, {"title": "Fatty Acid Synthesis .txt", "text": "So let's see what the step actually consists of."}, {"title": "Fatty Acid Synthesis .txt", "text": "So firstly, the enzyme that catalyzed this step is a carboxylase."}, {"title": "Fatty Acid Synthesis .txt", "text": "More specifically, it's acetylco enzyme A carboxylase."}, {"title": "Fatty Acid Synthesis .txt", "text": "And just like any other carboxylase, this carboxylase requires three different things."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number one is it means an energy source and that's where ATP comes into play."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number two is it means a carbon source."}, {"title": "Fatty Acid Synthesis .txt", "text": "Why?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, because as this name applies, the carboxylase will actually attach a carbon dioxide onto the ceiling."}, {"title": "Fatty Acid Synthesis .txt", "text": "Co enzyme A molecule, elongating this molecule by one carbon."}, {"title": "Fatty Acid Synthesis .txt", "text": "And that's why we have the bicarbonate."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number three is attached."}, {"title": "Fatty Acid Synthesis .txt", "text": "Covalently onto the carboxylase is biotin and biotin is a vitamin B seven molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, the reaction as shown on the board is actually the sum of two individual reactions."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this is actually the overall net reaction of the sum of two different reactions that are not shown on the board."}, {"title": "Fatty Acid Synthesis .txt", "text": "But I'd like to talk about them for just a moment because they actually demonstrate the importance of biotin."}, {"title": "Fatty Acid Synthesis .txt", "text": "So what happens in step number one in this reaction?"}, {"title": "Fatty Acid Synthesis .txt", "text": "So in step number one, we have the hydrolysis of ATP by this carboxylase and the energy that is released in the hydrolysis of ATP helps us attach a carbon dioxide onto the biotin."}, {"title": "Fatty Acid Synthesis .txt", "text": "So in step number one we form, and that's not shown aboard, but we form a complex that consists of carbon dioxide attached onto biotin, which is also attached onto the carboxylase."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, in the second step that once again is not shown, that carbon dioxide is transferred from the biotin onto the Cecil coenzyme A molecule and we generate malanyl coenzyme A."}, {"title": "Fatty Acid Synthesis .txt", "text": "So that's the importance of biotin."}, {"title": "Fatty Acid Synthesis .txt", "text": "Biotin allows the binding of that carbon dioxide which ultimately transfers that carbon dioxide onto the CEO coenzyme A to form this Malnol coenzyme A."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now this step is very important for three reasons."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number one is it commits the CETO coenzyme A molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number two is it's the rate limiting step."}, {"title": "Fatty Acid Synthesis .txt", "text": "And number three is this is the enzyme that is regulated to basically either inhibit or activate fatty acid synthesis."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, we're not going to focus on the regulation of this enzyme because that's actually pretty complicated."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we'll save that discussion for a later lecture."}, {"title": "Fatty Acid Synthesis .txt", "text": "So remember three things about this step."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number one is it commits the molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "Number two is it's a regulatory step?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Number three is it's a rate limiting step?"}, {"title": "Fatty Acid Synthesis .txt", "text": "And we'll come back to this step when we'll look at step number four."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, once we form the Malno Co enzyme A molecule, let's put it aside for a moment and let's look at step number one."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, the enzyme that catalyzes steps one through step seven is fatty acid syntax."}, {"title": "Fatty Acid Synthesis .txt", "text": "And remember that fatty acid synthase or simply SAS is a single polypeptide chain that actually contains seven different catalytic sites, seven different catalytic domains, as well as an ACP domain."}, {"title": "Fatty Acid Synthesis .txt", "text": "And the ACP domain stands for Acyl carrier protein."}, {"title": "Fatty Acid Synthesis .txt", "text": "Remember, the Acyl carrier protein actually contains a phosphate group and that group contains this sulf hydro group."}, {"title": "Fatty Acid Synthesis .txt", "text": "And that will allow the binding of certain molecules as we'll see in just a moment."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this is our FAS and we have this ACP that contains the phosphate that is not shown, that contains this sulf Hydrol group and that will bind this molecule, the CETO coenzyme A as we'll see in just a moment."}, {"title": "Fatty Acid Synthesis .txt", "text": "In addition, you also have to be aware of the cysteine residue that is also present in this FAS molecule because it will also play an important role as we'll see in just a moment."}, {"title": "Fatty Acid Synthesis .txt", "text": "So step number one is catalyzed by one of the catalytic domains we call acetil transasilise and that is found on this FAS molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "And so what this enzyme does or what this catalytic domain does is it catalyzed the attachment of this acetyl coenzyme A molecule onto this sulf hydro group and we generate this intermediate shown here."}, {"title": "Fatty Acid Synthesis .txt", "text": "In addition, we kick off the coenzyme A as shown here."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, this acetyl coenzyme A is not the same as this acetyl Co enzyme A."}, {"title": "Fatty Acid Synthesis .txt", "text": "So like I said, we're basically putting this malnozyme A away for just a moment because we're going to use it in one of these later steps."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, once we generate this intermediate, the next step is to actually move this acetyl group from this sulf Hydrol to this sulf Hydrol shown here."}, {"title": "Fatty Acid Synthesis .txt", "text": "And so in step number two, all we're doing is we're transferring this acetyl group onto this cysteine which acts as a temporary holding group."}, {"title": "Fatty Acid Synthesis .txt", "text": "So it holds this molecule in place because ultimately what we're going to do is we're going to combine them and elongate that fatty acid chain so we see that in the next step, the Cetal group is transferred onto the 16 residue as shown in this particular diagram."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, once we form that, what happens next?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, in the next step, this is where the melanoc coenzyme A comes into play."}, {"title": "Fatty Acid Synthesis .txt", "text": "So the melanoco enzyme A that we form in this step now is a reactant in step number three."}, {"title": "Fatty Acid Synthesis .txt", "text": "And in step number three, what happens is we have another catalytic domain that is part of the FAS molecule known as malanil transasilise catalyzed, the formation of a bond between this molecule here and this sulf hydro group of that ACP group found on that FAS."}, {"title": "Fatty Acid Synthesis .txt", "text": "And so we generate this intermediate."}, {"title": "Fatty Acid Synthesis .txt", "text": "And now in this intermediate, we have that acetyl group attached onto the cysteine, and we have the marinade group that's attached onto that sulfidel of this ACP molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, one important difference between this catalytic domain and this catalytic domain is this catalytic domain is much more specific for this molecule than this domain is specific for this molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "In fact, this domain here can actually bind other carbon molecules."}, {"title": "Fatty Acid Synthesis .txt", "text": "In fact, it can bind proponel coenzyme A."}, {"title": "Fatty Acid Synthesis .txt", "text": "And that's how we're able to actually form odd chain fatty acid molecules."}, {"title": "Fatty Acid Synthesis .txt", "text": "But in this case, we're only going to focus on the even chain fatty acid molecules."}, {"title": "Fatty Acid Synthesis .txt", "text": "So once again, in step three, the melania transatcelase domain of the fatty acid synthase catalyze the transfer of the malinate group from the malanil coenzyme A that we formed here onto the ACP domain."}, {"title": "Fatty Acid Synthesis .txt", "text": "This enzyme domain is highly specific for the malcoenzyme A, unlike this catalytic domain that is not that specific for this acetyl group."}, {"title": "Fatty Acid Synthesis .txt", "text": "And this basically helps prepare the molecule for step four, in which we have a condensation step in which we elongate that fatty acid chain."}, {"title": "Fatty Acid Synthesis .txt", "text": "So let's take a look at step four."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, step four is a very important step."}, {"title": "Fatty Acid Synthesis .txt", "text": "Why?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, because this is a step that actually drives this entire reaction forward."}, {"title": "Fatty Acid Synthesis .txt", "text": "So remember, what we did in this step here is we hydrolyzed the high energy ATP molecule, and we use that energy to actually carboxylate this acetyl coenzyme A to form this malcoenzyme A."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, what we do here is a decarboxylation step, and we break a thio ester bond."}, {"title": "Fatty Acid Synthesis .txt", "text": "And this pretty much releases enough energy for us to actually drive this reactant forward."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this step is a crucial step in fatty acid synthesis because it drives the overall reaction forward."}, {"title": "Fatty Acid Synthesis .txt", "text": "What happens is the enzyme acyl, malno ACP condensing enzyme, basically decarboxylates this group, and that prepares these two molecules for nucleophilic attack."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this nucleophilically attacks this, and that breaks this thioester bond that releases a good amount of free energy, so lowers the free energy of this product molecule, and that helps drive the equilibrium toward the product side."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we ultimately move this acetyl group from the 16 onto the ACP, and we generate this molecule here, which we call aceto, acetoacetyl coand, acetoacetatel, ACP intermediate."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we see that the Zekerboxylation of the Melania group sets up the reaction for a nucleophilic attack that cleaves the high energy Thioester bond."}, {"title": "Fatty Acid Synthesis .txt", "text": "This bond here and the product of this is aceto, acetyl attached onto the ACP molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this is what we call the condensation step."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, notice what else this step actually tells us."}, {"title": "Fatty Acid Synthesis .txt", "text": "It tells us that even though we used this as a carbon source to actually generate the Malaco enzyme A in this step here, that carbon source, namely the carbon dioxide, is actually removed."}, {"title": "Fatty Acid Synthesis .txt", "text": "And what that implies is all the carbon atoms that are found in that fatty acid chain that is synthesized in this process, they come from acetyl coenzyme A and not from that carbon dioxide."}, {"title": "Fatty Acid Synthesis .txt", "text": "So carbon dioxide is ultimately removed from that fatty acid chain."}, {"title": "Fatty Acid Synthesis .txt", "text": "It does not contribute to those carbon atoms."}, {"title": "Fatty Acid Synthesis .txt", "text": "So, again, very important step because it allows us to drive the equilibrium of this reaction toward the product side."}, {"title": "Fatty Acid Synthesis .txt", "text": "So ultimately, it's the indirect action of ATP that sets up this reaction and allows us to undergo this decarboxylation step that drives this reaction forward."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, let's move on to step number five."}, {"title": "Fatty Acid Synthesis .txt", "text": "So in step number five, this acetoacetal group is our reactant molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, this step number five is a reduction step."}, {"title": "Fatty Acid Synthesis .txt", "text": "And the reductant molecule that we use is NADPH."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we use NADPH to basically transform this carbonyl group into an alcohol group and we form this molecule, as shown here, the enzyme domain on that FAS that I catalyze this step is known as beta keto acel ACP reductase."}, {"title": "Fatty Acid Synthesis .txt", "text": "It's a reductase because it uses this reducing molecule to actually generate this alcohol from this carbonyl group."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, we call it beta keto ACL because this is actually a beta keto molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "So when the beta ketoaceel ACP reductase domain of ACP uses the reducing power of NADPH, we ultimately generate that D three hydroxybutyl molecule that we have here."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this is a reducing step."}, {"title": "Fatty Acid Synthesis .txt", "text": "Let's move on to step number six."}, {"title": "Fatty Acid Synthesis .txt", "text": "In step number six, we ultimately want to actually remove this hydroxyl group and we want to transform this alcohol into a double bond."}, {"title": "Fatty Acid Synthesis .txt", "text": "And the enzyme that catalyzes this is three hydroxy acyl ACP dehydrates."}, {"title": "Fatty Acid Synthesis .txt", "text": "And again, this is one of the seven catalytic domains that we find on FAS."}, {"title": "Fatty Acid Synthesis .txt", "text": "So in this step, we basically have the dehydration step in which this group and this group are combined to form water."}, {"title": "Fatty Acid Synthesis .txt", "text": "They are removed, and we form this double bond."}, {"title": "Fatty Acid Synthesis .txt", "text": "So the three hydroxy acid ACP dehydrates domain of FAS catalyzes the dehydration reaction in which we generate a double bond and release water, thereby forming a molecule that we call Croatinil that is attached onto the ACP."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we have a condensation step, we have a reduction step, we have a dehydration step."}, {"title": "Fatty Acid Synthesis .txt", "text": "And in step seven, this is a second reduction step."}, {"title": "Fatty Acid Synthesis .txt", "text": "And again, we use NADPH as our reducing molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "So this is catalyzed by Enoil ACP reductase why?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, because this molecule here is an Enoil."}, {"title": "Fatty Acid Synthesis .txt", "text": "More specifically, it's a trans delta two Enoil intermediate."}, {"title": "Fatty Acid Synthesis .txt", "text": "And so we take this crotinil molecule and we reduce it to basically remove this double bond and basically form this single bond."}, {"title": "Fatty Acid Synthesis .txt", "text": "And so we see ultimately, when we go from step five to step seven, what we do is we are more specifically when we go from yeah, we can say from step five to step seven, we transform this beta keto group to a methylene group."}, {"title": "Fatty Acid Synthesis .txt", "text": "That's the point of step five through step seven."}, {"title": "Fatty Acid Synthesis .txt", "text": "Why do we do that?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, because the fatty acid that we generate at the end only contains single bonds."}, {"title": "Fatty Acid Synthesis .txt", "text": "So we want to form a saturated fatty acid molecule."}, {"title": "Fatty Acid Synthesis .txt", "text": "So in this step, we have the second reduction step."}, {"title": "Fatty Acid Synthesis .txt", "text": "We generate the Uteril group that is shown here, attached onto the ACP, and this basically completes the first elongation step."}, {"title": "Fatty Acid Synthesis .txt", "text": "Now, why do I say the first elongation step?"}, {"title": "Fatty Acid Synthesis .txt", "text": "Well, because all we did so far is generate a fatty acid chain that contains only four carbon."}, {"title": "Structure of Long Bones .txt", "text": "Long bones are one of the five different types of bones that are found inside our body."}, {"title": "Structure of Long Bones .txt", "text": "And they contain long, curved shafts that basically give the bone its strength."}, {"title": "Structure of Long Bones .txt", "text": "Now, long bones are found in the fingers and the toes as well as in the arms and legs."}, {"title": "Structure of Long Bones .txt", "text": "Now, long bones can be divided into three different regions."}, {"title": "Structure of Long Bones .txt", "text": "We have the upper region known as as the epithesis."}, {"title": "Structure of Long Bones .txt", "text": "We have the middle portion known as our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "And what connects our Epiphesis to our diaphysis is a section known as aromataphesis."}, {"title": "Structure of Long Bones .txt", "text": "And these two sections are also found on the bottom of the bone."}, {"title": "Structure of Long Bones .txt", "text": "So we have the epithesis on the bottom most and the topmost, we have the middle section, the shaft, that's our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "And we have the metaphysis that connects our epithesis to our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "So let's discuss the individual components of the structure of our long bones."}, {"title": "Structure of Long Bones .txt", "text": "And let's begin with this purple section found on this side as well as on this side, which is not shown."}, {"title": "Structure of Long Bones .txt", "text": "So this is known as our articular cartilage."}, {"title": "Structure of Long Bones .txt", "text": "So articular simply means that's the connecting point between the bone and our joint."}, {"title": "Structure of Long Bones .txt", "text": "And we'll discuss what the joint is and what types of joints we have in our body in a future lecture."}, {"title": "Structure of Long Bones .txt", "text": "So basically, this consists of a type of cartilage known as the highland cartilage, where the Hylin simply means it's transparent."}, {"title": "Structure of Long Bones .txt", "text": "And this highland cartilage connects our bone to our joint."}, {"title": "Structure of Long Bones .txt", "text": "Now, the next portion we're going to discuss is our epithesis."}, {"title": "Structure of Long Bones .txt", "text": "And the epithesis contains a special type of bone structure known as our spongy bone, also known as the cancellus bone, as well as our trabicular bone."}, {"title": "Structure of Long Bones .txt", "text": "And it's called trabicular because the structure resembles a honeycomb, it resembles a sponge."}, {"title": "Structure of Long Bones .txt", "text": "Now, inside the spongy bone, which is not dense, by the way, so that means it's relatively light and flexible."}, {"title": "Structure of Long Bones .txt", "text": "Inside the spongy bone, we have a specialized region known as the red bone marrow."}, {"title": "Structure of Long Bones .txt", "text": "And the red bone marrow is where we basically produce our red blood cells as well as our white blood cells."}, {"title": "Structure of Long Bones .txt", "text": "And the process by which we produce these blood cells is known as hematopoasis."}, {"title": "Structure of Long Bones .txt", "text": "So hematopoasis takes place in the red bone marrow of our spongy bone inside the epithesis of our bone."}, {"title": "Structure of Long Bones .txt", "text": "Now let's move on to our metaphosis."}, {"title": "Structure of Long Bones .txt", "text": "Inside the metaphysis, we have a special region known as our Epiphysical plate."}, {"title": "Structure of Long Bones .txt", "text": "Now, the Epiphysical plate is basically the region where in children as well as young adults, that's where our bone grows and elongates and basically increases in length."}, {"title": "Structure of Long Bones .txt", "text": "So this plate is found in our metaphysis section of our long bone."}, {"title": "Structure of Long Bones .txt", "text": "Now, once our organism, once our human basically becomes a full adult, when they reach the age of 25, this plate essentially stops growing and the Epiphysical plate turns into our Epiphysical line."}, {"title": "Structure of Long Bones .txt", "text": "That means it stops growing."}, {"title": "Structure of Long Bones .txt", "text": "Now let's move on to this long section that actually consists of our curved shaft."}, {"title": "Structure of Long Bones .txt", "text": "This is known as our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "So the long shaft region of the bone is called our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "And this contains a section known as armidoolery cavity, also known as the marrow cavity."}, {"title": "Structure of Long Bones .txt", "text": "And this is basically the innermost portion of our cell."}, {"title": "Structure of Long Bones .txt", "text": "Now this small layer that basically lines the innermost portion is our endosteum."}, {"title": "Structure of Long Bones .txt", "text": "The endosteum is basically a covering of the innermost portion of the bone."}, {"title": "Structure of Long Bones .txt", "text": "Now, right next to our medullary cavity we have this white portion shown by this section here that basically goes around the bone in both directions."}, {"title": "Structure of Long Bones .txt", "text": "This is known as our compact bone and the compact bone is also known as the cortical bone."}, {"title": "Structure of Long Bones .txt", "text": "This is a very dense and a very heavy portion of the bone."}, {"title": "Structure of Long Bones .txt", "text": "The compact bone basically contains the yellow bone marrow and the yellow bone marrow is responsible for actually storing the adipose tissue."}, {"title": "Structure of Long Bones .txt", "text": "The adipose tissue or the cell contains the cells that store our fat in the form of triglycerides."}, {"title": "Structure of Long Bones .txt", "text": "Now this compact bone also is responsible for giving our bone strength, for giving our bone tensile strength as well as our compressive strength."}, {"title": "Structure of Long Bones .txt", "text": "And it's our compact bone that consists of the individual units known as osteons that we spoke about previously."}, {"title": "Structure of Long Bones .txt", "text": "So the long shaft region, the bone, is called our diaphysis."}, {"title": "Structure of Long Bones .txt", "text": "This contains our medullary cavity, also known as the marrow cavity, which is the innermost part of the bone."}, {"title": "Structure of Long Bones .txt", "text": "This is this section here."}, {"title": "Structure of Long Bones .txt", "text": "Now the lining of the inner portion of the bone is known as our endosteum, while our outermost lining of the cell, so the membraneous fibrous covering found outside the entire bone is known as our periosteum."}, {"title": "Structure of Long Bones .txt", "text": "Now the periosteum basically is involved in bone healing and bone growth."}, {"title": "Structure of Long Bones .txt", "text": "And that basically means inside the periosteum we have these cells that are capable of differentiating into osteoblasts where osteoblasts are the cells that are involved in bone growth as well as bone healing."}, {"title": "Structure of Long Bones .txt", "text": "Now the periosteum covers the bone so it is also involved in a protective function."}, {"title": "Structure of Long Bones .txt", "text": "It protects our bone and it also serves as the attachment points for tendons that connect muscles to our bones."}, {"title": "Structure of Long Bones .txt", "text": "So this is the structure of our long bones."}, {"title": "Major Histocompatibility Complex .txt", "text": "One of the most important roles of our immune system of the leukocytes, the white blood cells of our immune system is to be able to differentiate and distinguish between the healthy cells of our body and the infected cells as well as the different types of pathogens that can invade our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now the question is what exactly allows these leukocytes to not only communicate with one another but also to distinguish between the healthy cells and our infected cells?"}, {"title": "Major Histocompatibility Complex .txt", "text": "Well, it's a complex of proteins found on the membrane of our cells that allows this process to take place."}, {"title": "Major Histocompatibility Complex .txt", "text": "And the complex of proteins is known as the major histocompatibility complex or simply MHC."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, specifically in humans because MHC is found in all animals."}, {"title": "Major Histocompatibility Complex .txt", "text": "If we're talking about humans, then the major histocompatibility complex is also known as the human leukocyte antigens."}, {"title": "Major Histocompatibility Complex .txt", "text": "And we'll see why it's given this name in just a moment."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, there are three different types, three different classes of major histocompatibility complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "We have MHC class one, MHC class two and MHC class three."}, {"title": "Major Histocompatibility Complex .txt", "text": "And in this lecture, we're only going to focus on MHC class one and MHC class two."}, {"title": "Major Histocompatibility Complex .txt", "text": "So let's begin with MHC class one."}, {"title": "Major Histocompatibility Complex .txt", "text": "And this is the diagram that describes this complex, this protein complex found on the cell membrane of a healthy cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "So we essentially have four different polypeptide units that are connected as shown."}, {"title": "Major Histocompatibility Complex .txt", "text": "And we have alpha one, alpha two, alpha three, beta two subunits."}, {"title": "Major Histocompatibility Complex .txt", "text": "And the alpha three is connected to the cell membrane of our cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, what exactly is the purpose of the MHC class one complex?"}, {"title": "Major Histocompatibility Complex .txt", "text": "Well, basically this is the major histocompatibility complex that actually allows the leukocytes, the white blood cells of our body, to distinguish the healthy cells of our body from the infected cells of our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "Those cells that were infected by some type of pathogen, some type of virus or some type of parasite."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, most cells in our body that are nucleated, which contain a nucleus have the MHC class one complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "So let's actually discuss how this complex works."}, {"title": "Major Histocompatibility Complex .txt", "text": "Well, a healthy cell will bind one of its normal proteins, peptides that it creates inside the cell onto this clef portion of our MHC class one complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "So if we take a look at the following diagram, we have a healthy cell of our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "We have our major histocompatibility complex, class one."}, {"title": "Major Histocompatibility Complex .txt", "text": "And some type of protein that the cell produces inside our cell, it brings out and it binds onto this region right here."}, {"title": "Major Histocompatibility Complex .txt", "text": "So when a leukocyte essentially approaches this healthy cell and it recognizes this peptide as a normal peptide, as a normal self antigen, so we call this a self antigen, which basically means that it's an antigen, it's a protein that is formed by this cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "So when the leukocide recognizes a self antigen, it basically leaves that cell alone."}, {"title": "Major Histocompatibility Complex .txt", "text": "It knows that that is a healthy cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, what happens if a cell is actually infected by some type of pathogen."}, {"title": "Major Histocompatibility Complex .txt", "text": "For example, a virus."}, {"title": "Major Histocompatibility Complex .txt", "text": "Let's suppose now we look at an infected cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "So the infected cell now contains viral components that have been created by that cell itself."}, {"title": "Major Histocompatibility Complex .txt", "text": "So we have these different types of viral proteins."}, {"title": "Major Histocompatibility Complex .txt", "text": "And what the cell does is it essentially takes a viral protein and it places on this complex here inside the cleft instead of this self antigen."}, {"title": "Major Histocompatibility Complex .txt", "text": "So now we have a pathogenic antigen and antigen that comes from that pathogen, our virus."}, {"title": "Major Histocompatibility Complex .txt", "text": "And now when the leukocyte swims by and notices this pathogenic antigen it will bind to it and initiate a set of different types of immune responses that will ultimately destroy this infected cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "So we see that the major histocompatibility complex, class one is actually responsible for allowing our leukocytes to distinguish our healthy cells from the infected cells of our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, what about the second class?"}, {"title": "Major Histocompatibility Complex .txt", "text": "What about MHC Class Two?"}, {"title": "Major Histocompatibility Complex .txt", "text": "Well, these are the complexes found on our cells specifically on certain types of immune cells of our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "And these are used predominantly in communication between different types of leukocytes in our body."}, {"title": "Major Histocompatibility Complex .txt", "text": "So these protein complexes are found only on specific immune cells such as B, lymphocytes, macrophages, our dendritic cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "And we'll discuss what these cells are in the next several lectures as well as certain types of Tea lymphocytes."}, {"title": "Major Histocompatibility Complex .txt", "text": "So basically these look very similar in the sense that they both are composed of four subunits of polypeptides."}, {"title": "Major Histocompatibility Complex .txt", "text": "But notice we have these homologous pairs."}, {"title": "Major Histocompatibility Complex .txt", "text": "We have alpha one and alpha two."}, {"title": "Major Histocompatibility Complex .txt", "text": "And we have beta one and beta two."}, {"title": "Major Histocompatibility Complex .txt", "text": "And both of these are attached to our cell membrane, as shown."}, {"title": "Major Histocompatibility Complex .txt", "text": "And just like this one has a special cleft that can attach a certain type of protein."}, {"title": "Major Histocompatibility Complex .txt", "text": "This one also has a special cleft as shown in the following diagram."}, {"title": "Major Histocompatibility Complex .txt", "text": "So MHC class one are used to distinguish between healthy and infected cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "But MHC class two is actually used by the leukocytes to communicate between different types of leukocytes."}, {"title": "Major Histocompatibility Complex .txt", "text": "And we'll see exactly what we mean by that in just a moment."}, {"title": "Major Histocompatibility Complex .txt", "text": "So these protein complexes function in helping immune cells to communicate with one another."}, {"title": "Major Histocompatibility Complex .txt", "text": "So let's suppose we have the following scenario."}, {"title": "Major Histocompatibility Complex .txt", "text": "So suppose some type of macrophage as shown in diagram one."}, {"title": "Major Histocompatibility Complex .txt", "text": "So this is diagram one."}, {"title": "Major Histocompatibility Complex .txt", "text": "We have the macrophage."}, {"title": "Major Histocompatibility Complex .txt", "text": "Inside the macrophage we have the organelles, we have our nucleus and we have these green structures which are the lysosomes."}, {"title": "Major Histocompatibility Complex .txt", "text": "They contain digestive enzymes that can hydrolyze and break down the things that the macrophages actually engulfed."}, {"title": "Major Histocompatibility Complex .txt", "text": "So let's suppose we have some type of pathogen."}, {"title": "Major Histocompatibility Complex .txt", "text": "Let's suppose a bacterial cell, as shown in red."}, {"title": "Major Histocompatibility Complex .txt", "text": "And the macrophage finds our bacterial cell and engulfs that bacterial cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "And so in diagram two we form this phagosome, this vacuole inside our macrophage."}, {"title": "Major Histocompatibility Complex .txt", "text": "And these lysosomes fuse with this vacuum and they begin to break down that bacterial cell."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, as they break down the bacterial cell, they essentially take some of those pathogenic proteins or antigen and the cell places our antigen onto our MHC class two complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "So the major histocompatibility complex class two, as shown in the following diagram."}, {"title": "Major Histocompatibility Complex .txt", "text": "So, now that the macrophage actually contains this MHC class two complex, along with this complementary antigen that came from our bacterial cell, it can basically release special types of chemicals known as interleukin one."}, {"title": "Major Histocompatibility Complex .txt", "text": "And what this chemical does is it goes on to recruit, it calls upon helper T cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "Remember, helper T cells are special type of T lymphocyte."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, once the helper T cell comes to this area, it basically has this receptor on the membrane that can recognize this antigen that is bound to the MHC class two complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "And once it binds, it begins to release its own chemicals."}, {"title": "Major Histocompatibility Complex .txt", "text": "Specifically, it releases into Lucan two."}, {"title": "Major Histocompatibility Complex .txt", "text": "And what that chemical does is it moves on to B lymphocytes and T lymphocytes and it forces these two cells to essentially differentiate into their specialized form."}, {"title": "Major Histocompatibility Complex .txt", "text": "So B lymphocytes produce memory B cells as well as plasma cells, while these T lymphocytes produce the memory T cells as well as our cytotoxic T cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "So the cytotoxic T cells now contain the specific antibody on the membrane that can bind to this specific antigen."}, {"title": "Major Histocompatibility Complex .txt", "text": "And so, when the cytotoxic cell actually comes in close proximity to this type of bacteria that carries that same antigen, this antibody will be able to bind onto that bacteria."}, {"title": "Major Histocompatibility Complex .txt", "text": "And once they are bound, the cytotoxic cell will begin to release these powerful proteins that will drill holes in those bacterial cells, killing off those bacterial cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "Now, we also produce the plasma cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "And what the plasma cells do, they essentially produce those specific antibodies that are complementary, that are specific to this antigen that was found on the MHC class two complex."}, {"title": "Major Histocompatibility Complex .txt", "text": "And so we see that these MHC class II complexes are used by arrow leukocytes, by the white blood cells, to basically communicate between one leukocyte, let's say, the macrophage, and another leukocyte, let's say, the helper T cell, and then that can communicate with other leukocytes, for example, B lymphocytes and T lymphocytes, to produce even more specialized immune cells."}, {"title": "Major Histocompatibility Complex .txt", "text": "So, once again, to recap the way that our immune system actually distinguishes between our healthy cells and infected cells is by using the major histocompatibilitylly complex, class one."}, {"title": "Major Histocompatibility Complex .txt", "text": "So MHC Class one."}, {"title": "Major Histocompatibility Complex .txt", "text": "But the way our immune cells actually communicate with one another is by using a slightly different type of major histocompatibility complex known as MHC class two."}, {"title": "Major Histocompatibility Complex .txt", "text": "So these are the ways by which our leukocytes are able to actually distinguish between healthy and infected cells and the way that they can find these pathogenic cells inside our body."}, {"title": "Properties of Cell Membranes .txt", "text": "The fourth and final class of biological molecules that we're going to focus on are lipids, also known as fats."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, lipids, just like proteins, nucleic acids and carbohydrates, are very important biological molecules that play many different roles inside our cells and inside our body."}, {"title": "Properties of Cell Membranes .txt", "text": "To basically demonstrate the importance of lipids, let's focus in this lecture on this cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "So the cell membrane is a structure that encloses every single cell inside our body and it consists predominantly of lipids."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, what exactly are some functions of the cell membrane?"}, {"title": "Properties of Cell Membranes .txt", "text": "Well, the cell membrane has four important functions."}, {"title": "Properties of Cell Membranes .txt", "text": "Function number one is it creates a protective barrier between the outside and the inside environment of the cell."}, {"title": "Properties of Cell Membranes .txt", "text": "It basically prevents toxins and other pathogenic agents from actually entering the cell and it prevents molecules from actually spontaneously exiting the cell in the first place."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, function number two is that in transport, as we'll see in just a moment, within a cell membrane, we have proteins."}, {"title": "Properties of Cell Membranes .txt", "text": "And these proteins basically create these channels or pumps that basically allow the selective movement of certain things outside or into that cell."}, {"title": "Properties of Cell Membranes .txt", "text": "So this is a semipermeable membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that means is the cell actually picks and chooses what to allow into the cell and what to not allow into the cell."}, {"title": "Properties of Cell Membranes .txt", "text": "Function number three is that in signal transduction, what that means is certain molecules, for instance, hormones, can actually interact with the outside portion of the cell membrane and that will create many different types of signals and processes inside the cell, as we'll see in future lectures."}, {"title": "Properties of Cell Membranes .txt", "text": "And function number four, energy storage."}, {"title": "Properties of Cell Membranes .txt", "text": "So as we'll see in just a moment, there's actually an electric difference."}, {"title": "Properties of Cell Membranes .txt", "text": "So there's a charge difference between the outside and the inside of the cell."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that creates is an electric potential difference, a voltage difference."}, {"title": "Properties of Cell Membranes .txt", "text": "So there are electric field lines that exist within the cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that means is there is a certain amount of energy that is storage that is stored within the electric field that exists inside the cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "So four important functions act as a protective barrier, basically acts in transport, in signal transduction, as well as energy storage."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, every single cell inside our body contains this cell membrane and all these cell membranes have the same properties."}, {"title": "Properties of Cell Membranes .txt", "text": "So let's examine what these properties are."}, {"title": "Properties of Cell Membranes .txt", "text": "Property number one is these cell membranes are relatively thin and they enclose that entire cell."}, {"title": "Properties of Cell Membranes .txt", "text": "They create a closed boundary."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, the fact that the cell membranes are thin basically means they only consist of two layers of molecules, two layers of lipids, as we'll see in a future lecture."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, on top of that, inside the cell, inside eukaryotic cells, which are cells found inside our body, we also have individual organelles that themselves contain membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "So things like the nucleus, the Golgi complex, the endoplasm reticulum, lysosomes, paroxysomes, all these organelles also contain their own membrane that basically plays the same type of role as the cell membrane found around the actual cell."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, property number two, cell membranes are made up of not only lipids, but also proteins and carbohydrates."}, {"title": "Properties of Cell Membranes .txt", "text": "And the additional proteins and carbohydrates basically diversify the functionality of that cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, depending on the type of cell and the activity of cell, the ratio of lipids to proteins to carbohydrates basically varies."}, {"title": "Properties of Cell Membranes .txt", "text": "Now property number three, the cell membrane consists of a phospholipid bilayer and that can be seen in the following diagram."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, generally speaking, as we'll see in a future lecture, lipids are amphatic molecules and what that means is they contain both hydrophobic and hydrophilic regions, non polar and polar regions."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, one part of that phospholipid found inside the membrane is polar and that is known as the polar head."}, {"title": "Properties of Cell Membranes .txt", "text": "And these are shown in blue."}, {"title": "Properties of Cell Membranes .txt", "text": "And the polar heads basically orient themselves to the outside or the inside because the outside and inside contains an aqueous polar environment."}, {"title": "Properties of Cell Membranes .txt", "text": "But the non polar hydrophobic region shown in red of these lipids basically aggregate at the center of that cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "And as we can see from the diagram, the non polar region of the membrane basically predominates and that makes the membrane predominantly non polar."}, {"title": "Properties of Cell Membranes .txt", "text": "And so what that implies is the cell membrane basically serves as a barrier for polar and charged molecules."}, {"title": "Properties of Cell Membranes .txt", "text": "If polar or charged molecules want to make their way into the cell or outside the cell, they have to use these channels."}, {"title": "Properties of Cell Membranes .txt", "text": "These pumps we call proteins, as we'll see in just a moment."}, {"title": "Properties of Cell Membranes .txt", "text": "So the lipid molecules are emphatic."}, {"title": "Properties of Cell Membranes .txt", "text": "They contain both polar and non polar regions in an aqueous environment, which basically means in a polar environment that consists of water, the polar regions of the lipids interact with the environment while the non polar regions aggregate inside the membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "This makes the membrane mostly hydrophobic and it serves as a barrier to polar and charged molecules."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, what that also means, if a non polar molecule such as a cholesterol molecule, for instance, wants to make its way across the cell membrane, it can easily do so because the cell membrane is predominantly nonpolar."}, {"title": "Properties of Cell Membranes .txt", "text": "Property number four, the cell membrane is held together by non covalent interactions."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, if we examine any one of these individual molecules inside the cell membrane, for instance, we examine the protein molecule, the protein molecule itself."}, {"title": "Properties of Cell Membranes .txt", "text": "The atoms in the protein molecule are held together by covalent bonds, but the individual molecules."}, {"title": "Properties of Cell Membranes .txt", "text": "So for instance, the lipids and the proteins inside the cell membrane are held together by non covalent interactions, intermolecular bonds."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that means is, although these intermolecular bonds are weaker than the covalent bonds, because we have so many of these intermolecular bonds, the collective aggregate of all these bonds basically makes that membrane an effective barrier."}, {"title": "Properties of Cell Membranes .txt", "text": "So the individual lipid and protein molecules are held together by intermolecular bonds."}, {"title": "Properties of Cell Membranes .txt", "text": "And although they are weak compared to the covalent bonds that actually hold the atoms in any one of these molecules."}, {"title": "Properties of Cell Membranes .txt", "text": "The collective aggregate of older forces make the membrane an effective barrier."}, {"title": "Properties of Cell Membranes .txt", "text": "Or property number five is the membrane is not rigid, it is not stationary, it is fluidlike."}, {"title": "Properties of Cell Membranes .txt", "text": "And that's because of these relatively weak non covalent interactions."}, {"title": "Properties of Cell Membranes .txt", "text": "So basically, these proteins and these phospholipids, the lipid molecules, can move along the membrane without any problem."}, {"title": "Properties of Cell Membranes .txt", "text": "So there's a constant state of motion among all these different molecules in the lateral direction on that cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "So due to relatively weak intermolecular bonds, lipids and most proteins are in a constant state of lateral motion."}, {"title": "Properties of Cell Membranes .txt", "text": "The reason I say most proteins is because some of these proteins are actually attached to other things and so they don't actually move."}, {"title": "Properties of Cell Membranes .txt", "text": "Property number six, proteins diversify the properties of cell membranes."}, {"title": "Properties of Cell Membranes .txt", "text": "And this is what I mentioned earlier."}, {"title": "Properties of Cell Membranes .txt", "text": "So basically, proteins create many additional functions."}, {"title": "Properties of Cell Membranes .txt", "text": "For instance, it's the proteins that play a role in transport and they actually selectively choose what enters the cell and what doesn't."}, {"title": "Properties of Cell Membranes .txt", "text": "So there are many types of transport proteins."}, {"title": "Properties of Cell Membranes .txt", "text": "For instance, we have pumps that use energy, we also have channels and so forth."}, {"title": "Properties of Cell Membranes .txt", "text": "And we'll discuss these in much more detail in a future lecture."}, {"title": "Properties of Cell Membranes .txt", "text": "Now, proteins are the molecules that basically act in signal transduction."}, {"title": "Properties of Cell Membranes .txt", "text": "So, for instance, some type of hormone can bind onto a protein and that's the protein that will create that signal inside the cell, that will lead to some type of process inside the cell."}, {"title": "Properties of Cell Membranes .txt", "text": "So proteins function as transporters."}, {"title": "Properties of Cell Membranes .txt", "text": "They also function as enzyme receptors, and they mediate energy storage."}, {"title": "Properties of Cell Membranes .txt", "text": "For instance, one will discuss the electron transport chain."}, {"title": "Properties of Cell Membranes .txt", "text": "The electron transport chain is basically a series of proteins that are found on the inner membrane of the mitochondria."}, {"title": "Properties of Cell Membranes .txt", "text": "And what the electron transport chain does is it ultimately establishes a proton gradient."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that means is the electron transport chain are these proteins that create an electric potential difference between the two sides of the membrane of the mitochondria, and that stores energy across the cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "So proteins are important because they mediate energy storage, as well as act as enzymes, receptors and transporters."}, {"title": "Properties of Cell Membranes .txt", "text": "So number seven, which is what we mentioned earlier and just a moment ago, membranes are polar."}, {"title": "Properties of Cell Membranes .txt", "text": "And what that means is, compared to the outside of the cell, the inside of the cell basically differs in the charge."}, {"title": "Properties of Cell Membranes .txt", "text": "And because we have a separation of charge between the two sides of the membrane, from basic physics, we know that that creates establishes an electric potential difference, an electric dipole moment."}, {"title": "Properties of Cell Membranes .txt", "text": "So there is a dipole moment that exists between the two sides will have electric field, an electric field that will exist within this region and that will basically store energy within that region."}, {"title": "Properties of Cell Membranes .txt", "text": "It will give the membrane a voltage difference."}, {"title": "Properties of Cell Membranes .txt", "text": "And number eight, membranes are not symmetric structures."}, {"title": "Properties of Cell Membranes .txt", "text": "So if we compare one side of the cell membrane to the opposing side of the cell membrane, we'll see that there is a certain asymmetry to it."}, {"title": "Properties of Cell Membranes .txt", "text": "And that's because we have a different density and distribution of proteins and carbohydrates between different regions along the cell membrane."}, {"title": "Properties of Cell Membranes .txt", "text": "And so the density and distribution of the proteins is not symmetric along the cell membrane, which means the two phases of the membrane are never actually the same."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Hemoglobin is the primary oxygen carrier in our blood."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "It delivers the oxygen from the lungs to the tissues of our body."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, recall that hemoglobin consists of four individual polypeptide subunits."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And each one of these polypeptide subunits contains a single Hen group that is capable of binding oxygen molecules."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, because these four polypeptides can interact with one another our hemoglobin displays something called Cooperativity."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And what that means is if we take a fully unsaturated deoxy hemoglobin protein and one of the heme groups accepts an oxygen molecule then that will create a conformational change in the entire structure and that will cause the other three unoccupied hein groups to become much more likely to accept additional oxygen molecules."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Likewise, if we have a fully saturated oxymoglobin molecule and one of the hein groups unloads or releases an oxygen molecule then that will create a conformational change in the structure of the four polypeptides and that will make it more likely for the other three occupied hein groups to actually release an oxygen molecule."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So this is what we mean by Cooperativity."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, this leads to the sigmoidal shape the S shape of the oxygen hemoglobin dissociation curve that can be seen in the following diagram."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So the blue curve is the oxygen hemoglobin dissociation curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So this S shaped sigmoidal curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, the Y axis is, as always, the percent saturation of hemoglobin for this blue curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And the X axis is the partial pressure of oxygen given to us in millimeters of mercury."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, when the hemoglobin actually takes the oxygen from the lungs and brings it to the muscle tissue of our body, it has to drop that oxygen off."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, the question is, what exactly picks up that oxygen?"}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So once oxygen is delivered to our muscle tissue the tissue must be able to store that oxygen for later use."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And the protein that is responsible for storing the oxygen in our muscle tissue is known as myoglobin where Mayo means muscle and Globin means a polypeptide subunit."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, in fact, if we compare the structure of hemoglobin to myoglobin we'll see that myoglobin, unlike hemoglobin, actually consists of only a single polypeptide Subun."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And that single polypeptide subunit contains one heme group."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And that means that myoglobin can only bind a single diatomic oxygen molecule."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "On top of that, because we don't have more than two polypeptide subunits within myoglobin to actually interact with one another and create Cooperativity, that implies that myoglobin will not display Cooperativity and so it will not create a sigmoidal curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And the shape of our oxygen myoglobin dissociation curve is given by the red curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So once again, the y axis is percent saturation of myoglobin and the X axis is the partial pressure of diatomic oxygen given in millimeters of mercury."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, the next question is what exactly determines the difference between these two curves?"}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Well, it's basically the Cooperativity, the fact that hemoglobin is cooperative."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "It consists of four individual polypeptide subunits and these units interact with one another that creates this S shape."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "But because myoglobin does not have those four polypeptide subunits, it only contains one."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "It contains the following curve."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, the next question is what exactly is the physiological significance of these two curves?"}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And how do these curves actually correspond to the function of these two different proteins?"}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So let's begin inside our lungs."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So inside our lungs, we have a partial pressure of oxygen that is equal to about 100 mercury."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So if we take a look at the following curve and we plot a vertical line going up from the 100 points, and then we check the corresponding Y value for both of these curves, we see that according to these curves, both myoglobin and hemoglobin are about 98% saturated with oxygen when inside our lungs."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, this is not the important point."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "The important point lies in this line."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So when our tissue is exercising, its partial pressure of oxygen can drop to as low as 20 mercury."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So let's suppose this is the partial pressure of our oxygen inside the exercising lines, inside the exercising tissue."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And if we draw a straight vertical line upward and now we check the corresponding Y values for both of these curves, this is where our difference will actually lie."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "For the case of hemoglobin, we see that at 20 mmhg, our saturation, percent saturation is equal to about 32%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "But for our myoglobin, the percent saturation is still above 90%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "It's around 91%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And what that means is our hemoglobin is a much better carrier of oxygen because it's actually able to efficiently and effectively deliver that oxygen to the tissues that are exercising inside our body."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "While Myoglobin has a much greater affinity for oxygen, and it is much better at actually storing that oxygen until the partial pressure of oxygen inside our tissues is extremely low, So once again, according to the hemoglobin curve, the percent saturation of hemoglobin in the exercising tissues is about 32%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "However, the percent saturation of myoglobin in the at the same partial pressure value of 20 mmhg, is equal to about 91%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So if we find the difference in percent of hemoglobin and the difference in percent of myoglobin between these two points between the lungs and the exercising tissue, then for the case of hemoglobin, we have a difference in 66%, which basically means there will be a change in 66%."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So 66% of our hemoglobin will fully unload the oxygen to the tissues of our body, but only 7% of the myoglobin, this difference here will unload that oxygen to our tissues."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So this information tells us that myoglobin binds oxygen much more tightly than our hemoglobin does."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And this means that myoglobin would not make a very good oxygen carrier inside our blood because it will not be able to effectively and quickly unload our oxygen to the exercising tissues of our body that require that oxygen."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "Now, on the other hand, myoglobin, because it has a very high affinity to oxygen."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "It is a very good protein because it is a very good protein store, which basically means it can actually store our oxygen inside the muscle tissue until our partial pressure drops to very low value."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "In fact, we see from this graph that when the partial pressure of oxygen inside the muscle tissue drops to about 2 mercury, which is a very small value, the myoglobin will only unload about 50% of that oxygen."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So that means myoglobin has a very high affinity to oxygen, much more than Hemoglobin does."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "And it only unloads that oxygen when the partial pressure when the oxygen level inside arrivation drops to an extremely low quantity below 2 mercury."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "So this is the major difference between myoglobin and hemoglobin and their functionality."}, {"title": "Myoglobin Dissociation Curve .txt", "text": "They're a difference in functionality can be explained by these two different hemoglobin dissociate oxygen hemoglobin and oxygen myoglobin dissociation curves."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Just like there are abnormalities that exist in our autosomal chromosomes, there can also be abnormalities in our sex chromosomes."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "We're going to examine three different types of abnormalities on our sex chromosomes."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we're going to discuss an abnormality known as Klinfelter syndrome, which is basically described by the Xx Y carryotype."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Then we're going to briefly look at the XO carreotype, which describes Turner's syndrome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And then we're going to finish off with the XYY carryotype."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So in individuals with Clinfelter syndrome, there is an extra copy of the X chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So instead of having, let's say, the Xx or the XY chromosome, we have the Xx Y chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, the reason that this exists is a result of nondisjunction that can take place either in meiosis one or meiosis two, more specifically in anaphase one or anaphase two or of meiosis."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So to see exactly what we mean by that, let's take a look at the following diagram that describes nondisjunction taking place in anaphase II of meiosis."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So let's suppose we have a normal female individual, and that normal female individual produces Xcel."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So this is the precursor cell that eventually gives rise to four X cells."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, because we're dealing with a normal female individual, we have two X chromosomes, x chromosome number one and X chromosome number two."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, during interface, before meiosis actually takes place, each one of these X chromosomes is actually replicated."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we have this X chromosome number one, and it's identical cystochromatid and X chromosome number two, and it's identical replicated cystochromatid."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we have a pair of these cystochromatids."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we have interface taking place and then meiosis begin."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So let's fast forward to metaphase one of meiosis."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So this is when our tetrimers basically line up at the equatorial plate of the cell."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And also what happens is the mitotic spindle apparatus forms and these spindle fibers permeate extend from these centrioles, and they are supposed to attach, at least in a normal case, to these cystochromatid pairs."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So let's suppose that this process takes place normally."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so what that means is these will segregate, will move to opposite poles, and after meiosis one takes place, we form these two haploid cells, as shown."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So haploid cell number one and haploid cell number two."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, let's assume nondisjunction takes place."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And let's say that nondisjunction takes place within this cell."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So what happens is this centriole basically fails to extend the fiber, and that bonding between the fiber and this particular cystochromatid failed to actually take place."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, let's suppose that non disjunction does not take place within this particular cell."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So this cell correctly undergoes meiosis too."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so when these two identical cister chromosomes segregate to opposite poles and the two cells form, these will be the identical cystochromatids, the identical cells that will contain the identical correct X cells."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, because nondisjunction took place within this second haploid cell, because this failed to form the proper connection."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "This entire pair of identical sister chromosomes basically moved to opposite side and none of those sex chromosomes move to the other side."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so eventually, when we form our two X cells from this particular cell, we form cell number one and cell number two."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And these two cells, cell number one and cell number two are abnormal."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "They're called an applied."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And that's because this one lacks a copy of a sex chromosome and this one has an extra copy one more than it should."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we have one copy and the second copy of that additional copy of that X sex chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So notice that two of these are normal."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "These two are normal and these two are abnormal."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So let's suppose the normal female individual produced these abnormal gametes as a result of nondisjunction."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And now let's suppose this individual mates with a normal male individual that has normal sperm cells."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So if a normal sperm cell that is carrying a Y chromosome fuses with cell number two, we're going to form a Zygote that contains three instead of two sex chromosomes."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And because we're dealing with this abnormal X cell, we have two X chromosomes, two identical X chromosomes."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so because these two identical X chromosomes fuse with the sperm cell that contains the Y chromosome, we see that the genotype, the carriotype, will be XXY."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so this Zygold will eventually form an individual and that individual is said to have the XXY carriotype, which is also known as Clinfelter's syndrome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, what are some of the symptoms of individuals that have the syndrome?"}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Well, because they have that Y chromosome, these will be males."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, they will be unusually told and because of that additional X chromosome they're going to have female like breasts."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And about 50%, about half of them will have some type of mental disability."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "However, they do live normal lives, so they generally live normal lives."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, let's move on to the X or the XO carreotype."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, in individuals with Turner syndrome, they have one X sex chromosome and they lack the second sex chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And the reason we use the o symbol is to basically represent the fact that we have an absence of the second Y chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So let's see how this can actually arise."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So once again, this can arise as a result of nondisjunction."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "But now let's study nondisjunction as it takes place in the male individual."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So in this case, we begin by assuming we have a normal female individual."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, we're going to assume we have a normal male individual and that means we have one X and we have one Y."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, during interface we have replication taking place and so we produce this identical cystochromatid with respect to this one and this identical system chromatid with respect to this one."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And if we fast forward to metaphase one of meiosis, we basically get these chromosomes line up the tetramer of chromosomes lineup at the equatorial plate."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So once again, let's assume that nondisjunction takes place in anaphase two and not anaphase one."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so what that means is these mitotic spindle apparatuses or the spindle apparatus basically forms correctly and these fibers extend into onto these cystochromatid pairs and now segregation takes place and we form these two cells as shown."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So these two haploid male cells and now once again, let's assume that nondisjunction took place during the second phase of meiosis."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we have metaphase two."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, this cell basically divides normally and so these fibers are able to attach to each one of these cystochromatids."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So this one and this one."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so what happens is because nondisjunction does not take place, they segregate correctly and so eventually they will form this normal cell number one and normal sperm cell number two, where each and every one of them will have the X chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "On the other hand, because nondisjunction we're assuming nondisjunction takes place within this cell once again this spindle fiber is not able to connect directly with this cystochromatid and so both of these cystochromatids are connected to this spinal fiber and they are pulled to that side during anaphase II of meiosis."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so what we end up forming is these two abnormal sperm cells."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "In sperm cell four we lack any sex chromosome and in sperm cell three we basically have two identical Y chromosomes."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, if we take a normal Xcel that contains a single X chromosome, and that normal Xcel combines with this abnormal sperm cell number four, then what happens is the Zygo that is formed will only have a single sex chromosome, the X chromosome, because there is no Y chromosome within this particular sperm cell."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And this is what we mean by the Xokaryotype, also known as Turner's Syndrome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So when a normal X cell combines with the anuplooid sperm cell number four the Zygote will contain an Xocaryotype and that Zygote will eventually develop into individual that is said to have Turner's syndrome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, what are some of the symptoms of this particular syndrome?"}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Well, notice that because we don't have a Y chromosome and the Y chromosome is needed to develop that male individual these individuals with Turner syndrome basically develop into females."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "However, these females are sterile and that's because that second X sex chromosome is needed to actually fully develop the ovaries."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "And so these individuals are basically sterile because they do not have developed fully developed ovaries and fully developed female genitalium."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now let's move on to the final type of sex chromosome abnormality, the XYY."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, unlike the XXY and the XO, this is not actually a syndrome because individuals that have this type of caraotype live normal lives and they don't really have too many abnormalities."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "They have a normal phenotype and they are fully fertile."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So suppose that instead of combining sperm cell number four we took sperm cell number three."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we took sperm cell number three and we combined it with a normal X cell as shown in this diagram."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "What would we form then?"}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Well, we have two identical Y chromosomes, one X chromosome."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So we form a Zygote that has an XY genotype distribution and that's what we mean by an XY carreotype."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "Now, it turns out that Zygotes with the XYY caraotype, the XXY genotype, the XYY genotype generally develop into fertile males and aside from being unusually tall and having extreme acne problems, they are generally normal."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "That is, they are ah, they are fertile and they can basically form offspring."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "They can basically mate without with other normal female individuals to produce offspring."}, {"title": "Sex Chromosomal Abnormalities .txt", "text": "So these are the three different types of abnormalities that exist on sex chromosomes."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Fats, also known as lipids, are hydrophobic."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "They are nonpolar, and that means they will not easily dissolve in the lumen of the small intestine."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And that's exactly why many fat molecules and many lipid molecules combine to form particles known as fat globules inside our lumen."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, that's exactly why we use both to break down the fat globules into much smaller units in a process known as emulsification."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And then we digest those smaller units and we form my cells."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "My cells are very small, very tiny spheres that contain a fatty acid or a cholesterol molecule."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And these myoscils are so small, and that means they can easily pass across the membrane of intelligence."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So my cells fuse with the membrane and they bring the fatty acids into the cells of our small intestine, into the interacy."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And once inside the cells, these fatty acids form triglycerides in the smooth endoplasmic reticulum."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So a triglyceride contains three fatty acids and a single glycerol."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, within the lumen of the smooth endoplasmic reticulum of anterocides, many of these triglycerides, as well as cholesterol and phospholipid molecules, combined to form a particle known as the kylomycran."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, the kylomycran also contains proteins, and that means it must be modified in the Golgi apparatus."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And because it contains fats lipids as well as proteins, a kylomycrane is a lipoprotein."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "In fact, the kylomycran is the largest type of lipoprotein, as we'll see in just a moment."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So this is what the chylomicrin actually looks like."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So inside, in the core, at the sensor, we have thousands of cholesterol and triglyceride molecules, as shown in green and orange."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, we also have this single layer of phospholipids that protect the hydrophobic core from the hydrophilic solution found in our surrounding environment."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And we also have these proteins known as apoproteins."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "APO simply means the protein does not have its substrate."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "It doesn't have its coenzyme or cofactor attached to the protein."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, we can also call the apoprotein an apollipoprotein because the apoprotein is attached to our lipid, as shown."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "This is the hydrophilic section of the protein, and this is the hydrophobic section."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, as we'll see in just a moment, these apoproteins are used to actually recognize this kylomicrine."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "They are used to attach onto special receptor proteins found on the membrane of certain target cells."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So the majority of the fats or lipids inside the sites, inside the cells of the small intestine, are stored and packaged in these particles known as kylomycrans."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, notice, the kylomycran is not a molecule, but a particle."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And the difference is, a particle consists of thousands of these different molecules."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So inside we have thousands of these fat molecules."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "We have the phospholipids, and we also have the proteins."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, our kylomicrins exit our basilateral membrane side of the anteracide, and they basically go directly into our lactial, which ends up in our lymph system."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So this is in contrast to proteins and sugars that end up in the blood system these Kylamicrins first go into our lactial, into our lymph system before they end up in our blood system."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So once inside the lactel, they travel via the lymph vessels, and eventually, they're dumped into our blood system via the thoracic duct, which is found in the neck that basically connects with the left subclavian vein."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So what this basically means is the Kylomicrine, before actually going inside our blood system, it first travels through our lymph vessel."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And this is in contrast to amino acids and sugars that go directly into our blood system via our intracis, found in the small intestine."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, once inside the bloodstream, once inside the blood plasma, these Kylomycrans will travel to their target cells, which are usually liver cells and fat cells, also known as adiposides."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So what happens is these Kylo migrants use their apoproteins to basically bind to special receptor proteins found on the membrane of endolefial cells that line the blood capillaries in our blood vessel system."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So the membrane of these endolethial cells contain special proteolytic enzymes known as lipoprotein lipases."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And these are responsible for breaking down the triglycerides into fatty acids and glycerol."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, once on the membrane, once the Kylomicrin is on the membrane of these and the endolethial cells, the lipoprotein lipase breaks down these triglycerides."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And those fatty acids, those glycerol molecules and those cholesterol molecules can then easily diffuse into the target cell, the liver or the fat cell."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And once inside the liver of the fat cell, these fatty acids and glycerol can once again be used to form triglycerides in a smooth endoplasmic reticulum."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And now we store these triglycerides until the body needs to use energy."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So if we have plenty of energy inside our body, our cells do not have to use triglycerides."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "But if we need energy in certain cells in our body, the liver and fat cells can release these fatty acids into our blood system."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And now, because these fatty acids cannot dissolve in the blood plasma, they must be carried by special protein carriers known as albumin."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So, basically, the fatty acids, the fats, travel from the small intestine to our blood system via our Kylomicines."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "But once those fats actually end up in the target liver and fat cells, when they are released into our blood system once again, then they travel in our blood via albumin."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So, albumin is the protein carrier that carries fatty acids inside our blood plasma."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, earlier, I mentioned that arachylomycrane is the largest type of lipoprotein."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, lipoproteins are basically molecules that contain protein components as well as lipid components."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And lipoproteins are often used to transport fats inside our blood plasma, as we just saw."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And there are five different categories of lipoproteins."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "One of them is the Kylamicrin."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Another two important types, two important categories of lipoproteins are the low density lipoprotein, or LDL, and the high density lipoprotein, or HDL."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "Now, LDL are those lipoprotein particles that are responsible for carrying the fat from the liver or small intestine and two, our fat cells."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And these are the lipoproteins that are found attached to our blood capillaries."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And that's exactly why if we have a high concentration of LDL inside our blood, that is a bad thing because it can lead to clogging of our blood vessels, a condition known as atherosclerosis."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "On the other hand, we also have high density lipoproteins, or HCL, and these are the lipoprotein particles that are responsible for actually taking those fats and lipids away and bringing those into the liver to recycle those lipids and to excrete those lipids from our body."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "So basically, LDL are those lipoproteins that are bad for you because in large amounts they can clog the arteries, they can clog the blood vessels."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "And our HDL are the good lipoproteins because they basically break down."}, {"title": "Absorption of Fats in Small Intestine .txt", "text": "They take those lipids and fans, they bring them to liver cells and liver cells recycles and breaks down those lipids."}, {"title": "Promoter and Termination Sites .txt", "text": "RNA polymerase molecules are these biological catalysts that are used by our cells to basically synthesize RNA molecules from DNA molecules."}, {"title": "Promoter and Termination Sites .txt", "text": "So this process is called transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "And in transcription we basically copy the genetic information found in the DNA onto the RNA molecule and then it's the RNA molecule that is used in a variety of different ways to basically synthesize the proteins that are needed for the survival of that cell."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, we know that DNA molecules are very long molecules."}, {"title": "Promoter and Termination Sites .txt", "text": "They consist of many, many nucleotides."}, {"title": "Promoter and Termination Sites .txt", "text": "The question is how exactly does the RNA polymerase know where to begin the process of transcription on that DNA molecule?"}, {"title": "Promoter and Termination Sites .txt", "text": "So if we have many of these genes and many of these nucleotides how exactly does the RNA polymerase know where to bind and begin the process of transcription of some particular gene of interest?"}, {"title": "Promoter and Termination Sites .txt", "text": "Well, basically in prokaryotic as well as eukaryotic cells we have these regions on the DNA known as promoter regions or promoter sites."}, {"title": "Promoter and Termination Sites .txt", "text": "And what these promoter sites are, there are specific sequences of nucleotides that can bind very well to the RNA polymerase."}, {"title": "Promoter and Termination Sites .txt", "text": "And so when the RNA polymerase binds onto the promoter side, it knows it has to begin the process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, even though both bacterial cells, which are prokaryotic cells and human cells which are eukaryotic cells contain these promotocides, they are slightly different."}, {"title": "Promoter and Termination Sites .txt", "text": "So let's begin by discussing the promotosides we would normally find in a prokaryotic cell such as a bacterial cell."}, {"title": "Promoter and Termination Sites .txt", "text": "So we have two sequences that act as promoters."}, {"title": "Promoter and Termination Sites .txt", "text": "One of these sequences is found ten units, ten nucleotides to the left of that initial start of that transcription process."}, {"title": "Promoter and Termination Sites .txt", "text": "So to the left of that bacterial gene that we want to transcribe."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, the negative simply means it's to the left."}, {"title": "Promoter and Termination Sites .txt", "text": "It's upstream with respect to that bacterial gene."}, {"title": "Promoter and Termination Sites .txt", "text": "And this sequence is known as the primal box."}, {"title": "Promoter and Termination Sites .txt", "text": "So the primal box contains a consensus sequence, a sequence that doesn't change when we go from one organism to another organism."}, {"title": "Promoter and Termination Sites .txt", "text": "And the sequence is Tat, where T is thymine and A is adenine."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, we have another promoter that has found 35 nucleotides upstream to the left of that bacterial gene and this contains a consensus sequence of TTGACA."}, {"title": "Promoter and Termination Sites .txt", "text": "So we see that one of these promoter sites is found 35 nucleotides from the start of that transcription process."}, {"title": "Promoter and Termination Sites .txt", "text": "And the other one, called the primal box, is found ten nucleotides from the start."}, {"title": "Promoter and Termination Sites .txt", "text": "And so when that RNA polymerase is traveling along our double stranded DNA molecule in that bacterial cell it eventually travels very, very quickly until it locates these regions."}, {"title": "Promoter and Termination Sites .txt", "text": "And the reason it slows down is because it binds well to these regions."}, {"title": "Promoter and Termination Sites .txt", "text": "And once it binds well, it begins the process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "Now remember, RNA polymerase reads our DNA molecule from the three to five end and it synthesizes from the five to three end."}, {"title": "Promoter and Termination Sites .txt", "text": "And so as the RNA polymerase travels along the double strand DNA molecule it doesn't use this molecule as the template, but it uses the complementary DNA strand as the template."}, {"title": "Promoter and Termination Sites .txt", "text": "So if we look at the complementary strand for this particular molecule, it will basically begin on the three end and at the five end."}, {"title": "Promoter and Termination Sites .txt", "text": "And it's that particular DNA molecule that the RNA polymerase uses as its template."}, {"title": "Promoter and Termination Sites .txt", "text": "So once again, in this diagram, this is not the template, but the complementary sequence to this DNA molecule is that template."}, {"title": "Promoter and Termination Sites .txt", "text": "That the RNA molecule, the RNA polymerase actually uses."}, {"title": "Promoter and Termination Sites .txt", "text": "Now let's move on to eukaryotic cells."}, {"title": "Promoter and Termination Sites .txt", "text": "In eukaryotic cells, just human cells, we also have these promoter regions, but we also have additional sections of the DNA that play an important role in basically enhancing this transcription process."}, {"title": "Promoter and Termination Sites .txt", "text": "So we have two important promoter regions."}, {"title": "Promoter and Termination Sites .txt", "text": "One of them is known as the Tata box."}, {"title": "Promoter and Termination Sites .txt", "text": "And the reason we call it a Tata box is because it has a consensus sequence, Tata."}, {"title": "Promoter and Termination Sites .txt", "text": "This Tata box is also known as the Hoganess box, and it is found 25 nucleotides to the left, to the start of that transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "So to the start to where our eukaryotic gene is found."}, {"title": "Promoter and Termination Sites .txt", "text": "Now we also have a cat box."}, {"title": "Promoter and Termination Sites .txt", "text": "And we call this a cat box because it has a consensus sequence, CAAT."}, {"title": "Promoter and Termination Sites .txt", "text": "So the full consensus sequence is Ggmcaatct, but this is the CAAT."}, {"title": "Promoter and Termination Sites .txt", "text": "That's why we call it our CAD box."}, {"title": "Promoter and Termination Sites .txt", "text": "So this is found 75 nucleotides to the upstream side of our initial gene, where we initiate that process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "And finally, something that we don't find in prokaryotic cells, we have this section known as the enhancer sequence."}, {"title": "Promoter and Termination Sites .txt", "text": "And this enhancer sequence is not actually a promoter sequence, but it's basically a sequence onto which a special protein can bind to."}, {"title": "Promoter and Termination Sites .txt", "text": "And then once that protein binds onto the enhancer sequence, this moves all the way to this region here and it forms a complex and that essentially promotes that process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "It basically increases the efficiency of that RNA polymerase molecule."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, the thing about these enhancer regions is they can be found either upstream to the left or downstream to the right with respect to where that eukaryotic gene is found."}, {"title": "Promoter and Termination Sites .txt", "text": "And these enhancer sequences are found very far away from that eukaryotic gene, usually thousands of nucleotides away."}, {"title": "Promoter and Termination Sites .txt", "text": "So in this particular case, this is 1000 nucleotides away from this eukaryotic gene."}, {"title": "Promoter and Termination Sites .txt", "text": "So we see that the RNA polymerase travels very quickly along our DNA molecule until it locates these promoted regions at which it binds onto the promoter region and it begins the process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "It transcribes that bacterial cell and it uses the DNA molecule that is complementary to this DNA molecule that is shown here."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, the question is, how does it know when to stop that transcription process?"}, {"title": "Promoter and Termination Sites .txt", "text": "Well, in the same exact way that we have these promoter sections that initiate the process of transcription, we also have these termination sections, termination sites or termination sequences that essentially terminate or end the process of transcription."}, {"title": "Promoter and Termination Sites .txt", "text": "So essentially, the RNA polymerase will continue transcribing until it reaches a termination sequence."}, {"title": "Promoter and Termination Sites .txt", "text": "So in this particular diagram, this is our gene and this is our termination sequence."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, what's so special about the termination sequence that it allows this process to basically end?"}, {"title": "Promoter and Termination Sites .txt", "text": "Well, the termination sequence usually codes for a special type of structure on that RNA molecule, for example, a hairpin."}, {"title": "Promoter and Termination Sites .txt", "text": "And when that hairpin structure is formed, that RNA polymerase molecule will spontaneously dissociate from that RNA molecule."}, {"title": "Promoter and Termination Sites .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Promoter and Termination Sites .txt", "text": "So let's suppose that this is the complementary sequence to this gene here."}, {"title": "Promoter and Termination Sites .txt", "text": "And so this is the three n, because this is the five end and this is the five n here."}, {"title": "Promoter and Termination Sites .txt", "text": "And what that means is as the RNA polymerase moves along this DNA molecule, it essentially stops here and it begins transcribing that complementary template, that DNA molecule."}, {"title": "Promoter and Termination Sites .txt", "text": "And as it transcribes that molecule, it will continue forming that RNA molecule until it reaches this termination sequence."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, it will form that termination sequence, but once it forms the termination sequence, that termination sequence encodes for a signal we call a hairpin."}, {"title": "Promoter and Termination Sites .txt", "text": "And this hairpin structure contains this stem section and the loop section."}, {"title": "Promoter and Termination Sites .txt", "text": "So the hairpin is also known as the stem loop structure."}, {"title": "Promoter and Termination Sites .txt", "text": "And as our RNA molecule forms this structure, because the bonding is no longer strong enough, it will dissociate from that hairpin."}, {"title": "Promoter and Termination Sites .txt", "text": "And so now we form that RNA molecule."}, {"title": "Promoter and Termination Sites .txt", "text": "And that RNA molecule can be modified in different ways if it is found inside eukaryotic cells."}, {"title": "Promoter and Termination Sites .txt", "text": "Now, another way by which we can terminate the process of transcription is by using a special protein known as row."}, {"title": "Promoter and Termination Sites .txt", "text": "And we'll discuss what the mechanism of this protein is in a future lecture."}, {"title": "Promoter and Termination Sites .txt", "text": "So the important point about this lecture is there are these promoter sites and these termination sites which basically work with that RNA polymerase and allow that RNA polymerase to basically transcribe that gene of interest."}, {"title": "Promoter and Termination Sites .txt", "text": "It allows these promoter sites, allows the RNA polymerase to locate and detect where that gene is."}, {"title": "Promoter and Termination Sites .txt", "text": "And these termination sites basically allow the RNA polymerase to terminate or end the process of transcription."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "With factor ten."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "It activates factor eight to combine with factor nine, as well as this VWF, which stands for Von Willebrand Factor, which is another protein that is needed to basically stabilize factor eight."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "It activates the complex that goes on to activate more of ten to form this complex."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "And Thorambin also activates via positive feedback mechanism, more of eleven and eleven is needed to activate nine."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "So we see that we have a really extensive network of positive feedback mechanisms that ultimately greatly amplify."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "They magnify the number of blood clots that can be formed in this process."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "And this is important because, as we know, shock is a very dangerous medical condition and we don't want that individual to go into shock."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "And so this has to be an extremely effective and efficient process."}, {"title": "Blood Clotting Cascade (Part II).txt", "text": "And that's why we have many of these amplification positive feedback mechanisms."}, {"title": "Blood Flow in the Heart .txt", "text": "The human heart consists of two different pumps."}, {"title": "Blood Flow in the Heart .txt", "text": "We have a right pump and we have a left pump."}, {"title": "Blood Flow in the Heart .txt", "text": "And each of these pumps consists of two different chambers."}, {"title": "Blood Flow in the Heart .txt", "text": "We have an atrium and we have a ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "So the right pump, found on the right side of the heart contains the right atrium and the right ventricle while the left pump contains the left ventricle and the left atrium that is found on the left side of our heart."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, these two individual pumps are placed in serious with respect to one another."}, {"title": "Blood Flow in the Heart .txt", "text": "And what that means is they work together in a simultaneous way to create a movement of blood that is unidirectional and continuous."}, {"title": "Blood Flow in the Heart .txt", "text": "And this is exactly what we're going to focus on in this lecture."}, {"title": "Blood Flow in the Heart .txt", "text": "We're going to discuss the way that our blood actually moves within the four chambers of the heart."}, {"title": "Blood Flow in the Heart .txt", "text": "So let's begin with stage number one."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, in stage number one, stage number two, and stage number three, we're taking a cross section of the heart so that we expose the four different chambers."}, {"title": "Blood Flow in the Heart .txt", "text": "And we're examining the heart from a front side perspective."}, {"title": "Blood Flow in the Heart .txt", "text": "So we have the right side of the heart and the left side of the heart."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, the right side of the heart contains the right pump that had the right atrium this chamber here, and the right ventricle, this chamber here, while the left side of the pump contains this left pump that contains our left atrium and our left ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, we also have the four different types of valves."}, {"title": "Blood Flow in the Heart .txt", "text": "We have this right atrial ventricular valve, also known as the tricuspid valve."}, {"title": "Blood Flow in the Heart .txt", "text": "And we have the left atria ventricular valve, also known as the mitral or the Bicuspid valve."}, {"title": "Blood Flow in the Heart .txt", "text": "And we have these two semi lunar valves."}, {"title": "Blood Flow in the Heart .txt", "text": "We have the pulmonary semi lunar valve and we have the aortic semi lunar valve."}, {"title": "Blood Flow in the Heart .txt", "text": "So let's begin with stage number one."}, {"title": "Blood Flow in the Heart .txt", "text": "In stage number one, the atrium of the heart, and that includes the right atrium and the left atrium, are fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "And at this moment in time, they both receive blood from the rest of our body."}, {"title": "Blood Flow in the Heart .txt", "text": "So let's begin with the right pump that contains the right atrium."}, {"title": "Blood Flow in the Heart .txt", "text": "So our blood, that is deoxygenated returns from the upper portion of the body via the superior vena cava."}, {"title": "Blood Flow in the Heart .txt", "text": "And the de oxygenated blood comes from the lower portion of the body via the inferior vena cava."}, {"title": "Blood Flow in the Heart .txt", "text": "And these two blood systems basically connect and they empty out into the right atrium of our heart, which is this chamber here."}, {"title": "Blood Flow in the Heart .txt", "text": "So the right atrium begins to fill with deoxygenated blood and at this moment in time, it is fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, at the same exact moment in time, the oxygenated blood that is coming back from the left lung found in this section and the right lung, found in this section that blood is coming back via the right and the left pulmonary vein."}, {"title": "Blood Flow in the Heart .txt", "text": "So we have the right pulmonary vein which is shown in the back of this diagram, and this is the left pulmonary vein."}, {"title": "Blood Flow in the Heart .txt", "text": "And they both empty out our oxygen blood and begin to fill the left atrium of the heart."}, {"title": "Blood Flow in the Heart .txt", "text": "So this takes place at the same exact moment in time."}, {"title": "Blood Flow in the Heart .txt", "text": "So our two atria are fully relaxed and blood begins to fill these two atria, the only distance is here we have deoxynated blood, and here we have the oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "Now let's move on to stage number two."}, {"title": "Blood Flow in the Heart .txt", "text": "In stage number two, the right atrium is now fully filled with our de oxygenated blood, and the left atrium is also filled with our oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "And this causes the two atrium to contract."}, {"title": "Blood Flow in the Heart .txt", "text": "And when they contract, they open up the tricuspid valve and they also open up our bicuspid, or mitral valve."}, {"title": "Blood Flow in the Heart .txt", "text": "So let's begin with the right pump."}, {"title": "Blood Flow in the Heart .txt", "text": "So the right atrium is fully filled with the deoxynative blood and it contracts and enforces the opening of our tricuspid valve."}, {"title": "Blood Flow in the Heart .txt", "text": "And that moves the deoxynative blood and begins to fill the right ventricle of the right pump of our heart."}, {"title": "Blood Flow in the Heart .txt", "text": "So at this moment in time, the right atrium is contracting, but the right ventricle, which begins to fill, is fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, this also means, because our right ventricle is being filled, we don't want the backflow of blood from these blood vessels, which are basically the pulmonary arteries, back into the right ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "And that's exactly why the pulmonary semi lunar valve, this valve right here, is closed so that we have a one way movement, a unidirectional movement of blood this way from the right atrium to the right ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, at the same exact moment in time, this is what begins to take place at the left side of our heart in the left pump."}, {"title": "Blood Flow in the Heart .txt", "text": "So just as the right atrium is fully filled, the left atrium is also fully filled, but it's filled with oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "And this causes the contraction of this left atrium."}, {"title": "Blood Flow in the Heart .txt", "text": "And that opens up the bicuspid valve, also known as the mitral valve."}, {"title": "Blood Flow in the Heart .txt", "text": "And our oxygen blood now flows into the fully relaxed left ventricle of our heart."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, this valve, which is known as the aortic valve, is also fully closed, as this valve here to prevent the back flow of blood from the aorter back into our left ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "So this takes place at the same exact moment in time."}, {"title": "Blood Flow in the Heart .txt", "text": "So in stage one, the atria are both fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "In stage number two, both atria contract while both ventricles fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "And now let's move on to stage number three."}, {"title": "Blood Flow in the Heart .txt", "text": "So as the blood fills our two ventricles, they basically fill up with the blood."}, {"title": "Blood Flow in the Heart .txt", "text": "So let's begin with the right pump."}, {"title": "Blood Flow in the Heart .txt", "text": "So once the right ventricle is fully filled with our deoxygenated blood, what happens is there is a build up of pressure."}, {"title": "Blood Flow in the Heart .txt", "text": "And what that means is this ventricle, the right ventricle, begins to contract and that causes the closure of this tricuspid valve and it causes the opening of the pulmonary valve."}, {"title": "Blood Flow in the Heart .txt", "text": "And now our de oxygenated blood can flow via the pulmonary arteries and into the left and the right lung."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, at the same exact moment in time we have our filling of this left ventricle."}, {"title": "Blood Flow in the Heart .txt", "text": "Because it is now fully filled with oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "It causes contraction of the left ventricle closing this valve known as the mitral or the bicuspid valve."}, {"title": "Blood Flow in the Heart .txt", "text": "At the same time, it forces the opening of the aortic valve and it forces the movement of our oxygenated blood into the aorter of our body."}, {"title": "Blood Flow in the Heart .txt", "text": "And that aorta basically diverges into many smaller arteries and that moves our oxygenated blood into the rest of our body."}, {"title": "Blood Flow in the Heart .txt", "text": "And these two processes, one taking place in the right pump and the other one taking place in the left pump take place simultaneously at the same exact moment in time."}, {"title": "Blood Flow in the Heart .txt", "text": "So here we have the contraction of our right ventricle and the contraction of the left ventricle that takes place at the same exact moment in time."}, {"title": "Blood Flow in the Heart .txt", "text": "And if we examine these three stages these three stages basically take place over and over and over."}, {"title": "Blood Flow in the Heart .txt", "text": "And this creates a unidirectional and a continuous flow of blood not only inside the four chambers of the heart but also inside the entire cardiovascular system of our body."}, {"title": "Blood Flow in the Heart .txt", "text": "So, once again, in stage number one we have the right atrium and our left atrium that are fully relaxed and they are accepting, they are receiving blood inside those atrium."}, {"title": "Blood Flow in the Heart .txt", "text": "The right atrium is receiving deoxnated blood while our left atrium is receiving oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "They are being filled, they are fully relaxed."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, in stage number two, now, our two atria contract because they are fully filled."}, {"title": "Blood Flow in the Heart .txt", "text": "That opens up these two atrial ventricular valves and allows the movement of our blood from the atria and into our two ventricles."}, {"title": "Blood Flow in the Heart .txt", "text": "Here we have the oxygenated blood, but here we have oxygenated blood."}, {"title": "Blood Flow in the Heart .txt", "text": "Now, at this point, these two ventricles are fully relaxed while these two atria are fully contracted or they're contracting."}, {"title": "Blood Flow in the Heart .txt", "text": "And in stage number three, it's these ventricles that are now fully filled."}, {"title": "Blood Flow in the Heart .txt", "text": "As a result, they contract and they move our blood into the rest of our body."}, {"title": "Blood Flow in the Heart .txt", "text": "This moves the blood into our pulmonary arteries and that moves it into our lungs while this ventricle moves our blood into the order and into the rest of our systemic circulation of our body into the organs and tissues found in the upper and lower portion of our body."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Previously, we discussed the binding change mechanism of ATP synthase and we said that the binding change mechanism is actually the mechanism by which the catalytic structure the alpha three, beta three Heximer of ATP synthase actually generates those ATP molecule synthesizes, those ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, in this lecture, I'd like to focus on two important questions."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Question number one how does the movement of the protons across ATP synthase actually help us generate those ATP molecules?"}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And question number two is how many protons, how many hydrogen ions actually have to move through ATP synthase to actually generate a single ATP molecule?"}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And to answer these two important questions we actually have to describe the mechanism of the F zero region of ATP synthase."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So remember, the ATP synthase consists of two different regions."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "One of the regions is known as the f one region."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And this is what we focus on in the previous lecture."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "In this lecture, we're going to focus on the F zero region."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now remember that the F zero region actually consists of two types of polypeptide subunits."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "We have the C subunit and we have the A subunit."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, we only have a single A subunit."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "But for the C subunits we have anywhere from ten to 14 C subunits that aggregate together to form something called the C ring."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And it's the C ring, as we'll see in just a moment that actually rotates within the ATP synthase and that allows that gamma epsilon stalk to actually rotate and cause the binding change mechanism that we discussed in the previous lecture."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So let's focus on the following diagram."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So we have the inner membrane of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "This is the matrix of the mitochondria and this is the intermembrane space."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And this entire structure is the F knot region."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And the F knot region lies within the membrane of the mitochondria within the inner membrane."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, in this particular case, I've drawn ten of these individual C subunits that form this cring."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And we have the A subunit that is found in close proximity to this C ring."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, if we zoom in onto this A subunit this is basically what we're going to see."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, even though we don't exactly know what the structure of the A subunit actually looks like this is what we believe the structure looks like."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the structure of the A subunit seems to consist of two hydrophilic half channels that do not span the entire membrane of the A subunit."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "One of these half channels is open to the matrix side while the other one is open to the intermembrane side."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So we have one of these half channels which only spans half the membrane that is open to the intermembrane side and the other half channel is open to the matrix side."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And these two channels, as we'll see in just a moment will actually play an important role and allow the movement of the protons from the intermembrane space the high concentration to the matrix, the low concentration."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, if we zoom in into the center of each one of these C subunits showed in orange, we're basically going to find an aspartate 61 residue."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And the special thing about the aspartate 61 residue is the side chain actually contains this negative charge."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And the negative charge can actually grab a proton under acidic conditions."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the A subunit, this purple structure here, is positioned to interact with the C sub units."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "At the center of each one of these C subunits is an aspartate residue that can readily bind protons under acidic conditions."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So now that we know what the structure of what the structure of the f one region is, we can actually deduce what the mechanism of proton movement looks like."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So let's take a look at the following three steps."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And these are the diagrams that correspond to each one of these steps."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So let's begin with diagram number one."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So again we have the inner mitochondrial membrane."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "This is the intermembrane space and this is the matrix of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now we know along the matrix we have a low concentration of protons relative to the intermembrane space because remember, complexes one, three and four of the electron transport chain basically use the movement of electrons to generate that proton electrochemical gradient."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So we have a proton rich environment in the intermembrane space and we have a proton poor environment in the matrix of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So in the first step, what happens is we have this hydrophilic half channel is open to the matrix of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And at the center of that half channel is this aspartate 61 residue that bears a negative charge."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so the proton will move from a high concentration through this half channel and it will bind onto that aspartate 61 residue found at the center of this C subunit that lies along this half channel."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, once that movement actually takes place, once the movement takes place and the H plus binds onto this aspartate residue, we form aspartic acid."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And aspartic acid is not as hydrophilic as aspartate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so because aspartic acid is actually more hydrophobic, that aspartic acid that is formed when the H plus ion binds until aspartate 61 will want to move into the hydrophobic region of the inner membrane of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so this subunit here, the C subunit, will tend to rotate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And let's say the rotation is in a clockwise direction."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And as this C subunit rotates, it causes the entire C structure to actually rotate with it."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so what happens once this H plus ion moves into this section?"}, {"title": "Proton Movement in ATP Synthase .txt", "text": "It binds until the aspartate residue forming the spartic acid, because of spartic acid is more hydrophobic."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "It wants to move into the core of the inner membrane of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So this rotates and that causes the entire Ce ring to actually rotate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so what happens is this negative charge of the aspartate 61 on this C subunit basically moves into this position shown here."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And this aspartic acid basically that is found within this C submune moves into this position."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And now this H plus ion can move from this area to an area where we have a low proton concentration in the matrix of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And in this fashion we see that the movement of these protons from the high concentration to the low concentration basically powers the movement of this C rink."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So once again in diagram one an H plus ion will enter the half channel of the A subunit facing the intermembrane space and it will bind to that aspartate residue of the nearby C subunit."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And once the binding takes place it transforms aspartate 61 of that particular C subunit into a spartic acid."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Because a spartic acid is more hydrophobic it wants to move into the core of that inner membrane of the mitochondria and out of this half channel."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so as that rotation takes place it causes the entire serring to actually rotate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the entire searring then rotates until a C Subian with an aspartic acid enters the half channel that faces the proton poor environment of the matrix of the mitochondria."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And once this is found in this position the H plus ion can then move from the hydrophilic environment of this particular hemichannel and, say, the environment that contains a low concentration of those H plus ions."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so we conclude that the movement of the H plus ions through the half channels powers the rotation of that entire Cring."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And remember from our previous discussion the C ring is actually directly connected to that gamma epsilon stalk that runs through that central cavity of that alpha three beta three hexamer."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so what happens is since the ceiling is directly connected to the gamma epsilon central stock it causes that central stock to actually rotate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And when this central stalk actually rotate it stimulates the binding change mechanism that takes place within alpha three beta three hexamer that actually allows the synthesis and the release of those ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so ultimately it's the movement of the protons across the hemi channels across the semichannels of the F Naught region that allows the synthesis of these ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, I have to mention the following important idea."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the only thing that rotates in ATP synthase is the searing as well as the gamma epsilon structure."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Everything else remains stationary."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So that includes the A subunit."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the A subunit of the F knob region doesn't actually move."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So this purple structure that contains the half channels actually remains stationary."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "It's the searing that actually rotates."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And as that searing rotates it causes this red section, the gamma structure and the blue section, the epsilon structure to actually rotate."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And even though the gamma epsilon central stalk actually rotates through the central cavity of the alpha three beta three Heximer because this A subunit does not rotate and the A subunit is connected to this delta structure through these 2D subunits."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "This entire alpha three beta three hexamer doesn't rotate as well."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So this alpha three beta three heximur structure remains stationary because it is connected via this structure to this stationary A subunit of the f not region."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So the movement of the protons through this ATP synthase rotates the Ce ring and that in turn rotates the gamma epsilon stock but everything else actually remains stationary."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So now we basically answered question one."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So now we know how the movement of the protons across ATP synthase actually allows it to generate the ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So once again, it's the movement of these hydrogen ions through the half channels of the f zero region that allows the rotation of the searing and that intern rotates that gamma epsilon stalk and that powers the synthesis of the ATP molecules within the stationary alpha three beta three hexamer structure."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "The final question is how many protons actually have to move across the inner membrane of the mitochondria to synthesize a single ATP molecule?"}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Well, as we saw in the previous lecture, a rotation of 360 degrees of the gamma epsilon structure actually produces a total of three ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Why?"}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Well, because in the alpha three beta three structure we have a total of three beta structures and each one of these beta structures actually synthesizes a single ATP molecule."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so when this gamma epsilon structure rotates 360 degrees it is able to generate the three ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "Now, as I mentioned in the beginning, in this searing structure we have anywhere from ten to 14 C subunits and that means anywhere from ten to 14 of these H plus ions can actually move across the searing every time the searing rotates 360 degrees."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So 360 degree rotation of the epsilon of the gamma epsilon stock produces three ATP molecules."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "We multiply that by the range of ten to 14 H plus ions that move across the ATP synthase in a single 360 degree rotation."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "We see that ten divided by three gives us about 3.33 and 14 divided by three gives us about 4.67."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so this is the range of protons that are needed to actually synthesize a single ATP molecule."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "And so we see that on average about four protons must move through the ATP synthase to actually generate a single ATP molecule."}, {"title": "Proton Movement in ATP Synthase .txt", "text": "So again, this range actually describes the number of protons that have to move across the ATP B synthase found on the inner membrane of the mitochondria to actually generate a single ATP molecule."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "In order for the cells of our body to actually be able to function effectively and efficiently, they have to have a large enough supply of oxygen because it's the oxygen that is used in aerobic cellular respiration to produce ATP energy molecules."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, the hemoglobin molecule is the protein that is responsible for carrying the oxygen from the lungs and to the tissues and cells of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So if our cells are to function correctly, the hemoglobin must be able to bring enough oxygen and release enough oxygen in the tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And previously we spoke about one allosteric effector molecule, namely two, three BPG that binds into the center pocket in that deoxy hemoglobin, stabilizing the T state of the deoxy hemoglobin and decreasing the affinity of hemoglobin for oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this is precisely what allows that hemoglobin to basically release enough oxygen to the tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, as it turns out, two, three BPG is not the only allosteric effect."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Therefore hemoglobin, there are two other molecules found inside our body, inside the red blood cells that can bind onto a special region of the hemoglobin other than the oxygen binding side and decreased affinity of hemoglobin for oxygen, thereby shifting the oxygen binding curve to the right side."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And these two molecules are hydrogen ions and carbon dioxide."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So once again, 23 BPG is not the only atmosphericic effect that improves the efficiency of hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Hydrogen ions and carbon dioxide are also allosteric effectors that increase the amount of oxygen that is released by hemoglobin in the exercising tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this effect is known as the Bore effect."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So the Bore effect is basically the ability of hydrogen ions and carbon dioxide to bind onto the hemoglobin molecule, stabilizing its T state and decreasing its affinity for oxygen, thereby shifting the curve to the right side."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And to see what we mean by this, let's take a look at the following diagram."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, this diagram describes three different oxygen binding curves for hemoglobin under three different conditions."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So the black curve describes the condition in which we don't have any carbon dioxide present and we have a normal PH of 7.4, which is the PH found inside our lungs."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "The blue curve describes the conditions in which we don't have any carbon dioxide, but we decrease our PH."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So we increase the hydrogen ion concentration, the PH decreases to about 7.2 and the rec curve describes the condition under which we have about 40 mercury of carbon dioxide present in that surrounding area and we also decrease the PH to 7.2."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So once again, we increase the hydrogen ion concentration as compared to this case here."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And notice that when we don't have any CO2 present but we lower the PH, the black curve actually shifts to the blue position."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And when we keep the PH a 7.4 and we add carbon dioxide, the blue curve shifts to where the red curve is."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So we see that hydrogen ions and carbon dioxide together create the Bore effect, which actually shifts that entire oxygen binding curve of fumiglopin towards the right side."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And what that means is it decreases the affinity of hemoglobin for oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And what that means is it allows the hemoglobin to actually unload and release more oxygen to the tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And to see how much more is actually released, let's take a look at this graph."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, let's begin inside the lungs."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, inside the lungs, we basically have a concentration of oxygen of about 100 mercury."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So the Y coordinate of all these three different curves is exactly the same."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "It's around zero point 98, which is equivalent to 98% saturation of hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, when we go into the exercising tissues, the concentration of our oxygen drops to about 20 mercury."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And notice that at this particular point, we have three different Y coordinates."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "For this black curve, the Y coordinate is around zero point 32."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "For the blue curve, the coordinate is around zero point 21."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And for the red curve, the corden point is around 0.1."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And what that means is, for that black curve, when we have a PH of 7.4 and no carbon dioxide present inside our exercising tissues, the hemoglobin will be 32% saturated with oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "However, if we drop the PH to about 7.2, and once again, no CO2 is present, now, in the exercising tissues, the hemoglobin will be able to unload more oxygen, because our fractional saturation drops."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "We now have about 20% saturation of hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And finally, if we drop the PH and we increase the concentration of carbon dioxide to about 40 mercury, then at a partial pressure of 20 mercury for oxygen, inside the exciting tissues, we're going to have 10% saturation of hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And so, these will be the percentages of hemoglobin that are going to be able to unload and release that oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, in this particular case, the black curve, tells us 98% -32% gives us 66% of the hemoglobin will be able to release the oxygen to the tissues, in the case of the absence of carbon dioxide, but a lower PH."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So a higher concentration of hydrogen ions, we're going to be able to unload 98 -21 or 77% of that oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, 77% of the hemoglobin will unload and release that oxygen, and finally, for this case, in the presence of carbon dioxide, and a lower PH meaning a higher concentration of H plus ions, 88% of the hemoglobin will be able to unload that oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, we see not only does two three BPG shift the curve to the right side and lower the affinity of hemoglobin for oxygen, but so does the hydrogen ion concentration and the carbon dioxide concentration."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And these three molecules, 23 BPG, H plus ions, and CO2 molecules together create a very effective hemoglobin molecule that is able to actually unload a lot of many of those oxygen molecules to the tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So a higher concentration of CO2 and a lower PH, meaning a higher amount of H plus ions."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Because remember, as we increase the H plus ions, we decrease our PH."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So these two things shift the curve to the right, thereby decreasing the affinity of hemoglobin for oxygen and allowing the hemoglobin to unload or release more of those oxygen molecules into the exercising tissues, the cells of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, how does this actually take place?"}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, let's begin with the PH effect."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And let's focus on this blue curve here."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So as of now, we're not focusing on increasing or decreasing the CO2 concentration."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "We're only increasing, we're only focusing on the PH effect, increasing the H plus ion."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So why is it that when we increase the H plus ions in the red blood cells and in our blood system, why is it that the curve shifts to the right?"}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "How do these H plus ions actually affect that hemoglobin molecule?"}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Well, it turns out that in the hemoglobin molecule, we have several groups that can actually bind H plus ion."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So one of the group is basically the terminal residue, the amino group on the terminal residue of the alpha subunits."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And the other group are the histidine residues found on the beta 146 position and the alpha 122 position."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So these groups on the hemoglobin molecule can actually bind H plus ions."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And by binding H plus ions, those ions can then participate in forming stabilizing salt bridges."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So this is the histidine 141 residue found on the beta one subunit."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this is a nearby residue on the same beta one subunit, the aspartate 94."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, notice in this particular case, so at a relatively high PH of, let's say, 7.4, which is the PH inside our lungs, this nitrogen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So by the way, this is the nitrogen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "These are carbons, and these blue ones are oxygen atoms."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this orange one is an H ion."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So basically, this is the histidine residue and this is the aspartate residue."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And at a relatively high PH, so let's say at a normal PH of 7.4, the PH is not low enough to actually add an H plus ion onto this nitrogen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And so this nitrogen will be missing an H plus ion and no bond will be formed between these two groups."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "But as we lower the PH and increase the concentration of the H plus ions, now we approach the PKA value of this residue, which is about seven."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And so what that means is we have enough H plus ions so that the H plus ions can protonate this nitrogen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And by protonating this nitrogen, we basically create this nitrogen hydrogen bond."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And now the hydrogen, which bears a partial positive charge, can interact with the negatively charged oxygen atom of the side chain of the aspartate 94 amino acid."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this forms a salt bridge."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "A salt bridge is basically a stabilizing electric interaction between these two adjacent atoms."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And by forming this sold bridge, we essentially decrease the net charge in that localized region and that stabilizes the T state, the 10th state of that deoxy hemoglobin molecule."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And what that does is it lowers definitive hemoglobin for oxygen and makes it more likely to unload that oxygen to the tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And that means it shifts the entire curve to the right side."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And that's precisely why when we go from no CO2 PH of 7.4 to no CO2 and a PH of 7.2 because we increase our h plus iron concentration, we essentially form these sold bridges."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And that basically shifts the black curve to the blue position shown here."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So once again, as the hydrogen ion concentration increases, the histidine side chain becomes protonated."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So this nitrogen is protonated to form this bond here."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And this allows us to form sold bridges, which are stabilizing electric interaction with the nearby Aspartate side chain."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "This sold bridge stabilizes the t state of the deoxy hemoglobin, thereby lowering its affinity for oxygen and allowing to unload more of the oxygen to the tissue."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So this is our stabilizing salt bridge."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "It's called a salt bridge because we have a partial positive charge and a partial negative charge on this side."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So this is how the PH effect actually creates or allows the hemoglobin to unload more oxygen."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, what about the carbon dioxide effect?"}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So carbon dioxide is produced inside the exercising cells of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So if our muscles are contracting, we're producing more CO2 molecules."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, the thing about CO2 molecules is they're non polar molecules and they can easily move across the cell membrane of the tissue."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Cells move into our blood system and then move into the red blood cells because they don't have a charge and they can easily pass across the cell membrane."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Along with that, we also have special protein transporters in the cell membrane that allow the carbon dioxide to basically be brought into the red blood cell."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, once the CO2 is inside the red blood cell, it reacts with water."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And with the help of a special enzyme known as carbonic and hydrase, we transform CO2 and water into carbonic acid."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And then, because carbonic acid is a relatively good acid, it will dissociate into H plus ions and into bicarbonate ions."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "The bicarbonate ion will have a negative charge."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "The h plus ion will have a positive charge."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, notice one important thing."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "When We Have A Higher Concentration of CO2."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "That Means We're Going To Produce a Higher concentration of H plus ions."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So one mechanism by which CO2 shifts the curve to the right side is actually by increasing the h plus concentration and therefore decreasing the PH and causing the PH effect."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "And for the reason we spoke just a moment ago."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "By increasing the H plus concentration and decreasing the PH, we formed these solve bridges, which stabilize the structure of the T state of the deoxy hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "That decreases the affinity of hemoglobin for oxygen, shifts the curve to the right side, and allows the hemoglobin to release more o, two molecules to the exercising tissues of our body."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "Now, the next question is, how does CO2 directly affect our hemoglobin's affinity for oxygen?"}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So, just like HP plus ions can bind onto the hemoglobin molecule at special groups, the CO2 molecules can also bind onto the hemoglobin on special groups."}, {"title": "The Bohr Effect and Hemoglobin.txt", "text": "So it turns out that carbon dioxide can also bind onto."}, {"title": "Colorblind Genetics Example .txt", "text": "So now that we know what sex chromosomes are, let's take a look at the following example that deals with genetics and the Punnett square."}, {"title": "Colorblind Genetics Example .txt", "text": "So suppose a colorblind male."}, {"title": "Colorblind Genetics Example .txt", "text": "So a hemisitis recessive male has a child with a heterozygous normal female."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, in part A, what is the probability that the child is colorblind?"}, {"title": "Colorblind Genetics Example .txt", "text": "In part, what is the probability that the child is male and colorblind?"}, {"title": "Colorblind Genetics Example .txt", "text": "In Part C, if the child is female, what is the probability that she is normal?"}, {"title": "Colorblind Genetics Example .txt", "text": "And in Part D, if the couple has two children, what is the probability that both of them are normal?"}, {"title": "Colorblind Genetics Example .txt", "text": "Now, before we actually examine A through D, let's determine what the genotype is of each one of our parents."}, {"title": "Colorblind Genetics Example .txt", "text": "So let's begin with the heterozygous normal female."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, remember, the female contains two X sex chromosomes."}, {"title": "Colorblind Genetics Example .txt", "text": "So let's designate those X sex chromosomes with the following picture."}, {"title": "Colorblind Genetics Example .txt", "text": "So, we have the first Xx chromosome and the second X chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "So we have an X, and we have an X."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, we're going to use X with a blue uppercase C subscript SuperScript to basically describe the gene found on the X chromosome that codes for the normal color vision."}, {"title": "Colorblind Genetics Example .txt", "text": "So we have normal color vision."}, {"title": "Colorblind Genetics Example .txt", "text": "On the other hand, we're going to use X lowercase red C as the SuperScript to basically describe the gene that codes for color blindness."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, because we're dealing with a heterozygous female individual, that means one of the X chromosomes will carry the normal gene."}, {"title": "Colorblind Genetics Example .txt", "text": "The other one will carry the color blind gene."}, {"title": "Colorblind Genetics Example .txt", "text": "So one of these will be uppercase blue."}, {"title": "Colorblind Genetics Example .txt", "text": "So let's fill this in as blue."}, {"title": "Colorblind Genetics Example .txt", "text": "So this is our gene, and the other one will be lowercase C. So let's draw this in with red."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, what about the colorblind male?"}, {"title": "Colorblind Genetics Example .txt", "text": "Well, unlike the female, the male only contains one X chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "The other one is the Y chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "And only the X chromosome actually carries this color blind gene."}, {"title": "Colorblind Genetics Example .txt", "text": "And so what that means is only one of the sex chromosomes, namely the X chromosome, will carry that gene."}, {"title": "Colorblind Genetics Example .txt", "text": "For this particular trait, the Y chromosome doesn't actually carry anything."}, {"title": "Colorblind Genetics Example .txt", "text": "And that's exactly why this X will get the red lowercase C because the person is color blind, and the Y doesn't actually get anything because the Y chromosome doesn't actually contain that particular gene."}, {"title": "Colorblind Genetics Example .txt", "text": "Okay, so now we know what the layout is."}, {"title": "Colorblind Genetics Example .txt", "text": "Now we know what the genotypes of these individuals are."}, {"title": "Colorblind Genetics Example .txt", "text": "Let's actually carry out the mating process."}, {"title": "Colorblind Genetics Example .txt", "text": "So when these mates, before they actually mate, each one of these produce sex cells."}, {"title": "Colorblind Genetics Example .txt", "text": "The heterozygous normal female produces two types of egg cells."}, {"title": "Colorblind Genetics Example .txt", "text": "The colorblind male produces two types of sperm cells."}, {"title": "Colorblind Genetics Example .txt", "text": "So basically, we have replication taking place."}, {"title": "Colorblind Genetics Example .txt", "text": "Then meiosis take place, takes place."}, {"title": "Colorblind Genetics Example .txt", "text": "And at the end, we produce two types of X cells."}, {"title": "Colorblind Genetics Example .txt", "text": "One X cell contains this chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "The other type of Xcel contains this chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "So if this row describes our X cells, then both of these X cells will carry the X chromosome."}, {"title": "Colorblind Genetics Example .txt", "text": "One of it will be normal."}, {"title": "Colorblind Genetics Example .txt", "text": "So uppercase blue C and the other one will be colorblind, so lowercase seed."}, {"title": "Colorblind Genetics Example .txt", "text": "So let's suppose that this is the female XLS right here."}, {"title": "Colorblind Genetics Example .txt", "text": "So these are the female XLS."}, {"title": "Colorblind Genetics Example .txt", "text": "Let's suppose that these right here are the male sperm cells."}, {"title": "Colorblind Genetics Example .txt", "text": "Okay?"}, {"title": "Colorblind Genetics Example .txt", "text": "And so in the process of meiosis, when these segregate and at the end we form our haploid sperm cells, one sperm cell type will contain the X chromosome with the lowercase C, the red C. So let's suppose this is our X chromosome and the other sperm cell will simply contain the Y."}, {"title": "Colorblind Genetics Example .txt", "text": "So now let's actually carry out the Punnett square."}, {"title": "Colorblind Genetics Example .txt", "text": "Let's complete the Punnett square."}, {"title": "Colorblind Genetics Example .txt", "text": "So when this sperm cell combines with this X cell to produce the Zygote, the Zygote will have two X's."}, {"title": "Colorblind Genetics Example .txt", "text": "And what that means is we're going to have a female."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, this female will be heterozygous normal."}, {"title": "Colorblind Genetics Example .txt", "text": "And that's because we're going to have that dominant blue seed that will inhibit that recessive red sea."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, what about this sperm cell combining with this Xcel?"}, {"title": "Colorblind Genetics Example .txt", "text": "Once again, we're going to have a female."}, {"title": "Colorblind Genetics Example .txt", "text": "But now that female will be colorblind because we have two lowercase red C's."}, {"title": "Colorblind Genetics Example .txt", "text": "Now what if the Y, the sperm cell, combines with this XL?"}, {"title": "Colorblind Genetics Example .txt", "text": "So now we produce a male because we have an XY and this male will be normal."}, {"title": "Colorblind Genetics Example .txt", "text": "Why?"}, {"title": "Colorblind Genetics Example .txt", "text": "Well, because that X chromosome will carry that normal color vision given by uppercase blue C. This one will also be male Y and an X."}, {"title": "Colorblind Genetics Example .txt", "text": "But we're going to have lowercase red C. And so that means this individual will be colorblind just like this color blind parents."}, {"title": "Colorblind Genetics Example .txt", "text": "So now that we have the pun and square, let's go to A-B-C and Z."}, {"title": "Colorblind Genetics Example .txt", "text": "And let's begin with A."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, before we jump to A, notice that we have four individual cases and each one of these case and each one of these cases have equal likelihood of taking place."}, {"title": "Colorblind Genetics Example .txt", "text": "So we have a 25% chance of this event taking place, a 25% chance of this event taking place, a 25% chance here and a 25% chance here."}, {"title": "Colorblind Genetics Example .txt", "text": "And together, if we add up these likelihoods, we get 100%."}, {"title": "Colorblind Genetics Example .txt", "text": "So it's 100% likelihood that we're going to have a child."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, in part A, what is the probability that the child is color blind?"}, {"title": "Colorblind Genetics Example .txt", "text": "And we don't care if the child is male or a female."}, {"title": "Colorblind Genetics Example .txt", "text": "We simply want to know what is the probability that he or she is colorblind?"}, {"title": "Colorblind Genetics Example .txt", "text": "Well, out of these four cases, two of these cases produce a colorblind individual."}, {"title": "Colorblind Genetics Example .txt", "text": "So case number one, this colorblind female, and case number two, this color blind male."}, {"title": "Colorblind Genetics Example .txt", "text": "Both of these cases are normal."}, {"title": "Colorblind Genetics Example .txt", "text": "So that means two out of four children or two out of four cases produce a color blind individual."}, {"title": "Colorblind Genetics Example .txt", "text": "And we know that two out of four is the same thing as 0.5."}, {"title": "Colorblind Genetics Example .txt", "text": "And so that means we have a 50% chance that the child will actually be colorblind."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, what is the probability that the child is not only colorblind but also male?"}, {"title": "Colorblind Genetics Example .txt", "text": "And what that means is we want to look at that square that contains a male and that male is colorblind."}, {"title": "Colorblind Genetics Example .txt", "text": "And the case that we want to look at is this square right here."}, {"title": "Colorblind Genetics Example .txt", "text": "So we have only one of these four squares, satisfies condition B, where we have a male and that male is actually color blind."}, {"title": "Colorblind Genetics Example .txt", "text": "And so we have a one fourth chance, which is equivalent to zero point 25, which is equivalent to fifth or 25%."}, {"title": "Colorblind Genetics Example .txt", "text": "Let's move on to C. So if the child is a female, so we begin Part C by assuming that the child is in fact a female."}, {"title": "Colorblind Genetics Example .txt", "text": "The question is, knowing that the child is a female, what is the probability that she is normal?"}, {"title": "Colorblind Genetics Example .txt", "text": "So now, because we know that the child is female, the only thing we want to look at is this square."}, {"title": "Colorblind Genetics Example .txt", "text": "And this square."}, {"title": "Colorblind Genetics Example .txt", "text": "We don't want to consider these two squares because they contain the Y chromosome and that means they are male."}, {"title": "Colorblind Genetics Example .txt", "text": "So what is the probability?"}, {"title": "Colorblind Genetics Example .txt", "text": "So given that the child is male, so these two box, or the child is female, these two boxes, what is the probability that she is normal?"}, {"title": "Colorblind Genetics Example .txt", "text": "Well, by normal we mean they are not colorblind."}, {"title": "Colorblind Genetics Example .txt", "text": "So she's not colorblind."}, {"title": "Colorblind Genetics Example .txt", "text": "And that means this case is she is normal."}, {"title": "Colorblind Genetics Example .txt", "text": "This case is she is colorblind."}, {"title": "Colorblind Genetics Example .txt", "text": "And so we have one out of two cases is colorblind or one out of two cases is normal."}, {"title": "Colorblind Genetics Example .txt", "text": "So that means one over two because only one of these cases produces a normal individual within these female cases."}, {"title": "Colorblind Genetics Example .txt", "text": "So that is equivalent to 0.5, which is equivalent to 50%."}, {"title": "Colorblind Genetics Example .txt", "text": "And finally, let's do Part D. So in Part D, if the couple has two children, what is the probability that they are both normal?"}, {"title": "Colorblind Genetics Example .txt", "text": "So we have child number one and child number two."}, {"title": "Colorblind Genetics Example .txt", "text": "So let's begin with child number one."}, {"title": "Colorblind Genetics Example .txt", "text": "What is the probability that child number one?"}, {"title": "Colorblind Genetics Example .txt", "text": "So let's say child number one is normal."}, {"title": "Colorblind Genetics Example .txt", "text": "Well, the probability is 50%, as we saw in case A."}, {"title": "Colorblind Genetics Example .txt", "text": "So we saw that there is a 50% likelihood that the child is colorblind, which means it is a 50% likelihood that the child is normal."}, {"title": "Colorblind Genetics Example .txt", "text": "So child one is normal with a 50% likelihood and this is equivalent to 0.5."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, what about child number two?"}, {"title": "Colorblind Genetics Example .txt", "text": "Well, likewise there's a 50% likelihood by the same exact reasoning that child number two is normal."}, {"title": "Colorblind Genetics Example .txt", "text": "And that means we have a 0.5 likelihood."}, {"title": "Colorblind Genetics Example .txt", "text": "Now, because these two events are actually they do not depend on one another."}, {"title": "Colorblind Genetics Example .txt", "text": "They're independent."}, {"title": "Colorblind Genetics Example .txt", "text": "What that means is to calculate the actual probability, we have to multiply these two out."}, {"title": "Colorblind Genetics Example .txt", "text": "This is known as the product law."}, {"title": "Colorblind Genetics Example .txt", "text": "So if we multiply zero five by 0.5, we get zero point 25, which means there is a 25% likelihood that if these two individuals have two children, that both of those children will actually be normal."}, {"title": "Colorblind Genetics Example .txt", "text": "So this is basically how you use the sex chromosomes and the punitive square to determine different types types of probability values in these types of genetic problems."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Following exercise we generally tend to ingest a meal that is rich in carbohydrate molecules and the reasoning behind that is we want to give our cells, our liver cells and skeleton muscle cells to basically replenish their supplies of glycogen that were used up during that exercise."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now how does this process actually take place?"}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So how do our cells, cells specifically our liver cells actually regenerate and replenish their supplies of glycogen?"}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "This is what I'd like to focus on in this lecture and I'd like to focus on how insulin and how glucose molecules actually affect liver cells."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So after adjusting a meal rich in carbohydrates the blood glucose levels in our body rise above the normal five millimolar value."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And what our liver cells will try to do is they will try to maintain the proper level of glucose in our blood and they will uptake that glucose into the cell."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now what will also happen is the beta cells of the pancreas will begin to produce and secrete a small peptide hormone known as insulin."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And insulin will travel through the bloodstream and eventually will make its way into a special receptor protein found on the membrane of liver cells known as the insulin receptor."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And once the insulin binds onto the insulin receptor that initiates a signal transduction pathway."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now what this signal transduction pathway does is it ultimately stimulates protein kinases."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So let's see how that takes place."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So insulin binds onto the insulin receptor that creates a conformational change on the inner portion of the receptor and that causes a self asphorylation process."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And what that does is it basically transforms the IRS molecules from the inactive into the active form by phosphorylating these IRS molecules."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Remember IRS stands for insulin receptors substrate."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now these insulin receptorsubstrate molecules in their active form they basically follow a series of steps that ultimately helps activate protein kinases into the active form."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So this is basically the insulin signal transduction pathway and once these protein kinases are activated they go on to stimulate target enzyme and target proteins."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And in this particular case these protein kinases go on to inactivate glycogen synthase kinase into the inactive form."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So by phosphorylating the glycogen synthase kinase these protein kinases basically inactivate the glycogen synthase kinase."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now let's remember what the purpose of glycogen synthase kinase is."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So in their active form the glycogen synthase kinase molecules phosphorylate glycogen synthase A and they transform the glycogen synthase A which are the molecules in their active form into glycogen synthase B which exists predominantly in their inactive form."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now remember that glycogen synthase is the molecule that is responsible in the active form to actually create the glycogen molecule."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So these glycogen synthase A in their active form stimulate glycogenesis, the production, the synthesis of glycogen molecules from glucose precursors."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "But if the glycogen synthase kinase is active then it keeps the glycogen synthase in the glycogen synthase B the inactive form and that prevents glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So in this particular case when we ingest the meal rich in carbohydrates that ultimately stimulates the release of insulin."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "That creates the insulin signal transduction pathway that ultimately produces protein kinases which inactivate the glycogen synthase kinase."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And when the glycogen synthase kinase is inactivated, it no longer carries out this process."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "It no longer phosphorylates the glycogen synthase A into Glycogen synthase B."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now what that basically means is we're not going to carry out this process but there must be something that stimulates this process."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So even though we inactivate the glycogen synthase kinase, that doesn't mean that that's going to stimulate glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "What must also take place is we must somehow convert the glycogen synthase B in the inactive form back to the glycogen synthase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And what happens in this particular case is we have to activate another enzyme known as PP one where PP one stands for protein phosphatase one because it's protein phosphatase one in the active form that defosphorylates glycogen synthase B and forms the active form of glycogen synthase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And only glycogen synthase A can actually stimulate glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we see that from steps 12345 and six insulin ultimately causes the inactivation of glycogen synthase kinase, the enzyme that keeps glycogen synthase in the inactive form."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now, in order to actually transform this glycogen synthase B into the active form, the glycogen synthase A, our liver cells must initiate glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And to do this they have to actually activate PP one because it's protein phosphatase one that stimulates this conversion."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And that's what allows the glycogen synthase A to induce the process of glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So in this diagram we're basically going to describe how the PP one is actually activated."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So let's move on to diagram seven."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So in diagram seven we have the protein phosphatase one."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And as we discussed in the previous lecture, protein phosphatase one is bound to a regulatory region and that's the region shown here."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now this molecule is in its inactive form, the PP one is in its inactive form and the reason is because it is bound to phosphorase A in the art state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So phosphorase A in the art state basically means it's in a relaxed state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And when phosphorase A is in a relaxed state, it is fully active."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So phosphorase A is fully active but it's bound to this and that makes the protein phosphatase one inactive."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now we want to activate this molecule and so what our body does is when there is a rise in glucose levels in our blood that causes the uptake of glucose into the liver cells."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And so the cytoplasmic glucose concentration increases within the liver cells following the ingestion of the meal that is rich in carbohydrates."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And these phosphorlase A molecules basically serve as glucose sensors because they're able to actually bind the glucose molecule."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we have these two pockets on the phosphorlase A in the r state that can bind the glucose."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And once the glucose is bound to these two sections, that causes the transformation of the phosphorase A in the R state, the active state into the inactive T state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So the glucose bind onto phosphorlase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "They cause the transformation from the R state, the relaxed active state into the T state, the 10th state and the 10th state is the inactivated state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So upon the rise of glucose concentration it basically stimulates the transformation of our state into the T state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "At the same time it decreases the traction between the protein phosphatase one and the phosphorase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So upon the binding of glucose these two structures basically dissociate."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So let's suppose one goes here, this is phosphorase A in a T state and the remaining portion goes here."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And as soon as the dissociation takes place that activates this protein phosphatase one."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And once protein phosphatase one is active it goes on and acts on glycogen synthase B."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And remember that phosphatases they devosphorylate that molecule."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So in this particular case, the protein phosphatase one along with the regulatory chain they go on to defosphorylate the glycogen synthase B into the glycogen synthase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And remember, because of this particular pathway the protein kinases inactivate the glycogen synthase kinase and this process does not take place."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we're only going in this direction here."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And once we stimulate glycogen synthase A that stimulates the process of glycogenesis, the building of those glycogen molecules from glucose precursors."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now, what also happens is the following once the phosphorylase A and the T state dissociates, we don't want this molecule to reassociate with this structure."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And to keep it from reassociating this same molecule, the protein phosphatase One goes on and defosphorylates this phosphorylase A in the T state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And that transforms the phosphorylase A in the T state to phosphorlase B in the T state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And this molecule has a lower affinity for this structure here."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And so these will not associate, these will not reassociate and this protein phosphor taste one can continually stimulate this molecule to go into the active form and that will stimulate the process of glycogenesis."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we see that in seven phosphorase A is used to sense actually, let's begin from the beginning and let's summarize what we just said."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So let's suppose we just exercised and now we ingested a meal that is rich in carbohydrates."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And so what that does is it helps our liver cells replenish their glycogen supplies."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "How?"}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Let's take a look at this summary."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we have the beta cells of our pancreas secrete insulin."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Insulin binds onto the insulin receptor protein that initiates the insulin signal transduction pathway and that ultimately leads to the activation of protein kinases."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "These protein kinases then go on to deactivate glycogen synthase kinase into its inactive form."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So it stimulates the inactivation of this molecule."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now, this molecule in the active state keeps the glycogen synthase A in the inactive state."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "But as soon as we inactivate it now there's nothing that actually transforms the glycogen synthase A into the glycogen synthase B."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "But we still need that molecule, the protein phosphatase One, to stimulate the conversion of this inactive glycogen synthase into the active form for us to actually form the glycogen molecules."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And so this is what happens here."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "We have the phosphorylase A in the r state that is bound to this protein phosphatase One."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And because of that association, this molecule is not active."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now, phosphorylase A in the art state acts as a glucose sensor."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And when the glucose levels in the cytoplasm of that liver increase, they begin to bind the glucose."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And the glucose acts as an allosteric inhibitor."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "It basically transforms the active r state into the inactive T state, and that leads to the dissociation of these two molecules."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "So we basically form the phosphorylase A and the ten state and our protein phosphatase One."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "Now, to keep this molecule from reassociating with this, the phosphatase essentially defaults the phosphorase A into phosphorase B, and the phosphatase also goes on and activates the glycogen synthase B into glycogen synthase A."}, {"title": "Insulin and Glucose Regulation of Glycogenesis .txt", "text": "And this is what allows our liver cells to actually regenerate and replenish their supplies of glycogen."}, {"title": "Alpha Beta T-cells .txt", "text": "Previously we focused on B lymphocytes which are the cells that make up our humoral immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "Now let's focus on T lymphocytes or T cells which are the white blood cells that make up our cell mediated immunity of our adaptive immune system."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, just like B cells T cells also have special receptors on the membrane we call T cell receptors."}, {"title": "Alpha Beta T-cells .txt", "text": "And because there are two different types of T cell receptors we categorize T lymphocytes into two categories."}, {"title": "Alpha Beta T-cells .txt", "text": "We have AlphaBeta T cells which consist of special T cell receptors that have an alpha and a beta polypeptide subunit."}, {"title": "Alpha Beta T-cells .txt", "text": "And we also have gamma delta T cells which contain T cell receptors that consist of a gamma and a delta polypeptide subunit."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, it turns out that we know much more information about AlphaBeta T cells than we do about gamma delta T cells."}, {"title": "Alpha Beta T-cells .txt", "text": "And that's exactly why in this lecture we're going to focus primarily on alpha beta T cells."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, before we take a look at these alpha beta T cells let's recall what an antigen presenting cell is or an APC."}, {"title": "Alpha Beta T-cells .txt", "text": "So an antigen presenting cell is a type of white blood cell whose function is to engulf our antigens and take those antigens and present those antigens on the membrane of those APCs."}, {"title": "Alpha Beta T-cells .txt", "text": "So basically, these antigen presenting cells contain these protein complexes on the membrane known as the major histocompatibility complex."}, {"title": "Alpha Beta T-cells .txt", "text": "And what these protein complexes do is they're capable of binding these antigens that the cells actually engulf."}, {"title": "Alpha Beta T-cells .txt", "text": "Now what the role of the AlphaBeta T lymphocyte is is to actually bind to these antigen MHC complexes once the antigen presenting cell actually engulfs that antigen and places it onto that MHC in the first place."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, on top of having that T cell receptor that consists of an alpha and a beta subunit these T lymphocytes also contain glycoproteins that are necessary to actually bind to the antigen presenting cells."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, we have two different types of glycoproteins."}, {"title": "Alpha Beta T-cells .txt", "text": "We have CD four glycoproteins and we have CD eight glycoproteins."}, {"title": "Alpha Beta T-cells .txt", "text": "And the difference between these two different glycoproteins is their ability to bind to different types of major histocompatibility complexes."}, {"title": "Alpha Beta T-cells .txt", "text": "So let's begin with the CD four AlphaBeta T cell."}, {"title": "Alpha Beta T-cells .txt", "text": "So let's suppose we have the CD four T cell."}, {"title": "Alpha Beta T-cells .txt", "text": "And what that basically means is it contains a T cell receptor that contains an alpha unit shown in purple and the beta unit shown in red."}, {"title": "Alpha Beta T-cells .txt", "text": "And it also contains a special glycoprotein that extends from the cell membrane and that is shown in blue."}, {"title": "Alpha Beta T-cells .txt", "text": "Now let's suppose our APC, the antigen presenting cells such as, let's say, a macrophage engulfs that pathogenic antigen takes that pathogenic antigen and places it onto the MHC class two complex."}, {"title": "Alpha Beta T-cells .txt", "text": "So this is the MHC class two complex and this green part is our antigen."}, {"title": "Alpha Beta T-cells .txt", "text": "And once the antigen binds onto the MHC class two complex only then can the CD four AlphaBeta T lymphocyte actually approach and bind onto this complex forming an interaction between the APC, the antigen presenting cell and our T lymphocyte."}, {"title": "Alpha Beta T-cells .txt", "text": "So it turns out that T cells that have CD four glycoproteins can only bind onto the major histocompatibility complex class two."}, {"title": "Alpha Beta T-cells .txt", "text": "And as we'll see in just a moment, we also have a major histocompatibility complex class one which these glycoproteins cannot actually bind to."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, the question is what exactly takes place when this binding is initiated?"}, {"title": "Alpha Beta T-cells .txt", "text": "So basically, once the binding process takes place, the T cells can stimulate our immune system in two different ways."}, {"title": "Alpha Beta T-cells .txt", "text": "They can either stimulate the humoral immunity or they can stimulate the cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "So let's suppose the CD four T cell that binds onto the APC is a helper T cell in such a case when this binding process takes place."}, {"title": "Alpha Beta T-cells .txt", "text": "And let's suppose the APC is a B lymphocide."}, {"title": "Alpha Beta T-cells .txt", "text": "In such a case, the helper T cell, which is our CD four T cell, will stimulate that B lymphocyte, our APC to actually begin to undergo mitosis and create more clone cells, identical cells that contain the same exact B cell receptor."}, {"title": "Alpha Beta T-cells .txt", "text": "And they can also stimulate those B lymphocytes to actually undergo the process of differentiation and differentiate into plasma cells and memory B cells."}, {"title": "Alpha Beta T-cells .txt", "text": "So plasma cells are those cells that produce antibodies while memory B cells store a copy of that antibody in case reinfection ever takes place."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, instead of the CD four being a helper T cell, let's suppose we have some other type of T lymphocyte that binds to, let's say, a macrophage."}, {"title": "Alpha Beta T-cells .txt", "text": "In such a case, we can actually stimulate the cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "So CD four T cells can also bind to APts such as macrophages and dendritic cells and they release these chemicals known as lymphocines."}, {"title": "Alpha Beta T-cells .txt", "text": "And these lymphocines will stimulate our cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "And that means it will call upon other macrophages, other wide blood cells that will come to that infected area and begin our defensive mechanism response engulfing those pathogenic agents."}, {"title": "Alpha Beta T-cells .txt", "text": "So our CD four T cells can either stimulate the humoral immunity or they can stimulate the cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "On the other hand, as we'll see in just a moment, the CDAT cells can only stimulate the cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "So what exactly is a CDAT cell?"}, {"title": "Alpha Beta T-cells .txt", "text": "Well, a CDAT cell contains that same AlphaBeta subunit, that same T cell receptor but it contains a different glycoprotein."}, {"title": "Alpha Beta T-cells .txt", "text": "It contains a CDA glycoprotein."}, {"title": "Alpha Beta T-cells .txt", "text": "And what the CDA glycoprotein does is it is able to bind to the major histocompatibility complex class one and not the class two one."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, the class one MHC is the protein complex that is used by our wide blood cells to differentiate between healthy cells and infected cells of our bodies, our cells that have been infected by some type of viral or parasitic agent."}, {"title": "Alpha Beta T-cells .txt", "text": "So it turns out that CD eight T cells are those cells that help destroy the infected cells of our body."}, {"title": "Alpha Beta T-cells .txt", "text": "So once again, these T cells contain the CDA glycoprotein."}, {"title": "Alpha Beta T-cells .txt", "text": "Next to their AlphaBeta protein receptor."}, {"title": "Alpha Beta T-cells .txt", "text": "These cells can only bind to the MHC class one complex."}, {"title": "Alpha Beta T-cells .txt", "text": "And recall that this is the complex that is used by our white blood cells to differentiate between healthy cells and infected cells."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, one example of a T cell that contains a CD eight glycoprotein is the cytotoxic T cell, also known as the killer T cell."}, {"title": "Alpha Beta T-cells .txt", "text": "That is part of the cell mediated immunity."}, {"title": "Alpha Beta T-cells .txt", "text": "So cytotoxic T cells are example of CD eight plus T cells."}, {"title": "Alpha Beta T-cells .txt", "text": "The plus simply means these cells have this glycoprotein."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, generally speaking, these cytotoxic T cells and all CD eight T cells are those cells that can differentiate infected cells from healthy cells and kill off those infected cells."}, {"title": "Alpha Beta T-cells .txt", "text": "So, to see what we mean, let's consider the following example."}, {"title": "Alpha Beta T-cells .txt", "text": "Let's suppose that we have the common flu and what that means is a special type of viral agent known as influenza infected our body."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, what this virus does is it infects our healthy cells and it creates infected cells."}, {"title": "Alpha Beta T-cells .txt", "text": "So the infected cell begins to produce the viral agents that are needed by the virus to essentially reproduce."}, {"title": "Alpha Beta T-cells .txt", "text": "But what the infected cell also does is it takes a piece of that virus, some type of antigen and places it onto the major histocompatibility complex, class one as shown in the diagram."}, {"title": "Alpha Beta T-cells .txt", "text": "So this is the MHC class one of the infected cell."}, {"title": "Alpha Beta T-cells .txt", "text": "And this green portion is the antigen that came from the viral agent that infected our cell."}, {"title": "Alpha Beta T-cells .txt", "text": "Now, once the cell is infected and once the infected cell displays the antigen, when the CD eight T cell, for example, the cytotoxic T cell approaches this, the CD eight glycoprotein can bind onto this MHC class one complex."}, {"title": "Alpha Beta T-cells .txt", "text": "And this T cell receptor recognizes this antigen."}, {"title": "Alpha Beta T-cells .txt", "text": "And when the binding process takes place, what the CD eight T cell usually does is it begins to release these very powerful proteolytic proteins that begin to drill holes and digest our membrane of that infected cell."}, {"title": "Alpha Beta T-cells .txt", "text": "And what that ultimately does is it kills off that infected cell and destroys it before that infected cell can infect other healthy cells of our body."}, {"title": "Types of RNA .txt", "text": "DNA molecules are extremely important biological molecules because they store the genetic information that is needed to produce the different types of proteins used by the cell."}, {"title": "Types of RNA .txt", "text": "Now because of that any type of damage or any type of mutation to the DNA molecule will lead to disastrous consequences."}, {"title": "Types of RNA .txt", "text": "And to prevent this from happening we don't actually want to use the DNA directly to synthesize the proteins every single time we need to produce some type of protein."}, {"title": "Types of RNA .txt", "text": "So instead of continually using the DNA molecules over and over to produce proteins we use these intermediate nucleic acids known as RNA molecules."}, {"title": "Types of RNA .txt", "text": "So an RNA molecule is essentially a copy of the segment of the DNA that we essentially want to use to carry out some type of function for example, produce some given protein."}, {"title": "Types of RNA .txt", "text": "And by using these intermediate RNA molecules our cells eventually prevent damage to the DNA molecules."}, {"title": "Types of RNA .txt", "text": "So what types of RNA molecules are found in our cells?"}, {"title": "Types of RNA .txt", "text": "Well, the three major components of the RNA molecules of our cells are the messenger RNA, mRNA transfer RNA tRNA and ribosomal RNA or RNA."}, {"title": "Types of RNA .txt", "text": "And we also have trace amounts of other types of RNA molecules as we'll see in just a moment."}, {"title": "Types of RNA .txt", "text": "So let's begin by focusing on these three RNA molecules and let's begin with messenger RNA."}, {"title": "Types of RNA .txt", "text": "Now the messenger RNA molecule is basically the molecule that is eventually used by the ribosomes of our cells to synthesize the proteins in a process known as translation."}, {"title": "Types of RNA .txt", "text": "So in prokaryotic cells what happens is we take the DNA of that prokaryotic cell and then we transcribe the mRNA molecule and then that mRNA molecule can be used directly to synthesize the protein or proteins."}, {"title": "Types of RNA .txt", "text": "So the mRNA molecule in prokaryotic cells can sometimes code for more than one protein but in eukaryotic cells it's slightly different."}, {"title": "Types of RNA .txt", "text": "In eukaryotic cells we take the DNA and then we produce a precursor mRNA a pre mRNA molecule."}, {"title": "Types of RNA .txt", "text": "And before we can actually synthesize the proteins from that premRNA molecule we have to modify that pre mRNA molecule to produce the fully mature and functional mRNA molecule and only then can we actually synthesize the proteins."}, {"title": "Types of RNA .txt", "text": "And unlike in prokaryotic cells in eukaryotic cells a distinct mRNA molecule is produced for every one of the genes that is found on the DNA molecule."}, {"title": "Types of RNA .txt", "text": "And the messenger RNA molecule makes up about 5% of the total RNA composition found in our cell."}, {"title": "Types of RNA .txt", "text": "Now let's move on to transfer RNA or tRNA."}, {"title": "Types of RNA .txt", "text": "So transfer RNA makes up about 15% of the total cellular RNA found inside our cells."}, {"title": "Types of RNA .txt", "text": "And tRNA has this distinct stem loop shape that we spoke about previously."}, {"title": "Types of RNA .txt", "text": "And what the function of tRNA molecule is, is to basically take an activated amino acid found in the cytoplasm and bring it to the ribosil to help synthesize that polypeptide chain."}, {"title": "Types of RNA .txt", "text": "And each amino acid has at least one tRNA molecule made specifically to carry and bring that amino acid to that ribosome to synthesize the protein."}, {"title": "Types of RNA .txt", "text": "Now ribosomal RNA or RNA is the major component."}, {"title": "Types of RNA .txt", "text": "It makes up about 80% of the total composition of RNA found in our cells."}, {"title": "Types of RNA .txt", "text": "Now rRNA is a major constituent in the ribosomes found inside our cells and the ribosomes are the cell machinery responsible for synthesizing the polypeptide chains, the proteins."}, {"title": "Types of RNA .txt", "text": "Now rRNA gives the ribosome not only its three dimensional structure but the rRNA also acts as a catalyst and it catalyzes the formation of the peptide bonds in that polypeptide chain and we'll discuss how that actually takes place in a future lecture."}, {"title": "Types of RNA .txt", "text": "Now in prokaryotic cells there are three types of rRNA molecules found in the ribosome."}, {"title": "Types of RNA .txt", "text": "We have the 23s, we have the we have the five S. Now in addition to these three major components of the RNA molecules found inside our body we have these additional RNA molecules that also serve their own unique function and purpose."}, {"title": "Types of RNA .txt", "text": "Let's discuss what some of these RNA molecules are and let's begin with small nuclear RNA or SN RNA."}, {"title": "Types of RNA .txt", "text": "Now earlier when I discussed the messenger RNA molecule I said that in eukaryotic cells we actually have to first modify the pre mRNA molecule before it becomes a fully mature and fully functional mRNA molecule."}, {"title": "Types of RNA .txt", "text": "And one way by which we modify it is by removing the introns and splicing together gluing together the axons."}, {"title": "Types of RNA .txt", "text": "Now what the function of small nuclear RNA is is to basically splice together the exons to form that fully mature mRNA that can then be used by the ribosomes to basically synthesize that given polypeptide chain."}, {"title": "Types of RNA .txt", "text": "Now let's move on to microRNA or miRNA."}, {"title": "Types of RNA .txt", "text": "Now the reason we call this microRNA is because it's actually a very tiny RNA molecule."}, {"title": "Types of RNA .txt", "text": "It only consists of about 20 nucleotides and what it does is essentially binds onto the complementary mRNA molecule and it prevents it inhibits the process of translation so the synthesis of the polypeptide chain."}, {"title": "Types of RNA .txt", "text": "Now, what about Small RNA?"}, {"title": "Types of RNA .txt", "text": "Well small RNA is basically a constituent of this biological molecule found in a cytoplasm of our cells known as the signal recognition particle."}, {"title": "Types of RNA .txt", "text": "Now remember from biology the signal recognition particle is this complex that binds onto the protein that synthesize polypeptide chain and then brings it to its final destination be it in the cell or outside of cell."}, {"title": "Types of RNA .txt", "text": "So the small RNA molecule helps form the signal recognition particle that directs the synthesized protein to their intracellular or extracellular final destination."}, {"title": "Types of RNA .txt", "text": "Let's move on to small interfering RNA molecules or siRNA molecules."}, {"title": "Types of RNA .txt", "text": "And what these molecules do is they essentially bind onto the mRNA molecule and they stimulate the breakdown, the degradation of the messenger RNA molecule."}, {"title": "Types of RNA .txt", "text": "So remember we don't always want to synthesize a given protein inside our cells because first of all protein synthesis uses up a lot of ATP molecules."}, {"title": "Types of RNA .txt", "text": "And so if we have plenty of a given polypeptide in our cell we don't actually want to synthesize anymore."}, {"title": "Types of RNA .txt", "text": "So at times we want to break down our messenger RNA molecule and it's the small interfering RNA that helps break down and stimulate the breakdown of the messenger RNA molecule."}, {"title": "Types of RNA .txt", "text": "And finally, we also have something called telomerase RNA component."}, {"title": "Types of RNA .txt", "text": "Now, remember, inside eukaryotic cells we have these enzymes known as telomerase enzymes."}, {"title": "Types of RNA .txt", "text": "And what telomerase basically does is it regulates the ends of our DNA molecules."}, {"title": "Types of RNA .txt", "text": "So inside our cells, unlike in bacterial cells, inside our cells we have a linear DNA molecule and that means we have a beginning and we have an end."}, {"title": "Types of RNA .txt", "text": "And the two ends the sequences of nucleotides on the two ends of the DNA molecule are known as telomeres."}, {"title": "Types of RNA .txt", "text": "And every time we replicate our DNA molecule those telomeres have to be regulated and controlled and it's the telomerase enzyme that regulates and modifies these telomere ends."}, {"title": "Types of RNA .txt", "text": "And so the telomerase RNA molecule is a component of this telomerase and we'll discuss this in much more detail when we'll focus on the process of DNA replication."}, {"title": "Types of RNA .txt", "text": "So these are the different types of RNA molecules that exist inside our cells I'm sorry, RNA molecules that exist inside ourselves."}, {"title": "Bone Metabolism.txt", "text": "Human bone consists of living connective tissue."}, {"title": "Bone Metabolism.txt", "text": "And what that basically means is inside the bone we have living cells that continually undergo different types of processes."}, {"title": "Bone Metabolism.txt", "text": "Now, one very important type of process that takes place in the bone on a continual basis throughout the lifetime of the organism is a process known as bone metabolism or or bone remodeling."}, {"title": "Bone Metabolism.txt", "text": "Bone remodeling is the process by which specialized types of cells break down and rebuild the extracellular matrix that surrounds our cells inside the bone."}, {"title": "Bone Metabolism.txt", "text": "Now, there are two specialized types of cells that are involved in this process of bone remodeling."}, {"title": "Bone Metabolism.txt", "text": "We have osteoblasts and we have osteoclasts."}, {"title": "Bone Metabolism.txt", "text": "Now, osteoblasts are those cells that build the matrix of the bone."}, {"title": "Bone Metabolism.txt", "text": "These cells are capable of producing the protein collagen and releasing secreting this collagen into the extracellular matrix, where the organic component of the matrix consists predominantly of this protein collagen."}, {"title": "Bone Metabolism.txt", "text": "Now, on the other hand, these osteoblasts are also capable of creating the inorganic component of the matrix."}, {"title": "Bone Metabolism.txt", "text": "They can basically absorb the calcium as well as phosphate from the blood and deposit these ions onto the matrix in the form of crystals known as hydroxyapatite."}, {"title": "Bone Metabolism.txt", "text": "So remember, hydroxyapatite is the inorganic component of our matrix."}, {"title": "Bone Metabolism.txt", "text": "It consists of calcium phosphate and hydroxide."}, {"title": "Bone Metabolism.txt", "text": "So it's the collagen that gives our bone the ability to resist ten style forces."}, {"title": "Bone Metabolism.txt", "text": "But it's the hydroxy appetite that gives the bone the ability to resist compressive forces."}, {"title": "Bone Metabolism.txt", "text": "Now, this process of bone remodeling, so breaking down our bone and rebuilding our bone takes place during the lifetime of the organism and it also helps us rebuild our bones when we fracture those bones."}, {"title": "Bone Metabolism.txt", "text": "So let's discuss the different steps involved in this bone metabolism, bone remodeling process."}, {"title": "Bone Metabolism.txt", "text": "So let's begin with step A."}, {"title": "Bone Metabolism.txt", "text": "In step A, we basically have our resting bone."}, {"title": "Bone Metabolism.txt", "text": "We have the matrix of the bone, as shown."}, {"title": "Bone Metabolism.txt", "text": "So this is our bone."}, {"title": "Bone Metabolism.txt", "text": "We have the lining of the bone and these are the cells found on the lining of that bone."}, {"title": "Bone Metabolism.txt", "text": "Now, let's suppose we want to actually recruit certain cells, the osteoclast, to a certain location to break down that bone."}, {"title": "Bone Metabolism.txt", "text": "So we basically activate these osteoclasts, we recruit them and we signal exactly where we want our rebuilding process to take place."}, {"title": "Bone Metabolism.txt", "text": "Remodeling process to take place."}, {"title": "Bone Metabolism.txt", "text": "Let's suppose it's here."}, {"title": "Bone Metabolism.txt", "text": "So these osteoclasts children in red are activated, they're recruited and eventually they bind."}, {"title": "Bone Metabolism.txt", "text": "They attach onto the surface of this section, as shown in this diagram."}, {"title": "Bone Metabolism.txt", "text": "And as soon as the osteoclast attach, they begin the process of resorbing."}, {"title": "Bone Metabolism.txt", "text": "So they basically resorb our bone."}, {"title": "Bone Metabolism.txt", "text": "They break down the bone and release these constituents, such as calcium and phosphate, into our bloodstream."}, {"title": "Bone Metabolism.txt", "text": "So once resorption actually takes place and once we break down the bone, the matrix, what happens is these cells basically depart, they detach and move away while the osteoblasts shown in blue are now recruited and activated."}, {"title": "Bone Metabolism.txt", "text": "And these cells basically go on to attach to the same exact region where the resorption basically took place, as shown in this diagram."}, {"title": "Bone Metabolism.txt", "text": "And once they bind to that section, they begin to rebuild our bone by creating collagen secreting that collagen into this area, as well as absorbing the calcium and phosphate from the blood to create the hydroxy appetite."}, {"title": "Bone Metabolism.txt", "text": "And eventually, when some time passes, we basically fill this entire section up with the newly formed matrix."}, {"title": "Bone Metabolism.txt", "text": "So this consists of our hydroxy appetite, which is the dominant portion of the inorganic component of the matrix, as well as the collagen protein, which is the dominant portion of the organic component of that matrix."}, {"title": "Bone Metabolism.txt", "text": "And once these osteoblasts form our matrix, they can basically differentiate into our cells, known as osteocides, as shown in that diagram."}, {"title": "Bone Metabolism.txt", "text": "So these are the processes that are involved in the process of bone remodeling that takes place inside the bone on a continuous basis throughout the entire lifetime of our organism."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Glycolysis is the process by which we transform glucose into pyruvate molecules and other types of molecules such as ATP, NADH, water and H plus ions."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, glycolysis takes place in the cytosol of the cell, in the fluid portion of the cytoplasm of the cell."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And glycolysis is an anaerobic process, which means it takes place in the presence or in the absence of oxygen."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So for one glucose that basically is broken down in glycolysis, we produce two pyruvate molecules, as shown in this region."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, once these pyruvates are formed, they are present in the cytosol."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And if we have oxygen present in the cell, the cell can basically undergo a process known as cellular respiration."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So if the cell contains oxygen and it commits to cellular respiration, these two pyruvate molecules are then transported into the mitochondrial matrix of the mitochondrion inside that cell."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So let's say this is the cytoplasm of the cell."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "This is the mitochondrion, which contains the outer membrane, the inner membrane."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "We have the intermembrane space and we have the mitochondrial space."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, if our cell commits to cellular respiration in the presence of oxygen, these two pyruvates are transported via specialized proteins known as integral proteins."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So we have integral proteins on the outer membrane and integral proteins on the inner membrane, shown in green."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And these pyruvates are basically transported via these membranes into the mitochondrial matrix of this mitochondrion found inside that cell."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, once our pyruvate molecules are inside the mitochondrial matrix, they will undergo a process known as oxidative decarboxylation, and this process is known as pyruvate decarboxylation."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So basically, three enzymes joined together to form an enzyme complex known as pyruvate dehydrogenase complex."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And what this complex basically does is it takes the pyruvate, it uses two Cofactors, one NAD plus and one coenzyme A, or simply COA, to transform the pyruvate into acetyl coenzyme A."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So basically, the pyruvate is decarboxylated to produce our Co to the carbon dioxide."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And then the remaining two carbon molecule mixes with the coenzyme A to produce acetyl coenzyme A."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And we also reduce our NAD into NADH and we form the hion."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So basically, these are the products and these are the reactants of the pyruvate decarboxylation process that takes place within the mitochondrial matrix."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, because we form two pyruvate molecules, when we break down one glucose, these two pyruvate molecules will both undergo the decarboxylation reaction."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "And so this reaction will take place twice per a single glucose molecule."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So actually, the products are these products multiplied by two."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So we have two acetylco enzymes A, two CO2 molecules, two Nadhs, and two H plus ions."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, what exactly is the purpose of pyruvate decarboxylation?"}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Well, basically, it links it connects the process of glycolysis and the citric acid cycle that also takes place within the mitochondrion, which we'll discuss in detail in the next lecture."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "So pyruvate decarboxylation is the link between glycolysis and the citric acid cycle, and it produces an important molecule known as acetylco enzyme A that is used as the fuel source in the citric acid cycle."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, one last point that I want to emphasize is the following."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Now, Pyruvate decarboxylation does not actually need oxygen to take place."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "Meaning, there's no oxygen in the reacting or the product portion of this pyruvate decarboxylation."}, {"title": "Pyruvate Decarboxylation Reaction .txt", "text": "But even though this reaction doesn't actually use oxygen directly, this pyruvate is only transported into the mitochondria hydro matrix if there is oxygen present in the cell."}, {"title": "Introduction to Endocrine System .txt", "text": "In order for multicellular organisms to actually function effectively and efficiently the individual cells must be able to communicate with one another and this is known as intracellular communication."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the way that our cells communicate with one another is via chemicals via special types of molecules."}, {"title": "Introduction to Endocrine System .txt", "text": "So a single cell can basically release a chemical."}, {"title": "Introduction to Endocrine System .txt", "text": "The chemical kill can travel to a different cell and create some type of change in that cell so it can activate that cell or in some cases, it can inhibit that cell."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, we actually already spoke about one type of communications system."}, {"title": "Introduction to Endocrine System .txt", "text": "We discussed the nervous system of the human body and the nervous system uses a special type of chemical known as the neurotransmitter in intracellular communication."}, {"title": "Introduction to Endocrine System .txt", "text": "So the neurotransmitter basically travels over a very short distance basically across the synapse between the neuron and our adjacent cell."}, {"title": "Introduction to Endocrine System .txt", "text": "And the neurotransmitter basically only binds to specific cells and it creates a very quick and rapid response."}, {"title": "Introduction to Endocrine System .txt", "text": "But this response is relatively short lived."}, {"title": "Introduction to Endocrine System .txt", "text": "It only takes place over several seconds."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, we're going to discuss a different type of system."}, {"title": "Introduction to Endocrine System .txt", "text": "Our communication system in the body known as the endocrine system."}, {"title": "Introduction to Endocrine System .txt", "text": "And the endocrine system creates a special type of chemical known as a hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the hormone is released by the cell into the bloodstream or into the lymph system and the hormone, unlike the neurotransmitter actually travels over a very long distance throughout the entire body before it actually affects the target cell."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, neurotransmitters are very specific to the type of cell that they bind to but hormones are not that specific."}, {"title": "Introduction to Endocrine System .txt", "text": "That means they can bind to many different types of cells and some of these cells can be affected in an activating manner whilst other cells can basically be inhibited by that same hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "So unlike neurotransmitters which basically acts over very short distances and act very quickly and are short lived our hormones travel over very long distances."}, {"title": "Introduction to Endocrine System .txt", "text": "They act relatively slowly so over hours or days or even longer and they basically can infect the organism over long term."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the endocrine system consists of special types of glands that produce our hormones."}, {"title": "Introduction to Endocrine System .txt", "text": "These are known as endocrine glands."}, {"title": "Introduction to Endocrine System .txt", "text": "Endocrine glands basically means our hormones are released into the bloodstream ore into our lymph system."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, this is in contrast to a different type of system that uses different types of glands."}, {"title": "Introduction to Endocrine System .txt", "text": "This system is known as the exocrine system and it uses exocrine glands."}, {"title": "Introduction to Endocrine System .txt", "text": "These axocrine glands basically release the chemicals into our ducts and these ducts carry these chemicals into the external environment."}, {"title": "Introduction to Endocrine System .txt", "text": "And one example of an exocrine gland is the sweat gland also known as our pseudoriferous gland."}, {"title": "Introduction to Endocrine System .txt", "text": "And the pseudoriferous gland basically creates sweat."}, {"title": "Introduction to Endocrine System .txt", "text": "It releases the sweat through a duck and onto our skin so onto our external environment."}, {"title": "Introduction to Endocrine System .txt", "text": "So this is basically exocrine glands but endocrine glands are found in the endocrine system."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, before we discuss the different types of hormones that are produced by the endocrine glands."}, {"title": "Introduction to Endocrine System .txt", "text": "Let's discuss the three ways by which our cells can basically communicate with one another using chemicals, using molecules."}, {"title": "Introduction to Endocrine System .txt", "text": "Now we basically have an autocrine signaling pathway, we have a paracrine signaling pathway and we have the endocrine signaling pathway that is used by the endocrine system."}, {"title": "Introduction to Endocrine System .txt", "text": "Now an autocrine signaling basically means that our cell produces some type of chemical."}, {"title": "Introduction to Endocrine System .txt", "text": "That cell releases that chemical into the extracellular fluid and then that chemical binds onto that same cell that release that chemical and creates some type of change."}, {"title": "Introduction to Endocrine System .txt", "text": "And some examples of this will be seen in the immune system when we'll discuss the immune system of the human body."}, {"title": "Introduction to Endocrine System .txt", "text": "Now the second type of signaling pathway is our paracrine signaling pathway."}, {"title": "Introduction to Endocrine System .txt", "text": "And in this case, our cell creates a chemical."}, {"title": "Introduction to Endocrine System .txt", "text": "That chemical is released into the extracellular fluid and then that chemical travels to nearby cells, to cells found in close proximity and affects those cells."}, {"title": "Introduction to Endocrine System .txt", "text": "And one example of such a chemical is the prostaglandin."}, {"title": "Introduction to Endocrine System .txt", "text": "And we'll discuss these chemicals in detail when we'll discuss these in the next several lectures."}, {"title": "Introduction to Endocrine System .txt", "text": "Now the final type of pathway is our endocrine signaling pathway."}, {"title": "Introduction to Endocrine System .txt", "text": "This is the pathway that is actually used by the endocrine system."}, {"title": "Introduction to Endocrine System .txt", "text": "In this pathway the cell creates our chemical, the hormone and releases it into the bloodstream or the lymph system."}, {"title": "Introduction to Endocrine System .txt", "text": "And then that hormone travels over a very long distance, it circulates in our blood before it actually binds onto our target cell and affects that target cell in some way or form."}, {"title": "Introduction to Endocrine System .txt", "text": "So the endocrine system uses the endocrine signaling pathway."}, {"title": "Introduction to Endocrine System .txt", "text": "It contains endocrine glands that synthesize our hormones."}, {"title": "Introduction to Endocrine System .txt", "text": "But how many hormones do we have?"}, {"title": "Introduction to Endocrine System .txt", "text": "Well, we have many different hormones and all these different types of hormones that we're going to discuss in the next several lectures can be broken down into three categories."}, {"title": "Introduction to Endocrine System .txt", "text": "We have peptide hormones that are formed from proteins, we have our steroid hormones that are formed from cholesterol and we have tyrosine derivative hormones that are formed from tyrosine amino acids."}, {"title": "Introduction to Endocrine System .txt", "text": "So let's discuss these three different types of hormones."}, {"title": "Introduction to Endocrine System .txt", "text": "Let's begin with our peptide hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "So the peptide hormone is formed in the rough endoplasm reticulum of our cell and then moves on to the Golgi apparatus."}, {"title": "Introduction to Endocrine System .txt", "text": "Inside the Golgi complex, the peptide hormone can basically be modified in some way or form."}, {"title": "Introduction to Endocrine System .txt", "text": "For example, we can add a sugar component onto the peptide hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, once we modify the peptide hormone, it travels into our bloodstream or into our lymph system."}, {"title": "Introduction to Endocrine System .txt", "text": "And because the bloodstream consists predominantly of water and because our peptide hormone is made from peptide, that means peptide hormones are water soluble."}, {"title": "Introduction to Endocrine System .txt", "text": "And that means they can easily dissolve inside the bloodstream and do not actually need to use any type of carrier protein."}, {"title": "Introduction to Endocrine System .txt", "text": "So these peptide hormones can travel in the bloodstream by themselves."}, {"title": "Introduction to Endocrine System .txt", "text": "Now eventually these peptide hormones will arrive at the target cell."}, {"title": "Introduction to Endocrine System .txt", "text": "Now these peptide hormones are water soluble, they are not lipid soluble."}, {"title": "Introduction to Endocrine System .txt", "text": "And that means they cannot actually pass across the plasma membrane of the target cell because the plasma membrane is made predominantly of hydrophobic tails of hydrophobic fatty acids."}, {"title": "Introduction to Endocrine System .txt", "text": "So that basically means peptide hormones bind on to receptor proteins found on the plasma membrane of the target cell."}, {"title": "Introduction to Endocrine System .txt", "text": "And once they bind, they can create some type of change."}, {"title": "Introduction to Endocrine System .txt", "text": "For example, they can open up a channel protein that will change an ion concentration, or they can basically use some type of secondary messenger system that uses some type of secondary messenger, such as cyclic amp, to create some form of change."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the second type of hormone that we're going to discuss is our steroid hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the steroid hormone is basically synthesized from cholesterol or from some type of lipid."}, {"title": "Introduction to Endocrine System .txt", "text": "And now steroid hormone is synthesized either in the smooth endoplastic reticulum or in the mitochondria of the cell."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, steroid hormones are lipid soluble, and that means they cannot dissolve in the blood."}, {"title": "Introduction to Endocrine System .txt", "text": "And so they actually require carrier proteins to carry them to their target cell."}, {"title": "Introduction to Endocrine System .txt", "text": "So once inside the bloodstream, the steroid hormones need carrier proteins."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, once these steroid hormones actually arrive at a target cell, they can easily transport themselves."}, {"title": "Introduction to Endocrine System .txt", "text": "They can easily move across the cell membrane, and that's because these are lipid soluble."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, once inside a cytosol of our cell, these steroid hormones will basically bind onto receptor proteins found in a cytosol."}, {"title": "Introduction to Endocrine System .txt", "text": "And then the receptor protein hormone complex can then travel into the nucleus of our cell."}, {"title": "Introduction to Endocrine System .txt", "text": "And once inside the nucleus, the steroid hormone can basically create or induce some type of transcriptional change."}, {"title": "Introduction to Endocrine System .txt", "text": "So that means it can basically induce the synthesis of certain proteins that are needed by the cell at that given moment in time."}, {"title": "Introduction to Endocrine System .txt", "text": "Now, the final type of hormone we're going to discuss is our tyrosine derivative hormone, or simply the tyrosine hormone."}, {"title": "Introduction to Endocrine System .txt", "text": "So the tyrosine hormone is a type of hormone that is synthesized either in the cytosol by special types of enzymes or in the rough and the plasmic reticula."}, {"title": "Introduction to Endocrine System .txt", "text": "So these protein or these hormones can basically either be water soluble, in which case they do not need any type of carrier protein in the bloodstream, and they bind on to receptor proteins on the plasma membrane of the target cell."}, {"title": "Introduction to Endocrine System .txt", "text": "Or they can also be lipid soluble, in which case they bind to receptors in the nucleus of that cell and they create some type of transcription change."}, {"title": "Introduction to Endocrine System .txt", "text": "So these are the three different types of hormones."}, {"title": "Introduction to Endocrine System .txt", "text": "We have three categories."}, {"title": "Introduction to Endocrine System .txt", "text": "We have peptide hormones, steroid hormones, and tyrosine hormones that are used by the endocrine system of our bodies."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "Will be expressed more on the membrane, and that will ensure that the liver cells and kidney cells can uptake all that glucose from the blood."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "So insulin helps express proteins such as phosphor, fructose, pyruvate kinase and glucose and glucose transporter."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "So remember that in Glycolysis, phosphorokinase transforms the fructosex phosphate into fructose One six bisphosate and Pyruvate."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "Clinades transforms the phosphorino Pyruvate into the Pyruvate molecule to also form ATP."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "And glucose transporters such as Glute four are basically those glucose transporter proteins found in cells such as muscle cells, for instance."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "And if we express more of these transporters, that means the high blood glucose levels will decrease back to normal because the cells are going to be able to actually uptake those glucose molecules back into the cytoplasm of the cell."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "Now, Glucagon essentially reciprocates, reverses what insulin does."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "Glucagon, on the other hand, essentially inhibits the expression of phosphorptokinase and pyruvate kinase because it inhibits glycolysis and it helps express those proteins involved in gluconeogenesis."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "So proteins such as fructose One six bisphosphatase and phosphateenopyruvate carboxy kinase."}, {"title": "Regulation of Glucose in Blood Part II .txt", "text": "So this is how the liver and kidney cells actually regulate the process of glycolysis and gluconeogenesis to maintain and regulate the blood level, the blood glucose level in our body."}, {"title": "Cell Determination and Differentiation.txt", "text": "Within the dull human organism, we have billions upon billions of individual cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "And on top of that, we have over 200 different types of cells that each carry out their own specific function which have their own specific role in our body."}, {"title": "Cell Determination and Differentiation.txt", "text": "For example, one specialized type of cell is a neuron."}, {"title": "Cell Determination and Differentiation.txt", "text": "A neuron propagates electrical signals and allows communication to take place between different types of cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "And we have many examples of these specialized cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now that's pretty fascinating because if we go way back to the beginning of embryological development when we first form that zygote, the zygote is actually only a single cell and it is not specialized in any way whatsoever."}, {"title": "Cell Determination and Differentiation.txt", "text": "Yet that zygote somehow knows to divide and somehow knows to form the different types of cells that exist within our adult human body."}, {"title": "Cell Determination and Differentiation.txt", "text": "So the question we're going to address in this lecture is how exactly does an unspecialized cell know to begin a certain set of processes that eventually allows it to form a special type of cell?"}, {"title": "Cell Determination and Differentiation.txt", "text": "So how does an unspecialized cell know, for example, to form a muscle cell and not a nerve cell?"}, {"title": "Cell Determination and Differentiation.txt", "text": "So these are the questions we're going to address in this lecture."}, {"title": "Cell Determination and Differentiation.txt", "text": "So let's begin with the zygote stage."}, {"title": "Cell Determination and Differentiation.txt", "text": "So when we form the zygote, the next step that happens is mitosis and the zygote begins to divide."}, {"title": "Cell Determination and Differentiation.txt", "text": "So it forms this two cell embryo stage where we have two identical cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "This process continues."}, {"title": "Cell Determination and Differentiation.txt", "text": "We form four cells, eight cells, 16 cells, 32 cells and so on and so on until we form the billions of cells that are found inside the individual organism."}, {"title": "Cell Determination and Differentiation.txt", "text": "So now in the stage of the zygote and the two cell embryo stage, these cells are said to be totipotent."}, {"title": "Cell Determination and Differentiation.txt", "text": "And what that means is they have a great deal of potential and they can form any and all the cells that make up that adult human organism."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, as the process of development continues, as the cells continue to divide and grow, their potential decreases and eventually their cellphate becomes determined."}, {"title": "Cell Determination and Differentiation.txt", "text": "And this process is known as cell determination."}, {"title": "Cell Determination and Differentiation.txt", "text": "So cell determination is the process by which a given unspecialized cell chooses the pathway that is going to follow, which eventually will lead it to forming a special type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So this means that its cell fate is completely determined following cell determination."}, {"title": "Cell Determination and Differentiation.txt", "text": "And now it will follow a certain specific set of processes that will eventually lead it to forming that specialized type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So, to see what we mean, let's take a look at the following diagram."}, {"title": "Cell Determination and Differentiation.txt", "text": "So let's suppose we have some type of unspecialized cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So when this unspecialized cell undergoes cell determination, what happens is now it basically knows to follow a certain set of steps that will eventually allow it to form a specialized type of cell such as a neuron."}, {"title": "Cell Determination and Differentiation.txt", "text": "And these steps, following cell determination that allows it to form that specialized cell is known as cell differentiation."}, {"title": "Cell Determination and Differentiation.txt", "text": "So before cell differentiation can take place, cell determination has to occur."}, {"title": "Cell Determination and Differentiation.txt", "text": "So first it's cell determination followed by cell differentiation."}, {"title": "Cell Determination and Differentiation.txt", "text": "And that's when we form that specialized type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, a good analogy to this is the way that we choose our careers."}, {"title": "Cell Determination and Differentiation.txt", "text": "So we know at the early stage of a person's life before they begin school, they have the potential to become any professional."}, {"title": "Cell Determination and Differentiation.txt", "text": "So they can become a physician, they can become a nurse, they can become a police officer, a banker, a quantitative analyst."}, {"title": "Cell Determination and Differentiation.txt", "text": "So basically at the early stages of our lives, we are totipotent."}, {"title": "Cell Determination and Differentiation.txt", "text": "However, when we begin school and eventually when we get to college, in college, we have to choose our major."}, {"title": "Cell Determination and Differentiation.txt", "text": "And once we choose our major, we basically determine the pathway that we're going to follow."}, {"title": "Cell Determination and Differentiation.txt", "text": "And that pathway will eventually lead us to a certain type of career."}, {"title": "Cell Determination and Differentiation.txt", "text": "And in an analogous way, at the early stages of life, at the early stages those cells are totipotent."}, {"title": "Cell Determination and Differentiation.txt", "text": "They can become any cell whatsoever."}, {"title": "Cell Determination and Differentiation.txt", "text": "But as the process of development continues, eventually cell determination takes place."}, {"title": "Cell Determination and Differentiation.txt", "text": "They choose their majors and eventually they undergo these set of processes called cell differentiation that allows them to become that nerve cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So cell differentiation, for example, is analogous to a person choosing the pre medical path and then following a certain set of processes taking the prerequisite courses, taking the MCAT, volunteering, applying to medical school, going to medical school, and so forth."}, {"title": "Cell Determination and Differentiation.txt", "text": "And these processes eventually allow that person to differentiate into that physician."}, {"title": "Cell Determination and Differentiation.txt", "text": "So these are the two processes that must take place before that specialized cell is actually produced."}, {"title": "Cell Determination and Differentiation.txt", "text": "So next, let's discuss something called differential gene expression."}, {"title": "Cell Determination and Differentiation.txt", "text": "So what exactly is differential gene expression?"}, {"title": "Cell Determination and Differentiation.txt", "text": "Well, differential gene expression is actually what allows a cell that has been determined to produce that specialized type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So let's suppose we have the following diagram."}, {"title": "Cell Determination and Differentiation.txt", "text": "So in this diagram we have an unspecialized cell that undergoes cell determination and that process chooses pathway one."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now we have a second type of unspecialized cell and the same type of cell is here."}, {"title": "Cell Determination and Differentiation.txt", "text": "But this cell chooses pathway number two."}, {"title": "Cell Determination and Differentiation.txt", "text": "So pathway number one leads to a neuron while pathway number two leads to a skeletal muscle cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So what exactly is the difference between pathway one and pathway two?"}, {"title": "Cell Determination and Differentiation.txt", "text": "Well, before we answer that question, let's examine what the difference is between a neuron and a skeletal muscle."}, {"title": "Cell Determination and Differentiation.txt", "text": "So the most evident difference is the types of components and structures found within these two different types of cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "So the neuron contains an axon, it contains dendrites, it contains the axon hillock, it contains the axon terminal, while the skeletal muscle contains a specialized type of cell membrane known as the sarcolema."}, {"title": "Cell Determination and Differentiation.txt", "text": "It contains a specialized type of endoplasma take limb known as the sarcoplasma taylor."}, {"title": "Cell Determination and Differentiation.txt", "text": "It also contains these long fibers made of actin as well as myosin."}, {"title": "Cell Determination and Differentiation.txt", "text": "So what differentiates these two cells or any two specialized cells for that matter is the presence of different types of structures and components inside those cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "So it's those components that give these specialized cells their specific and unique characteristics."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, all these different components are actually either formed by proteins or they are composed of proteins."}, {"title": "Cell Determination and Differentiation.txt", "text": "And proteins come from DNA."}, {"title": "Cell Determination and Differentiation.txt", "text": "So remember, inside the DNA we have genes and the genes actually code for the proteins."}, {"title": "Cell Determination and Differentiation.txt", "text": "So what differentiates pathway one from pathway two is the type of genes that are expressed and the type of proteins that are formed."}, {"title": "Cell Determination and Differentiation.txt", "text": "So this is known as differential gene expression."}, {"title": "Cell Determination and Differentiation.txt", "text": "So it's differential gene expression that allows cell one to follow pathway to and form a neuron while cell two follows pathway two to form a skeleton muscle cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So it's differential gene expression that allows cell differentiation to actually take place."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, what about cell determination?"}, {"title": "Cell Determination and Differentiation.txt", "text": "What exactly is the mechanism by which cell determination actually takes place?"}, {"title": "Cell Determination and Differentiation.txt", "text": "What is the mechanism by which that cell chooses that major to follow and then follows that major to produce that specialized type of cell?"}, {"title": "Cell Determination and Differentiation.txt", "text": "Well, in most cases cellular determination is due to a process known as inductive signaling that takes place between cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, during inductive signaling one cell produces a special type of inductive signal, a molecule known as a ligand."}, {"title": "Cell Determination and Differentiation.txt", "text": "And that ligand moves on to a second cell and it influences the second cell to basically choose that major to begin following a specific type of instruction set of instructions, that is cell differentiation to basically produce a special type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, we have three mechanisms of inductive signaling."}, {"title": "Cell Determination and Differentiation.txt", "text": "We have one called diffusion, one called direct contact and the other one called gap junctions."}, {"title": "Cell Determination and Differentiation.txt", "text": "So let's begin with diffusion."}, {"title": "Cell Determination and Differentiation.txt", "text": "So in diffusion, what happens is one cell that is next to another cell begins to produce a special type of ligand molecule and that molecule diffuses across the cell membrane into the extracellular matrix and eventually this ligand moves on to a nearby cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "It attaches onto a special protein receptor found on the membrane and by attaching it creates some type of secondary mechanism response."}, {"title": "Cell Determination and Differentiation.txt", "text": "And so let's say some type of part of that protein on the other side basically detaches and then creates a secondary metric system that eventually influences the transcription and the translational process of that cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "And that allows the production of specific types of proteins that eventually lead to forming the specific type of components and structures that are found within those specialized cells."}, {"title": "Cell Determination and Differentiation.txt", "text": "So this is mechanism one of inductive signaling that allows cell determination to actually take place."}, {"title": "Cell Determination and Differentiation.txt", "text": "Now, mechanism number two is direct contact."}, {"title": "Cell Determination and Differentiation.txt", "text": "So in this case it was a ligand that was produced by one cell and moved to a second cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "In this case, those cells actually physically interact."}, {"title": "Cell Determination and Differentiation.txt", "text": "So what happens is a protein on one cell interacts with the protein on the membrane of the other cell and when they bind by binding, that initiates the creation of some type of internal signal."}, {"title": "Cell Determination and Differentiation.txt", "text": "And then what that signal does is it alters the gene expression of that cell and that ultimately determines what type of pathway that cell will follow and what type of cell it will actually produce."}, {"title": "Cell Determination and Differentiation.txt", "text": "And finally, we have gap junctions."}, {"title": "Cell Determination and Differentiation.txt", "text": "So some cells are actually physically connected to one another via special type of junction known as a gap junction."}, {"title": "Cell Determination and Differentiation.txt", "text": "And so in this case, what happens, one of the cells produces some type of signal."}, {"title": "Cell Determination and Differentiation.txt", "text": "That signal moves along this gap junction and into the second cell and it influences the nearby cell to determine its pathway."}, {"title": "Cell Determination and Differentiation.txt", "text": "And eventually that will lead to a specific type of set of pathways."}, {"title": "Cell Determination and Differentiation.txt", "text": "So cell differentiation and it will form some specialized type of cell."}, {"title": "Cell Determination and Differentiation.txt", "text": "So these are the three mechanisms by which inductive signaling takes place which allows that cell to actually determine the fate of that cell, the pathway it will follow to produce some specialized type of cell."}, {"title": "Overview of Glycolysis .txt", "text": "In the previous several lectures, we discussed the details of the three stages of glycolysis."}, {"title": "Overview of Glycolysis .txt", "text": "So now it's actually put all that information together into a single lecture to actually try to make sense of things."}, {"title": "Overview of Glycolysis .txt", "text": "And let's summarize our results."}, {"title": "Overview of Glycolysis .txt", "text": "So glycolysis is the breakdown of glucose into pyruvate molecules, ATP molecules and NADH molecules."}, {"title": "Overview of Glycolysis .txt", "text": "And all this takes place in the cytoplasm of the cell."}, {"title": "Overview of Glycolysis .txt", "text": "Now, we typically break down glycolysis into three stages."}, {"title": "Overview of Glycolysis .txt", "text": "We have stage one that consists of three steps."}, {"title": "Overview of Glycolysis .txt", "text": "We have stage two that consists of two steps."}, {"title": "Overview of Glycolysis .txt", "text": "And we have the most complex stage, stage three, that consists of five steps."}, {"title": "Overview of Glycolysis .txt", "text": "Now, the reason we break down glycolysis into these three stages is because each one of these stages actually carries out its own specific purpose."}, {"title": "Overview of Glycolysis .txt", "text": "It has its own specific purpose, it carries out a specific function."}, {"title": "Overview of Glycolysis .txt", "text": "So let's begin with stage one."}, {"title": "Overview of Glycolysis .txt", "text": "In stage one, the entire point of stage one is to take that glucose molecule, trap that glucose molecule inside a cell so that it can't actually leave that cell, and begin preparing that glucose molecule for cleavage, which takes place in stage two."}, {"title": "Overview of Glycolysis .txt", "text": "So the entire point of stage one is to prepare that molecule for stage two where it basically is cleaved into two identical three carbon molecules."}, {"title": "Overview of Glycolysis .txt", "text": "And once it is cleaved in stage two, it's the third stage where we harvest some of that energy, we capture some of that energy to form ATP molecules, as we'll see in just a moment."}, {"title": "Overview of Glycolysis .txt", "text": "So as we discuss each one of these individual processes, keep that in mind because ultimately, for instance, in stage one, each one of these reactions takes place and each one of these reactions essentially wants to accomplish that end goal."}, {"title": "Overview of Glycolysis .txt", "text": "So each one of these reactions in stage one wants to trap that molecule in the cell and wants to destabilize the molecule, make it more reactive so that eventually it is prepared for stage two to break down into smaller molecules."}, {"title": "Overview of Glycolysis .txt", "text": "So let's begin with stage one, process one, step one."}, {"title": "Overview of Glycolysis .txt", "text": "So our glucose makes its way into the cyto plasma in the cell."}, {"title": "Overview of Glycolysis .txt", "text": "What happens is an enzyme known as hexokinase."}, {"title": "Overview of Glycolysis .txt", "text": "HEXO means we have 123456 carbons in our sugar kinase, means we're going to phosphorylate that glucose."}, {"title": "Overview of Glycolysis .txt", "text": "So a phosphoryl group is taken from the ATP by the hexokinase and is added onto carbon number six."}, {"title": "Overview of Glycolysis .txt", "text": "And so we form glucose phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "We break down the ATP into ATP and also the H ion is released as well."}, {"title": "Overview of Glycolysis .txt", "text": "And this reaction releases this amount of energy."}, {"title": "Overview of Glycolysis .txt", "text": "So it's an exergonic reaction."}, {"title": "Overview of Glycolysis .txt", "text": "That's because the ATP is broken down into a more stable molecule and that drives this exergonic reaction."}, {"title": "Overview of Glycolysis .txt", "text": "Now, the point of this step is to one destabilize the glucose to make it more reactive and begin preparing it for stage two."}, {"title": "Overview of Glycolysis .txt", "text": "And the second point is, by adding this polar component, we trap that glucose in a cell, it will not be able to exit that cell because one, it can't pass the membrane and B, it cannot use any of those transport membrane proteins because its structure is different."}, {"title": "Overview of Glycolysis .txt", "text": "Now let's move on to step two."}, {"title": "Overview of Glycolysis .txt", "text": "In step two, the goal is to basically take that glucose phosphate and transform it into an isomer, into fructose six phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "Why?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, because in stage two we basically want to produce two identical three carbon molecules."}, {"title": "Overview of Glycolysis .txt", "text": "And to produce those two identical three carbon molecules, we have to have symmetry in our molecules."}, {"title": "Overview of Glycolysis .txt", "text": "So this is not symmetric, but this is symmetric."}, {"title": "Overview of Glycolysis .txt", "text": "And so the glucose six phosphate is transformed into fructose six phosphate to make sure we get those two identical three carbon molecules in stage two."}, {"title": "Overview of Glycolysis .txt", "text": "So you might ask, well if I keep this molecule in the glucose six phosphate stage, what will happen in stage two?"}, {"title": "Overview of Glycolysis .txt", "text": "Well if we keep it in the glucose, then in stage two we're going to form one molecule that has two carbons and one molecule that has four carbons and that is not symmetric."}, {"title": "Overview of Glycolysis .txt", "text": "So that's why we carry out step two."}, {"title": "Overview of Glycolysis .txt", "text": "Again, the entire goal in stage one is to prepare that glucose for cleavage which happens in stage two."}, {"title": "Overview of Glycolysis .txt", "text": "And the enzyme that catalyzes this, well this is an isomerization reaction."}, {"title": "Overview of Glycolysis .txt", "text": "We transform one isomer into another and this molecule is a glucose that contains a phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "And so phosphor glucose isomerate."}, {"title": "Overview of Glycolysis .txt", "text": "So makes sense."}, {"title": "Overview of Glycolysis .txt", "text": "And again just like this one, this is an exergonic reaction."}, {"title": "Overview of Glycolysis .txt", "text": "It takes place spontaneously under physiological conditions."}, {"title": "Overview of Glycolysis .txt", "text": "Let's look at step three."}, {"title": "Overview of Glycolysis .txt", "text": "So the point of step three is to continue destabilizing that molecule."}, {"title": "Overview of Glycolysis .txt", "text": "So in step one we destabilized it, increased its energy and made it more reactive because we made it more polar, we added a charge and here we add a second charge and that makes it even more reactive and more likely to actually undergo cleavage in stage two."}, {"title": "Overview of Glycolysis .txt", "text": "So we take the fructose six phosphate and again, because we want to add a pisphory root, what type of enzyme are we going to have?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, a kinase."}, {"title": "Overview of Glycolysis .txt", "text": "What type of kinase?"}, {"title": "Overview of Glycolysis .txt", "text": "Well what type of molecule is this?"}, {"title": "Overview of Glycolysis .txt", "text": "It's a fructose that contains a phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "So phosphoructose kinase, phosphorylates this process and adds that phosphoryl group onto this oxygen."}, {"title": "Overview of Glycolysis .txt", "text": "And now we have asymmetrical molecule."}, {"title": "Overview of Glycolysis .txt", "text": "And once the cleavage takes place in stage two, that will ultimately allow us to produce two, three carbon molecules."}, {"title": "Overview of Glycolysis .txt", "text": "And notice this stage one, because we're essentially investing to prepare that molecule for cleavage, we actually use energy molecules, we use one two ATP molecules in stage one."}, {"title": "Overview of Glycolysis .txt", "text": "That's why we call this the investment stage."}, {"title": "Overview of Glycolysis .txt", "text": "Now stage two we call the cleavage state because this is where we break down this molecule that we form in stage one."}, {"title": "Overview of Glycolysis .txt", "text": "So we take the fructose one six bisphosphates and under the guidance of an enzyme called aldolase."}, {"title": "Overview of Glycolysis .txt", "text": "Why?"}, {"title": "Overview of Glycolysis .txt", "text": "Aldalase well because this is an aldol reaction and in fact going backwards is an aldol condensation."}, {"title": "Overview of Glycolysis .txt", "text": "And so that's why we call this an aldolase."}, {"title": "Overview of Glycolysis .txt", "text": "So essentially what the aldalase does is it cleans the the bond here and it forms these two, three carbon molecules."}, {"title": "Overview of Glycolysis .txt", "text": "So again, the entire point of this step was to basically create the isomer so that once this process takes place, we produce two, three carbon molecules, and not a two carbon and a four carbon molecule."}, {"title": "Overview of Glycolysis .txt", "text": "So we have two, three carbon molecules."}, {"title": "Overview of Glycolysis .txt", "text": "One of them is DHAP, which stands for dihydroxy acetone phosphate, and the other one is Gap, which stands for glycerol dehyd three phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "Now, this molecule is the one that will go on to stage three."}, {"title": "Overview of Glycolysis .txt", "text": "So once we form this gap, it doesn't do anything else, but the DHAP doesn't lie directly on the path of glycolysis."}, {"title": "Overview of Glycolysis .txt", "text": "And so what we have to do is we have to take this molecule and we have to transform it into this molecule."}, {"title": "Overview of Glycolysis .txt", "text": "Now, just like glucose is an isomer to fructose, DHAP is an isomer to gap because both of these are triosis and a trios is a three carbon sugar."}, {"title": "Overview of Glycolysis .txt", "text": "So we have one, two, three carbons, one, two, three carbons."}, {"title": "Overview of Glycolysis .txt", "text": "Both of these are triosis."}, {"title": "Overview of Glycolysis .txt", "text": "So again, we have to depend on an enzyme called isomerase."}, {"title": "Overview of Glycolysis .txt", "text": "What type of isomerase?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, trios phosphate, isomerase trios, because these are triosis and they contain phosphate groups, one each."}, {"title": "Overview of Glycolysis .txt", "text": "And so trio's, phosphate, isomerase basically converts this DHAP, the dihydroxy acetone phosphate, into the glyceroaldehyde three phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "And once stage two takes place, we essentially took so the net result of stage two is we took the fructose one six bisphosphate and we cleaved it into two identical three carbon molecules, these gap molecules."}, {"title": "Overview of Glycolysis .txt", "text": "So let's move on to stage three."}, {"title": "Overview of Glycolysis .txt", "text": "So essentially, in this stage, I've only listed the reactions for a single gap molecule."}, {"title": "Overview of Glycolysis .txt", "text": "But you should know that all these steps actually take place twice because we have these two molecules that were formed in stage two."}, {"title": "Overview of Glycolysis .txt", "text": "So let's move on to stage three."}, {"title": "Overview of Glycolysis .txt", "text": "So remember, this is our investment stage."}, {"title": "Overview of Glycolysis .txt", "text": "We invest energy to prepare it for the cleavage."}, {"title": "Overview of Glycolysis .txt", "text": "Once we cleave it, we basically go on to stage three."}, {"title": "Overview of Glycolysis .txt", "text": "And this is where we're actually going to produce those ATP molecules and Pyruvate molecules."}, {"title": "Overview of Glycolysis .txt", "text": "So the entire goal here is to basically destabilize the molecule and eventually create a molecule that contains a high potential to transfer for sporal groups."}, {"title": "Overview of Glycolysis .txt", "text": "And we'll see why that's important."}, {"title": "Overview of Glycolysis .txt", "text": "Just a moment."}, {"title": "Overview of Glycolysis .txt", "text": "So let's take a look at step six."}, {"title": "Overview of Glycolysis .txt", "text": "So in step six, what we basically want to do is we want to transform the gap molecule into one three BPG."}, {"title": "Overview of Glycolysis .txt", "text": "Why?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, because we want to transform a molecule that has a relatively low potential to transfer phosphoryl to a molecule that has a relatively high potential to transfer that phosphoryl group."}, {"title": "Overview of Glycolysis .txt", "text": "And so we basically take the gap, we mix it with our NAD plus and we also use an orthophosphate."}, {"title": "Overview of Glycolysis .txt", "text": "And in the presence of gap dehydrogenase, so dehydrogenase basically means we're going to have a reaction which there will be a transfer of a Hydride group."}, {"title": "Overview of Glycolysis .txt", "text": "And so this will be reduced into NADH."}, {"title": "Overview of Glycolysis .txt", "text": "We're going to release an H ion and that phosphate."}, {"title": "Overview of Glycolysis .txt", "text": "The orthophosphate will basically attack this molecule and bind onto this carbon here."}, {"title": "Overview of Glycolysis .txt", "text": "And so now we have these two phosphate groups on this molecule."}, {"title": "Overview of Glycolysis .txt", "text": "So on the first position and the third position."}, {"title": "Overview of Glycolysis .txt", "text": "And that's why this molecule is essentially a molecule that has a higher potential to actually transfer that phosphoryl group."}, {"title": "Overview of Glycolysis .txt", "text": "And so now in the next step, we can use one three BPG, the same molecule to basically transfer that phosphoryl group onto an ADP molecule, thereby producing an ATP and the molecule that catalyzes this, well, again, it must be a kinase."}, {"title": "Overview of Glycolysis .txt", "text": "Why?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, because this is a phosphorylation reaction."}, {"title": "Overview of Glycolysis .txt", "text": "And so we use our phosphoglycerate kinase phosphoglycerate because this is a one three bisphosphoglycerate."}, {"title": "Overview of Glycolysis .txt", "text": "So we mix up with the ATP because this will accept this group here."}, {"title": "Overview of Glycolysis .txt", "text": "And so once the process takes place, we essentially form an ATP molecule and we form a three phosphaglycerate."}, {"title": "Overview of Glycolysis .txt", "text": "Now, what happens with the three phosphoglycerate?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, in the next step, in step eight, we basically want to transform the three phosphorylycerate into a less stable molecule."}, {"title": "Overview of Glycolysis .txt", "text": "So we want to take this and destabilize it and that will make it more reactive so that in step nine it can actually react."}, {"title": "Overview of Glycolysis .txt", "text": "So to destabilize this, the goal is we want to take this phosphate and bring it closer to this negative charge."}, {"title": "Overview of Glycolysis .txt", "text": "So we have a negative charge of negative one and a charge of negative two."}, {"title": "Overview of Glycolysis .txt", "text": "And if we basically decrease the distance between the negative charge, that will destabilize this molecule."}, {"title": "Overview of Glycolysis .txt", "text": "And so we have an enzyme known as phosphoglycerate mutates."}, {"title": "Overview of Glycolysis .txt", "text": "A mutate is simply an enzyme that takes a group on the molecule and changes its position."}, {"title": "Overview of Glycolysis .txt", "text": "And so we have the phosphollycerate."}, {"title": "Overview of Glycolysis .txt", "text": "So phosphorlycerate mutates will be the enzyme that will take this group and bring it onto the second carbon."}, {"title": "Overview of Glycolysis .txt", "text": "And so now we have not three phosphorlycerate, but a two phosphollycerate."}, {"title": "Overview of Glycolysis .txt", "text": "And notice this is an endergonic process."}, {"title": "Overview of Glycolysis .txt", "text": "So under physiological conditions, it will not be spontaneous."}, {"title": "Overview of Glycolysis .txt", "text": "We have to input energy and so this molecule will be less stable than this molecule."}, {"title": "Overview of Glycolysis .txt", "text": "So now that we have this less stable molecule, we can basically react it in step nine and we can transform it into a molecule that prepares it to form that Pyruvate."}, {"title": "Overview of Glycolysis .txt", "text": "So we take this molecule and we use Enlase to transform it into an enol."}, {"title": "Overview of Glycolysis .txt", "text": "So we have Phospholenol, Pyruvate or Pep."}, {"title": "Overview of Glycolysis .txt", "text": "We essentially form a double bond between these and the H and the oh combines and the water is kicked off."}, {"title": "Overview of Glycolysis .txt", "text": "And so this is a dehydration reaction."}, {"title": "Overview of Glycolysis .txt", "text": "Once we form this molecule, this molecule is not very stable and it has a very high phosphoryl transfer potential."}, {"title": "Overview of Glycolysis .txt", "text": "Why?"}, {"title": "Overview of Glycolysis .txt", "text": "Well, because this is essentially trapped in the enol state."}, {"title": "Overview of Glycolysis .txt", "text": "And it's trapped because this oxygen doesn't have an age, it has this phosphoryl group."}, {"title": "Overview of Glycolysis .txt", "text": "And so what must happen in the final stage is this phosphoryl group must be donated to an ADP molecule and replaced with an H. And once it is replaced with an H, it can transform into the more stable ketone state, the Pyruvate molecule."}, {"title": "Overview of Glycolysis .txt", "text": "And that's exactly what happens in a final stage."}, {"title": "Overview of Glycolysis .txt", "text": "We take this molecule that is high in energy, so it contains very active bonds and that makes it a very good molecule that actually transfers that phosphoral group onto ADP."}, {"title": "Overview of Glycolysis .txt", "text": "And so in the presence of ADP and H plus, we take this molecule and by the action of Pyruvate kinase so again, we form Pyruvate in the last step and this reaction is a phosphorylation reaction."}, {"title": "Overview of Glycolysis .txt", "text": "So we're using a kinase and we form the Pyruvate in the ketone state and that ATP molecule."}, {"title": "Overview of Glycolysis .txt", "text": "And because this process takes place twice, we form two ATP molecules here."}, {"title": "Overview of Glycolysis .txt", "text": "We form two ATP molecules here."}, {"title": "Overview of Glycolysis .txt", "text": "So a total of four ATP molecules in stage five."}, {"title": "Overview of Glycolysis .txt", "text": "We use two ATP molecules in stage one."}, {"title": "Overview of Glycolysis .txt", "text": "And the net result is we form two ATP molecules in glycolysis per glucose that we actually use up."}, {"title": "Overview of Glycolysis .txt", "text": "So if we sum all these individual reactions and we basically sum up all these individual energy values, keeping in mind that all these take place twice."}, {"title": "Overview of Glycolysis .txt", "text": "And so we have to multiply, multiply these energy values by two for these five steps, we basically get the following net results."}, {"title": "Overview of Glycolysis .txt", "text": "So we have a glucose, we have two ADP, we have two NAD, plus we have two PiS."}, {"title": "Overview of Glycolysis .txt", "text": "That's our net input."}, {"title": "Overview of Glycolysis .txt", "text": "And the net output is."}, {"title": "Pyrimidine Synthesis.txt", "text": "Nucleotides are important biological molecules used by our cells for a variety of different reasons."}, {"title": "Pyrimidine Synthesis.txt", "text": "We not only use nucleotides to synthesize DNA and RNA molecules, but we also use them to synthesize glycogen."}, {"title": "Pyrimidine Synthesis.txt", "text": "We use them for energy conversion and we also use them in many different types of signal transduction pathways."}, {"title": "Pyrimidine Synthesis.txt", "text": "So there are two types of nucleotides we have permitted and we have purines."}, {"title": "Pyrimidine Synthesis.txt", "text": "And in this lecture, we're going to focus on primidines."}, {"title": "Pyrimidine Synthesis.txt", "text": "So how do we synthesize primidines within our cells?"}, {"title": "Pyrimidine Synthesis.txt", "text": "Well, our cells use two different pathways."}, {"title": "Pyrimidine Synthesis.txt", "text": "The first pathway is what we call the salvage pathway, and the second pathway is called the novosynthesis of primidines."}, {"title": "Pyrimidine Synthesis.txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Pyrimidine Synthesis.txt", "text": "So how do we build primidines?"}, {"title": "Pyrimidine Synthesis.txt", "text": "Well, we basically begin by building the perimedine ring, the six membered ring molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "And then we attach a sugar component to form the perimedine."}, {"title": "Pyrimidine Synthesis.txt", "text": "So let's see exactly how this process takes place."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this process is outlined on the board and this process takes place within the cytoplasm of the cell."}, {"title": "Pyrimidine Synthesis.txt", "text": "So the first step, or actually the first three steps, are catalyzed by an enzyme known as carbomolphostate synthetase."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, recall in the urea cycle, we also use a carbon phosphate synthetase enzyme, but that enzyme is type one and it lies in the mitochondria."}, {"title": "Pyrimidine Synthesis.txt", "text": "This enzyme is type two and it's found in a cytoplasm."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this is actually not the same enzyme that we saw in the urea cycle."}, {"title": "Pyrimidine Synthesis.txt", "text": "So what this enzyme does is it catalyzes three steps."}, {"title": "Pyrimidine Synthesis.txt", "text": "And so it contains three different active sites."}, {"title": "Pyrimidine Synthesis.txt", "text": "So it uses Bicarbonate, it uses two ATP molecules and it also utilizes glutamine to basically form something called carbon oil phosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So let's see exactly how this process takes place."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we begin with bicarbonate."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, Bicarbonate by itself is a stable molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "It's low in energy."}, {"title": "Pyrimidine Synthesis.txt", "text": "And so in the first step, what we want to do is we want to increase the energy of this molecule, make it more reactive."}, {"title": "Pyrimidine Synthesis.txt", "text": "And so we use an ATP, we essentially phosphorylate this carbon and we form the carboxy phosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So now this molecule, unlike this one, has an additional negative charge and that makes it more reactive."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, we also generate an ADP molecule that is not shown."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, once we form the carboxy phosphate, what happens is the following."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this same enzyme, carbon oil phosphate synthetase, takes a glutamine molecule and hydrolyze the glutamine."}, {"title": "Pyrimidine Synthesis.txt", "text": "And once we hydrolyze glutamine, we form two things."}, {"title": "Pyrimidine Synthesis.txt", "text": "We form a glutamate and we also form ammonia."}, {"title": "Pyrimidine Synthesis.txt", "text": "And it's this ammonia that is used to basically attach it onto this carboxy phosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we kick off the orthophosphate we attach the amino group onto this carbon to form this carbonic acid."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, this carbonic acid is then phosphorylated with a second ATP molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we attach the phosphoryl group onto this carbon on the other side to form the carbon well phosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this molecule now contains an amino group on one side and this highly charged component on the opposing side."}, {"title": "Pyrimidine Synthesis.txt", "text": "And this entire process is catalyzed by single enzyme."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, once we form carbon well phosphate, this then leaves the active side of CPS and it moves into the active side of aspartade, transcarbolase a different enzyme."}, {"title": "Pyrimidine Synthesis.txt", "text": "What this enzyme does is it takes an amino acid aspartate it attaches it onto this carbon here and it kicks off this orthophosphate group to form carbon oil aspartate."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, in the next two steps, what we ultimately want to achieve is we want to build that six membered primidine ring, as shown here, that we're ultimately going to use to attach onto a sugar molecule to form that perimedine nucleotide."}, {"title": "Pyrimidine Synthesis.txt", "text": "So in this step, we basically have a dehydration step."}, {"title": "Pyrimidine Synthesis.txt", "text": "We essentially release a water molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we have one H plus ion coming in."}, {"title": "Pyrimidine Synthesis.txt", "text": "We take off one H atom from this nitrogen and we use this oxygen to basically form this water molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "In the process, we form a sigma bond between this nitrogen and this carbon."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we close this structure to form this ring."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, in the next step, we have a reduction step, we have an oxidation reduction reaction in which we have this NAD plus that we use to take electrons from these atoms here, from these carbon atoms here."}, {"title": "Pyrimidine Synthesis.txt", "text": "And we essentially form a pi bond between this carbon here and this carbon here."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we generate NADH, we kick off an H ion and we form this six membered molecule known as ortate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this ring is ultimately going to be used, as we'll see in just a moment, to synthesize that primidine."}, {"title": "Pyrimidine Synthesis.txt", "text": "So once we synthesize the orotate, what do we do next?"}, {"title": "Pyrimidine Synthesis.txt", "text": "Well, now we can attach the sugar component onto this orotate and the molecule that we use at that sugar component is PRPP, where PRPP stands for phosphoribacyl pyrophosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "And the enzyme that catalyzes this is primidine."}, {"title": "Pyrimidine Synthesis.txt", "text": "Phosphoribacy transfers."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, we'll see where this molecule comes from in a future lecture."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we basically use this molecule, we kick off this Pyrophosphate molecule and we generate this intermediate."}, {"title": "Pyrimidine Synthesis.txt", "text": "So ultimately this entire blue structure shown here is the sugar component that came from PRPP."}, {"title": "Pyrimidine Synthesis.txt", "text": "And the final step in this process basically kicks off a carbon dioxide."}, {"title": "Pyrimidine Synthesis.txt", "text": "So this carbon dioxide shown here is basically kicked off, it's eliminated."}, {"title": "Pyrimidine Synthesis.txt", "text": "So we have a decarboxylation step that is catalyzed by this decarboxylase enzyme and we form this UMP molecule."}, {"title": "Pyrimidine Synthesis.txt", "text": "So urine monophosphate."}, {"title": "Pyrimidine Synthesis.txt", "text": "Now, once we form UMP, this UMP is then transformed into UDP urine diphosphate by UMP kinase."}, {"title": "Pyrimidine Synthesis.txt", "text": "And finally UDP is transformed into UDP by nucleotide diphosphate kinase."}, {"title": "Pyrimidine Synthesis.txt", "text": "And we can use this UTP to synthesize CTP, the other primidine molecule."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Aside from antigen A and antigen B, which can both be found on the membrane of red blood cells and which actually determine the type of blood group that the individual has."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Another group of antigens that can also be found on the membrane of red blood cells is a group we call the RH factor."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, by far the most common type of antigen within the RH facto group of the human body is known as antigen D. In fact, about 85% of the individuals living in the United States that came from Western Europe have a gene on their DNA that codes for the antigen D protein."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So an individual with the gene on their DNA that codes for antigen D is known as an RH positive individual."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And what this means is an RH positive individual will have the gene to create the antigen Z protein."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So their red blood cells will contain that antigen D. On the other hand, an individual that is essentially RH negative does not have the gene on their DNA and so will not code and create that protein and will not have antigen D on the membrane of their red blood cells."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So in this particular diagram, we're describing a person that is blood type A and which is RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, unlike the Abo blood group, an RH negative individual will not normally produce the antibody against antigen D. However, if they are actually ever exposed to that antigen D, only then will their immune system begin producing the antibody against antigen D. And to see what we mean, let's once again look at the following diagram."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Let's suppose we have an RH negative individual that is that has the blood group A, blood type A."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "What that means is they will have antigen A on their membrane and will not have antigen B."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And it also means that because they don't have antigen B, their immune system will or readily produce antibodies against antigen B and those antibodies will circulate in the blood."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, what it means for the individual to be RH negative is the following."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "They don't have that antigen D on their membrane, but their immune system will not necessarily produce the antibody against antigen D. The immune system will only begin producing that antibody against antigen D if they are actually exposed to that antigen D. And we'll see an example of this in just a moment when we discuss the process of pregnancy and childbirth."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, it turns out that the gene that codes for the RH factor, the protein antigen D, is actually dominant to the recessive trait."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So the gene that does not code for it."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So to see what we mean by that, let's suppose we have a father that is heterozygous for that trait."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So we have a dominant uppercase R and a recessive lowercase R. And let's suppose the father mates with a mother, a female that is also heterozygous for that same trait."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So uppercase R, lowercase R, so we have the father and the mother and they have an offspring, a child."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, what this describes is the probability of the child being RH positive or RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So because the gene is dominant to the recessive trait that means upper case R and uppercase R will be RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And so will uppercase R and lowercase R because uppercase R is dominant over lowercase R. So we have one, two, three out of four will be our RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And so 75% will be RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And there's a 25% chance that it will be RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So we get RH negative only if we have lowercase R, lowercase R. Now, instead of mating a father who is uppercase R, lowercase R and a mother who is uppercase R and lowercase R, let's suppose a woman who is RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So lowercase R, lowercase R decides to have a child with a man with a male who is RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, we know there are two different types of RH positives."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "We have uppercase R, uppercase R, which is homozygous dominant and we have the heterozygous, as shown."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So let's suppose we have a man who is heterozygous and a female who is homozygous recessive and we have a female who is homozygous recessive and a male who is homozygous dominant."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "In both cases, when these individuals made to produce a child, an offspring there is a probability that the offspring will be RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "In this case, there is a 50% chance of the child being RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So we have 1250 percent and 50% of the child being RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "But in this case, it's 100% likelihood that the child will be R H positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So let's assume for the time being that the fetus that is produced is actually R H positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And that means that inside the fetus, inside the blood of the fetus the fetus will have red blood cells that contain the antigen D on the membrane of those red blood cells."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "The question is how will this actually affect that pregnancy and how will it affect any future pregnancy that the woman may have?"}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So to answer this question, let's begin with the following diagram."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So this is our fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "This is the placenta that connects the bloodstream of the fetus to the bloodstream of our female, of the mother."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And this is the blood vessel of our mother."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, normally, because the red blood cells are too large, they cannot pass across the placental membrane."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "But during pregnancy, during childbirth, that is, there is a small likelihood that there can be exchange of red blood cells."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "There is a leakage of red blood cells and some of the red blood cells can be exchanged between the fetus and Arab woman."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, we know that because the woman is RH negative that means within the bloodstream the woman will not have any antibodies against antigen D because that woman was never exposed to antigen D before that."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And so she is RH negative."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "But because the child, the fetus is RH positive inside their blood they do have red blood cells that contain antigen D. And when during childbirth some of these red blood cells of the fetus leak into the blood system of the mother, some of these antigen D red blood cells end up in the mother's bloodstream."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And now, because the mother is exposed to antigen D for the first time, the immune system will kick in and begin producing antibodies against the antigen D found on those red blood cells that essentially leak into the mother from the fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now this will not actually affect this fetus in any way because this process takes place during and after childbirth."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "But it will affect any further pregnancies that the mother can actually have, especially if that next child is also RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So once again, during the first pregnancy some of the red blood cells of the fetus that have antigen DRH factor can leak into the mother's blood."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now this leakage of red blood cells that contain antigen D into the mother's bloodstream that is who is RH negative, will cause the immune system of the mother to begin producing antigen D antibodies."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "However, since the fetal red blood cells usually leak during childbirth, this will not affect that fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "But let's suppose the same woman who has been exposed to these antigen D proteins and now contains those antibodies against antigen D. Let's suppose she once again becomes pregnant with a fetus who is once again RH positive."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "What will happen now?"}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Well, now we're going to have something called RH incompatibility."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And what that means is because these antibodies that were produced as a result of that first pregnancy are floating around in the bloodstream of the mother and because they're small enough, they can pass across the fetal membrane into the bloodstream of that fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Now, how is this a problem?"}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Well, the fetus is assumed to be RH positive and that means it contains red blood cells that contain the antigen D. Now, when these antibodies travel through the membrane of the placenta and into the bloodstream of the fetus, they will bind onto the antigen D proteins of the red blood cells of the fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And once down, they will destroy, they will lyse the cell."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And when the cell breaks, when it licenses, it releases dangerous chemicals into the bloodstream of that fetus."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "And that can ultimately damage the organs of that fetus, including the brain and other organs."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So we can see how as a result of our immune system trying to protect our body, it can actually damage that fetus during the process of pregnancy second time around."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "So once again to conclude, antigen A and antigen B, the antigens that determine our blood group, are not the only antigens that can be found on the membrane of red blood cells."}, {"title": "Rh Factor and Rh Incompatibility.txt", "text": "Another type of antigen is antigen D. And this is part of a group of antigens found in humans known as the R h factor."}, {"title": "Ubiquitination of Proteins .txt", "text": "So let's suppose some particular protein found inside our cell needs to be broken down into its constituent amino acids."}, {"title": "Ubiquitination of Proteins .txt", "text": "Why?"}, {"title": "Ubiquitination of Proteins .txt", "text": "Well, let's suppose it was damaged."}, {"title": "Ubiquitination of Proteins .txt", "text": "How exactly does the cell know to break down that particular protein that was damaged and leave all the other normal proteins untouched?"}, {"title": "Ubiquitination of Proteins .txt", "text": "Well, the answer lies in a 76 amino acid population polypeptide known as Ubiquitin."}, {"title": "Ubiquitination of Proteins .txt", "text": "So Ubiquitin is this marker for those proteins that needs to be broken down."}, {"title": "Ubiquitination of Proteins .txt", "text": "And before the protein is actually broken down, it undergoes a process known as Ubiquit nation."}, {"title": "Ubiquitination of Proteins .txt", "text": "That is, we attach many Ubiquitant molecules onto that target protein that needs to be broken down."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now let's take a look at the following diagram."}, {"title": "Ubiquitination of Proteins .txt", "text": "So let's suppose this is our Ubiquitan molecule, that 76 amino acid polypeptide chain."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now on the carboxylate end of that particular molecule we have a glycine residue, a glycine amino acid, and it's this glycine amino acid that is found on the carboxylate end of that Ubiquitin that is actually attached onto that target protein that needs to be broken down."}, {"title": "Ubiquitination of Proteins .txt", "text": "And it's the lysine residues on the target protein that are used to actually generate a bond to attach the Ubiquitin to that target protein."}, {"title": "Ubiquitination of Proteins .txt", "text": "So suppose this is our target protein and this here is the side chain group of a lysine residue of a lysine amino acid."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we use this nitrogen on the lysine side chain group to form a bond between this nitrogen and this carbon."}, {"title": "Ubiquitination of Proteins .txt", "text": "And this bond here is known as the isopeptide bond."}, {"title": "Ubiquitination of Proteins .txt", "text": "So the carboxyl terminal group of the ubiquitous is extended and it contains a glycine residue and it's this glycine residue that is covalently attached onto the epsilon amino group of lysine residues found on target proteins."}, {"title": "Ubiquitination of Proteins .txt", "text": "And this bond is known as the isoppeptide bond."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now, as we will see in just a moment, the formation of this isopeptide bond is carried out by the hydrolysis of an ATP molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we have to hydrolyze an ATP molecule to actually gain enough energy to carry out this process by which we attach a Ubiquitin onto that target protein."}, {"title": "Ubiquitination of Proteins .txt", "text": "So in this lecture, we're going to look at the process by which we attach Ubiquitin onto the target protein."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now this process of Ubiquitination actually involves three different enzymes and three different processes."}, {"title": "Ubiquitination of Proteins .txt", "text": "So enzyme number one, or step number one, basically utilize the enzyme we called Ubiquitin activating enzyme."}, {"title": "Ubiquitination of Proteins .txt", "text": "And what this enzyme ultimately does is it harvests the energy that is released when we hydrolyze ATP and utilize that energy to actually activate that Ubiquitin molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "And that prepares the ubiquitin It gives it enough energy to actually attach it ultimately onto that target protein."}, {"title": "Ubiquitination of Proteins .txt", "text": "So the first step is catalyzed by Ubiquitin activating enzyme or E one."}, {"title": "Ubiquitination of Proteins .txt", "text": "And this is catalyzed via the hydrolysis of ATP and the carboxyl."}, {"title": "Ubiquitination of Proteins .txt", "text": "And the Ubiquitin is essentially linked to the enzyme via a thio ester bond."}, {"title": "Ubiquitination of Proteins .txt", "text": "So on enzyme number one, on enzyme one, E one, we have a cysteine."}, {"title": "Ubiquitination of Proteins .txt", "text": "And the side chain of that cysteine is used to attach that ubiquitous molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "So let's take a look at the following diagram to see exactly what we mean."}, {"title": "Ubiquitination of Proteins .txt", "text": "So, we have our Ubiquitin in its nonactive form."}, {"title": "Ubiquitination of Proteins .txt", "text": "So in step one, we take an ATP molecule and we essentially transfer an amp from the ATP onto the Ubiquitin and we release a Pyrophosphate."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we see that the product of this particular reaction is an active ubiquitous molecule that contains this amp group."}, {"title": "Ubiquitination of Proteins .txt", "text": "And so now it's a high energy molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "We release the Pyrophosphate and now E One, this enzyme, the Ubiquitan activating enzyme, basically catalyze the transfer of this blue region onto the active side of E One."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we see that the active side contains a cysteine."}, {"title": "Ubiquitination of Proteins .txt", "text": "And this is the S atom that is part of the side chain group of the cystine and it attaches onto the carbon of this ubiquitous molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "And so we see that this amp is released in the process."}, {"title": "Ubiquitination of Proteins .txt", "text": "So this is ultimately step number one that we have here."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now, step number two is catalyzed by an enzyme we call the Ubiquitin conjugating enzyme conjugating enzyme or E Two."}, {"title": "Ubiquitination of Proteins .txt", "text": "And what this enzyme ultimately does is it transfers that Ubiquitin from the enzyme E One onto the enzyme E Two."}, {"title": "Ubiquitination of Proteins .txt", "text": "So just like the enzyme E One contains this sulfidel group in the active side, enzyme Two also contains a cysteine residue that contains that sulfhydrol group."}, {"title": "Ubiquitination of Proteins .txt", "text": "And so we simply have a shutter link, a transferring of the Ubiquitin from enzyme One to enzyme two."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we see that the activated version of Ubiquitin that we formed in step number one is now transferred onto the second enzyme by attaching it onto the cysteine residue of enzyme Two, E Two."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now, in the final step, this is basically what happens."}, {"title": "Ubiquitination of Proteins .txt", "text": "So we have the final enzyme, E Three, which is known as the Ubiquitin protein ligase, basically enters the picture."}, {"title": "Ubiquitination of Proteins .txt", "text": "And now what it does is it transfers the Ubiquitin group onto this protein target here."}, {"title": "Ubiquitination of Proteins .txt", "text": "So let's suppose this is the target protein that we actually want to break down into its constituent amino acids."}, {"title": "Ubiquitination of Proteins .txt", "text": "And let's suppose this is the residue of the lysine amino acid that we're about to add that ubiquitous molecule to."}, {"title": "Ubiquitination of Proteins .txt", "text": "So ultimately, this carbon here forms a bond with this nitrogen and we form this final product molecule."}, {"title": "Ubiquitination of Proteins .txt", "text": "At the same time, E Two and enzyme E Three basically depart and we form this final product."}, {"title": "Ubiquitination of Proteins .txt", "text": "Now, this is not actually the final step of this reaction."}, {"title": "Ubiquitination of Proteins .txt", "text": "In order to actually target that particular protein for degradation, we have to actually add many more Ubiquitant molecules."}, {"title": "Ubiquitination of Proteins .txt", "text": "In fact, we have to add at least four ubiquitous molecules to actually target that protein for degradation."}, {"title": "Ubiquitination of Proteins .txt", "text": "And the way the Ubiquitin is added is in a process of manner."}, {"title": "Ubiquitination of Proteins .txt", "text": "And what that means is once we attach that Ubiquitin onto this protein, we actually attach more ubiquitous molecules onto this ubiquitin."}, {"title": "Ubiquitination of Proteins .txt", "text": "So once with this process happens, if we examine Ubiquitin, the 48th residue of Ubiquitin is a Lysine."}, {"title": "Ubiquitination of Proteins .txt", "text": "And that Lysine is used in the same way that we use the Lysine of this target protein to basically attach a second Ubiquitin molecule in this same fashion here."}, {"title": "Ubiquitination of Proteins .txt", "text": "So if we study the structure of Ubiquitin, ubiquitin at its 48th position will have a Lysine."}, {"title": "Ubiquitination of Proteins .txt", "text": "And that Lysine will contain this nitrogen atom that will be able to form a bond in the same fashion that we show here."}, {"title": "Ubiquitination of Proteins .txt", "text": "And so we'll form an isoppeptide bond, and we'll attach a second ubiquitous, then a third ubiquitous, a fourth ubiquitous."}, {"title": "Ubiquitination of Proteins .txt", "text": "And at that point, we target that protein for degradation."}, {"title": "Ubiquitination of Proteins .txt", "text": "But this process can happen many more times than just four times."}, {"title": "Ubiquitination of Proteins .txt", "text": "And in fact, this process happens on different Lysine residues on that target protein."}, {"title": "Ubiquitination of Proteins .txt", "text": "So essentially, once we undergo the process of Ubiquit nation, it's that then that we can actually target that particular protein for breakdown."}, {"title": "Ubiquitination of Proteins .txt", "text": "And it's then that the proteosome complex actually finds that particular protein and begins to break it down and begins to break it down into its constituent amino acids."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So let's say you have a protein and that protein has a specific amino acid sequence."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, suppose you want to take your protein and modify that protein in a very slight way."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So all we want to do with our protein is change one amino acid in that protein to a different amino acid."}, {"title": "Site-Directed Mutagenesis.txt", "text": "How exactly can we carry out this process?"}, {"title": "Site-Directed Mutagenesis.txt", "text": "Well, we can use a protein process in recombinant DNA technology known as side directive mutagenesis, also known as oligonucleotide directive mutagenesis."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So proteins can be modified at a single amino acid by using this process we call side directive mutagenesis."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, to demonstrate how this process works, let's suppose we have a protein and we want to change an amino acid glutamate to the amino acid aspartate in that protein."}, {"title": "Site-Directed Mutagenesis.txt", "text": "How exactly can we do this?"}, {"title": "Site-Directed Mutagenesis.txt", "text": "Well, we need two things."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Number one, we need that double stranded DNA molecule that contains the gene that encodes for that protein in the first place, the correct sequence of nucleotides."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And we also actually need to know the sequence of nucleotides around that area that we want to modify."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So in that area where we want to change that codon sequence that codes for glutamate to the codon sequence that codes for aspartate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So we need two things."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Number one, a DNA molecule that contains the gene that encodes for that protein."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Number two, to know the nucleotide sequence on that gene around the side that is actually to be altered."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, the important step in this procedure is to basically create a special DNA primer that is complementary to the nucleotide sequence along that gene where we want to make that alteration."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And the way that we want to build the DNA primer is we want to change the sequence in that DNA primer so that we change the codon that goes from glutamate to the codon that codes for aspartate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So, let's suppose that the DNA molecule that contains the gene that encodes for the protein is this DNA molecule here."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So we have a circular single strand of DNA that came from some type of plasmid, for example."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, this is our sequence."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So T-A-T GCC tgcct, this is the sequence on the DNA template that we want to build the DNA primer for."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so this above is the DNA primer that we build in a laboratory."}, {"title": "Site-Directed Mutagenesis.txt", "text": "But notice what we do with the DNA primer."}, {"title": "Site-Directed Mutagenesis.txt", "text": "We modify the sequence of the DNA primer."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, if we look at this codon here, CTT, this codon would have a complementary sequence, a correct complementary sequence of GAA."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And GAA would code for the glutamate amino acid in that protein."}, {"title": "Site-Directed Mutagenesis.txt", "text": "But instead of creating a DNA primer with the correct GAA sequence, we can create a DNA primer that contains a mismatched base."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Instead of having an a here, we can place a c. And so instead of having GAA that codes for glutamate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "We simply modify this last nucleotide in the codon sequence and we form GAC."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And we know from the genetic code that GAC codes for aspartate, which is the amino acid that we want to build in the first place."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And notice that because C will not pair up with tea, no hydrogen bonds are actually formed between these two nucleotides."}, {"title": "Site-Directed Mutagenesis.txt", "text": "But that's okay, because this will still hybridize."}, {"title": "Site-Directed Mutagenesis.txt", "text": "It will still anneale because all the other bases are paired up correctly."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So as long as we use the exact temperature conditions needed for annealing to take place."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Remember, annealing is the process by which two complementary sequences of nucleotides essentially hybridized."}, {"title": "Site-Directed Mutagenesis.txt", "text": "They bond, they form these hydrogen bonds."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so as long as we use the proper temperature conditions, this annealing process will still take place because all the other bases are paired up correctly."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So, once again, the important step of this procedure is to create a short DNA primer that is complementary to the side to be altered."}, {"title": "Site-Directed Mutagenesis.txt", "text": "However, this primer should be changed in a way to make sure the protein will contain aspartate instead of glutamate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And notice that even though one of the bases are mismatched, the DNA primer will still uneal to that DNA molecule because all the other bases are paired up correctly, assuming we also use the correct temperature conditions."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, this DNA primer with that mismatched base, also known as a point mutation, can now be used to synthesize the protein of interest, as we'll see in just a moment."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So this base pair mutation is known as a point mutation because we essentially mutate our base at a single point, we exchange an A for C. And that's exactly why we call this site directed mutagenesis, because we make this point mutation at that single site."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, the reason we also call it a ligonucleotide directed mutagenesis is because this DNA primer that we create in this particular case, it consists of these 50 nucleotides that describes an oligonucleotide molecule."}, {"title": "Site-Directed Mutagenesis.txt", "text": "OligA simply means we have about ten to 20 to 30 of these nucleotides found inside that DNA molecule."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So we synthesize an artificial oligonucleotide in the lab, and then we change the sequence ever so slightly to basically accommodate a codon that will create the aspartate instead of glutamate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, let's actually take a look at the following three steps that we have to follow to basically form that protein that will contain the aspartate instead of the glutamate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So, in step one, we basically take that plasma double stranded DNA molecule that contains this DNA template that we studied in this diagram."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so this is our plasmid."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Notice the plasma contains the same DNA sequence that we discussed in this diagram."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so before we can replicate, we actually have to separate these two strands of DNA and we have to isolate this DNA template of interest."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So we basically heat our solution that contains this plasma, and then we separate one of the strands of DNA."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So this strand right over here, the inner one, which has the sequence tat, GCC, CTT, TGC, CCT, the same sequence that we discussed here."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, in step two, we now create that DNA primer that contains that point mutation and we add it into our solution at the right temperature so that the kneeling process will take place."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so now the DNA primer will essentially hybridize with this section of that DNA template that we're going to use to basically synthesize our polynucleotide chain."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And now we add our DNA polymerase along with the four types of building blocks, the four types of deoxy nucleus cytrophosphate molecules."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And now the DNA polymerase will bind onto the primer and begin synthesizing in the five to three direction from this end to this end."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So it will move all the way along this DNA template."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And we'll use that DNA template to synthesize that new strand of DNA that now contains this codon sequence GAC that codes for glutamate."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So now notice we have this DNA molecule where one of the strands is this DNA template strand and the other strand is the newly synthesized green strand that contains this, this slightly modified codon sequence."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, if we take this plasmid and repeat step one and two, so essentially we heated, we separated, then we basically isolate that green DNA molecule that was synthesized in step two."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And now we add that DNA polymerase as well as the four types of deoxy nucleuside triphosphates."}, {"title": "Site-Directed Mutagenesis.txt", "text": "Now, the DNA polymerase will use this green strand that contains that point mutation to basically synthesize the complementary strand to the green strand."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And so after step three, we essentially produce that plasmid molecule, the double stranded DNA molecule that will contain that point mutation."}, {"title": "Site-Directed Mutagenesis.txt", "text": "And now we can use this modify double stranded DNA molecule to basically synthesize that protein in which we replace the glutamate with the aspartape molecule."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So another round of separation and replication of this DNA plasmid yields the modified DNA of interest that can be used to synthesize the protein with that aspartate instead of that gluten made."}, {"title": "Site-Directed Mutagenesis.txt", "text": "So we see that side directive mutagenesis is a very, very useful technique used in DNA in recombinant DNA technology to basically change protein sequences by a single amino acid."}, {"title": "Thymus .txt", "text": "The Thymus is an endocrine gland that is found beneath our sternum bone."}, {"title": "Thymus .txt", "text": "So if the sternum bone is found here, the Thymus is found right beneath that."}, {"title": "Thymus .txt", "text": "So it's located in between the right and the left lung, as shown in this diagram."}, {"title": "Thymus .txt", "text": "So the thymus is shown in red."}, {"title": "Thymus .txt", "text": "So the thymus consists of two lobes."}, {"title": "Thymus .txt", "text": "We have the right lobe and our left lobe."}, {"title": "Thymus .txt", "text": "And this Thymus releases a type of hormone known as thyomosin."}, {"title": "Thymus .txt", "text": "Now, as we'll see in just a moment, thyomosin is actually involved in building up our immune system."}, {"title": "Thymus .txt", "text": "And that's exactly why we'll focus on the thymus in much more detail and how it actually works when we'll discuss the immune system of our body."}, {"title": "Thymus .txt", "text": "Now, unlike other endocrine glands that function in our body which function throughout the entire lifetime of the organism, the thymus is special in that it only functions, it only stays active until about puberty."}, {"title": "Thymus .txt", "text": "And after that, the thymus basically begins to break down."}, {"title": "Thymus .txt", "text": "It begins to deteriorate and eventually is replaced by our fat cells by out of post tissue."}, {"title": "Thymus .txt", "text": "Now, what exactly is the function of the thymus?"}, {"title": "Thymus .txt", "text": "Well, earlier we mentioned that the thymus is involved in building up our immune system."}, {"title": "Thymus .txt", "text": "So how exactly does this take place and what do we mean by this?"}, {"title": "Thymus .txt", "text": "Well, inside the bone marrow of our bones, we have white blood cells."}, {"title": "Thymus .txt", "text": "And these white blood cells eventually differentiate into different types of specialized cells that are used by our immune system for different purposes."}, {"title": "Thymus .txt", "text": "And one of these cells is the T cell, also known as the T lymphocyte, where the T actually stands for thymus."}, {"title": "Thymus .txt", "text": "So inside the bone marrow, we produce cells called arithmicides."}, {"title": "Thymus .txt", "text": "And these thymicides are eventually carried into our thymus."}, {"title": "Thymus .txt", "text": "And inside the thymus, the thymus uses our hormone thymicine to basically test the immunity response of our T cells of arithmeticides."}, {"title": "Thymus .txt", "text": "Now, if the thymicides fail the test, if they're not able to actually detect the proper antigens, the proper viral agents, in that case the Thiamas, destroys our cells."}, {"title": "Thymus .txt", "text": "But if the Thiamicides actually pass the test, then they mature, then they become our T cells."}, {"title": "Thymus .txt", "text": "And then those T cells are released into our lymph system and they basically end up at our lymph nodes where they can basically fight different types of disease viral agents as well as infections."}, {"title": "Thymus .txt", "text": "And we'll discuss this and these types of cells and how this actually takes place inside the Thiamis when we'll discuss the immune system system of the human body."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "It uses a twostep reaction to basically produce an important inflammatory molecule we call prostaglandin H Two."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And what prostagland H Two does is it basically initiates the inflammation response."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "It basically stimulates that inflammation response that is carried out by our immune system, and it also acts, actually regulates the secretion of gastric acid by the gastric cells of Aristonic."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "So this is a two step process that it catalyzes."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "So the substrate molecule of this particular enzyme is the arachidonic acid."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And the arachidonic acid exists in its deprotonated state."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "What it does, this arachidonic acid basically is found within the hydrophobic region of the membrane."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "It moves into the active side of this enzyme, and it moves into the active side without actually having to interact with the aqueous environment of the Er lumen."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "Why?"}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "Well, because it moves from inside the core of that membrane and directly into the active side."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And that's important because this substrate is predominantly not polar."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "It will not want to dissolve or interact with the water molecules in the aqueous environment."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And so, basically, this moves into the active side, it is transformed into prostagladin GH, and then that is transformed into prosthlatin H Two."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And so we see that there are many different examples of inter proteins and peripheral proteins, but together, all these proteins that basically constitute the membranes of our body are responsible for carrying out these different types of functions."}, {"title": "Integral and Peripheral Membrane Proteins Part II .txt", "text": "And we'll look at many, many more examples in the lectures to come."}, {"title": "Antigen Presenting Cells .txt", "text": "All pathogenic antigens that eventually make their way into the tissues of our body must be presented to tillymphocytes the cells of our cellmediated immunity."}, {"title": "Antigen Presenting Cells .txt", "text": "The problem is these telemphicides cannot actually directly bind onto these antigens."}, {"title": "Antigen Presenting Cells .txt", "text": "What must happen before these T lymphocytes interact with the antigen is a special type of immune cell known as the antigen presenting cell must actually engulf our antigen."}, {"title": "Antigen Presenting Cells .txt", "text": "And once it engulfs the antigen it takes that antigen and it places it onto a special protein complex found on the membrane of the antigen presenting cell."}, {"title": "Antigen Presenting Cells .txt", "text": "And this protein complex is known as the major histocompatibility complex class Two or simply a MHC Class Two."}, {"title": "Antigen Presenting Cells .txt", "text": "And only when the antigen is bound to this MHC Class Two complex can the lymphocyte actually see and interact with the antigen and bind onto this antigen."}, {"title": "Antigen Presenting Cells .txt", "text": "And once it binds only then can it begin some type of defensive mechanism as we'll see in just a moment."}, {"title": "Antigen Presenting Cells .txt", "text": "So the three types of antigen presenting cells that we're going to focus on in this lecture are macrophages dendritic cells as well as B lymphocytes, the cells of our humoral immunity system."}, {"title": "Antigen Presenting Cells .txt", "text": "So let's begin with macrophages."}, {"title": "Antigen Presenting Cells .txt", "text": "So let's suppose we have some type of infection taking place, let's say a bacterial cell infects our tissue."}, {"title": "Antigen Presenting Cells .txt", "text": "Now as soon as that infection takes place the innate immune system will try to prevent that infection from spreading."}, {"title": "Antigen Presenting Cells .txt", "text": "It will try to localize that infection via the process of inflammation."}, {"title": "Antigen Presenting Cells .txt", "text": "And what inflammation does is it dilates our blood vessels."}, {"title": "Antigen Presenting Cells .txt", "text": "It brings more blood to that area and that brings specialized antigenpresenting cells known as macrophages."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, what do macrophages actually do?"}, {"title": "Antigen Presenting Cells .txt", "text": "Well, macrophages engulf pathogens."}, {"title": "Antigen Presenting Cells .txt", "text": "Let's suppose we have the bacterial cell as shown in red."}, {"title": "Antigen Presenting Cells .txt", "text": "And this is our macrophage."}, {"title": "Antigen Presenting Cells .txt", "text": "And the macrophage engulfs that particular bacterial cell."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, once that bacterial cell is inside the macrophage the macrophage forms the phagosome which contains lysosomes."}, {"title": "Antigen Presenting Cells .txt", "text": "And the lysosomes contain digestive proteolytic enzymes that break down and digest that pathogen."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, when digestion takes place what the macrophage does is because it's an antigen presenting cell it begins to build the MHC class Two complex."}, {"title": "Antigen Presenting Cells .txt", "text": "And it takes that complex and places it on the membrane of the macrophage."}, {"title": "Antigen Presenting Cells .txt", "text": "And then it takes a small peptide, the antigen from that bacterial cell and it places it on that MHC class II complex."}, {"title": "Antigen Presenting Cells .txt", "text": "So we have this antigen MHC class Two complex that forms."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, as soon as this actually takes place we have a special type of T lymphocyte whose membrane contains a special glycoprotein known as CD four."}, {"title": "Antigen Presenting Cells .txt", "text": "Only T lymphocytes that contain the CD four glycoprotein can actually go on and bind onto the antigen MHC class II complex."}, {"title": "Antigen Presenting Cells .txt", "text": "So for example, we have some type of inactivated helper T cell that contains the CD four glycoprotein on the membrane goes on and binds onto this complex of the macrophage."}, {"title": "Antigen Presenting Cells .txt", "text": "And once this binding process takes place that ultimately activates the helper T cell."}, {"title": "Antigen Presenting Cells .txt", "text": "And that also releases many different types of chemicals involved in our immune system and that activates T cells."}, {"title": "Antigen Presenting Cells .txt", "text": "For example, it produces cytotoxic T cells."}, {"title": "Antigen Presenting Cells .txt", "text": "It also activates our B cells into plasma cells and memory B cells."}, {"title": "Antigen Presenting Cells .txt", "text": "And that begins the process of defending and protecting our body from these pathogens."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, let's move on to the second type of antigen presenting cell known as a dendritic cell."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, basically, all these different types of antigen presenting cells do the same exact thing."}, {"title": "Antigen Presenting Cells .txt", "text": "They basically engulfed our antigen and then they present that antigen on this special type of protein membrane complex known as the major histocompatibility complex, class Two."}, {"title": "Antigen Presenting Cells .txt", "text": "So what exactly is a dendritic cell?"}, {"title": "Antigen Presenting Cells .txt", "text": "Well, a dendritic cell is a specialized type of immune cell that is found in those areas of our body that are close to the outside environment."}, {"title": "Antigen Presenting Cells .txt", "text": "And that includes places tissues like our skin, our gut, our stomach and our digestive tract as well as our lungs."}, {"title": "Antigen Presenting Cells .txt", "text": "So the air pathogeways of our lungs, like the trachea, the bronchi and our bronchial."}, {"title": "Antigen Presenting Cells .txt", "text": "So this is what a derivative cell actually looks like."}, {"title": "Antigen Presenting Cells .txt", "text": "It has these projections, these dendrites."}, {"title": "Antigen Presenting Cells .txt", "text": "So let's suppose some type of foreign antigen is found inside our tissue and it comes from, let's say, some type of bacterial cell, the same cell that we spoke of earlier."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, what this centring cell does is it basically phagocytizes this antigen and it basically engulfs it."}, {"title": "Antigen Presenting Cells .txt", "text": "And the lysosomes break it down and a small part of it is then expressed, it's then displayed on this MHC class Two complex that is formed by the cell as shown in the following diagram."}, {"title": "Antigen Presenting Cells .txt", "text": "Now, the dendritic cell is motile."}, {"title": "Antigen Presenting Cells .txt", "text": "And what that means is it can then move into the spleen or the lymph nodes of our immune system and it basically begins to interact with some type of T lymphocytes that once again has the CD four glycoprotein, the proper T cell receptor found on the membrane of that T lymphocyte."}, {"title": "Antigen Presenting Cells .txt", "text": "And when these two cells interact once again it elicits some type of defensive immune response."}, {"title": "Antigen Presenting Cells .txt", "text": "Now let's move on to our B lymphocytes."}, {"title": "Antigen Presenting Cells .txt", "text": "So recall that B lymphocytes are those immune cells of their humoral immunity, the antibody mediated immunity."}, {"title": "Antigen Presenting Cells .txt", "text": "So B lymphocytes can also engulf and take in these antigens that come from different types of pathogens found inside our tissues."}, {"title": "Antigen Presenting Cells .txt", "text": "So beelymphocytes are part of the humoral immunity."}, {"title": "Antigen Presenting Cells .txt", "text": "When they approach foreign antigens floating around in our tissue, they bind to them via special receptors and then they undergo receptive mediated endocytosis and that takes in that antigen into the cell."}, {"title": "Antigen Presenting Cells .txt", "text": "And once that happens, these B lymphocytes build the MHC class Two complex and they place that antigen onto that complex."}, {"title": "Antigen Presenting Cells .txt", "text": "And only then can some type of T cell T lymphocyte with this CD four Glycoprotein bind onto this MHC class Two complex that contains air antigen."}, {"title": "Antigen Presenting Cells .txt", "text": "And once this binding takes place, that ultimately stimulates this B lymphocyte to undergo mitosis divide."}, {"title": "Antigen Presenting Cells .txt", "text": "Many times and it basically differentiates into two different types of cells the plasma cells that basically produce the antibodies found inside our blood, swimming around our blood and lymph system."}, {"title": "Antigen Presenting Cells .txt", "text": "And they also produce those memory B cells that are involved if reinfection ever actually takes place."}, {"title": "Antigen Presenting Cells .txt", "text": "So once again, we can conclude that the antigen presenting cell is a type of cell of our body that allows these T lymphocytes to actually interact with the antigens."}, {"title": "Antigen Presenting Cells .txt", "text": "What these cells do is they engulfed these antigens and then they build these special protein complexes and then they take that antigen and place it on that protein complex."}, {"title": "Antigen Presenting Cells .txt", "text": "And only then can our T lymphocyte that contains the CD four glycoprotein receptor actually interact with this antigen MHC class II complex and create some type of mechanism, some type of defensive immune response."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Another important physiological consequence of the two three BPG molecule has to do with the developing fetus."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "But before we discuss that, let's recall what we discussed about the two three BPG molecule."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So two three BPG, or simply two three biphosphoglycerate, is this biological molecule that acts as an allosteric effector of heat hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So what it does is it binds onto the hemoglobin molecule at a special location that is not the same location that oxygen binds to, and it stabilizes the T state of that hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And by stabilizing the T state, it lowers the affinity of hemoglobin for oxygen."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So it basically shifts the entire curve, the oxygen binding curve to the right side with respect to pure hemoglobin that does not contain the two three BPG."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, how do we say that two three BPG binds onto hemoglobin?"}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So what we said was at the center of the hemoglobin is this positively charged pocket, is this region of space that contains a positive charge or positive charges."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And these positive charges come from six different amino acids which are found on the beta one and the beta two subunits."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So let's take a look at the following diagram which we spoke about in the previous lecture."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So this is our normal hemoglobin, and hemoglobin contains the beta one and the beta two subunits, as well as these two alpha subunits."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, at the center of these individual subunits are the heme groups."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And at the center of the actual hemoglobin molecule is this pocket of space."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And in the pocket of space, we have three amino acids coming from the beta one subunit, we have histidine 141, Lysine 82, and HistoGene two."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And we also have three amino acids coming from the beta two, also the HistoGene two, the Lysine 82 and the histadine 143."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And each one of these amino acids contain side chain groups, which contain a positive charge."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And so together, these six amino acids create a relatively large positive charge at the center of that hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And this molecule, the two three BPG, contains 12345 negative charges."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And that's exactly why this molecule is able to bind at the center pocket, because there is a strong electric attraction between these negative charges and the positive charges found along the following six amino acids."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So this is the two three BPG molecule, and it binds the electrostatic forces with these six amino acids."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, this is normal hemoglobin that is found in our bodies."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "But when the fetus is developing inside the mother, the gene that expresses the hemoglobin expresses a slightly different hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So the fetal hemoglobin molecule also contains the alpha one and the alpha two subunits, but it does not contain beta one and beta two."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Instead, it contains a slightly different type of submune we call gamma one and gamma two."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, what's the major difference between the beta and the gamma subunits?"}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Well, as it turns out, in the gamma subunit, the gamma subunit does not have histidine 143."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Instead of histidine 143, histidine is replaced with serene."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And serene, as we know, does not have a positive charge."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So serine is neutral."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And what that means is in the pocket of fetal hemoglobin there is a smaller positive charge because these two histidines histidine 143 on this subunit and HistoGene 143 on this subunit are replaced with serene."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And so instead of having a positive sit charge we essentially have a positive four charge, a smaller positive charge."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, what is the physiological consequence of that?"}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Well, because we have a smaller positive charge the two three BPG will not be able to bind as strongly to that center pocket as it binds in the normal hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And so what that means is the fetal hemoglobin will not bind the two three BPGS strongly."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And so because of that, the fetal hemoglobin will have a higher affinity for oxygen than the normal hemoglobin found inside the blood of the mother."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And what that means is the fetal hemoglobin will be much more attractive to the oxygen."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And that's important because it needs to be able to effectively and efficiently take the oxygen from the mother's blood and deliver it into the blood system of that developing fetus."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Now, if we examine the oxygen binding curve we see that this green curve basically describes the oxygen binding curve for the fetal hemoglobin while the blue curve describes the oxygen binding curve for the hemoglobin found in the mother's blood, the normal hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And we see that our blue curve is shifted to the right with respect to the green curve."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And that makes sense because what that means the blue curve, the regular hemoglobin has a slightly lower affinity than this green curve than the fetal hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So the fetal hemoglobin, at the same partial pressure will be able able to buy more oxygen than that mother's normal hemoglobin."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "And that's important because we have to have an effective method by which that fetus actually obtains the oxygen from the mother's blood."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "So this is one more important physiological consequence of this molecule."}, {"title": "Fetal Hemoglobin and 2,3 BPG .txt", "text": "Two, three BPG."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "One of the many important functions of our endocrine system is to control blood, as molarity is to control the amount of blood volume and the blood pressure inside our vessels."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, one mechanism by which our body can basically increase the blood pressure when the blood pressure drops."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And our body is by following a pathway known as the renamed angiotens outdosed their own pathway or system."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And what this system basically does is it increases the blood volume, it increases the blood pressure inside our blood vessels."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So let's discuss how this pathway actually works."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And let's begin by discussing a portion of the kidney known as the Juxtaglomerol apparatus."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So this is basically a structure that consists of three different types of cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, two of these different types of cells are the maculadens of cells and the juxtaplamelmerolar cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And these two different types of cells basically have their own unique function."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So, basically, when our blood volume drops inside our vessels, when our blood pressure drops, and when the profusion rate inside our kidneys drops that simply means when the rate at which our fluid is passing through the kidneys drops, this causes our maculodenta cells to basically release a prostaglandin that travels to our juxtaglomero cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And this causes those cells to release an enzyme called rena."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, note that juxtaplinaril cells don't have to be activated, they don't have to be stimulated by the macula density to actually release Rena."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And that is they can release Renan independently without being stimulated by the maculodeensa cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So basically, this apparatus, the juxtaglomero apparatus, contains special types of cells that can sense a drop in blood volume, a drop in blood pressure, and these cells release Renan into our blood system."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So if we take a look at the following diagram, a low blood volume, a low blood pressure, and a low kidney perfusion rate basically positively stimulates the kidneys to produce and release our renal enzyme into our bloodstream."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, at the same exact time, the liver, the cells inside the liver basically produce a xiaomogen enzyme known as angiotensinogen."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, this is released into our bloodstream."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And when this angiotensinogen mixes with our Renan, the Rena basically cleaves this zymogen at a specific location on that amino acid sequence and it activates the angiotensinogen into the angiotensin one form."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So basically, once in the bloodstream, renan goes on to activate the Xymogen angiotensinogen into angiotensin one by cleaving it proteollytically at a specific specific position along the amino acid sequence."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Angiotensinogen is produced inside our liver cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, once we activate the angiotensin one, it basically goes on, travels through our blood system and eventually ends up at lung cells as well as in our kidney cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And once it's found in those cells, the cells basically contain a special type of enzyme known as ace, which stands for angiotensin converting enzyme."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And what that enzyme basically does is it converts angiotensin one into angiotensin II by basically cleaving two residues on that particular enzyme."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So angiotensin one hormone then travels to lung cells and kidney cells."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "There an enzyme called angiotensin converting enzyme or ace, basically transforms angiotensin one into angiotensin two."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, angiotensin two is basically one of the final products of this pathway because it itself can actually stimulate our blood vessels to constrict, and it also stimulates the increase in our blood volume and blood pressure inside our blood vessels."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, the question is, how exactly does it achieve this?"}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Well, once angiotensin two is produced and released into our bloodstream, what happens is it basically goes on to special cells inside our adrenal cortex known as the zona glomer lucia."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And this zone, this region that contains these special types of cells, basically releases our hormone known as aldosterone."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And aldosterone, as we know from our discussion on the adrenal cortex, basically causes our kidneys to become more permeable to certain ions."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So the rate at which sodium and the chloride increases, so the rate at which these two ions traveled back into the plasma increases, and we excrete more potassium and hydrogen ions."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And what this creates is a net movement of ions back into the blood, and this forces more water to be reabsorbed by the blood."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So this increases the amount of blood volume inside our blood, and this causes increase in our blood pressure."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, what the angiotestin two also does is it basically goes on and stimulates the release of the antidiauretic hormone ADH that is stored inside the posterior pituitary gland and produced by the hypothalamus."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So ADH, also known as vasopressin, basically causes our kidneys to reabsorb more water."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "It becomes more permeable to water the cell membrane."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And so water increases inside our blood plasma, and this increases our blood pressure inside our blood vessel."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, angiotensin two actually also constricts our blood vessels, and that causes an increase inside our blood vessels."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So more specifically, it causes the constriction of our arterioles throughout the body as well as inside our kidneys."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, when our blood pressure increases, when our blood volume increases, the increase in the blood volume can basically create a negative feedback loop and that will basically go on and cause our Rena to stop being secreted by the kidney."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So let's take a look at the following diagram that basically describe summarizes the renal angiotestin aldosterone system."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So let's suppose inside our blood, we have a low volume of blood plasma, we have low blood pressure, and that means we have a low profusion rate inside our kidneys."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So this will basically cause special types of cells, known as juxtaglomeroth cells inside the kidneys to release our enzyme known as Rena."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And at the same time, liver cells produce and release a zymogen known as angiotensinogen into the bloodstream."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And when these two mix, the Renan will basically cleave our angiotensinogen and form angiotensin one."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, once we form angiotensin one, it will then travel into lung cells and also into kidney cells, and it will be activated by using the angiotensin converting enzyme into angiotensin II."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And then angiotensin II basically goes on to activate the ADH, the vasoppressin released by the posterior pituitary, which causes our kidneys to become more permeable to water and reabsorb more water into our blood vessels."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "Now, it also causes the release of aldosterone, which basically causes our kidneys also to reabsorb more water by creating a net movement of ions back into the blood."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And it also constricts our arterios, which increases our blood pressure."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "So all these three effects result in an increase in blood volume, increase in blood flow rate, our perfusion rate inside our kidney, and also increases our blood pressure."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "And when our blood pressure increases, that can basically react in a negative feedback loop to cause our kidneys, the juxtag glomeryla cells, to stop releasing renan and this is basically how we control our blood pressure inside our body."}, {"title": "Renin-angiotensin-Aldosterone System.txt", "text": "This is the method by which the endocrine system can basically control the blood level, the blood osmolarity, as well as our blood pressure inside our body."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Whenever our cells break down amino acids, they generate ammonium as a byproduct."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And as we know, ammonium is very toxic."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So our liver, and to a smaller extent, our kidneys, undergo the urea cycle."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And this cycle allows us to transform this toxic molecule, ammonium, into a less toxic form, urea, which is then transported via the bloodstream into our kidneys, where this molecule is eliminated by the kidneys via urine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And this is the only way by which our body can actually eliminate this ammonium, the byproduct of amino acid metabolism from our body."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So what do you think would happen if there is some type of defect or deficiency in any one of the enzymes involved in the urea cycle?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, since this is the only way by which we rid the body of ammonium, that implies a deficiency in any one of these enzymes will decrease the ability of our liver body to actually eliminate ammonium."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And that will drive the levels of ammonium inside our body up."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So that will cause a medical condition we call hyperammonemia, high levels of ammonia inside our blood."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, this is a very dangerous condition and it's especially devastating in infants who are born with defects in any one of these enzymes."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So if an infant is born with the defect in any one of these enzymes, that will drive the levels of ammonium leading to this condition."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, why is that dangerous?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, we think that high levels of ammonium inside our brain can essentially change the zamotogradient between the inside and the outside of the cell because high levels of ammonium will essentially increase the levels of Glutamine, because the enzyme Glutamine synthetase found in the brain essentially combines the ammonium with Glutamate to form Glutamine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And high levels of Glutamine basically changes the somatic gradient."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And that can lead to brain swelling and brain damage."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And that's why hyperamnemia is dangerous in infants who are born with defects in any one of these enzymes."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So to explore more of this concept, let's take a look at some of these defects, some of these inborn deficiencies."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And let's begin with Argininosuxenase deficiency."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So Arginosuxinase is the enzyme that essentially catalyzes step four, the conversion of Arginosuxanate to Arginine and also forming the fumarate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, normally what this does is this reaction continually replenishes the Arginine, which essentially keeps reaction five, which keeps reaction five going."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so by keeping this reaction going, we produce the ornathine that we need for step number two."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And we also produce the urea, which is ultimately excreted by our kidney."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, if this reaction stops, so let's stop this reaction."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So this reaction no longer takes place or takes place at a low rate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Why?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, because we have a deficiency in this enzyme and so that will begin to decrease the levels of Arginine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "By decreasing the levels of this molecule, we decrease the levels of the reactant in this reaction."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And that drives the rate of reaction five to the ground."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so we no longer are producing the urea and we're no longer generating the ornathan that we need for step number two, because in step number two, this carbon well phosphate combines with the ornithine to form the citrulline."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so ultimately, that's what causes high levels of ammonia and that's what causes hyperammenemia."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, how do we treat a patient with this condition?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, number one is we have to limit protein intake."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "By limiting the total protein intake in individual, we decrease amino acid metabolism and so we decrease the production of ammonia."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And number two is we have to increase the uptake of Arginine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "How would that help?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, by increasing the levels of Arginine, we essentially will replace the arginine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So we will increase the levels of Arginine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And by increasing the concentration of this reactant, we'll increase the rate of reaction five."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so by increasing the rate of this reaction, we produce the only thing that we need in step number two."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so essentially, if we continually replace the Arginine, we give the patient the arginine, we drive this reaction."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so that will allow step two to take place and that will also allow step three to take place, because once we produce the citrulline, by combining this molecule and this molecule, we essentially combine the aspartate with citrulline to combine Arginosuxanate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now, once we form this, by replacing this, the reaction still can't go this way, but luckily, our body has a way to actually eliminate Arginosuxanate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so ultimately our body will get rid of that extra ammonium by combining the ammonium into this molecule and then continually forming citrulline."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And then the second amino group will come from aspartate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And ultimately our body, instead of ridding itself of ammonium via urea, it will rid itself of ammonium by getting rid of the our genosuxinate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Now let's explore anodeficiency and let's focus on step number one and step number two."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So let's suppose if we have a problem either in carbon mole phosphate synthetase or ornathine transcarbolus, what would happen now?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, notice that reaction one and two are before this cycle actually takes place."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So if we just follow this circular arrow here, if we have a problem here or here, it's before the cycle takes place."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so by replacing any one of these intermediates citrulline, this molecule Arginine, this molecule that will do nothing in a person with carbon oil phosphate deficiency or, ornithine transcarbol deficiency."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so what will help?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, again, we have to limit the total protein intake because that will decrease amino acid metabolism and decrease the ammonia production."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "But more importantly, what we have to do is we have to somehow rid the body of glutamine as well as glycine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Why?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, as I mentioned earlier, if we have high levels of ammonia that will increase the levels of Glutamine in the body, it will also increase glycine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so what we want to do is we want to somehow decrease the levels of glycine and glutamine inside our body."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so in a patient with either one of these deficiencies, we can give the patient benzoate and phenyl acetate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Why?"}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Well, because benzoate in the presence of Coenzyme A and ATP will form benzoyl, coenzyme A, and this molecule will react with glycine to form Hippurate."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And Hippurate can essentially be excreted by our kidneys."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so if we give the patient this drug here, then it will ultimately help eliminate that glycine from the body."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "Likewise, by giving the patient phenyl acetate, that will combine with ATP and Coenzyme A to form phenyl acetal, coenzyme A."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And this ultimately rips the body of the glutamine build up."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "So it combines with glutamine to form phenyl acetyl, glutamine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so this can also be eliminated by the kidneys."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so in a patient with a problem in either one of these two enzymes, the ultimate goal is to get rid of that glycine and glutamine, because high levels of ammonia will cause high lobes of glycine and glutamine."}, {"title": "Defects in Urea cycle and hyperammonemia .txt", "text": "And so we give these two drugs, we limit the amount of protein intake, and that will alleviate some of the symptoms that are associated with this particular defect."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Once a woman becomes pregnant she is no longer only responsible for her own body but she is now responsible for the body of that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that's precisely why she must take a great deal of caution with the things that she eats and the things that she ingests and drinks with the people she interacts with and the places she visits."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Because there are many different types of factors found in in our surrounding environment that can have a negative impact on the way that fetus develops inside the uterus of that pregnant individual."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So in this lecture we're going to briefly discuss eight different categories of factors that can have a negative impact on that development on that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So let's begin with number one smoking, perhaps the most common one."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So why is smoking bad for us?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Why are cigarettes bad for us?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, the cigarette butt contains many different types of carcinogens and a carcinogen is a cancer causing agent."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So it's a molecule that when reacts with molecules in the cells of our body, can basically lead to cancer and cancer cells."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So when that individual smokes, they inhale all those different carcinogens and those carcinogens eventually end up in the blood of that individual."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, the problem with that is, remember, the placenta is the organ that basically exchanges nutrients and gas products between the fetal blood and that placenta and that mother's blood."}, {"title": "Factors Affecting Fetal Development .txt", "text": "The problem with these carcinogens is they can easily cross across that placental membrane."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And so all those carcinogens that end up in the blood can also end up within that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And these carcinogens can cause different types of developmental problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, what else do we have in cigarettes?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, we also have nicotine."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And nicotine is that addicting agent that causes the addiction and as a result, that woman becomes addicted."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that fetus can also become addicted to nicotine."}, {"title": "Factors Affecting Fetal Development .txt", "text": "On top of that, when an individual smokes, one other byproduct is carbon monoxide."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And carbon monoxide is toxic to hemoglobin."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Hemoglobin the carrier of oxygen."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So once the woman inhales carbon monoxide, the carbon monoxide can bind to hemoglobin and decrease the Vinity of hemoglobin for oxygen."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And what that does is it lowers the amount of oxygen content in the blood of that mother and that will lower the amount of oxygen that is received by that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So eventually smoking can basically cause many different types of problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, it can lead to premature birth."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can also lead to an underweight fetus, a fetus that is below the normal weight."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, it can also produce different types of birth defects."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can produce different types of problems within the heart."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, it can produce an atrial septal defect."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And what that means is there's a hole between the atria within the heart."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can also lead to different types of placental problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So remember all those carcinogens, the nicotine and the other molecules have to cross across the placental membrane."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And as they cross they can cause different types of damaging effects."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So they can cause problems within the placenta."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now why is that a problem?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, that's a problem because the placenta is the organ where nutrient exchange and gas exchange takes place."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And if the placenta is damaged, then that fetus cannot actually obtain enough nutrients to develop quickly and efficiently."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that's exactly why smoking is very, very bad for that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, let's focus on different types of drugs."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So we have medicinal drugs, we have recreational drugs and then we also have alcohol."}, {"title": "Factors Affecting Fetal Development .txt", "text": "All these things have a very bad effect on that developing embryo and that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, what do we mean by medicinal drugs?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, these are those legal drugs that you can get in a pharmacy or you can get at the physician's office."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And for example, one very common type of medicinal drug is aspirin."}, {"title": "Factors Affecting Fetal Development .txt", "text": "This basically is used to relieve headaches, to relieve different types of pains and so forth."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, almost every single type of medicine will have some type of effect on that developing fetus as long as that medicine can get across as long as that drug can get across the membrane of the placenta."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, aspirin can lead to maternal as well as fetal bleeding and that can produce many different types of problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So before actually taking any type of medicinal drug, that pregnant woman should consult her physician."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now what about recreational drugs?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, recreational drugs includes drugs like cocaine and heroin and so forth."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Marijuana is another recreational drug and all these different types of drugs can basically cause different types of problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, let's focus on cocaine."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So the problem with cocaine is that it can easily cross across that placental membrane and so that cocaine that damages that mother also ends up damaging that fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "The problem is the mother is already fully developed so the cocaine actually amplifies the damage on that fetus because the fetus is still in its developmental stage."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So cocaine basically leads to different types of physical deformities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can also lead to mental deformities as well."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So what do we mean by physical deformities?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, for example, fetuses that are born to mothers who use cocaine have a smaller head."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And because they have a smaller head, they will have a smaller brain."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that usually is associated with a smaller IQ."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can also lead to different types of mental disabilities and mental abnormalities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can lead to birth defects in the heart as well as the urinary tract."}, {"title": "Factors Affecting Fetal Development .txt", "text": "It can also lead to other problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, that fetus can actually have a stroke."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And if the fetus has a stroke, that can lead to brain damage."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So many, many different types of problems that are result of these recreational drugs such as cocaine, heroin, marijuana and other drugs."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now what about alcohol?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, alcohol is also a toxic substance."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Toxic substance."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Although we don't see alcohol as being a toxic substance."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Our body treats alcohol as if it was a toxic substance."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So when a woman who is pregnant basically drinks alcohol, that alcohol doesn't only affect her, it can also affect that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "In fact, heavy drinkers of alcohol develop."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Babies give birth to fetuses who have something known as Fetal Alcohol Syndrome."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, what exactly is fetal alcohol syndrome?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, this is basically a type of syndrome that is characterized by many different types of things."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, fetuses who have Fetal Alcohol syndrome develop different types of facial abnormalities and facial deformities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So physical deformities, they have problem with growth and developing properly."}, {"title": "Factors Affecting Fetal Development .txt", "text": "They have problems with their essential nervous system."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So the brain and the spinal cord, they also have a variety of different types of learning disabilities and physical disabilities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So alcohol, recreational drugs, medicinal drugs, smoking all these things are really bad not only for that mother, but these effects are amplified and are really bad for that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, let's move on to pathogens."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So by pathogens, we mean some type of agent that can infect the body as well as the fetus and basically cause harm to that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So we have many different types of examples."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, HIV."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So if a mother has HIV and she becomes pregnant, then that baby will also have HIV."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that's because that virus is small enough to actually cross along that placental membrane."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Another type of dangerous virus that can affect that fetus is rubella."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So if that woman somehow develops rubella, what that means is this virus is small enough to actually cross across that placental membrane."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And once it enters the circulatory system of that fetus, it can cause many damaging effects."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So the virus rubella basically interferes with many cellular metabolic processes and that can lead to children that are born with different types of abnormalities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, deafness, blindness, heart problems, mental problems and abnormalities as well as many other different types of abnormal conditions."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now let's move on to radiation."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So what exactly do we mean by radiation?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "So we don't mean things like UV radiation and light radiation."}, {"title": "Factors Affecting Fetal Development .txt", "text": "When we say radiation, we mean an ionizing form of radiation."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So very dangerous rays, for example, X rays and gamma rays, these types of radiating sources."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, why would X rays and gamma rays be dangerous?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, what X rays and gamma rays are they're really, really strong beams that carry a great deal of energy."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And when those X rays and those gamma rays hit the individual, those beams of energy can basically cause harm to the cells of that body as well as the cellular processes that take place within the body."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So women who are exposed to ionizing radiation ionizing simply means once that beam hits those molecules, they ionize those molecules by basically bumping electrons to higher energy levels."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So women who are exposed to ionizing radiation, such as X rays, gamma rays, et cetera, during pregnancy have a much higher chance of giving birth to children with different types of abnormalities, defects as well as cancer."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So, for example, a woman who is pregnant probably shouldn't be prancing around some type of nuclear power plant, a power plant or a place like Chernobyl because those places contain very radioactive atoms and very radioactive sources."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And if they are to actually ingest those radioactive sources, that can cause a lot of damage to that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And an unfortunate example of how radiation can affect the developing fetus are the children who are born to mothers who were exposed to the radiation that occurred at Chernobyl."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, the final two factors I want to briefly discuss is malnutrition and excessive levels of vitamins."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, what do we mean by malnutrition?"}, {"title": "Factors Affecting Fetal Development .txt", "text": "Well, clearly, one important thing that a woman has to do when she's pregnant is she has to have a well balanced diet."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that's because she's not only feeding herself but she's also providing the nutrients the glucose, the fats, the proteins, the vitamins to that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And so that fetus must be able to get enough nutrients so that they can basically develop the different types of organs and systems and tissues and so forth."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And when a pregnant woman does not consume enough nutrients that has a negative effect on that embryological and fetal development process."}, {"title": "Factors Affecting Fetal Development .txt", "text": "For example, if she doesn't get enough amino acids and proteins, that can lead to different types of mental abnormalities and learning disabilities."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Another example is insufficiency of vitamins."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So vitamins are very important to that fetus and that fetus has to get enough of these vitamins because these vitamins basically help those enzymes in that developing fetus basically function properly and effectively."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And so insufficiency of vitamins can also lead to problems with the central nervous system as well as other problems."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Now, just because that fetus needs vitamins that doesn't mean taking excessive vitamins is good for that fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "In fact, it has been shown that if you take vitamin DA or K excessively that will form different types of problems within that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So we see that there are many different types of factors that are found in the outside environment, outside of the body that can cause many different types of damages to that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "So a pregnant individual really has to be cautious about the different types of things that she eats and drinks with, the people that she interacts with because she doesn't want to get any type of pathogen that can basically cause damage to that developing fetus."}, {"title": "Factors Affecting Fetal Development .txt", "text": "She has to be careful about the places she visits and the things she does because she doesn't want to radiate that child."}, {"title": "Factors Affecting Fetal Development .txt", "text": "She doesn't want to give that child any type of damage as a result of the ionizing radiation."}, {"title": "Factors Affecting Fetal Development .txt", "text": "She wants to make sure that she follows a well balanced and a well nutritious diet and she doesn't want to ingest any type of dangerous agent for example, any type of medicinal drug that can cause harm to that fetus, any type of recreational drug or alcohol."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And she obviously does not want to smoke."}, {"title": "Factors Affecting Fetal Development .txt", "text": "And that includes not only cigarettes, but it also includes marijuana, because marijuana has been shown to cause different types of damages to that developing embryo."}, {"title": "Factors Affecting Fetal Development .txt", "text": "In fact, certain babies who are born to mothers who smoke marijuana basically become addicted to marijuana and show signs of withdrawal."}, {"title": "Factors Affecting Fetal Development .txt", "text": "Old following birth."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Skeletal muscle is a type of muscle found in the human body that is responsible for voluntary movement, for movements such as walking, running, riding a bicycle, swimming and so forth."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, there are three different types of skeletal muscles as we'll see in just a moment."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And although all these different types of skeletal muscle have their differences, they are all controlled by the somatic nervous system them and they all consist of the same type of general structure."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, what exactly are these muscles?"}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "What are their differences and similarities and what is their function?"}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So let's begin with type one skeletal muscle, also known as slow oxidative or slow twitch muscle."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, slow simply means the breakdown rate of ATP is slow."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these types of muscles break down ATP very slowly and that means the contraction speed of these muscles, the velocity at which these muscles contract is low."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these muscles basically contract relatively slowly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, the oxidative portion of slow oxidative simply means they use oxygen to basically form ATP."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that means the pathway of ATP production is aerobic."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So they use not only glycolysis, but they also use the CReP cycle and the electron transport chain to actually produce our ATP."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, because they have a lot of oxygen, that means they have a high concentration of myoglobin because myoglobin is the protein carrier that actually carries that oxygen in our muscle tissue."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that means we have a high amount of myoglobin and these muscles appear red."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that's exactly why these are also known as red muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, how exactly does oxygen actually get to our slow oxidative muscle?"}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Well, it's carried by the blood."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that means because these muscles have a lot of oxygen, they also have many capillaries that actually carry the oxygen to those particular muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, because these have a low contraction speed and because they break down ATP slowly, they also have a high amount of triglycerides."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And they have a high amount of triglycerides means our major source of fuel, our major source of ATP is our fatty acids."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these muscles use predominantly triglycerides to break down the fatty acids in aerobic respiration into ATP."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that also means that they have a low fatigue rate."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "That means we can use them for hours and hours before they actually run out of that fuel source."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So we can continually use our fats as our major storage fuel to form ATP."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that's exactly why these are the muscles that are used when we carry out very long activities such as running a marathon."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So if we're running a marathon, that basically means we have to use muscles that will not fatigue very quickly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that's why we use the type one muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, these are the muscles that also have a relatively low diameter."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So the thickness is low."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that's exactly why the force that is produced by these muscles is also low."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So when we're running a marathon, we don't actually have to exert a very strong force."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "We exert a very low force over a very long distance so that our muscles don't fatigue very quickly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these are the muscles that are used in that case."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "What about our type two A muscles known as fast oxidative or fast twitch muscles?"}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So fast simply means the breakdown of ATP is quick."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So we break down ATP very quickly and that means the muscle contraction is high."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, just like slow oxidative, fast oxidative also uses aerobic respiration and that means it also contains a high supply of oxygen."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "It also contains a lot of myoglobin."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these muscles also appear red but they also appear pink."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that means the amount of myoglobin is lower in fat oxidative than in slow oxidative."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, the major supply of fuel is not fatty acids but it's glycogen."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So the polymer version of sugar where we break down glycogen into glucose and then the glucose goes into the process of glycolysis, then into the crept cycle and onto the electron transport chain."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these also contain many mitochondria and many capillaries."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now it also used a type of molecule known as creatine phosphate."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Creatine phosphate itself is not actually used directly as an energy source."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "We use creatine phosphate to pass down the phosphate group onto ADP to form our ATP."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, the thickness of our muscle fiber for fast oxidative is higher than the thickness in our slow oxidative."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And so these produce a slightly higher force than in the case of the slow oxidative."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So we have a low diameter of muscle fiber in this case and a medium in this case."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that's why we produce a higher force."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, if these muscles can last us hours, these muscles basically last us minutes."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these are the muscles that are used in long distance events such as running a marathon."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "These are used in middle distance events such as for example, running a 400 meters distance run."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And these are the muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So type two B or FAS glycolytic are used in sprint events."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So for example, if we're diving or sprinting, let's say 100 meters or swimming 50 meters, these are the muscles that are basically used."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So let's discuss the fast glycolytic."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So fast simply means these also have a fast contraction speed and that's because they break down ATP quickly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, unlike these two muscles, these muscles basically do not use oxygen."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that means we have a low concentration of oxygen."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So we do not have too many capillaries and we use anaerobic respiration."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "That means we only use glycolysis to form our ATP and we also use creatine phosphate."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these have a large diameter."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "That means they produce the greatest contractile for us out of all these three muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And these basically fatigue very quickly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So that means when we're sprinting and that requires let's say, 10 seconds, these are the muscles that we're going to use."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So because we don't have too many capillaries, we don't have too much oxygen."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "That means we don't have too many myoglobin carrier proteins."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And so these muscles will appear white."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So these are known as the white muscles, but these two muscles are known as the red muscles because these have a fast contractile rate."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "That means these two are known as fast twitch muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "But this, which has a low contraction speed, this is known as a slow twitch muscle."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So once again, these are the muscles that are found predominantly in the back and the legs."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Because these muscles are the muscles that have a low fatigue rate, they can be used to basically support our body to give it posture."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "Now, these are the muscles that are used in middle distance events."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "For example, if we're running, let's say 400 or 800 meters, these are the muscles that we're going to use."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "These are the muscles that are used when we basically need to exert a very large force."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "For example, when we're lifting a very heavy weight."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And that only requires several seconds."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "These are the muscles that we're going to use predominantly."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "So we have three different types of muscles."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "We have slow oxidative type one, fast oxidative type two A, and fads likelytic type two B."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And these basically have many different similarities, but they're all a skeletal muscle and that means they're controlled by the somatic nervous system."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "And they all have the same type of contraction and they have the same type of structure."}, {"title": "Slow Oxidative, Fast Oxidative and Fast Glycolytic Muscles .txt", "text": "They're all composed of sarcomir units."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Inside the cells of our body, a process we call aerobic."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Cellular respiration uses oxygen to produce ATP molecules."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And these ATP molecules are used by ourselves as an energy source."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, what exactly delivers the oxygen to the cells of our body?"}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Well, we have two proteins inside our body that play this role."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "They deliver oxygen to the cells of our body."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And these two proteins are myoglobin and hemoglobin."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Myoglobin is a protein that consists of a single polypeptide chain and it is found in the muscle cells of our body."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "It is used by our muscle cells to store oxygen and give the muscle cells the oxygen when the concentration of oxygen becomes very, very low."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "On the other hand, hemoglobin is a protein that consists of four individual polypeptide chains."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "We have alpha one and alpha two, which are two identical alpha chains."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And we have beta one and beta two subunits, which are also identical subunits."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so these four polypeptide chains give the hemoglobin molecule quantumary structure."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And that's exactly what gives that hemoglobin the ability to bind oxygen cooperatively."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And we'll see what that means in the next lecture."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So what hemoglobin does is it essentially continually delivers the oxygen from the lungs and to the tissues and cells of our body."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And it also binds CO2 and brings the carbon dioxide back to the lungs so that the carbon dioxide can be expelled by our body."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, in this lecture, what I'd like to focus on is how these two proteins actually are capable of binding to oxygen in the first place."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So these two proteins contain a special prosthetic group known as the hein group that assists the protein in actually binding the oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And the heme group has the following structure."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So the heme group consists of two components."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "It has the organic component known as protoporphy that contains the carbon atoms, the nitrogen atoms, the hydrogen atoms and the oxygen atoms."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And this entire region, shown in black, is the protoporphine."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "It's the organic component of that Hen group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, at the center of that protoporphinen is an inorganic atom, a metal atom, the iron atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And this is what makes up the inorganic component of that Hen group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And it's this fe atom that is actually responsible to not only binding to the protein, but also to binding to that oxygen, as we'll see in just a moment."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now notice, as shown in this diagram, this fe atom is bound to four nitrogen atoms."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "We have 1234."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, fe can have an oxidation state of positive six."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And in this particular case, because we have four bonds, what that means is this fe is in its ferrous state."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And what that means is it has a state, an oxidation number of positive two."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so our fe atom at the center of the heme group can form two other bonds."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, one of the bond is formed between one of the amino acids of that polypeptide chain and this Is Shown In The Following Diagram."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So if we take the heme group and we flip it this way, so if the heme group lies on the plane of the board and we take it and we flip it this way, then at the bottom portion of that hen group, we have an amino acid."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "More specifically, we have a HistoGene amino acid that is part of the protein either myoglobin or that hemoglobin that is bound onto that fe atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So this purple circle is the fe atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "The green circle are the nitrogen atoms."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "The blue circles are the oxygen atoms."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And the purple circle is that metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "That Fe atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So on one side of the protoporphine plane, the iron atom is bound to the histodine residue of that polypeptide chain."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "That polypeptide chain can be part of the myoglobin or it can be part of the hemoglobin molecule."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So because each polypeptide chain contains a single heme group, myoglobin contains a single heme group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "But Hemoglobin contains four different heme groups."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And that means Myoglobin can only bind onto one oxygen, while Hemoglobin can bind four different oxygen atoms, as we'll see in just a moment."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So on the bottom of that fe, we have the bond form between the nitrogen of this histogine residue and this metal atom found in that heme group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, in this particular state, the electron density around that fe is simply too large for that fe to actually fit inside the center of that plane."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And that's exactly why this fe atom will be found slightly below the protoporphine plane, as shown in the following diagram."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So in deoxy hemoglobin or deoxy myoglobin."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "When the protein is not bound to the oxygen, the iron atom remains unbound to oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And in this case, the fe metal atom is simply too large."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "It has too large of an electron density around that proton nucleus for that entire metal atom to actually fit snugly in the center of that protoporphine."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so what that means is this fe atom will be found slightly below."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, in this particular case, this fe atom has 12345 bonds."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And what that means is it can form one more bond with some other Atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so on."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "The top portion of that fe, that is exactly where that bond will be formed between the diatomic oxygen and that metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Remember, it's this metal iron atom of the hemegroup that binds directly and holds onto that diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So if this is the unbound state of our protoporphy, then when the oxygen actually binds, what happens is this diatomic oxygen moves from the top position of that fe, and it begins to pull away some of that electron density from that metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Remember, oxygen is the second most electronegative atom on the periodic table, and it is much more electronegative than this metal iron atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so what that means is the electron density will be pulled away from that metal atom, decreasing the radius and the size of that metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so what happens is, because the size of this iron atom decreases, it now is able to fit at the center of that protoporphyrin group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so this is what it will look like when it will be bound to that diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So this is a diatomic oxygen that is bound to this metal atom, and it pulls away the electron density, decreasing the size of the metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And now the metal atom is able to fit into the center of that protoporphine plane."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, what exactly is the structure that describes this complex here?"}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Well, this complex between the metal atom and the diatomic oxygen can be described by a resonant stabilized structure as shown on the board."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So these are the two electron structures that describe the resonance stabilized complex between our fe atom and the diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So on this side, on this electron configuration, we have a dioxygen that contains a neutral charge and we have the iron that contains a positive two charge."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So it is in its ferro state."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "But what happens is, because the dioxygen, because the diatomic oxygen consists of these two electronegative atoms, they can pull away an electron readily from that ferrous atom and create a ferric ion that contains a positive three charge."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so one of the electrons will be pulled away from the metal atom and onto the oxygen, giving this diatomic oxygen a negative charge."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And this is called a superoxide ion."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "In fact, this superoxide ferric ion complex is the resonance structure that more closely describes what the structure is between these two atoms, the two oxygen atoms and the single metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So we see that when the diatomic oxygen binds onto that fe from the top, that diatomic oxygen develops a negative charge because it is more electronegative and it pulls away those electrons, that electron, from the metal atom."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And that's precisely what moves this entire residue up and what allows this metal atom to fit into the sensor portion of that protoporphy in group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, because the diatomic oxygen gains a negative charge, it becomes slightly less stable."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And so we have to be able to somehow stabilize this diatomic oxygen inside that heme group."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And in fact, what happens is we have another histidine residue that is part of the polypeptide chain inside that protein."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Either myoglobin or hemoglobin that binds creates a hydrogen bond with that negative charge."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And this is shown in the following diagram."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So the actual structure of the iron oxygen complex is resonant stabilized as shown in this diagram."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "One of it consists of this structure, and the other one consists of this structure here."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And notice that the superoxide oxygen form has a negative charge on that oxygen and that destabilizes it."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And to stabilize this structure, we see that a region of the protein, another histidine amino acid, forms a hydrogen bond with this oxygen, as shown in the following diagram."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And this residue is known as the distal histidine."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So this here is known as the proximal histidine."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And the proximal histidine is the amino acid of that polypeptide chain that forms a bond with that fe atom that holds the heme group to that protein."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And it's the distal histidine that is found on the opposite side, on the opposite plane of the protoporphy that is responsible in forming a hydrogen bond between this oxygen here of this diatomic oxygen and this nitrogen of that histidine, and this stabilizes that diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "So we see that if we're talking about myoglobin or hemoglobin, both of these proteins contain a heme group that is responsible for binding that diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And it's the iron atom, the metal atom at the center of that heme group that is actually responsible for directly binding onto that diatomic oxygen."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "Now, the other side of that iron atom is actually bound onto the amino acid found in that protein."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And it's that bond that holds the Hebrew inside that protein in the first place."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "We see that we have the distill histidine, which is another amino acid found inside that protein that is able to actually interact and stabilize that negative charge on the superoxide ion."}, {"title": "Heme Group of Hemoglobin and Myoglobin .txt", "text": "And as we'll discuss in a future lecture, it's this stabilization that also allows the unloading the release of this diatomic oxygen in its dioxygen form to the cells and the tissues of our bodies."}, {"title": "Ketogenesis .txt", "text": "The cells of our body can break down, can oxidize fatty acids into acetyl coenzyme A molecules."}, {"title": "Ketogenesis .txt", "text": "But what happens to these acetyl coenzyme A molecules next?"}, {"title": "Ketogenesis .txt", "text": "Well, it depends on the conditions inside our cells."}, {"title": "Ketogenesis .txt", "text": "So if we have high levels of oxylace inside the cell, then the oxylacetate can actually be combined with acetylco enzyme A to generate an internal immediate of the citric acid cycle."}, {"title": "Ketogenesis .txt", "text": "And that ultimately can be used to help form ATP molecules."}, {"title": "Ketogenesis .txt", "text": "So if we have high levels of oxylace, then we can feed the Ctlco enzyme A directly into the citric acid cycle to help us generate ATP."}, {"title": "Ketogenesis .txt", "text": "But what happens if we don't have enough oxylacetate inside our cells?"}, {"title": "Ketogenesis .txt", "text": "For example, if we're fasting, if we're fasting and we're not eating enough glucose molecules, then what the liver will do is it will begin the process of gluconeogenesis to ensure that the peripheral cells get enough glucose to use to produce ATP."}, {"title": "Ketogenesis .txt", "text": "So in the liver cells, the oxalo acetate will be used up to help form glucose via gluconeogenesis."}, {"title": "Ketogenesis .txt", "text": "And if we decrease the amount of oxyo acetate, then we won't have enough oxalo acetate to combine with the acetyl coenzyme A to help generate that intermediate of the citric acid cycle and ultimately generate ATP."}, {"title": "Ketogenesis .txt", "text": "And so low levels of oxyloacetate and high levels of acetyl coenzyme A molecules means the acetyl coenzyme A molecules cannot be fed into the citric acid cycle."}, {"title": "Ketogenesis .txt", "text": "And under such conditions, what will happen is that acetyl coenzyme A, produced via the beta oxidation pathway, will follow a different reaction pathway."}, {"title": "Ketogenesis .txt", "text": "It will follow the pathway we call ketonogenesis, the formation of ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So once again, acetal Co enzyme A, generated via the beta oxidation of fatty acids, can only be used to form ATP via the citric acid cycle if we have enough oxyloacetate inside the cell."}, {"title": "Ketogenesis .txt", "text": "So if our carbohydrate intake is low, for example, we're fasting or in diabetics, and we'll talk more about diabetics and ketogenesis in the next lecture."}, {"title": "Ketogenesis .txt", "text": "The liver will use up the majority of the oxalo acetate to help generate glucose via glucaneogenesis."}, {"title": "Ketogenesis .txt", "text": "And by driving the oxalo acetate levels to the ground, what that basically means is those acetyl coenzyme A molecules will be diverted to a different pathway known as ketogenesis, the formation of ketone bodies."}, {"title": "Ketogenesis .txt", "text": "Now, ketone bodies are actually energy fuel molecules, and we'll talk about that in just a moment."}, {"title": "Ketogenesis .txt", "text": "First, let's actually discuss how we form these ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So we have four important steps in the formation of ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So in step number one, let's suppose we have low levels of OXYL acetate, high levels of acetyl coenzyme a."}, {"title": "Ketogenesis .txt", "text": "So we can't convert that acetyl coenzyme A into an intermediate of the citric acid cycle."}, {"title": "Ketogenesis .txt", "text": "And what will happen is the acetyl coenzyme A molecules, two of them, will be combined via process catalyzed by thylase, and we form acetoacetal coenzyme A."}, {"title": "Ketogenesis .txt", "text": "We also release a coenzyme A."}, {"title": "Ketogenesis .txt", "text": "So in the first step, two molecules of acetylcoenzme A are combined to form acetoacetal coenzyme A."}, {"title": "Ketogenesis .txt", "text": "And this is a reversible reaction that is catalyzed by thylase."}, {"title": "Ketogenesis .txt", "text": "Now, in the next step, the next step is actually a rate determining step."}, {"title": "Ketogenesis .txt", "text": "And in fact, it's this step that drives this reaction forward."}, {"title": "Ketogenesis .txt", "text": "Because here we cleave a high energy thio etherbond via a hydrolysis reaction."}, {"title": "Ketogenesis .txt", "text": "So we use a water molecule and we also combine another CETL, coenzyme A."}, {"title": "Ketogenesis .txt", "text": "So we combine these two molecules, we cleave a thioester bond, release the coenzyme A, and we form an intermediate known as HMG coenzyme A."}, {"title": "Ketogenesis .txt", "text": "Now, HMG stands for the H stands for hydroxy, the M stands for methyl and the G stands for Gluterol."}, {"title": "Ketogenesis .txt", "text": "So we form three hydroxy, three methylgutral coenzyme A, or simply HMG coenzyme A."}, {"title": "Ketogenesis .txt", "text": "And since we're synthesizing this, the enzyme is known as HMG coenzyme A synthase."}, {"title": "Ketogenesis .txt", "text": "So this is once again the rate limiting step of this reaction."}, {"title": "Ketogenesis .txt", "text": "And as we'll see in a future lecture, this HMG coenzyme A molecule also appears in the synthesis of cholesterol."}, {"title": "Ketogenesis .txt", "text": "So this HMG coenzyme A can also be used to synthesize cholesterol molecules, but in this case, it is used to synthesize ketone bodies."}, {"title": "Ketogenesis .txt", "text": "Now, once we generate the HMG coenzyme A, it then reacts in the third step."}, {"title": "Ketogenesis .txt", "text": "And this is the first step where we actually form a ketone body."}, {"title": "Ketogenesis .txt", "text": "So there are three different types of ketone bodies and this is one of them."}, {"title": "Ketogenesis .txt", "text": "So HMG coenzyme A is cleaved by an enzyme known as HMG coenzyme A. Liase we release this entire molecule here and we generate the aceto acetate molecule and notice that this is the base version of the acid."}, {"title": "Ketogenesis .txt", "text": "And so what that means is when we actually produce these ketone bodies, we will increase the acidity inside our body."}, {"title": "Ketogenesis .txt", "text": "And that can actually be dangerous, as we'll discuss in the future lecture when we'll talk about diabetes and ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So this acetoacetate molecule is actually ketone body in itself and it will diffuse into the bloodstream."}, {"title": "Ketogenesis .txt", "text": "But some of these aceto acetate molecules will actually be converted to other ketone bodies in the liver."}, {"title": "Ketogenesis .txt", "text": "So let's see exactly how this takes place in step four."}, {"title": "Ketogenesis .txt", "text": "Now, acetoacetate has one of two fates."}, {"title": "Ketogenesis .txt", "text": "It can be converted in one of two molecules."}, {"title": "Ketogenesis .txt", "text": "So because acetoacetate is a beta ketoacid, it will undergo a slow and spontaneous reaction in which it will decarboxylate itself."}, {"title": "Ketogenesis .txt", "text": "And so we release a carbon dioxide, this molecule here, to form an acetone."}, {"title": "Ketogenesis .txt", "text": "And this takes place spontaneously without using any enzyme."}, {"title": "Ketogenesis .txt", "text": "Now, acetone cannot actually be metabolized by our bodies."}, {"title": "Ketogenesis .txt", "text": "So we do not use acetone to form any energy molecules."}, {"title": "Ketogenesis .txt", "text": "And what happens to acetone is it's simply released via the lungs, via breathing."}, {"title": "Ketogenesis .txt", "text": "And so physicians can actually test the breath of patients and they can detect high levels of acetone."}, {"title": "Ketogenesis .txt", "text": "And if that's the case, that implies that they have high levels of ketone bodies inside their body."}, {"title": "Ketogenesis .txt", "text": "Now, the other pathway that acetone, acetate can actually follow is an enzyme catalyzed pathway."}, {"title": "Ketogenesis .txt", "text": "And the enzyme that catalyzes process is known as d three hydroxybutyrate dehydrogenase."}, {"title": "Ketogenesis .txt", "text": "And that's because it produces D three hydroxybutyrate, the third and final ketone body inside our body."}, {"title": "Ketogenesis .txt", "text": "So we have acetoacitate, one ketone body, a second ketone body, the third ketone body."}, {"title": "Ketogenesis .txt", "text": "This is not metabolizable, but acetoacitate."}, {"title": "Ketogenesis .txt", "text": "And D three hydroxybuty can be broken down by ourselves to form energy molecules, as we'll see in just a moment."}, {"title": "Ketogenesis .txt", "text": "Now, this process requires NADH because it's a reduction step."}, {"title": "Ketogenesis .txt", "text": "Acetone acetate is reduced into this product by using NADH inside our liver."}, {"title": "Ketogenesis .txt", "text": "Now, what determines the concentration at equilibrium of these two molecules?"}, {"title": "Ketogenesis .txt", "text": "So do we have more of aceto acetate, or do we have more of this product?"}, {"title": "Ketogenesis .txt", "text": "Well, the answer to that lies to the ratio of NADH to NAD plus."}, {"title": "Ketogenesis .txt", "text": "High levels of NADH, or high ratio of NADH to NAD plus basically means we have way more reactants, and that will drive the reaction forward."}, {"title": "Ketogenesis .txt", "text": "And so high levels of NADH or high ratio of NADH to NAD plus basically means we'll have many D three hydroxybutyrate molecules compared to aceto acetate."}, {"title": "Ketogenesis .txt", "text": "So, once again, within the matrix of the mitochondria, the z three hydroxybutyrate dehydrogenase enzyme can reduce the acetoacetate into another ketone body known as z three hydroxybutyrate."}, {"title": "Ketogenesis .txt", "text": "And the equilibrium of these two molecules basically is determined by the ratio of NADH to NAD plus within the matrix of the mitochondria."}, {"title": "Ketogenesis .txt", "text": "Now, the other reaction that can take place is the spontaneous decarboxylation of the acetone acetate to this nonmetabolizable form, the acetone, which can be released via the breathing process."}, {"title": "Ketogenesis .txt", "text": "Now, when do we produce ketone bodies?"}, {"title": "Ketogenesis .txt", "text": "Well, actually, our liver produces small amounts of ketone bodies normally."}, {"title": "Ketogenesis .txt", "text": "Why?"}, {"title": "Ketogenesis .txt", "text": "Well, because certain cells actually prefer to use ketone bodies as the major energy source."}, {"title": "Ketogenesis .txt", "text": "In fact, the cells of the renal cortex and the heart prefer to use ketone bodies over glucose molecules."}, {"title": "Ketogenesis .txt", "text": "On the other hand, cells found in the brain prefer to use glucose over ketone bodies."}, {"title": "Ketogenesis .txt", "text": "But if we're under certain conditions, for example, starvation conditions, the brain will actually use ketone bodies."}, {"title": "Ketogenesis .txt", "text": "In fact, 75% of the energy needs of the brain will come from the breaking down of ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So we see that normally, acetoacetate and D three hydroxybutyrate are fuel molecules that are normally used by the heart and the renal cortex over glucose."}, {"title": "Ketogenesis .txt", "text": "In fact, under certain conditions, when we're starving, the brain will also use ketone bodies."}, {"title": "Ketogenesis .txt", "text": "In fact, 75% of the energy needs of the brain will come from the breaking down of ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So let's suppose our liver cell produces these ketone bodies."}, {"title": "Ketogenesis .txt", "text": "What will happen next?"}, {"title": "Ketogenesis .txt", "text": "Well, the ketone bodies will move into the blood."}, {"title": "Ketogenesis .txt", "text": "And the great thing about these ketone bodies is they can actually dissolve in the blood."}, {"title": "Ketogenesis .txt", "text": "They're water soluble, and so they do not actually need any type of protein to move them to the target cell."}, {"title": "Ketogenesis .txt", "text": "So we see that ketone bodies are water soluble, and they can move inside the blood without being transported by proteins such as albumin."}, {"title": "Ketogenesis .txt", "text": "Now, the ultimate goal of these ketone bodies when they arrive in the target cell is to transform those ketone bodies back into acetyl coenzyme A, because now in the target cell, we're going to use that acetyl coenzyme A combined with oxalo acetate to help us generate those ATP molecules."}, {"title": "Ketogenesis .txt", "text": "So in the case of d three hydroxybutyrate, that is transformed back into acetyl acetate by the activity of this enzyme."}, {"title": "Ketogenesis .txt", "text": "But now we use an NAD plus to form NADH, which is the opposite of this step here."}, {"title": "Ketogenesis .txt", "text": "If we have aceto acetate going into the target cell, that simply enters directly in this stage, and the acetyl acetate is transformed into acetoacy acetoacetal coenzyme A, and that is catalyzed by the enzyme COA transferase."}, {"title": "Ketogenesis .txt", "text": "And so this requires succinct coenzyme a."}, {"title": "Ketogenesis .txt", "text": "So you form succinate and acetoacetal coenzyme A."}, {"title": "Ketogenesis .txt", "text": "And then this acetyl coenzyme A reacts with a coenzyme a molecule and is catalyzed by thylase to form two acetyl coenzyme a molecules, which then can be used to generate these energy molecules."}, {"title": "Ketogenesis .txt", "text": "So we see that ketone bodies inside a target cell can be broken down into acetyl coenzyme a molecules."}, {"title": "Ketogenesis .txt", "text": "Now, we see that if we use d three hydroxybutyrate, then not only will we ultimately generate the acetyl coenzyme A, we will also generate NADH inside a target cell."}, {"title": "Ketogenesis .txt", "text": "And so the NADH can actually be used by the electron transport chain to generate those ATP molecules."}, {"title": "Ketogenesis .txt", "text": "But if we actually use aceto acetoacete, we will not generate the NADH because we bypass this step."}, {"title": "Ketogenesis .txt", "text": "We only generate the two acetal coenzyme a molecule."}, {"title": "Ketogenesis .txt", "text": "So we see that if the liver forms these d three hydroxybutyrate, then ultimately that target cell will be able to produce more ATP molecules because of this NADH compared to the aceto acetatee, that will not be able to form the NADH inside the target cell."}, {"title": "Ketogenesis .txt", "text": "Now, another thing that I'd like to mention is the following."}, {"title": "Ketogenesis .txt", "text": "If the liver cell produces these ketone bodies, what stops the liver cells from actually generating back these acetyl acetal coenzyme a molecules?"}, {"title": "Ketogenesis .txt", "text": "Well, inside the liver cells, it actually does not contain co enzyme a transphrase."}, {"title": "Ketogenesis .txt", "text": "So even though the other cells of our body do have coenzyme a transferase inside the mitochondrial matrix, the liver cells do not."}, {"title": "Ketogenesis .txt", "text": "And that's important because we don't want the liver to actually eat these ketone bodies to digest these ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So the liver generates the ketone bodies, but it cannot use the ketone bodies, so it can actually move those ketone bodies into the bloodstream so that other cells can use them."}, {"title": "Ketogenesis .txt", "text": "Now, the acetoacitate can actually also be used to decrease the levels of lipolysis, because high levels of aceto acetate means we have high levels of acetylco enzyme in our body, and we do not want to break down any more triglycerides inside our adipose tissue."}, {"title": "Ketogenesis .txt", "text": "And so we see that ketone bodies such as aceto."}, {"title": "Ketogenesis .txt", "text": "Acetate decreases by polysis in our adipose tissue."}, {"title": "Ketogenesis .txt", "text": "And a final thing that I'd like to mention is red blood cells."}, {"title": "Ketogenesis .txt", "text": "Remember that red blood cells do not have mitochondria."}, {"title": "Ketogenesis .txt", "text": "And so what that means is if red blood cells do not have mitochondria, they cannot actually use ketone bodies."}, {"title": "Ketogenesis .txt", "text": "So cells like liver cells and red blood cells will not be able to use ketone hetone bodies as a fuel source."}, {"title": "Biological Buffer Systems.txt", "text": "Previously, we discussed how changing the PH inside our body can lead to many different types of harmful reactions and that can harm the biological molecules inside our cells and inside our body."}, {"title": "Biological Buffer Systems.txt", "text": "For instance, we said that by changing the PH inside the nucleus of our cells, we can disrupt the molecular structure of DNA."}, {"title": "Biological Buffer Systems.txt", "text": "So by changing the PH PH drastically, we essentially disrupt the double helix structure of DNA."}, {"title": "Biological Buffer Systems.txt", "text": "And these two strands of DNA essentially separate to form these two individual strands of DNA."}, {"title": "Biological Buffer Systems.txt", "text": "And that can lead to many different complications."}, {"title": "Biological Buffer Systems.txt", "text": "In fact, anytime we have a substantial change in PH inside our body, be it in our cells, in our blood, or in any system in our body that can cause harm to the different types of biological molecules by disrupting their molecular structure."}, {"title": "Biological Buffer Systems.txt", "text": "And this includes not only DNA molecules, but also the different types of proteins and enzymes that are used by our cells and by our body."}, {"title": "Biological Buffer Systems.txt", "text": "So what that means is for our body and cells to actually function effectively and efficiently, there must be a system in place that allows our body to regulate and prevent these drastic changes in PH from actually happening in the first place."}, {"title": "Biological Buffer Systems.txt", "text": "The question is how?"}, {"title": "Biological Buffer Systems.txt", "text": "Because inside our body, we have many different types of acidbased reactions take place."}, {"title": "Biological Buffer Systems.txt", "text": "So within cells and outside of cells and in our blood, we continually have fluctuations in hydrogen ion concentrations."}, {"title": "Biological Buffer Systems.txt", "text": "So it's very, very important for our body to be able to control and regulate and prevent these drastic changes in PH from happening."}, {"title": "Biological Buffer Systems.txt", "text": "Well, as we'll see in just a moment, our body uses buffer system solutions that contain buffer systems."}, {"title": "Biological Buffer Systems.txt", "text": "And we'll see what that means in just a moment."}, {"title": "Biological Buffer Systems.txt", "text": "First, we want to basically ask and answer the following question if the solutions in our body consisted of nothing but pure water, would that be a good system to actually help prevent these drastic changes in PH?"}, {"title": "Biological Buffer Systems.txt", "text": "So, for instance, let's suppose we're inside the nucleus of our cell."}, {"title": "Biological Buffer Systems.txt", "text": "And inside the nucleus, we have nothing but the DNA molecules and pure water."}, {"title": "Biological Buffer Systems.txt", "text": "So what would happen if we add H plus ions into the nucleus?"}, {"title": "Biological Buffer Systems.txt", "text": "What would happen if we have an acid based reaction that takes place inside that nucleus where we have nothing but pure water and the DNA molecules?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, basically, this curve describes this situation."}, {"title": "Biological Buffer Systems.txt", "text": "This is the Titration curve for pure water."}, {"title": "Biological Buffer Systems.txt", "text": "So the y axis is the PH and the x axis is the acid base reaction."}, {"title": "Biological Buffer Systems.txt", "text": "So as we go along the x axis, we're essentially adding H plus ions into that solution."}, {"title": "Biological Buffer Systems.txt", "text": "So initially, when we haven't added those H plus ions yet, we are at a PH of seven."}, {"title": "Biological Buffer Systems.txt", "text": "And that's because we're dealing with pure water."}, {"title": "Biological Buffer Systems.txt", "text": "Now, notice what happens along the curve."}, {"title": "Biological Buffer Systems.txt", "text": "As soon as we add even a tiny amount of those H plus ions as soon as even a tiny number of those H plus ions are mixed into our solution."}, {"title": "Biological Buffer Systems.txt", "text": "Notice what happens to the curve."}, {"title": "Biological Buffer Systems.txt", "text": "The curve drops from seven all the way to two very drastically immediately following the addition of H plus ions."}, {"title": "Biological Buffer Systems.txt", "text": "And what that tells us is our cells and the outside portion of cells, even though it does consist of water, it cannot be pure water because pure water isn't a good system because it can prevent these drastic changes in PH from actually taking place."}, {"title": "Biological Buffer Systems.txt", "text": "So the curve shows that adding acid to pure water creates an immediate and drastic change in PH."}, {"title": "Biological Buffer Systems.txt", "text": "And if the cells of our body and the blood and the various biological systems in our body consisted of pure water and nothing else, then any acid based reaction that took place inside our body would change the PH abruptly destroying the many different types of biological molecules by disrupting their molecular structure."}, {"title": "Biological Buffer Systems.txt", "text": "As can be seen from the following curve."}, {"title": "Biological Buffer Systems.txt", "text": "Because this drop in our PH means a very, very large change in PH takes place for a very small amount of H plus ions that have been added to our mixture."}, {"title": "Biological Buffer Systems.txt", "text": "So what the cell does is or what our body does is for example, this is true for our blood, for our cells and other parts of our body."}, {"title": "Biological Buffer Systems.txt", "text": "What our body does is it uses instead of using pure water, it uses water and a mixture of a buffer system."}, {"title": "Biological Buffer Systems.txt", "text": "Now, what exactly is a buffer system?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, a buffer system is a solution in which we have water as a solvent, but we also have a certain concentration of an acid and an equal concentration of the conjugate base to that particular acid."}, {"title": "Biological Buffer Systems.txt", "text": "Now, why is that useful?"}, {"title": "Biological Buffer Systems.txt", "text": "Why is it helpful to have the acid and its conjugate base?"}, {"title": "Biological Buffer Systems.txt", "text": "Well."}, {"title": "Biological Buffer Systems.txt", "text": "Because if we begin to add H plus ions into our mixture because of some type of acid based reaction that takes place inside that solution, then the conjugate base that exists in the water can basically interact and consume some of those H plus ions, and that will decrease the amount of H plus ions in our mixture."}, {"title": "Biological Buffer Systems.txt", "text": "And what that does is it creates a gradual change in PH instead of a drastic change in PH."}, {"title": "Biological Buffer Systems.txt", "text": "And so if we examine the Titration curve for a buffering system, for example, if our acid is acetic acid and the conjugate base is acetate ion, we get the following curve as seen in this graph."}, {"title": "Biological Buffer Systems.txt", "text": "So if we look at this box in region, instead of having a drop in the PH, we have a very, very gradual move."}, {"title": "Biological Buffer Systems.txt", "text": "And so instead of adding a small amount to change our PH drastically, we have to add a lot of the acid to actually create the same drastic change in PH."}, {"title": "Biological Buffer Systems.txt", "text": "So this relatively flat curve basically means so the flat curve means that our system is able to actually resist and prevent drastic changes in PH from actually taking place."}, {"title": "Biological Buffer Systems.txt", "text": "So once again, by adding acid to a buffered solution to a water solution that contains a buffered system, there is a much more gradual change of PH as seen in this box region."}, {"title": "Biological Buffer Systems.txt", "text": "The question is, why does the PH change gradually?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, because of what we said earlier."}, {"title": "Biological Buffer Systems.txt", "text": "Because inside that buffered system, we have this acid, an equal concentration of its conjugate base."}, {"title": "Biological Buffer Systems.txt", "text": "So if this is our acid, then the concentration of the conjugate base is exactly the same."}, {"title": "Biological Buffer Systems.txt", "text": "And for this particular graph, the acid is once again acetic acid, and the conjugate base is the acetate ion."}, {"title": "Biological Buffer Systems.txt", "text": "And so when we add the H plus ions into our mixture, some of those conjugate based molecules, the acetate ion reacts with those H plus ions forming acetic acid."}, {"title": "Biological Buffer Systems.txt", "text": "And that decreases the amount of H plus ions."}, {"title": "Biological Buffer Systems.txt", "text": "It consumes, some of those H plus ions so that a PH does not change as drastically as it does in this particular case."}, {"title": "Biological Buffer Systems.txt", "text": "So, to see what we mean from a mathematical perspective, let's take a look at the following equation."}, {"title": "Biological Buffer Systems.txt", "text": "So basically, what we want to derive is an equation known as the Henderson Hasselbalk equation that you should be familiar with because it comes from general chemistry."}, {"title": "Biological Buffer Systems.txt", "text": "So basically, this equation is convenient when we're trying to determine the buffet systems that we want to use."}, {"title": "Biological Buffer Systems.txt", "text": "So let's begin with the dissociation equation for this particular acid."}, {"title": "Biological Buffer Systems.txt", "text": "So let's suppose we use some hypothetical acid, Ha, and it dissociates into H plus ions and its conjugate base."}, {"title": "Biological Buffer Systems.txt", "text": "Now, from chemistry, we know that the equilibrium constant expression for this equation is given by this expression."}, {"title": "Biological Buffer Systems.txt", "text": "So the acid association curve Ka is equal to the product of the concentration of these two products divided by the concentration of that acid."}, {"title": "Biological Buffer Systems.txt", "text": "So this is the acid that we're using in our buffer system, and this is its conjugate base."}, {"title": "Biological Buffer Systems.txt", "text": "Now let's take the log of both sides."}, {"title": "Biological Buffer Systems.txt", "text": "We get the following result."}, {"title": "Biological Buffer Systems.txt", "text": "Now, let's actually use a simple rule that we know for mathematics."}, {"title": "Biological Buffer Systems.txt", "text": "So in mathematics, we learn that if we take the log of the product of two values, a and B, then by the laws of logs, that is equal to log of A plus log of B."}, {"title": "Biological Buffer Systems.txt", "text": "So if we look at the following expression, the right side, let's suppose that this the concentration of H plus is A and the ratio of the conjugate base to its assets."}, {"title": "Biological Buffer Systems.txt", "text": "So A to ha is equal to the B value."}, {"title": "Biological Buffer Systems.txt", "text": "So log of a, B is equal to."}, {"title": "Biological Buffer Systems.txt", "text": "So we essentially expanded by using this rule, and we get the following result."}, {"title": "Biological Buffer Systems.txt", "text": "So now, if we multiply each term both sides by negative one, we get the following result."}, {"title": "Biological Buffer Systems.txt", "text": "And notice that this term is actually the definition of PKA."}, {"title": "Biological Buffer Systems.txt", "text": "So PKA is equal to negative log of Ka, and this is the definition of PH."}, {"title": "Biological Buffer Systems.txt", "text": "Negative log of the H plus concentration is equal to PH."}, {"title": "Biological Buffer Systems.txt", "text": "And this we leave as it is."}, {"title": "Biological Buffer Systems.txt", "text": "Now, if we take this expression, the log and bring it to the left side, we get our Henderson Hasselbalk equation."}, {"title": "Biological Buffer Systems.txt", "text": "So what this equation tells us is the PH of our solution that contains that Buffet system is equal to the PKA value of that particular asset that is used in that buffer system, plus the log of the ratio of the conjugate base to its acid."}, {"title": "Biological Buffer Systems.txt", "text": "Now, why is this equation a useful equation?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, let's get back to it in just a moment."}, {"title": "Biological Buffer Systems.txt", "text": "Let's go back to this graph for just a second."}, {"title": "Biological Buffer Systems.txt", "text": "So earlier I said that this particular curve describes an acid that is acetic acid and a base that is acetate ion."}, {"title": "Biological Buffer Systems.txt", "text": "So the question that I want to ask right now is why is it that in a buffered system we want equal concentrations of the acetic acid and acetate ion?"}, {"title": "Biological Buffer Systems.txt", "text": "So why must this actually be true?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, to answer that question, let's take a look at the following curve."}, {"title": "Biological Buffer Systems.txt", "text": "So, earlier I said that the flat of the curve is the greater the ability of that buffer system to actually prevent a drastic change in PH from actually taking place."}, {"title": "Biological Buffer Systems.txt", "text": "So based on the curve, where exactly is our flattest slope?"}, {"title": "Biological Buffer Systems.txt", "text": "So actually I've marked down the flattest slope."}, {"title": "Biological Buffer Systems.txt", "text": "It's right at this point."}, {"title": "Biological Buffer Systems.txt", "text": "This is the point where we have the flattest slope."}, {"title": "Biological Buffer Systems.txt", "text": "And so what that means is this is the point where we have the greatest ability of that buffer system to actually resist and prevent that change in PH from taking place."}, {"title": "Biological Buffer Systems.txt", "text": "Because the flat of the slope is the smaller the change in the y value is and the smaller our PH change is."}, {"title": "Biological Buffer Systems.txt", "text": "Now, if we look at this corresponding value along our y axis, we see that it's somewhere here."}, {"title": "Biological Buffer Systems.txt", "text": "And so this is equal to a PH of about 4.75."}, {"title": "Biological Buffer Systems.txt", "text": "So we see that for this particular buffered system in which we use acetic acid and acetate ion for that buffered system, the greatest ability of this buffered system to resist a change in PH is when the PH is equal to 4.75."}, {"title": "Biological Buffer Systems.txt", "text": "Now, what is the PKA of acetic acid?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, if you look up the PKA value of acetic acid, it's 4.75."}, {"title": "Biological Buffer Systems.txt", "text": "And that is not a coincidence, because if we go back to this equation and we plug in a PH of 4.75 and the PKA of 4.75, then we'll see that the PH is equal to the PKA only if the concentration of the base is equal to the concentration of that acid."}, {"title": "Biological Buffer Systems.txt", "text": "That is, if this is equal to this, then this ratio is equal to one, and only then will log of one be equal to zero."}, {"title": "Biological Buffer Systems.txt", "text": "And if this log is equal to zero, only then will the PH equal to the PKA."}, {"title": "Biological Buffer Systems.txt", "text": "So from this equation we see that if this is true, only then will the PH equal to the PKA."}, {"title": "Biological Buffer Systems.txt", "text": "So once again, from this previous graph, we basically describe the Titration curve for the buffer system in which we have acetic acid as that acid and acetate ion as the conjugate base."}, {"title": "Biological Buffer Systems.txt", "text": "Now, the PKA value of acetic acid is 4.75."}, {"title": "Biological Buffer Systems.txt", "text": "And notice that when the PH of the solution is 4.75, which is the same as the PKA, the curve has the flattest slope, and the flattest slope corresponds to the region with the least change in PH."}, {"title": "Biological Buffer Systems.txt", "text": "So what do we conclude from this discussion?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, basically, buffer functions best at PH values that correspond to the PKA of that asset that we're using in the first place."}, {"title": "Biological Buffer Systems.txt", "text": "So what that means in layman terms is if we want to have a solution that basically is at a specific PH and we want it to remain at that PH, then we have to find an acid that will serve as that buffer system that has a PK value that is equivalent to that particular PH value."}, {"title": "Biological Buffer Systems.txt", "text": "And that's exactly what our body does."}, {"title": "Biological Buffer Systems.txt", "text": "So we have different types of biological buffer systems in place."}, {"title": "Biological Buffer Systems.txt", "text": "For instance, we know that the physiological PH of our body, for example, of our blood, is around 7.4."}, {"title": "Biological Buffer Systems.txt", "text": "And what that means is most of the biological systems in our body have to remain as this PH."}, {"title": "Biological Buffer Systems.txt", "text": "Now, to resist PH change, our body uses these same buffer systems that we just described."}, {"title": "Biological Buffer Systems.txt", "text": "And we have various types of acids that are in place depending on what the PH is that we want to essentially stick around to."}, {"title": "Biological Buffer Systems.txt", "text": "For example, one acid that is used by our body is phosphoric acid."}, {"title": "Biological Buffer Systems.txt", "text": "So we have this acid, and this is the conjugate base."}, {"title": "Biological Buffer Systems.txt", "text": "Now, why do we use this asset?"}, {"title": "Biological Buffer Systems.txt", "text": "Well, because its PKA value is seven 7.21, and this is the PK value around which we want our PH to."}, {"title": "Permeability of Cell Membrane .txt", "text": "The phospholipid bilayer membrane is said to be a semipermeable membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And what that means is certain molecules which are permeable to the membrane are able to pass across the membrane without much difficulty."}, {"title": "Permeability of Cell Membrane .txt", "text": "But other molecules which are impermeable to the cell membrane cannot pass across the cell membrane without assistance of some type of protein molecule."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, inside our body, we have all these different types of molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "And the ability of these molecules to actually pass across the cell membrane varies over a wide range of value."}, {"title": "Permeability of Cell Membrane .txt", "text": "So the question that I'd like to discuss in this lecture is what exactly are the factors that determine the permeability of a given molecule?"}, {"title": "Permeability of Cell Membrane .txt", "text": "What determines the ability of a given molecule to actually pass across the cell membrane?"}, {"title": "Permeability of Cell Membrane .txt", "text": "So perhaps the most important factor is polarity."}, {"title": "Permeability of Cell Membrane .txt", "text": "So what does that actually mean?"}, {"title": "Permeability of Cell Membrane .txt", "text": "Well, we know that the core, the inside of the phospholipid bilayer membrane is predominantly nonpolar."}, {"title": "Permeability of Cell Membrane .txt", "text": "It is hydrophobic as a result of those hydrocarbon tails."}, {"title": "Permeability of Cell Membrane .txt", "text": "And what that means is for a molecule to actually be able to pass across the cell membrane, it must be able to dissolve inside the core of that phospholipid Bilay."}, {"title": "Permeability of Cell Membrane .txt", "text": "So that implies that the permeability of a molecule depends on its ability to actually dissolve in a nonpolar hydrophobic solution."}, {"title": "Permeability of Cell Membrane .txt", "text": "So the more nonpolar a molecule is, the more likely it is to actually dissolve within the hydrophobic core environment of that phospholipid bilayer membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "So what that means is for a nonpolar molecule, for a small non polar molecule to actually pass across the cell membrane, it basically dissolves inside that cell membrane as it moves across that cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "Permeability of Cell Membrane .txt", "text": "So, in diagram A, let's suppose we have a cross section of that phospholipid bilateral membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And on both sides, we have an Aqueous environment."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, remember, in an Aqueous environment, water molecules predominate."}, {"title": "Permeability of Cell Membrane .txt", "text": "Those are the solvent molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "And any other molecule present inside that solvent basically exists in the cage of water molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "And this is called a salvation shell."}, {"title": "Permeability of Cell Membrane .txt", "text": "So let's suppose we have a small nonpolar molecule shown in purple."}, {"title": "Permeability of Cell Membrane .txt", "text": "And this nonpolar molecule exists in the cage in a salvation shell that is shown in this diagram."}, {"title": "Permeability of Cell Membrane .txt", "text": "And before it actually makes its way into this non polar cell membrane, this nonpolar molecule must break free from this cage."}, {"title": "Permeability of Cell Membrane .txt", "text": "So it basically bounces back and forth, and eventually it makes its way out, eventually collides with this phospholipid bilayer membrane, and it makes its way into this nonpolar region."}, {"title": "Permeability of Cell Membrane .txt", "text": "So to enter that bilayer membrane, that non polar molecule must lose that salvation shell, the cage of water molecules around it."}, {"title": "Permeability of Cell Membrane .txt", "text": "And once that happens, it enters that hydrophobic region of the core of that phospholipid bilayer membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And so now what begins to happen is we have these Van Der Valley interactions."}, {"title": "Permeability of Cell Membrane .txt", "text": "So London dispersion forces, which basically exist between the non polar molecule and the tails, the hydrocarbon tails of these phospholipids."}, {"title": "Permeability of Cell Membrane .txt", "text": "So eventually, it moves across and makes its way back out on the other side."}, {"title": "Permeability of Cell Membrane .txt", "text": "And once again, that salvation shell, that cage of water molecules, is basically reformed."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, this discussion basically leads to the next important point."}, {"title": "Permeability of Cell Membrane .txt", "text": "If a molecule is polar or it has some type of charge, what that means is it will not be very likely to actually pass across the cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "Why?"}, {"title": "Permeability of Cell Membrane .txt", "text": "Well, let's suppose this molecule has a charge."}, {"title": "Permeability of Cell Membrane .txt", "text": "If this molecule here, shown in purple, actually has a charge, then that means these electrostatic interactions, which will be hydrogen bonds, will be very, very stabilizing."}, {"title": "Permeability of Cell Membrane .txt", "text": "And that charged molecule will not want to lose those energetically favorable interactions and enter an environment in which it cannot form those same energetically stabilizing bonds."}, {"title": "Permeability of Cell Membrane .txt", "text": "So a charged or a very polar molecule will not be able to dissolve and travel across the cell membrane because to do so, that means it must lose these hydrogen bonds, interactions between the water molecules, and then into an environment in which it cannot form those same stabilizing bonds."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we see that this also means that charged or very polar molecules did not readily pass across the membrane because such molecules, one, lose the strong interactions with water that exist in that salvation shell, that cage of water molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "And two, they cannot form those same stabilized interactions with the hydrocarbon tails found inside the core of that bilateral membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we see that ions such as sodium ions, potassium ions or chloride ions have a very low permeability."}, {"title": "Permeability of Cell Membrane .txt", "text": "They cannot pass across that cell membrane as shown in the following diagram."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we have a potassium ion, let's say, found on the outside of that cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And this is the phospholipid bilayer."}, {"title": "Permeability of Cell Membrane .txt", "text": "And notice that it exists in this cage, in this salvation shell, in which we have all these hydrogen bonds shown in green."}, {"title": "Permeability of Cell Membrane .txt", "text": "And so, because these bonds, these electric interactions, are so stabilizing, it doesn't actually want to leave and break these bonds, because if it dissolves inside the non polar region of that phospholipid biolare, it will not be able to form those same energetically favorable interactions."}, {"title": "Permeability of Cell Membrane .txt", "text": "So charged ions or molecule, charged ions or molecules do not easily pass across the membrane because they do not want to lose those energetically favorable water interactions that exist in that water cage."}, {"title": "Permeability of Cell Membrane .txt", "text": "And to basically describe what we mean, let's take a look at these two molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "So these two molecules are structurally similar, so they have very similar structures."}, {"title": "Permeability of Cell Membrane .txt", "text": "The only difference is at a PH of about seven, which is the physiological PH, this exists without a charge, while this tryptophan amino acid exists in its zvitarion form."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we'll have a full negative charge and a full positive charge."}, {"title": "Permeability of Cell Membrane .txt", "text": "And because this actually contains full charges and this one doesn't, the end, though, is 1000 times more likely to actually pass across that cell membrane and dissolve in that hydrophobic core section than that tryptophan amino acid."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we see that indo, an uncharged molecule that is structurally similar to the tryptophan amino acid, crosses the membrane 1000 times more likely or more quickly than the tryptophan in its zvitarion form, which is the form that exists at the physiological PH of around seven."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, so we can basically summarize the following result."}, {"title": "Permeability of Cell Membrane .txt", "text": "We see that for a molecule to actually dissolve across that cell membrane, it must be able to interact in a stabilizing way with those tails, with the hydrocarbon tails of those phospholipid molecules."}, {"title": "Permeability of Cell Membrane .txt", "text": "And so non polar molecules can dissolve across the membrane, but polar molecules cannot."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, technically, that is not actually the entire story because we see water molecules are actually an exception to that rule."}, {"title": "Permeability of Cell Membrane .txt", "text": "Water molecules can actually pass across the cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "In fact, water molecules are 1 billion times more likely to actually pass across the cell membrane than potassium or than potassium or sodium ions."}, {"title": "Permeability of Cell Membrane .txt", "text": "Now, water, as we know, is in fact a polar molecule."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we have a partial negative charge on the oxygen and partial positive charges on the hydrogen atoms."}, {"title": "Permeability of Cell Membrane .txt", "text": "It is a polar molecule, yet somehow it's able to actually dissolve across and pass across that cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "The question is why?"}, {"title": "Permeability of Cell Membrane .txt", "text": "Well, not only does the polarity determine the ability, the permeability of that molecule, but also the size and the concentration also determine its ability to actually pass across the cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "So water molecules are actually relatively small molecules and they can squeeze across the cell membrane with ease."}, {"title": "Permeability of Cell Membrane .txt", "text": "On top of that, if we discuss the polarity of the water molecule and we compare it to, let's say, the tryptophan or this potassium, the tryptophan and potassium actually have full charges."}, {"title": "Permeability of Cell Membrane .txt", "text": "And so they're much more polar than water."}, {"title": "Permeability of Cell Membrane .txt", "text": "So because water does not actually have a full charge, it can pass across the cell membrane with ease."}, {"title": "Permeability of Cell Membrane .txt", "text": "On top of that, we have many, many water molecules on the outside and inside of that bilayer membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And all these water molecules are continually colliding with the cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "And because we have such a high number of water molecules, some of them are likely to actually pass across when they collide."}, {"title": "Permeability of Cell Membrane .txt", "text": "So we see that water is the great exception to the rule above."}, {"title": "Permeability of Cell Membrane .txt", "text": "Water molecules can cross bilayer membranes with relative ease, 1 billion times more likely than these ions or these ions."}, {"title": "Permeability of Cell Membrane .txt", "text": "So now, this is because they do not contain a full charge."}, {"title": "Permeability of Cell Membrane .txt", "text": "There is a very high concentration of water outside and inside the cell."}, {"title": "Permeability of Cell Membrane .txt", "text": "And that means every time these collide, there's a likelihood that they're going to actually pass across."}, {"title": "Permeability of Cell Membrane .txt", "text": "And number three is they are relatively small."}, {"title": "Permeability of Cell Membrane .txt", "text": "So, for instance, if I compare, let's say, indol and water, the water is much more likely to actually pass across the cell membrane than indol because indol, even though it doesn't contain a full charge, indol is larger."}, {"title": "Permeability of Cell Membrane .txt", "text": "We don't find indol in high concentrations and indol."}, {"title": "Permeability of Cell Membrane .txt", "text": "When it collides, it cannot actually squeeze across that cell membrane because of its size and the fact that there are not too many collisions taking place between indo and the cell membrane in the first place."}, {"title": "Permeability of Cell Membrane .txt", "text": "So three things that you have to consider to basically determine the permeability of a molecule across the cell membrane."}, {"title": "Permeability of Cell Membrane .txt", "text": "So number one is, will it actually dissolve in that non polar core section of the phospholipid bilayer?"}, {"title": "Permeability of Cell Membrane .txt", "text": "So you have to look at the molecule's polarity."}, {"title": "Permeability of Cell Membrane .txt", "text": "Number two is you have to look at size."}, {"title": "Permeability of Cell Membrane .txt", "text": "Number three is you have to look at the concentration of that molecule outside or inside that particular phospholipid bilerin membrane."}, {"title": "Eukaryotes .txt", "text": "Eukaryotic cells, unlike prokaryotic cells, are those cells that contain a nucleus as well as other membrane bound organelles."}, {"title": "Eukaryotes .txt", "text": "And eukaryotic cells include animal cells and plant cells, as well as protist and fungi."}, {"title": "Eukaryotes .txt", "text": "And in this lecture, we're going to focus on the structure of the eukaryotic cell."}, {"title": "Eukaryotes .txt", "text": "We're going to discuss different types of organelles that exist within that that eukaryotic cell."}, {"title": "Eukaryotes .txt", "text": "And let's begin with the outermost structure that every single eukaryotic cell has."}, {"title": "Eukaryotes .txt", "text": "It's the cell membrane so basically enclosing the entire cell."}, {"title": "Eukaryotes .txt", "text": "And everything found inside that cell is a semipermeable phospholipid bilayer, a cell membrane that plays a role in cell transport."}, {"title": "Eukaryotes .txt", "text": "It basically allows things into the cell and out of the cell."}, {"title": "Eukaryotes .txt", "text": "It also functions in cell communication as well as protecting the cell from outside sources of harm."}, {"title": "Eukaryotes .txt", "text": "Now, other types of eukaryotic cells, not all, but some eukaryotic cells, for example, plant cells, also contain an additional second protecting barrier known as the cell wall."}, {"title": "Eukaryotes .txt", "text": "The cell wall protects plant cells and it also gives them the shape and structure."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to basically the organelle that defines the eukaryotic cell, known as the nucleus."}, {"title": "Eukaryotes .txt", "text": "The nucleus is basically an organelle that contains the genetic information and the nucleus contains its own phospholipid bilayer that is called the nuclear envelope or the nuclear membrane to differentiate it from the cell membrane."}, {"title": "Eukaryotes .txt", "text": "The nuclear membrane contains nuclear pores, very small openings that allow certain things into and out of that nucleus."}, {"title": "Eukaryotes .txt", "text": "Now, at the center, at the heart of our nucleus, is a region of specialized region known as the nucleolus."}, {"title": "Eukaryotes .txt", "text": "And the nucleolus is the region where we synthesize incomplete ribosomes, the ribosomes that end up being in this region, the endoplasmic reticulum, or as free ribosomes found inside the cytosol, which we'll talk about in just a moment."}, {"title": "Eukaryotes .txt", "text": "So let's move on to this region here."}, {"title": "Eukaryotes .txt", "text": "So we have the cell membrane, this is our nucleus, the nuclear envelope that contains those nuclear pores, as well as our DNA that is found inside the nucleus."}, {"title": "Eukaryotes .txt", "text": "And this is our region known as the nucleolus."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to region number four and region number five."}, {"title": "Eukaryotes .txt", "text": "Together, these two regions are known as the endoplasmic reticulum."}, {"title": "Eukaryotes .txt", "text": "Now, just outside the nucleus are a series of mazelike membranes called the endoplasmic reticulum, or simply the Er."}, {"title": "Eukaryotes .txt", "text": "And we have two types."}, {"title": "Eukaryotes .txt", "text": "We have the rough endoplasmic reticulum that contains these dots, and this smooth endoplasmic reticulum, shown in region five that lacks those dots."}, {"title": "Eukaryotes .txt", "text": "So the endoplasmic reticulum, right next to our nucleus contains ribosomes embedded in our membrane of that Er."}, {"title": "Eukaryotes .txt", "text": "And this gives it a granular appearance under the microscope."}, {"title": "Eukaryotes .txt", "text": "And that's exactly why we call it the rough Er, because it contains those ribosomes inside the membrane of the Er."}, {"title": "Eukaryotes .txt", "text": "Now, what exactly is the function, the purpose of our Er?"}, {"title": "Eukaryotes .txt", "text": "So basically the Er, the rough endoplasmic reticulum, functions to synthesize our proteins."}, {"title": "Eukaryotes .txt", "text": "It synthesizes proteins that end up either being secreted from the cell or end up in the cell membrane of our cell."}, {"title": "Eukaryotes .txt", "text": "So basically, we see that the nuclear envelope and the membrane of our Er are jointed."}, {"title": "Eukaryotes .txt", "text": "They're connected in these regions."}, {"title": "Eukaryotes .txt", "text": "And that's exactly why once our nucleolus synthesizes those incomplete ribosomes, those ribosomes can then be placed inside this Er to basically embed the ribosomes inside the membrane of the Er."}, {"title": "Eukaryotes .txt", "text": "And then those ribosomes can synthesize our proteins."}, {"title": "Eukaryotes .txt", "text": "Now, what about this section, the smooth Er shown by region five."}, {"title": "Eukaryotes .txt", "text": "This region also contains these membranes, but they do not contain ribosomes."}, {"title": "Eukaryotes .txt", "text": "And so that means this smooth Er isn't directly involved in synthesized proteins."}, {"title": "Eukaryotes .txt", "text": "Instead, the smooth Er functions to produce lipids or fats, as well as to detoxify toxins and drugs."}, {"title": "Eukaryotes .txt", "text": "Now, the next section we're going to examine is region number six."}, {"title": "Eukaryotes .txt", "text": "This is known as the Golgi apparatus, the Golgi complex, or simply the Golgi."}, {"title": "Eukaryotes .txt", "text": "It's named after scientists who came up who first noticed this type of structure within our cell."}, {"title": "Eukaryotes .txt", "text": "So basically, what happens is once our proteins are synthesized within our Er, then they travel into the Golgi apparatus."}, {"title": "Eukaryotes .txt", "text": "And the Golgi apparatus is a series of membrane bound sacks that functions as packaging and sorting center of our cell."}, {"title": "Eukaryotes .txt", "text": "It packages sorts as well as modifies proteins before they actually secreted by that cell."}, {"title": "Eukaryotes .txt", "text": "Now, proteins that leave our Golgi apparatus, once they are modified, leave in little sections, little structures known as secretory vesicles."}, {"title": "Eukaryotes .txt", "text": "And these are shown by these blue vesicles here."}, {"title": "Eukaryotes .txt", "text": "So once our protein is modified, for example, we add some type of sugar onto the protein."}, {"title": "Eukaryotes .txt", "text": "It leaves the Golgi apparatus inside a vesicle."}, {"title": "Eukaryotes .txt", "text": "And the reason it stays inside the vesicle is to protect the structure of our protein."}, {"title": "Eukaryotes .txt", "text": "So that vesicle can then basically go onto the membrane, and the protein can either remain in the membrane of the cell or it can secrete itself outside that cell."}, {"title": "Eukaryotes .txt", "text": "Now, we also have ribosomes that aren't actually attached to the membrane of our endoplasmic reticulum."}, {"title": "Eukaryotes .txt", "text": "And these ribosomes are known as free ribosomes."}, {"title": "Eukaryotes .txt", "text": "They are shown in this region."}, {"title": "Eukaryotes .txt", "text": "These two regions are our free ribosomes."}, {"title": "Eukaryotes .txt", "text": "So ribosomes are not organelles because they do not have any type of membrane."}, {"title": "Eukaryotes .txt", "text": "These ribosomes are simply structures."}, {"title": "Eukaryotes .txt", "text": "So ribosomes that are found in the cytosol, which is region number 14, it's this clear region shown on the entire cell."}, {"title": "Eukaryotes .txt", "text": "So we have ribosomes that are found in a cytosol and which are not bound to any type of membrane, are called free ribosomes."}, {"title": "Eukaryotes .txt", "text": "And they function to also synthesize protein."}, {"title": "Eukaryotes .txt", "text": "But these proteins synthesized by the free ribosomes end up staying within our cytosol."}, {"title": "Eukaryotes .txt", "text": "So that's the main difference between the ribosomes found inside the rough and the plasma reticulum and the free ribosomes, the ribosomes in the Er basically create proteins that either leave that cell or end up being in the cell membrane."}, {"title": "Eukaryotes .txt", "text": "However, the proteins created by the free ribosomes stay in the cytosol."}, {"title": "Eukaryotes .txt", "text": "Now, what exactly is the difference between cytosol and cytoplasm because the two are sometimes confusing or confused."}, {"title": "Eukaryotes .txt", "text": "Basically, the cytoplasm is the region between the cell membrane and the nucleus."}, {"title": "Eukaryotes .txt", "text": "And the cytoplasm includes all the organelles and all the structures found between these two sections."}, {"title": "Eukaryotes .txt", "text": "So that includes the mitochondria, which we'll discuss next."}, {"title": "Eukaryotes .txt", "text": "That includes the ribosomes, the goldie apparatus, the vesicles, our er, and everything else in between the cell membrane and the nucleus."}, {"title": "Eukaryotes .txt", "text": "Now, the cytosol is not exactly the cytoplasm."}, {"title": "Eukaryotes .txt", "text": "The cytosol is basically the cytoplasm minus all the structures and organelles."}, {"title": "Eukaryotes .txt", "text": "So if we take out all the organelles between the cell membrane and the nucleus, we are simply left with the fluid region."}, {"title": "Eukaryotes .txt", "text": "And the fluid is known as the cytosol."}, {"title": "Eukaryotes .txt", "text": "And the cytosol contains these free ribosomes that basically move about this entire fluid region."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to the mitochondria."}, {"title": "Eukaryotes .txt", "text": "The mitochondria is a very important structure in the eukaryotic cell."}, {"title": "Eukaryotes .txt", "text": "The mitochondria, in a way, is like the nuclear power plant because it transforms one type of energy into a different type of energy that the cell can then use to help power different types of processes."}, {"title": "Eukaryotes .txt", "text": "So the mitochondria is the power plant of the cell."}, {"title": "Eukaryotes .txt", "text": "It breaks down molecules, biomolecules and produces energies that can be harvested to power many different processes."}, {"title": "Eukaryotes .txt", "text": "Now, we'll discuss the details of the mitochondria organ now, in a different lecture, but here we'll mention that it contains an outer layer as well as an inner membrane layer."}, {"title": "Eukaryotes .txt", "text": "And it also contains its own DNA and can actually undergo its own process of replication."}, {"title": "Eukaryotes .txt", "text": "It can undergo a process known as binary fission."}, {"title": "Eukaryotes .txt", "text": "And we'll discuss that in more detail in a different lecture."}, {"title": "Eukaryotes .txt", "text": "So this is our mitochondria."}, {"title": "Eukaryotes .txt", "text": "It's the power plant of our cell."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to our Lysosomes, which are described by these two green vesicles here."}, {"title": "Eukaryotes .txt", "text": "So Lysosomes are essentially specialized vesicles that contain hydrolytic enzymes."}, {"title": "Eukaryotes .txt", "text": "So that means inside the environment of our Lysosome, we have a relatively low PH, it's about five."}, {"title": "Eukaryotes .txt", "text": "And these Lysosomes basically help break down unwanting material inside the cell."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to another type of specialized vesicle known as the paroxysome."}, {"title": "Eukaryotes .txt", "text": "The paroxysome are also known as microbodies."}, {"title": "Eukaryotes .txt", "text": "So very small bodies that contain that cell membrane and its own internal environment."}, {"title": "Eukaryotes .txt", "text": "So paroxysomes are specialized vesicles that create hydrogen peroxide, so H 202 that break down fats as well as detoxify dangerous substances, especially in the liver found inside our bodies."}, {"title": "Eukaryotes .txt", "text": "So the cells in the liver of our body contain lots of paroxysomes because we have to break down different types of toxins that we ingest into our bodies, such as alcohol, for example."}, {"title": "Eukaryotes .txt", "text": "Now let's move on to a region known as the centrioles."}, {"title": "Eukaryotes .txt", "text": "The centriole is basically this region here."}, {"title": "Eukaryotes .txt", "text": "And the primary function of our centrioles is during cell division."}, {"title": "Eukaryotes .txt", "text": "So when the cell decides to divide, these basically help to separate the cell into two different cells."}, {"title": "Eukaryotes .txt", "text": "And finally, the last thing we want to discuss is this taillike region here."}, {"title": "Eukaryotes .txt", "text": "This is known as our flagellum."}, {"title": "Eukaryotes .txt", "text": "Now, the flagellum is basically a structure that gives the cell motility."}, {"title": "Eukaryotes .txt", "text": "It gives the cell the ability to basically move."}, {"title": "Eukaryotes .txt", "text": "Now, both Prokaryotes and Eukaryotes have their own type of flagella that moves in its own way and is composed of its own type of protein."}, {"title": "Eukaryotes .txt", "text": "We'll discuss that when we focus on the flagella in a different lecture."}, {"title": "Eukaryotes .txt", "text": "Now, some other things that we should probably mention are glyciosomes, which is another type of microbody."}, {"title": "Eukaryotes .txt", "text": "So plant cells also contain microbodies, known as glyphosomes."}, {"title": "Eukaryotes .txt", "text": "And the glyciosomes also help to break down our lipids into some type of usable form of energy, such as sugar."}, {"title": "Eukaryotes .txt", "text": "So the two types of microbodies are paroxysomes, which are found mostly in animal cells, and glyphosomes, which are found mostly in plant cells."}, {"title": "Eukaryotes .txt", "text": "Now, by the way, centrioles are only found in animal cells."}, {"title": "Eukaryotes .txt", "text": "They are not found in plant cells."}, {"title": "Eukaryotes .txt", "text": "And one other thing, one other organelle that plant cells have and animal cells do not have is the chloroplast."}, {"title": "Eukaryotes .txt", "text": "The chloroplast is basically the organelle that uses oxygen and some type of carbon source."}, {"title": "Eukaryotes .txt", "text": "So CO2 and oxygen or actually, no, it uses CO2 and water to create sugar molecules and it releases oxygen into the atmosphere."}, {"title": "Eukaryotes .txt", "text": "That's the oxygen that we basically breathe in."}, {"title": "Eukaryotes .txt", "text": "So we can imagine that if our mitochondria is the nuclear power plant, the chloroplast is our solar power plant."}, {"title": "Eukaryotes .txt", "text": "It uses the energy that comes from sunlight and it combines carbon dioxide and water to form sugar molecules, usually starch."}, {"title": "Eukaryotes .txt", "text": "So basically, these are different types of organelles and structures that are found inside eukaryotic cells."}, {"title": "Eukaryotes .txt", "text": "And then the next series of lectures, we're going to discuss us each one of these organelles in detail."}, {"title": "Central Nervous System .txt", "text": "The central nervous system of the human body contains a spinal cord and a brain."}, {"title": "Central Nervous System .txt", "text": "So let's begin by looking at the brain."}, {"title": "Central Nervous System .txt", "text": "So let's suppose we look at the side view of the brain and we take a crosssection so that we obtain the following diagram."}, {"title": "Central Nervous System .txt", "text": "So this is the cross sectional view of the side of our brain."}, {"title": "Central Nervous System .txt", "text": "Now, the brain contains three important and sections."}, {"title": "Central Nervous System .txt", "text": "We have the upper portion known as the forebrain."}, {"title": "Central Nervous System .txt", "text": "That's the light purple region here."}, {"title": "Central Nervous System .txt", "text": "We have the mid brain, that's the center green region."}, {"title": "Central Nervous System .txt", "text": "And we have the hind brain, that's the lower portion that is shown in dark purple."}, {"title": "Central Nervous System .txt", "text": "Now, the forebrain and the high brain can be broken down into two subdivisions."}, {"title": "Central Nervous System .txt", "text": "In the case of the forebrain, we have our Teleencephalon and Dyncephalon regions."}, {"title": "Central Nervous System .txt", "text": "For the hive brain, we have the metincephalon and the myelincephalon."}, {"title": "Central Nervous System .txt", "text": "The midbrain consists of the methyphalon."}, {"title": "Central Nervous System .txt", "text": "Now, the Telentephalon contains three important structures."}, {"title": "Central Nervous System .txt", "text": "We have the cerebrum, which is this entire structure here."}, {"title": "Central Nervous System .txt", "text": "We have our hippocampus, this section here, and we also have the basal ganglia."}, {"title": "Central Nervous System .txt", "text": "The dime cellphalon contains the thalamus and the hypothalamus."}, {"title": "Central Nervous System .txt", "text": "This in this section, while the mid brain is this green section here."}, {"title": "Central Nervous System .txt", "text": "Now, the hind brain contains the methylcephalon that has the cerebellum in the puns, while the melancephalon contain the myelincephalon consists of aramidoula."}, {"title": "Central Nervous System .txt", "text": "So let's go through each one of these structures and discuss what the function of these structures is."}, {"title": "Central Nervous System .txt", "text": "And let's begin with the talentlon region of the forebrain."}, {"title": "Central Nervous System .txt", "text": "So that contains the cerebral, the hippocampus and the basal ganglia."}, {"title": "Central Nervous System .txt", "text": "Now, the basal ganglia is simply a collection of cells found at the bottom of the four brain."}, {"title": "Central Nervous System .txt", "text": "So basal means to be at the bottom of, to be at the base."}, {"title": "Central Nervous System .txt", "text": "Ganglia means a collection of cells, a collection of neurons."}, {"title": "Central Nervous System .txt", "text": "So a gang of cells."}, {"title": "Central Nervous System .txt", "text": "And so basal ganglia is a collection of cells at the bottom of the forebrain."}, {"title": "Central Nervous System .txt", "text": "And the role that the basal ganglia plays is to control our voluntary actions, our voluntary movements."}, {"title": "Central Nervous System .txt", "text": "Now, the hippocampus is a structure."}, {"title": "Central Nervous System .txt", "text": "It's this structure here that plays a role in the limbic system of our body."}, {"title": "Central Nervous System .txt", "text": "And the hippocampus plays a role in memory."}, {"title": "Central Nervous System .txt", "text": "Now, what about our Cerebral?"}, {"title": "Central Nervous System .txt", "text": "Well, the Cerebral is the structure, the forebrain that basically makes us human."}, {"title": "Central Nervous System .txt", "text": "It gives us the ability to think."}, {"title": "Central Nervous System .txt", "text": "It gives us the ability to reason."}, {"title": "Central Nervous System .txt", "text": "It gives us logic and intuition."}, {"title": "Central Nervous System .txt", "text": "It also gives us the ability to control our emotion and feelings and to control our voluntary action."}, {"title": "Central Nervous System .txt", "text": "Now, the Cerebral is a pretty large structure."}, {"title": "Central Nervous System .txt", "text": "It takes up this entire region here."}, {"title": "Central Nervous System .txt", "text": "And the Cerebral consists of the left and the right Cerebral hemisphere."}, {"title": "Central Nervous System .txt", "text": "So the left and the right hemispheres inside the Cerebral are connected by a bridge."}, {"title": "Central Nervous System .txt", "text": "And this bridge of cells is known as the Corpus Callosum."}, {"title": "Central Nervous System .txt", "text": "The Corpus callosum is a network of myelinated cells that connects the left to the right hemisphere of our Cerebral."}, {"title": "Central Nervous System .txt", "text": "Now, the outermost and the topmost portion of our cerebral is a section known as the cerebral cortex."}, {"title": "Central Nervous System .txt", "text": "And within our cerebral cortex, we have the higher level functioning processes taking place."}, {"title": "Central Nervous System .txt", "text": "So that is our teleencephalon."}, {"title": "Central Nervous System .txt", "text": "It contains the cerebral, the hippocampus and the basal ganglia."}, {"title": "Central Nervous System .txt", "text": "Let's move on to our dimecephalon of the forebrain."}, {"title": "Central Nervous System .txt", "text": "The Dynecephalon contains arthalamus and the hypothalamus."}, {"title": "Central Nervous System .txt", "text": "So the hypothalamus we're going to discuss in detail when we're going to look at the endocrine system."}, {"title": "Central Nervous System .txt", "text": "The hypothalamus is basically the control center of the endocrine system because it controls the pituitary gland, the master gland of our endocrine system."}, {"title": "Central Nervous System .txt", "text": "What about the thalamus?"}, {"title": "Central Nervous System .txt", "text": "Well, the thalamus in many different ways is like the secretary of our cerebral."}, {"title": "Central Nervous System .txt", "text": "What that means is it relays sensory and motor signals to and from our cerebral and inside our cerebral."}, {"title": "Central Nervous System .txt", "text": "Once those signals go inside our cerebral, that's where we process and integrate that information."}, {"title": "Central Nervous System .txt", "text": "Now what about the mid brain?"}, {"title": "Central Nervous System .txt", "text": "The mid brain consists of the methanephalon which is this green section here."}, {"title": "Central Nervous System .txt", "text": "And notice that the mid brain is situated right between our forebrain and the hind brain."}, {"title": "Central Nervous System .txt", "text": "So being situated between the forebrain and the hind brain, this small section basically relays auditory and visual information between the top portion and the bottom portion of the brain."}, {"title": "Central Nervous System .txt", "text": "And our midbrain is also involved in controlling the movement of our eyes."}, {"title": "Central Nervous System .txt", "text": "So let's move on to the hind brain, the lower portion of the brain that consists of these many structures."}, {"title": "Central Nervous System .txt", "text": "So within the metin cephalon, we have the cerebellum and the puns."}, {"title": "Central Nervous System .txt", "text": "Within the myelin cephalon we have our medulla, also known as the medulla omblongada."}, {"title": "Central Nervous System .txt", "text": "Now let's discuss our cerebellum, the cerebellum, because it looks like a little brain sometimes we call the cerebellum the little brain."}, {"title": "Central Nervous System .txt", "text": "So notice that we have the same infolutes on the cerebellum that we have on the cerebral of our forebrain."}, {"title": "Central Nervous System .txt", "text": "Now, the cerebellum's function is to basically control and coordinate the movement of our muscles."}, {"title": "Central Nervous System .txt", "text": "And although the cerebellum cannot actually initiate the movement of our muscles, it does coordinate the movement and precision timing of our muscles, our voluntary motions."}, {"title": "Central Nervous System .txt", "text": "Now, alcohol affects this part of the brain."}, {"title": "Central Nervous System .txt", "text": "So when we drink alcohol, that affects the regulation and control of our cerebellum."}, {"title": "Central Nervous System .txt", "text": "And that's exactly why if we drink too much, we end up stumbling and our coordination is not as good as it is when we're sober because alcohol affects the functionality of our cerebellum."}, {"title": "Central Nervous System .txt", "text": "Now, what about our myelin cephalon?"}, {"title": "Central Nervous System .txt", "text": "So the myelin cephalon contains our medulla, also known as the medulla umbilingada."}, {"title": "Central Nervous System .txt", "text": "And what Aramidoula actually does is it controls things like breathing, it controls our ventilation rate, our respiratory rate, it controls our heart rate as well as blood pressure and other automatic or involuntary motion."}, {"title": "Central Nervous System .txt", "text": "For example, it controls vomiting."}, {"title": "Central Nervous System .txt", "text": "So we have the forebrain, we have the mid brain and we have the hind brain."}, {"title": "Central Nervous System .txt", "text": "Now let's discuss our spinal cord."}, {"title": "Central Nervous System .txt", "text": "Now, the spinal cord basically is found below the medulla and extends all the way down our body into the lower back of our body."}, {"title": "Central Nervous System .txt", "text": "So if we take the cross sectional view of our spinal cord we get the following diagram and notice just like the brain consists of white and gray matter our spinal cord also consists of white and gray matter."}, {"title": "Central Nervous System .txt", "text": "So the spinal cord consists of bone and cartilage and also of our neurons."}, {"title": "Central Nervous System .txt", "text": "Now, white matter basically means our neurons do have myelination while the gray matter have neurons that do not have myelination on their axons."}, {"title": "Central Nervous System .txt", "text": "So the big difference between the brain and a spinal cord is on the brain."}, {"title": "Central Nervous System .txt", "text": "The gray matter is found towards the outside and the white matter is found inside."}, {"title": "Central Nervous System .txt", "text": "For the spinal cord, our white matter is on the outside."}, {"title": "Central Nervous System .txt", "text": "This is the white matter."}, {"title": "Central Nervous System .txt", "text": "And the gray matter is on the inside."}, {"title": "Central Nervous System .txt", "text": "This is the gray matter."}, {"title": "Central Nervous System .txt", "text": "So the spinal cord can also be broken down into four regions."}, {"title": "Central Nervous System .txt", "text": "We have the cervical region, the topmost portion."}, {"title": "Central Nervous System .txt", "text": "We have the thoracic region."}, {"title": "Central Nervous System .txt", "text": "Then we have our lumbar region and then we have our sacral region."}, {"title": "Central Nervous System .txt", "text": "So the spinal cord is broken down into four segments cervical, thoracic, lumbar and sacral."}, {"title": "Central Nervous System .txt", "text": "Now, the role of the spinal cord is basically to accept electrical signals from the peripheral system and send those signals to the brain as well as vice versa to receive the electrical signals from the brain and to send them out to different types of organs and tissues and muscles found inside our body."}, {"title": "Central Nervous System .txt", "text": "Now, the spinal cord actually is capable of expressing its own arc its own simple reflex arc without actually going into our brain."}, {"title": "Central Nervous System .txt", "text": "So this arc looks something like this."}, {"title": "Central Nervous System .txt", "text": "So let's suppose I pinch myself and what happens is the receptors on my finger basically translate that pressure into an electrical signal which is picked up by the sensory neuron."}, {"title": "Central Nervous System .txt", "text": "And the sensory neuron basically travels to the back portion of our spinal cord known as the Doral supportion."}, {"title": "Central Nervous System .txt", "text": "So this is a sensory neuron."}, {"title": "Central Nervous System .txt", "text": "It picks up that electrical signal and gives that electrical signal to an inter neuron that is shown in brown found in the gray matter of our spinal cord."}, {"title": "Central Nervous System .txt", "text": "And then that inter neuron, without actually translating that information to the brain, relay that information the brain basically gives it right back to the motor neuron that travels away from the front portion of our spinal cord known as the ventral side and back to our finger my finger so that I remove my hand really quickly."}, {"title": "Central Nervous System .txt", "text": "So this is known as the simple reflex arc."}, {"title": "Central Nervous System .txt", "text": "So, once again, the sensory neurons traveling into our spinal cord always travel or enter from the backside the Doral society and the ganglia."}, {"title": "Central Nervous System .txt", "text": "The neurons of the peripheral nervous system next to our spinal cord is known as the dorsal root ganglia."}, {"title": "Central Nervous System .txt", "text": "So these sensory neurons in your from the back and the motor neurons exit from the front which is known as the ventral side."}, {"title": "Central Nervous System .txt", "text": "So the spinal cord is basically involved with not only integrating the information, but it's also involved in accepting and sending information out to different parts of the body."}, {"title": "Central Nervous System .txt", "text": "So the spinal, spinal cord and the brain make up the central nervous system of the body."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Immune surveillance is the idea that certain white blood cells of our immune system are continually and constantly keeping a watchful eye for any abnormal cells that might develop in our body."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And these abnormal cells might develop as a result of some type of pathogenic infection or they might develop as a result of some type of carcinogenic."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So when healthy cells are exposed to carcinogens such as chemical agents, pathogenic agents or radiation for example UV or X ray radiation the healthy cells can essentially become cancer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Now, how exactly does a healthy cell become a cancer cell?"}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Well, these carcinogens essentially affect the DNA molecules within our healthy cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And when we develop a mutation in our DNA molecule we change the sequence of nucleotides on that DNA and that ultimately codes for different proteins and that can influence the functionality of the cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Now, we develop a cancer cell when our abnormal cell essentially loses its ability to control the way that it divides."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that's exactly why cancer cells divide rapidly and uncontrollably and eventually form large, visible NASA we call tumors."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And because these tumors are so large they can affect the way that our body functions and they can ultimately kill that organism, kill that individual."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "The question is not everybody actually develops cancer in their lifetime."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And because on a daily basis we produce anywhere from several to 1000 of these different cancer cells how exactly does our immune surveillance system, our immune system in general actually detect these cancer cells and destroy these cancer cells?"}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Well, since these cancer cells have a slightly different sequence of nucleotides on their DNA they will produce slightly different proteins."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And these different proteins that end up on the membrane of these cancer cells can be read by certain white blood cells as being foreign antigens."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And when these white blood cells locate these foreign antigens found on the cancer cells they can basically mark or label these cancer cells for destructions."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So let's actually discuss what the different types of cells are in our immune system that basically are used to control and destroy these cancer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So even though the immune system as a whole functions to detect and destroy these cancer cells two particularly important types of white blood cells involved in the process of destroying infected and cancer cells are natural killer cells as well as cytotoxic T cells also known as killer T cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And these are two different types of white blood cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So let's begin with natural killer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So natural killer cells are specialized lymphocytes and they have granules that carry digestive enzymes as we'll see in just a moment."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And these granules, these vesicles play an important role in destroying those cancer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Now let's recall the important points."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So the majority of the white blood cells in our immune system are able to differentiate normal cells from abnormal cells as well as communicate with one another."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "As a result of these special protein complexes found on the immune cells and our normal cells of our body known as the major histocompatibility complex MHC."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And we have several classes."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "For example, we have MHC class One and we have MHC class two."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Class one is used to differentiate abnormal cells from healthy cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And class two is used to actually communicate between the white blood cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So virtually all cells in our body, all white blood cells, require these major histocompatibility complexes to actually interact with one another and to detect these abnormal cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "But the very unique thing about natural killer cells which, by the way, are part of the innate immunity of our immune system, the very unique thing about these natural killer cells is that they don't actually need the major histocompatibility complex to actually find what our abnormal cell actually is."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Unlike most other cells of our body, including cytotoxic T cells, the other white blood cell that destroys cancer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And this is a good thing because sometimes the cancer cells or infected cells lose the ability to create the MHC class One or the MHC class two complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that means it no longer contains these complexes on their membrane."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that makes it virtually invisible to all the cells of our body, all the white blood cells that require the MHC class One or class Two to actually detect those cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So the special thing about these natural killer cells is that they can bind and destroy these cancer cells regardless of whether or not they have the MHC complex on the membrane."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So once again, natural killer cells are lymphocytes that are part of our innate immunity."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Now, majority of the white blood cells of our immune system can only recognize an abnormal cell, such as a cancer cell if it contains an antigen that is bound onto the MHC, the major histocompatibility complex membrane protein."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "However, natural killer cells are the exception."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "They are unique because they do not require the presence of the major histocompatibility complex on the membrane of that particular abnormal cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Interestingly, some infected or cancer cells sometimes are missing the MHC entirely from their membrane which makes them virtually invisible to all the other white blood cells of our body except these natural killer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So let's take a look at the following diagram and examine exactly what the mechanism is by which the natural killer cell detects as well as destroys our cancer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So when cells display little or no MHC proteins on their membrane, then that triggers the natural killer cell to basically approach and bind onto that cancer cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So in this particular case, we have a normal cell, a normal cell and a normal cell that contains a normal antigen, a normal cell antigen shown in green, as well as the MHC class one complex shown in brown."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "But this cancer cell loses the proper sequence of nucleotides to create the proper protein known as the MHC class One."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And so we have none of these MHC class One proteins found on the membrane."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that is what triggers the natural killer cell to approach this cancer cell, bind to it, and begin releasing these granules that contain digestive enzymes."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And these digestive enzymes poke holes inside the membrane of the cancer cell and that lysis and destroys the cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And then a macrophage can swim by and pick up that remaining debris that essentially came from that lysed cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Now, what about cytotoxic T cells, also known as killer T cells?"}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So we said that natural killer cells are part of the innate immunity because they destroy in a nonspecific way."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "They are not looking for any specific cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "They're looking for any abnormal cell, including cancer cells and infected cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "On the other hand, cytotoxic T cells are part of the adaptive immunity."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that's because they are looking for specific infected cells, which also includes cancer cells that contain specific foreign antigens on the membrane."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So these cytotoxic T cells actually need the MHC class One to bind onto that infected or abnormal cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So these cytotoxic T cells contain special T cell receptors along with a CDA Glycoprotein that is needed to bind to the MHC Class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So let's take a look at the following diagram to see what the mechanism is by which the cytotoxic T cell actually kills off and finds finds and kills off that cancer cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So we have normal cells of our body that display the normal cell antigen shown in green on that MHC class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And we have this cancer cell that still has the MHC class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Remember, not all cancer cells actually destroy the MHC Class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "Some of them still actually have them."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And in this case, the cancer cell will now display a pathogenic, a foreign antigen on that MHC Class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And now this is when the cytotoxicy T cell comes into play."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "It has the CDA Glycoprotein and the complementary T cell receptor that can basically bind onto this particular specific antigen and onto the Mhclass One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And once they are bound, the cytotoxic T cell basically does the same exact thing that the natural killer cell does."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "It releases these digestive proteins that poke holes in the membrane and lice and destroy that cell."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So these are the two different types of white blood cells that make up the immunosurveillance system of our bodies."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So this is the system by which these white blood cells are continually trying to find these abnormal cells of our bodies, such as cancer cells, as well as our infected cells that might be infected by some type of outside pathogen."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "So the major difference between our natural killer cell and our cytotoxic T cell is the cytotoxic T cell only binds to the MHC class One complex, while our natural killer cell can bind to a cell that doesn't have that MHC class One complex."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And that's very important because sometimes these infected or cancer cells lose the ability to create these complexes that hold the antigens."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And so we've won't find any of these complexes on our membrane."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "And they will become virtually invisible to all cells of our body, including these cytotoxic T cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "But the exception is the natural killer cells."}, {"title": "Immunosurveillance and Cancer Cells .txt", "text": "These will be able to locate these cancer cells, these abnormal cells, and release these digestive enzymes that lice and destroy those cancer cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Previously we discussed how skeleton muscle cells of our body can actually regulate the process of glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And in that discussion, what we said was there are three major types of regulatory points in glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And these three regulatory points are actually some of the enzymes that regulate that process."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we have Phosphor, fructokinase, Hexokinase and Pyruvate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Iinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So this is the enzyme that catalyzes step three."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "This is the enzyme that catalyzes step one."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this is the enzyme that catalyzes step ten."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And the reason our cells use these three enzymes is because these catalyze Irreversible steps in glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, phosphor fructoclinase, as was said, is the most important regulatory enzyme and that's because it catalyzes the Irreversible commitment step."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So once the step actually takes place, this fructose one six bisphosphate that is transformed from fructose six phosphate by phosphorutokinase has to go on and complete the process of glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, we're going to talk about liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And before we actually begin, let's compare the functionality of muscle cells and liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So skeleton muscle cells essentially have one function and that function is to allow us to actually move voluntarily."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So if I want to move my hand back and forth, my skeleton muscle produces the ATP V glycolysis to allow that voluntary movement."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, what about liver cells?"}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Well, liver cells have a much more complex biochemical row."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And what that means is they not only use the glycolysis to produce ATP molecules that the liver cells actually need to survive, but the liver also has to do things like maintain the glucose levels in our blood."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "If the levels are too high, uptake that glucose and transform it into glycogen."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "If the levels are too low, break down that glycogen and release the glucose into our bloodstream so that the other cells of our body can essentially use that glucose to form ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And it has many, many other roles."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "For instance, it uses the glycolysis process to basically synthesize building blocks like fatty acids as well as amino acids and so forth."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So liver cells have many different types of functions."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And as a result, it's no surprise that the way that our liver cells regulate the process of glycolysis is more complex than the way that our skeleton muscle cells regulate the process of glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So in our discussion, we're going to focus on liver cells and how liver cells regulate the process of glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And although we'll see many similarities between skeletal muscle cells and liver cells, we'll see that liver cells use a slightly more complex regulatory pathway."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Let's begin with phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So once again, phosphorptokinase is the most important regulatory enzyme."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And what it does is it regulates that commitment step."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "It transforms the fructose six phosphate into the fructose one six bisphosphate which is committed to that step."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this is our enzyme that catalyzed that step."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, let's remember how skeletal muscle cells actually regulate this enzyme."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So they use ATP and ANP molecules so let's suppose we have a high energy charge in the cell and what that means is we have a high ratio of ATP to amp."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Remember, energy charge simply means the ratio of ATP to amp."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now if we're resting this is basically what we're going to have."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "We're going to have too many ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so what that means is we don't want to produce any more ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "We have plenty of ATP molecules to go around and so phosphorutokinase will be inhibited by that large concentration of ATP and ATP acts as an allosteric inhibitor."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "On the other hand, if we don't have many ATP molecules in a cell then we have a low energy charge value, so low ratio and we have many more amp molecules and they will bind onto the phosphorptokinase and essentially activate them."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "They will make them much more likely to actually convert the fructosex phosphate into the fructose one six biphosphate bisphosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So basically the takeaway lesson here is the same two alystaric molecules that are used by skeleton muscle cells to control phosphorinase is also used by liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "But there are many important differences."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Difference number one, in skeleton muscle cells the PH actually affects the activity of phosphop fructokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So in our discussion previously we said that a low PH or a very acidic environment basically inactivates inhibits phosphoruxokinase in skeletal muscle cells and that's because in skeletal muscle cells as we exercise there can be a build up in lactic acid."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "But in liver cells there is usually no buildup in lactic acid."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And that's partly because the liver cells actually are responsible for breaking down that lactic acid into glucose molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And that's exactly why the phosphorptokinase is not affected by the PH in liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now the second important difference is the molecule citrate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So citrate, as we'll see in just a moment, just like ATP molecules is another example of an allosteric inhibitor to phosphor fructosekinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's suppose in our liver cells we have a high oxygen content but we don't have many ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Well if we don't have many ATP molecules then the glycosis process will continue and will form many ATP molecules and also Pyruvate molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And because where under aerobic conditions the peruvate will essentially enter the mitochondria and carry out the citric acid cycle."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now one of the initial intermediates of the citric acid cycle is a molecule known as citrate and citrate is ultimately formed from the pyruvate molecule that enters that mitochondria."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, eventually, after we form many ATP molecules and the concentration of ATP rises and the energy charge of the cell increases, we will not want to form any more ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Because what that will mean is not only will we have enough ATP molecules to go around, we'll also have enough citrate molecules to actually create ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so in this particular case if we have plenty of ATP molecules that means we'll have plenty of Pyruvate molecules and plenty of citrate molecules circling in that crept cycle."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so if we have a high citrate concentration in the cytoplasm, that citrate will go on and buy until phosphorptokinase and it will basically increase the ability of the ATP to actually inhibit the phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so just like ATP, citrate is also an allosteric inhibitor to the phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this is the second important difference between the phosphorptokinase in skeletal muscle cells and the one in liver cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we can summarize that in the following diagram."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's say the glucose enters the cell, it's transformed into glucose six phosphate, then it becomes fructose six phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And then the phosphor Fructase transforms it into the fructose one bits phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And now we have many steps to take place and ultimately we form that pyruvate molecule."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And in the presence of oxygen, the pyruvate will enter the mitochondria and it will eventually form citrate intermediate molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And we also form ATP molecules after glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so if we essentially have many of these ATP molecules and citrate molecules, they will create a negative feedback loop that will go back and bind onto the phosphorptokinase and that will essentially diminish the activity of that phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So if we have many ATP, this will stop the process of glycolysis so that we don't overproduce the ATP molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, one of the functions of liver cells that I mentioned earlier is the fact that they're responsible for actually maintaining a concentration, a normal concentration of glucose."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Because if we have too many glucose in the blood, that can be toxic to our bodies."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's suppose we just ingest a meal that is rich in carbohydrates and so the concentration of ATP in our blood essentially increases."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And it's the job of the liver cells to basically uptake all that glucose to bring the blood level glucose back to normal."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, what does the cell actually do with the glucose?"}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Well, it can form ACP molecules, it can form many different types of building blocks, it can form glycogen."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And what that means is in these situations the phosphor fructokinase must be activated by some type of powerful activator molecule to actually uptake all those glucose molecules and convert those glucose molecules into these different types of things."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so something that we don't find in skeleton muscle cells that we have in liver cells is this feedback known as feed forward stimulation."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's take a look at the following diagram."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's suppose we ingest all these carbohydrates."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So in our blood we have a high level of glucose."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And what that means is these liver cells will begin to absorb those glucose and the glucose molecules will be transformed ultimately into fructose six phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, high levels of glucose means we'll have high levels of fructose six phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And when we have very high levels of fructose six phosphate in a cytoplasm, some of them will begin transforming into a molecule known as fructose 26 bisphosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, fructose 26 bisphosphate is a very potent, very powerful activator of phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And what it allows the cells to do is it allows them to convert all these glucose molecules uptake the glucose molecules from the blood, bring that glucose level back to normal and essentially convert those glucose molecules into either ATP molecules or other types of molecules."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we ultimately see there are two types of inhibitors and two types of activators."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we have ATP molecules and citrate molecules that inhibit the phosphor fructokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "But the amp molecules and the fructose 26 bisphosphate are actually activators of the fructose of the phosphor fructokinase enzyme."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So once again, when fructose six phosphate concentration is high, some of it is transformed into fructose 206 bisphosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this molecule is an allosteric activator of the enzyme."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "It binds to that enzyme, stimulates its activity and it continually carries out this process quickly and effectively."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now let's move on to hexokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So let's suppose inside our blood we have a high concentration of inside our cells we have a high concentration of ATP."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we're essentially at rest and the high amount of ATP will begin to inhibit the phosphorptokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, once phosphorkinase is inhibited, so this molecule is basically inhibited PFK is phosphorinase, then we're going to see that there is a build up of this substrate molecule that is a substrate to this enzyme fructose six phosphates."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So by the way, this is step one of glycolysis, step two of glycolysis and step three of glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And once there is a build up of this molecule, because of the inhibition of this molecule by the ATP, this molecule is in equilibrium with this molecule."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And so if we increase the concentration of this, if there's a build up of this bilaterally as principle, it will shift this way and increase the concentration of glucose six phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now glucose six phosphate is the product molecule to this reaction."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So glucose is transformed by hexagonase in the first step of glycolysis to form glucose six phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And as we increase the concentration of glucose six phosphate due to the inhibition of PFK, that increase in concentration will inhibit the hexokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this same exact regulatory mode is actually used by skeleton muscles as well."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So just as in skeleton muscle cells, glucosex phosphate is also an allosteric inhibitor to hexokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And this is the process that allows the phosphor fructokinase to actually communicate with the hexokinase and essentially tell it to turn off that first step in glycolysis."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And once these two irreversible steps are essentially turned off, that greatly diminishes the rate at which the glycolytic pathway actually takes place."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, there is one important difference between hexokinases in liver cells and hexokinases in skeletal muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "In liver cells we have this same hexacionase that we also have in muscle cells."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "But in liver cells we have an important isozyme to this particular hexacinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now let's recall what an isozyme is."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So two protein molecules that are different are said to be isozymes if they essentially catalyze that same, similar type of process."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And the isozyme to the hexokinase that is found in liver cells but is not found in skeleton muscle cells, is glucokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So, unlike in skeleton muscle tissue, there is an isozyme to hexokinase present liver cells known as glucokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Now, what is the major difference between glucokinase and hexokinase?"}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Well, there are two important differences."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "Number one, glucokinase has a much lower affinity for that glucose substrate molecule than hexokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "In fact, hexokinase is 50 times more likely to bind to the glucose substrate than that glucokinase."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "And that will create a very important difference, as we'll see in just a moment."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "The second important difference between hexokinase and gluco kinase is that hexokinase is inhibited by glucose six phosphate when the concentration is high, but glucokinase is not effective, is not inhibited by that glucosex phosphate."}, {"title": "Regulation of Glycolysis in Liver Cells .txt", "text": "So we see that unlike hexokinase, which is inhibited by high amounts of glucosex phosphate."}, {"title": "Antibodies .txt", "text": "When every pathogen invades our body, it brings along its own proteins, its own Euclide acids and its own polysaccharides."}, {"title": "Antibodies .txt", "text": "Now, these different things that the pathogen brings are known as antigens."}, {"title": "Antibodies .txt", "text": "And the immune cells of our body are capable of identifying these different antigens."}, {"title": "Antibodies .txt", "text": "And once the immune cells, the white blood cells, identify the antigens, specialized types of B lymphocytes, known as plasma cells can begin producing antibodies which are highly specific proteins that can bind onto these antigens."}, {"title": "Antibodies .txt", "text": "And once the antibody is bound to that specific antigen for which it was built for, it elicits some type of defensive mechanism."}, {"title": "Antibodies .txt", "text": "It basically labels that antigen along with the pathogen for destruction by our immune system."}, {"title": "Antibodies .txt", "text": "And we'll see exactly how that takes place in just a moment."}, {"title": "Antibodies .txt", "text": "First, let's discuss the structure of our antibody."}, {"title": "Antibodies .txt", "text": "Now, our antibody is also known as our immunoglobulin, where immuno means our immune system and globulin means our protein."}, {"title": "Antibodies .txt", "text": "So immunoglobulin is written with the following two letters IG."}, {"title": "Antibodies .txt", "text": "And we'll see that there are actually five different types of immunoglobulins."}, {"title": "Antibodies .txt", "text": "We have IGD we have IGA IgM IgG and we have Ige And each one of these five different types of antibodies carry out a different type of mechanism."}, {"title": "Antibodies .txt", "text": "They function in a slightly different way to basically carry out the function of defending our human cells, our body cells, from these pathogenic invasions."}, {"title": "Antibodies .txt", "text": "Now, what about the structure of these antibodies?"}, {"title": "Antibodies .txt", "text": "So antibodies consist of four polypeptide subunits that basically bind together via disulfide bridges, disulfide bonds which are covalent bonds between sulfur atoms."}, {"title": "Antibodies .txt", "text": "And they bind in such a way to form a Y shaped structure as shown in the following diagram."}, {"title": "Antibodies .txt", "text": "Now, two of these polypeptides are heavy chains."}, {"title": "Antibodies .txt", "text": "They're large polypeptide chains."}, {"title": "Antibodies .txt", "text": "And the other two chains, shown in red, are the light chains."}, {"title": "Antibodies .txt", "text": "And that's because they're smaller than the heavy chain."}, {"title": "Antibodies .txt", "text": "So we have these two light chains that are bonded via disulfide bridges to these two heavy chains."}, {"title": "Antibodies .txt", "text": "And the two heavy chains are also bonded to each other by these disulfide bonds."}, {"title": "Antibodies .txt", "text": "Now, on every single antibody, we have a region known as the constant region and we have a region known as the variable region."}, {"title": "Antibodies .txt", "text": "Now, if we take a look at the following diagram of the antibody, these boxed in regions are the variable regions and the rest is the constant region."}, {"title": "Antibodies .txt", "text": "Now, what exactly is the variable region?"}, {"title": "Antibodies .txt", "text": "Well, as the name applies, these variable regions actually contain specific types of sequences that can bind to that antigen."}, {"title": "Antibodies .txt", "text": "Remember, proteins are sequences of amino acids and the variable regions is billed to contain a specific sequence of amino acids that can bind to that specific antigen for which it was actually built for."}, {"title": "Antibodies .txt", "text": "And that's exactly why these regions vary when we go from one antibody to a different antibody because we have to change the sequence of amino acids for them to actually bind onto different types of antigens."}, {"title": "Antibodies .txt", "text": "Now, on top of that, it's these variable regions that contain these clefts, that contain these regions that actually bind onto our antigen."}, {"title": "Antibodies .txt", "text": "So these are known as the antigen binding sites."}, {"title": "Antibodies .txt", "text": "Now, the region of the antigen that the antibody is actually built for, that binds onto the antigen binding side of the antibody is known as the antigenic determinant or simply the epitope."}, {"title": "Antibodies .txt", "text": "So if we look at the following diagram, we have our antibody that contains the constant region and it contains the variable region and it's the variable region that contains the antigenic binding sites, as shown, that can actually bind onto the epitope of our antigens."}, {"title": "Antibodies .txt", "text": "So let's suppose we have the antigens floating around in our blood or in our lymph or in our tissue."}, {"title": "Antibodies .txt", "text": "Now, when this specific antibody that was built by the plasma cell approaches these specific antigens for which it was built for in the first place, we have a binding process taking place and the epitome basically binds onto the antigen binding side of this antibody as shown in the following diagram."}, {"title": "Antibodies .txt", "text": "And then we form our antibody antigen complex which then elicits some type of defense or response as we'll discuss in just a moment."}, {"title": "Antibodies .txt", "text": "Now, what about the constant regions?"}, {"title": "Antibodies .txt", "text": "So basically earlier we said that we have five different types of five different classes or five different types of antibodies."}, {"title": "Antibodies .txt", "text": "Now, each class of antibody has the same exact constant region."}, {"title": "Antibodies .txt", "text": "But these constant regions do change when we go from one type to a different type."}, {"title": "Antibodies .txt", "text": "In fact, these constant regions determine the type of class that we're dealing with and they actually determine the mechanism that our antibody uses to basically fight off infections and fight off these pathogenic invasions."}, {"title": "Antibodies .txt", "text": "And on top of that, it's these constant regions, the bottom portion of these constant regions that actually bind onto the cell membranes of immune cells and other cells of our body."}, {"title": "Antibodies .txt", "text": "So now that we know what the structure of the antibody looks like, let's discuss what the mechanism is by which the antibody actually elicits a defensive response by our immune system."}, {"title": "Antibodies .txt", "text": "So antibodies can either be found bound onto the membrane of immune cells or they can float around as free antibodies within the blood or lymph of our body."}, {"title": "Antibodies .txt", "text": "And either way, when the antibody locates and binds onto that specific antigen for which it was actually built for, they form the antibody antigen complex."}, {"title": "Antibodies .txt", "text": "And once the complex forms, it elicits some type of response that begins a defensive mechanism to kill off that particular pathogen."}, {"title": "Antibodies .txt", "text": "Now, what type of mechanism do we actually have?"}, {"title": "Antibodies .txt", "text": "Well, we have three important types of mechanisms that we're going to focus on in this lecture."}, {"title": "Antibodies .txt", "text": "Let's begin with mechanism number one."}, {"title": "Antibodies .txt", "text": "So in this case, what happens is when we form when our antibody binds onto the antigen, it basically inactivates that antigen."}, {"title": "Antibodies .txt", "text": "So let's take a look at the following case."}, {"title": "Antibodies .txt", "text": "Let's suppose we have a virus that basically infects our body."}, {"title": "Antibodies .txt", "text": "So the virus is swimming around in our tissue."}, {"title": "Antibodies .txt", "text": "Now, our antibodies, which are specific to the antigens found on this virus, when they locate the virus, they will bind onto those antigens."}, {"title": "Antibodies .txt", "text": "And what happens is, because the virus uses these antigens to actually bind onto the cells of our body, because the antibody actually blocks these antigens, it also blocks and prevents the virus from actually binding onto our healthy cells."}, {"title": "Antibodies .txt", "text": "And that means the viral agent cannot actually infect our healthy cells."}, {"title": "Antibodies .txt", "text": "And so this is the process by which once the antibody antigen complex forms, it essentially inactivates that particular pathogen."}, {"title": "Antibodies .txt", "text": "Now, let's move on to number two."}, {"title": "Antibodies .txt", "text": "In number two, let's suppose we have some type of cell that was infected by our viral agent."}, {"title": "Antibodies .txt", "text": "Now, once the cell is infected, that infected cell releases some type of pathogenic antigen and places it onto the MHC class one complex."}, {"title": "Antibodies .txt", "text": "Remember, MHC is the major histocompatibility complex that our cells use to basically differentiate healthy cells from our infected cells."}, {"title": "Antibodies .txt", "text": "And once the pathogenic antigen is found on the MHC class one complex, some type of white blood cell, a macrophage, a neutrophil, or our cytotoxic T cell, a special type of T lymphocytes, can basically approach this infected cell."}, {"title": "Antibodies .txt", "text": "And if it contains the specific type of antibody that reflects this specific type of antigen, they can basically bind."}, {"title": "Antibodies .txt", "text": "And then the cytotoxic T cell can release powerful proteins that ultimately poke holes in this cell and lies the cell, killing that cell off."}, {"title": "Antibodies .txt", "text": "And then a macrophage can swim by and pick up the remaining debris from that infected cell."}, {"title": "Antibodies .txt", "text": "So, mechanism number three, we can also actually have a process known as Aglutination."}, {"title": "Antibodies .txt", "text": "And what Aglutination is, when we form the antibody antigen complex, many of these complexes can actually aggregate to form an insoluble complex."}, {"title": "Antibodies .txt", "text": "And this insoluble complex also inactivates our pathogen."}, {"title": "Antibodies .txt", "text": "And then that entire insoluble complex can be picked up by the macrophage."}, {"title": "Antibodies .txt", "text": "And basically that macrophage can break down that pathogenic agent."}, {"title": "Antibodies .txt", "text": "So earlier we said there are five different classes of immunoglobulins."}, {"title": "Antibodies .txt", "text": "We have immunoglobulin D, immunoglobulin A, immunoglobulin M g, as well as E. So the major difference between these five different types of classes of antibodies is the sequence of amino acids in these constant regions."}, {"title": "Antibodies .txt", "text": "And each one of these different classes of antibodies functions in its own way to basically defend our body from these pathogenic invasions."}, {"title": "Antibodies .txt", "text": "So let's very quickly look at some major distinctions between these five classes."}, {"title": "Antibodies .txt", "text": "So let's begin with IgG immunoglobulin g. So immunoglobulin g is actually the most common type of antibody that is found inside our blood."}, {"title": "Antibodies .txt", "text": "In fact, 75% of the antibodies found inside our blood are the immunoglobulin g types."}, {"title": "Antibodies .txt", "text": "So what these antibodies do is basically what we described earlier."}, {"title": "Antibodies .txt", "text": "This was an example of the immunoglobulin g. They basically float around, they swim around our blood and lymph and they locate those special types of antigens found on our pathogens."}, {"title": "Antibodies .txt", "text": "Now let's move on to IgM immunoglybulin M so these are found on B lymphocytes, on the membrane of B lymphocytes, and they're highly effective against killing off our viral agents."}, {"title": "Antibodies .txt", "text": "Now, Ige are those antibodies involved mostly in allergic reactions, and we'll talk about these in much more detail when we'll discuss what allergies actually are."}, {"title": "Antibodies .txt", "text": "Now?"}, {"title": "Antibodies .txt", "text": "What about IGD?"}, {"title": "Antibodies .txt", "text": "Well, immunoglobulin Deed are those antigens that are basically also found on the B lymphocytes, and they play a role in actually creating our antibodies."}, {"title": "Antibodies .txt", "text": "So they help us differentiate our B lymphocytes into plasma cells."}, {"title": "Antibodies .txt", "text": "And those plasma cells ultimately produce those antibodies that are essentially complementary to the antigens that bind onto these immunoglobulin D types."}, {"title": "Antibodies .txt", "text": "And finally, we have immunoglobulin A."}, {"title": "Antibodies .txt", "text": "So immunoglobulin A are those antibodies that are found inside our nasal cavities, inside our air passageways."}, {"title": "Antibodies .txt", "text": "So the trachea, the bronchioles, as well as the bronchi, and they're also found in our gut and our digestive tract, they're found in the breast milk."}, {"title": "Antibodies .txt", "text": "They are found in the mucous membrane along our air passageways."}, {"title": "Antibodies .txt", "text": "They're also found in our tears as well as in our saliva."}, {"title": "Antibodies .txt", "text": "So these are the five different types of immunoglobulin antibodies that are found inside our body, and all of them have this same exact shape."}, {"title": "Antibodies .txt", "text": "Now, these five different classes, of course, have five different types of sequences within our heavy chains, within our constant regions, because it's the constant region that determines the type of antibody that we are actually dealing with."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "In order to understand the catalytic properties of enzymes, we have to actually understand what takes place inside the active sites of enzymes."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And to gain a better understanding as to what takes place inside the active sites, we're going to study a specific example of a protease that is found inside our body, namely chimetrypsin."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So chimetrypsin is actually a serum protease that is found inside the small intestine, which basically hydrolyzes or catalyzes the hydrolysis, the cleavage of specific peptide bonds."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "It cleaves on the carboxyl side of relatively large and bulky hydrophobic side chain groups, and this includes methionine, phenylalanine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "It also includes tryptophan and tyrosine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So, if we take a look at the following hypothetical polypeptide chain that consists of seven amino acids, we have glycine, methionine, phenylalanine, tyrosine, alanine, tryptophan and glycine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And this is the corresponding threedimensional structure."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, let's take any one of these amino acids."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So let's suppose this amino acid here, and this happens to be the tyrosine because this is the side chain group of tyrosine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, this C carbon here is the central carbon atom."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "This side is the carboxyl side."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So the right side is the carboxyl side, and this is that carboxyl peptide bond, while the other side is the amino side."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And this is that amino peptide bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And what Chamotrypsin does is it only cleaves, methionine, phenylalanine, tyrosine and tryptophan on the carboxyl side on the right side of that amino acid."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So if we examine, let's say, methionine, so this is our side chain group of methionine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "This is the green bond that will be cleaved by the climate cryptIn."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Likewise, if we move on to phenylalanine, this is the phenylalanine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So on the right side, the carboxyl side, is where climate trypsin will cleave that bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Again, it's shown with green."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Let's move on to tyrosine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "This is tyrosine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "This is the bond that would be cleaved here."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And finally, tryptophan so climate trypsin cleaves on this side of that bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now let's take a look at Alanine."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Well, because Alanine is not a bulky hydrophobic or aromatic amino acid, what that basically means is this bond will not be cleaved by climatrypsin."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Likewise, this bond will also not be cleaved because glycine is not a bulky hydrophobic or aromatic amino acid."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So chimetrypsin is a serene protease that catalyzes the breaking the cleavage of peptide bond on the carboxyl side of bulky so, large hydrophobic or aromatic amino acids."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, carmitrypsin is a serene protease and chimetrypsin is an example of an enzyme that utilizes the covalent catalysis mechanism."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And what that means is inside the active side of kymatryptin, we have some type of nucleophilic residue that acts as the catalyst in forming a covalent bond, a temporary covalent bond between the active side of the enzyme and that peptide substrate molecule."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, we say that the covalent bond is temporary because at the end of the reaction, that bond is broken."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And that's important because we have to reform that unmodified enzyme, we have to regenerate that enzyme."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "At the end of any enzyme, catalyzed react."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Remember, enzymes are never changed or depleted at the end of the reaction."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "They always have to be regenerated."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And that's why this bond is only a temporary covalent bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, we said earlier that Chimetrypin is an example of a Serene protease."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And what that means is inside the active side of that Chimetrypsin, it's the serine molecule, the serine amino acid, that plays the role of the powerful nuclear fide that catalyzes the cleavage of that peptide bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "But how do we know that the active side contains this yearine molecule that plays the central role in catalysis?"}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Well, basically the way that science has discovered this is they probed the active side with a specific type of Irreversible inhibitor."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So they used the specific group inhibitor known as diisopropyl phosphorfluoridate or DIPF."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And this is the same Irreversible inhibitor that we spoke about in our lecture on Irreversible inhibitors."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So if we take DIPF and we mix it with an enzyme and inside the active site, we have a Serene molecule."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And if the reactivity of that serine molecule is quite high, then that DIPF will basically form a covalent bond with that oxygen of the Serene displacing, the H, and that will kick off this fluoride atom and we form a covalent bond between the oxygen and the phosphorus atom."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And once we create this covalent modification, the Irreversible inhibitor basically blocks the activity of that enzyme."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so we know that because the activity of the enzyme is inhibited, that means that the DIPF must be bound to a Serene found inside the active site."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, out of all the 28 Serene amino acids that we find in China Trypsin, this is the only serine that reacts with DIPF."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And this is found inside the active side."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so that implies that it's this Serene molecule."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And the serine molecule has a number of 195."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So if we count all the amino acids, beginning with the first one along the entire polypeptide chain, this Serene will be labeled as 195."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So among the 28 serum residues found on China Trypsin, only Serene 195 actually reacted with this irreversible inhibitor di isopropyl phosphoridate."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so this implied that serine 195 must be the one that plays a major catalytic role in the active side of that enzyme."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so that's how we know that Serene is the one that is involved in actually catalyzing the cleavage of the peptide bonds at these specific bulky hydrophobic amino acids."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, the next question is what is the general description of the reaction mechanism that takes place inside the active sites?"}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Well, basically, it's a two step catalytic mechanism."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And we'll discuss the steps involved in much more detail in the next several lectures."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "In this lecture, we're simply going to paint a general description, a general picture of what takes place inside the active site and how Serene is actually involved in breaking and catalyzing those peptide bonds so we see that experimental data suggests that Chimotrypsin uses a two step mechanism to actually hydrolyze peptide bonds."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, the way that scientists actually studied the reaction mechanism of Chimotrypsin is by using a special type of substrate molecule that once we react that substrate molecule with the activity, the product that is produced gives off a color."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so we can study the absorption of light when that colored product is produced."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And that will give us information as to what happens in that reaction when we use climate trypsin."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So, once again, to monitor the reaction progress, we generally use a substrate that changes color when it reacts with the active side."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So we have this special substrate molecule that when reacts with the serene inside the active side, it produces a product that has a certain color to it."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And we can essentially monitor the color change and the absorbance of light as we produce that particular product."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So if we take a look at the following graph the y axis is the absorbance of light of that product produced when the substrate is catalyzed by the active side and the x axis is basically the reaction progress."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So at the zero point at time zero we basically take our mixture of that special substrate and we mix it in with our enzyme and now our reaction begins and notice what kind of curve we actually produce."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So we see that initially we have a very steep slope, a very large slope and then the slope begins to level off and so here the rate of the reaction is low but here the rate of the reaction is very fast."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, what exactly does that tell us about the reaction mechanism of Chimetrypsin?"}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Well, what it tells us is we have this initial fast birth stage and that describes the first step of the reaction."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And the first step of reaction, the actual binding of the substrate onto that catalytic seren of the active side is a very quick step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "But as soon as that step takes place, we have a second step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And the second step is a slow step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so what happens is we have the initial very quick step taking place and then eventually, when the steady state conditions are reached when the intermediate concentration doesn't change too much we see that the slow begins to decrease."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so we have this relatively slow process taking place."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And that's essentially a result of the second step of the reaction being relatively slow."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So graphing the data that we obtained from experimental results this shows us that the fast initial burst of the color product followed by us slowing down and that's basically a result of us reaching the steady state condition and that second step being so much slower than that first step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So to see exactly what happens let's take a look at the following diagram so in this particular diagram we have the active side of the Chimetrypsin and this is Serene 195."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So let's suppose we add our chromogenic substrate."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Chromogenic simply means when that substance reacts to produce a product that product will change color."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And we can monitor the color change."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "We can basically determine the absorbance of light as the reaction progresses."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So we have this chromogenic substrate, we have the active side."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so what happens in the first step is we have an oscillation step taking place."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So an Acyl group found on this chromogenic substrate."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So this purple group basically attaches onto the oxygen."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so when that takes place, this blue section, the amide product is basically released and it's this amide product."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So RNH two where the other H atom basically came from, this group here, this is the thing that produces that colored product."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so as this reaction takes place, the oscillation reaction takes place very, very quickly and that's why we have a fast initial birth stage."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And as this is produced, this creates a color change and we can monitor that color change on the following graph."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, once this reaction takes place, this oxygen of the Serene and the active side is oscillated."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So this entire group is attached onto the oxygen as shown and this is the Covalent bond that is temporarily formed."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Remember, Chimetrypsin uses Covalent catalysis and that means we form a temporary Covalent bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So this intermediate is known as the acid enzyme intermediate."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And in the next step we have the water molecule that joins in the active side and it basically hydrolyzes the cleavage of the peptide bond."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So it ultimately breaks this bond here and informs the bond between the oxygen and this carbon."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so in the second step we have the deasylation step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So this acid group is removed from that oxygen."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "The age from the water molecule is given to that oxygen on the Serene."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so ultimately we regenerate that enzyme and then we also form that hydrolyzed final product in which we now have a peptide bond that has been broken."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so this is the very quick step that takes place that accounts for this relatively steep slope."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "But as we reach the steady state conditions, as the intermediate concentration basically does not change what begins to happen is this begins to level off."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And this describes the fact that the second step takes place much slower than that initial step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And so this is a two step catalytic mechanism that basically generalizes what takes place inside climate trypsin."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "So the first step is the fast oscillation step in which the Acyl group is added onto the enzyme and then the amide is released."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And it's the amide that is used to basically determine what the color change is."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "We use it to basically determine how much light is absorbed."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And then in the second step, the second step is a much smaller step."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "And in this step we basically break down the Acyl enzyme intermediate by using water as a nucleophile, and then we regenerate that enzyme and we form that hydrolyzed final prime."}, {"title": "Chymotrypsin and Covalent Catalysis .txt", "text": "Now, in the next several lectures, we're going to look at a much detailed discussion as to what actually happens inside the active side and what the reaction mechanism actually is."}, {"title": "Anterior Pituitary Gland.txt", "text": "The endocrine system of the human body uses endocrine glands to produce and release hormones into our bloodstream as well as into our lymph system."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now there are many examples of different endocrine glands in our body and the first type of endocrine gland that we're going to discuss is the pituitary gland also known as our hypothesis."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now the pituitary gland can actually actually be broken down into two sections."}, {"title": "Anterior Pituitary Gland.txt", "text": "We have the front portion which is known as the interior pituitary gland and the back portion known as the posterior pituitary gland."}, {"title": "Anterior Pituitary Gland.txt", "text": "In this lecture we're going to focus on the interior pituitary gland."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now the interior pituitary gland is actually controlled by a section of the forebrain known as our hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now the hypothalamus actually controls the anterior pituitary gland by using its own set of hormones and that's exactly why the hypothalamus is a gland of its own because it releases and produces hormones."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now in fact, the hypothalamus plays such an important role in the endocrine system we call the hypothalamus the master gland of the endocrine system of the human body."}, {"title": "Anterior Pituitary Gland.txt", "text": "So let's take a look at the following diagram."}, {"title": "Anterior Pituitary Gland.txt", "text": "So we have the hypothalamus of the forebrain."}, {"title": "Anterior Pituitary Gland.txt", "text": "We have the medium eminence which is the bottom portion of the hypothalamus and this is our pituitary gland also known as the hypothesis."}, {"title": "Anterior Pituitary Gland.txt", "text": "This is the front portion, the interior pituitary gland and the back portion, the posterior pituitary gland."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, what exactly connects, what links the hypothalamus to the interior pituitary gland?"}, {"title": "Anterior Pituitary Gland.txt", "text": "Well, it's basically a network of blood vessels, a network of capillaries and veins and arteries that actually connects the hypothalamus to our interior pituitary."}, {"title": "Anterior Pituitary Gland.txt", "text": "And because the pituitary gland is also known as the hypothesis, this network of blood vessels is also known as the hypothesia portal system."}, {"title": "Anterior Pituitary Gland.txt", "text": "So basically at the top portion of our blood vessel system we have the superior hypothesial artery."}, {"title": "Anterior Pituitary Gland.txt", "text": "Superior simply means at the top where this section is our inferior."}, {"title": "Anterior Pituitary Gland.txt", "text": "So this is the superior hypothesical."}, {"title": "Anterior Pituitary Gland.txt", "text": "Basically means we're dealing with our hypothesis."}, {"title": "Anterior Pituitary Gland.txt", "text": "Our pituitary gland and artery simply means it brings oxygenated blood and blood filled with nutrients to the hypothalamus of our body."}, {"title": "Anterior Pituitary Gland.txt", "text": "So basically this blood is carried into the medium eminence of the hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "It brings the oxygen and the nutrients to the hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "At the same time the hypothalamus basically produces and releases the hormones into this network of capillaries and then the hormone basically travels down into the portal veins through this region and into the capillaries found in the interior pituitary gland."}, {"title": "Anterior Pituitary Gland.txt", "text": "And we have many of these endocrine glands that can either be stimulated or inhibited by the hormone released by the hypothalamus and that can basically release some type of hormone from the interior pituitary gland into the blood vessel of the bloodstream of our body."}, {"title": "Anterior Pituitary Gland.txt", "text": "So there are six different types of hormones that we should know when it comes to our anterior pituitary gland."}, {"title": "Anterior Pituitary Gland.txt", "text": "So we have the human growth hormone also known as simply the growth hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "We have the drenocorticotropic hormone or ACTH."}, {"title": "Anterior Pituitary Gland.txt", "text": "We have the thyroid stimulating hormone or TSH."}, {"title": "Anterior Pituitary Gland.txt", "text": "We have prolactin and we also have the follicle stimulating hormone and our luteinizing hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "So let's go through each one of these hormones and discuss what their function is."}, {"title": "Anterior Pituitary Gland.txt", "text": "And also let's discuss what the hormone that is produced by the hypothalamus is that controls each one of these anterior pituitary gland hormones."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the first thing that we should know about all these six hormones that are released by the interior pituitary gland is they're all peptide hormones."}, {"title": "Anterior Pituitary Gland.txt", "text": "That means they're formed in the rough endoplasmic reticulum of our endocrine cells."}, {"title": "Anterior Pituitary Gland.txt", "text": "They are modified in the Golgi apparatus and they are released into our blood system."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, once they're inside the blood, they are water soluble and that means they do not need a carrier protein."}, {"title": "Anterior Pituitary Gland.txt", "text": "And once they locate the target cells, these six proteins, these six hormones all bind to receptor proteins found on the plasma membrane of the target cells."}, {"title": "Anterior Pituitary Gland.txt", "text": "So, because they can't actually pass across the cell membrane of the target cell, they have to bind to the surface of the plasma membrane of the target cells."}, {"title": "Anterior Pituitary Gland.txt", "text": "So let's discuss each one of these hormones."}, {"title": "Anterior Pituitary Gland.txt", "text": "Let's begin with the human growth hormone, also known as the growth hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "So basically, the hormone that is released by the hypothalamus, that stimulates the release of the human growth hormone is known as the growth hormone releasing hormone or GHRH."}, {"title": "Anterior Pituitary Gland.txt", "text": "So, GHRH is released by the hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "It travels down the portal veins into this capillary bed system that basically causes these endocrine cells to release our growth hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the human growth hormone basically stimulates almost all the cells in our body."}, {"title": "Anterior Pituitary Gland.txt", "text": "And what it does is the following."}, {"title": "Anterior Pituitary Gland.txt", "text": "It basically causes the non growing cells of the body to stop using glucose as the energy store, as the energy fuel."}, {"title": "Anterior Pituitary Gland.txt", "text": "And it causes these cells to use fatty acids instead to basically create ATP."}, {"title": "Anterior Pituitary Gland.txt", "text": "So that means the human growth hormone causes the liver to release our triglycerides, our fatty acids, from the liver cells into the bloodstream."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, at the same time, it builds up our supply of glucose in the growing cells, such as muscle cells and our bone cells."}, {"title": "Anterior Pituitary Gland.txt", "text": "And it causes these growing cells to basically grow in size because it increases the rate at which proteins are synthesized."}, {"title": "Anterior Pituitary Gland.txt", "text": "It also increases certain cells, it increases the rate at which they undergo mitosis."}, {"title": "Anterior Pituitary Gland.txt", "text": "So our human growth hormone builds up the supply of glucose so that cells can use that glucose to grow."}, {"title": "Anterior Pituitary Gland.txt", "text": "It also causes the non growing cells to increase the use of fatty acids and increases the size as well as the number of cells in our body."}, {"title": "Anterior Pituitary Gland.txt", "text": "And it's controlled by the GHRH hormone released by the hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, let's move on to the second type of hormone that is released by the interior pituitary gland known as our adrenal corticotropic hormone or ACTH."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the hormone that is released by the hypothalamus that stimulates the release of ACTH from the anterior pituitary gland is known as the corticotropin releasing factor or CTF."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, ACTH is released from the anterior pituitary gland at times of stress and it basically carries that hormone via the bloodstream into another endocrine glands in the body known as our adrenal cortex."}, {"title": "Anterior Pituitary Gland.txt", "text": "And ACTH causes our adrenal cortex to basically release a group of hormones known as glucocorticoids via a secondary messenger system."}, {"title": "Anterior Pituitary Gland.txt", "text": "And we'll discuss these in more detail when we'll focus on the adrenal cortex."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the third type of hormone is our thyroid stimulating hormone or TSH."}, {"title": "Anterior Pituitary Gland.txt", "text": "And the hormone that is released by the hypothalamus that stimulates the release of Tch is known as thyroid releasing hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the hypothalamus releases the thyroid releasing hormone and it travels down the portal veins into this system and that stimulates the release of our thyroid stimulating hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, TSH, the thyroid stimulating hormone, basically stimulates it causes the thyroid cells in our thyroid to not only increase in number but also increase in size."}, {"title": "Anterior Pituitary Gland.txt", "text": "And this induces, this increases the rate at which those thyroid cells basically produce two important types of hormones known as T three and T four."}, {"title": "Anterior Pituitary Gland.txt", "text": "And we'll discuss what these actually do when we'll look at the thyroid individually."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the one thing we have to know about this cycle is our TRH, the thyroid releasing hormone basically affects the entire pituitary in a positive manner."}, {"title": "Anterior Pituitary Gland.txt", "text": "So this is a positive feedback cycle and this is also a positive feedback cycle."}, {"title": "Anterior Pituitary Gland.txt", "text": "That basically means this build up in concentration causes this to build up in concentration and that causes our thyroid to basically increase the concentration of T three and T four."}, {"title": "Anterior Pituitary Gland.txt", "text": "But T three and T four, as this builds up in its concentration it creates a negative feedback loop in terms of the interior pituitary and the hypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the build up in this causes our interior pituitary and the hypothalamus to stop producing our TRH and the TSH."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the next hormone that is produced by the interior pituitary gland is our prolactin."}, {"title": "Anterior Pituitary Gland.txt", "text": "So prolactin is basically stimulated or actually it's not stimulated."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the interesting thing about prolactin is the hormone that is produced by the hypothalamus known as the prolactin inhibitory hormone actually inhibits the release of prolactin."}, {"title": "Anterior Pituitary Gland.txt", "text": "And this is the only hormone that basically does this."}, {"title": "Anterior Pituitary Gland.txt", "text": "All these other hormones are stimulated by the hypothalamus hormone but prolactin is inhibited by the release of our prolactin inhibitory hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the hypothalamus releases the prolactin inhibitory hormone or PIF."}, {"title": "Anterior Pituitary Gland.txt", "text": "PIH, this hormone basically can be replaced with factor."}, {"title": "Anterior Pituitary Gland.txt", "text": "So we have prolactin inhibitory factor."}, {"title": "Anterior Pituitary Gland.txt", "text": "That's why this is also known as PIF and this actually doesn't stimulate, it inhibits the release of prolactin."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, as we'll see in the next several lectures prolactin is involved in enabling milk production in females."}, {"title": "Anterior Pituitary Gland.txt", "text": "Among other things."}, {"title": "Anterior Pituitary Gland.txt", "text": "It basically allows the process of lactation to actually take place."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the fifth and the 6th hormone is the follicle stimulating hormone and the luteinizing hormone and both of these hormones are involved in the reproductive cycle of the human organism and we'll discuss their roles in more detail when we'll discuss the reproduction cycle."}, {"title": "Anterior Pituitary Gland.txt", "text": "For now, we're going to just say that our follicle stimulant hormone and the leeinizing hormone are both stimulated by the gonadotropin releasing hormone GnRH that is produced by Arrowhypothalamus."}, {"title": "Anterior Pituitary Gland.txt", "text": "So the hypothalamus releases arrowgonatotropin releasing hormone and it travels down to the endocrine cells and it causes the interior pituitary glands to release FSH the follicle stimulating hormone and LH the luteinizing hormone."}, {"title": "Anterior Pituitary Gland.txt", "text": "Now, the follicle stimulating hormone basically causes the production and the maturation of the follicle in females at the same time it stimulates the production of sperm cells in males while the luteinizing hormone basically causes our ovulation cycle to take place in females and it causes our males to basically produce our hormone known as testosterone."}, {"title": "Anterior Pituitary Gland.txt", "text": "So well there's discuss these in much more detail when we'll focus on the reproductive cycle of the human organism."}, {"title": "P-Type ATPases .txt", "text": "Protein pumps are transmembrane proteins that exist within the membranes of our cells that function to generate electrochemical gradients."}, {"title": "P-Type ATPases .txt", "text": "So they use some type of energy source to basically move these molecules against the electrochemical gradient across the cell membrane and that ultimately creates this electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "And then the protein channels, the other type of transmembrane proteins used for transport, can use these electrochemical gradients to basically move the molecules down the gradient without using any type of energy source."}, {"title": "P-Type ATPases .txt", "text": "So essentially, these membrane pumps use energy to establish these gradients and then the channels don't have to use energy because they use these electrochemical gradients to move the molecules in a natural and spontaneous direction."}, {"title": "P-Type ATPases .txt", "text": "So there are two categories of membrane pumps."}, {"title": "P-Type ATPases .txt", "text": "We have these Atpas and we have these secondary transporters."}, {"title": "P-Type ATPases .txt", "text": "In this lecture we're going to focus on ATPases."}, {"title": "P-Type ATPases .txt", "text": "Now, Atpas themselves can also be broken down into two classes."}, {"title": "P-Type ATPases .txt", "text": "We have the ptype Atpas that we're going to focus on in this lecture and we also have the ABC transporters."}, {"title": "P-Type ATPases .txt", "text": "Now, what exactly is a ptype Atpas?"}, {"title": "P-Type ATPases .txt", "text": "Well, the P basically stands for phosphoryl."}, {"title": "P-Type ATPases .txt", "text": "And in a ptype Atpas, they basically use ATP molecules, they hydrolyze NATP molecules, they use that phosphoryl group to attach it onto that membrane protein, that pump."}, {"title": "P-Type ATPases .txt", "text": "And then that creates a conformational change in the pump that allows the pump to actually move the molecule against the electrochemical grading as we'll see in just a moment."}, {"title": "P-Type ATPases .txt", "text": "And one well studied pump that we're going to focus on, one well studied ptype Atpas will be the calcium Atpas that we're going to focus on in this lecture."}, {"title": "P-Type ATPases .txt", "text": "And there are many other examples of ptype Atpas that we'll study in the future lecture."}, {"title": "P-Type ATPases .txt", "text": "For instance, we're going to also look at the sodium potassium Atpas, which is also an example of a ptype Atpas."}, {"title": "P-Type ATPases .txt", "text": "Now, where exactly do we find and what membrane do we find these calcium ATPases?"}, {"title": "P-Type ATPases .txt", "text": "Well, remember, from basic biology, calcium is used by muscle cells."}, {"title": "P-Type ATPases .txt", "text": "And so what that implies is the calcium Atpas must be found within muscle cells."}, {"title": "P-Type ATPases .txt", "text": "And that's exactly right."}, {"title": "P-Type ATPases .txt", "text": "In the membrane of the sarcoplasmic reticulum, the specialized type of endoplasm reticulum is found inside our muscle cells."}, {"title": "P-Type ATPases .txt", "text": "Within the membrane we find these calcium ATPases."}, {"title": "P-Type ATPases .txt", "text": "In fact, calcium Atpas makes up up to 80% of the protein content of the sarcoplasm reticulum."}, {"title": "P-Type ATPases .txt", "text": "So membrane."}, {"title": "P-Type ATPases .txt", "text": "So SR basically stands for sarcoplasm reticulum."}, {"title": "P-Type ATPases .txt", "text": "It's the specialized type of er which is basically used to store the calcium ions found within that muscle cell."}, {"title": "P-Type ATPases .txt", "text": "So let's remember how the muscle contraction actually takes place."}, {"title": "P-Type ATPases .txt", "text": "So our nervous system basically generates this action potential and electrical signal that moves into that muscle cell."}, {"title": "P-Type ATPases .txt", "text": "And once it moves into the muscle cell, what happens is within the membrane of the sarcoplas reticulum, we have these protein channels, not protein pumps, but protein channels."}, {"title": "P-Type ATPases .txt", "text": "And as a result of the action potential, these protein channels basically open up and then calcium begins to move down its electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "So inside the lumen of the sarcoplasm reticulum."}, {"title": "P-Type ATPases .txt", "text": "So this side, we have a very high concentration compared to the cytoplasm of the cell."}, {"title": "P-Type ATPases .txt", "text": "And so when the protein channels open up and these protein channels are not shown in this diagram, when they open up, the calcium begins to move naturally from a high to a low concentration."}, {"title": "P-Type ATPases .txt", "text": "And what that means is once the calcium moves into that cytoplasm, the calcium can then react with the actin filaments found within our muscle cells that exposes special type of mice and binding sites and then coupling with ATP, that muscle contraction actually takes place."}, {"title": "P-Type ATPases .txt", "text": "Now, to relax the muscle, what has to happen is these protein pumps must be able to very quickly and effectively take these calcium and move them back into the inside, into the lumen of the sarco plasma ticulum."}, {"title": "P-Type ATPases .txt", "text": "And when this is done, these calcium ions are moved against the electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "And ultimately, what this also does is it reestablishes that electrochemical gradient that is needed for the protein channels to move the calcium back into this direction so that the muscle contraction, the next muscle contraction can actually take place."}, {"title": "P-Type ATPases .txt", "text": "So we see that calcium is needed for muscle contraction."}, {"title": "P-Type ATPases .txt", "text": "And during contraction, calcium flows into the cytoplasm of the cell from the sarcoplas reticulum lumen down into its concentration, down its concentration gradient."}, {"title": "P-Type ATPases .txt", "text": "And once the contraction is over, to actually relax that muscle, these calcium ions must be sequestered back into the lumen of the sarcoplas reticulum."}, {"title": "P-Type ATPases .txt", "text": "And this is done by these pumps because this actually requires energy to move these calcium ions against their electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "And this is exactly where the calcium Atpas actually comes into play."}, {"title": "P-Type ATPases .txt", "text": "Calcium Atpas uses ATP molecules to move these calcium ions against the electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "And calcium Atpas is also sometimes called circa, where the S and E stands for sarcoplas reticulum, slash, endoplasm, reticulum."}, {"title": "P-Type ATPases .txt", "text": "The C stand, the the CA stands for calcium."}, {"title": "P-Type ATPases .txt", "text": "So the Surf stands for sarcoplasmic endoplasmic, the R stands for reticulum, and the CA stands for calcium."}, {"title": "P-Type ATPases .txt", "text": "Or perhaps the C stands for calcium."}, {"title": "P-Type ATPases .txt", "text": "The A stands for atpas."}, {"title": "P-Type ATPases .txt", "text": "I guess that's also a credible way to see it."}, {"title": "P-Type ATPases .txt", "text": "So we have these calcium."}, {"title": "P-Type ATPases .txt", "text": "ATPases use ATP to pump calcium back into the lumen, thereby reestablishing that gradient."}, {"title": "P-Type ATPases .txt", "text": "And once this process takes place, we essentially establish a gradient in which in the cytoplasm, we have a much smaller concentration than in the lumen."}, {"title": "P-Type ATPases .txt", "text": "And so we have about 0.1 millimolar in the cytoplasm and about 1.5 millimolar of calcium in the lumen."}, {"title": "P-Type ATPases .txt", "text": "And clearly, this is a much higher concentration than this."}, {"title": "P-Type ATPases .txt", "text": "So the pump uses ATP to establish this gradient."}, {"title": "P-Type ATPases .txt", "text": "And then when an action potential actually comes into that muscle cell, the protein channels not shown in this diagram open up."}, {"title": "P-Type ATPases .txt", "text": "And because of the existence of this electrochemical gradient, the calcium ions can quickly and effectively move into the cytoplasm where they are needed to basically contract that muscle."}, {"title": "P-Type ATPases .txt", "text": "So let's take a look at the following diagram."}, {"title": "P-Type ATPases .txt", "text": "This is basically the generalization of how the ptype ATPases actually work."}, {"title": "P-Type ATPases .txt", "text": "So let's begin with the general diagram."}, {"title": "P-Type ATPases .txt", "text": "And then let's look at the specifics."}, {"title": "P-Type ATPases .txt", "text": "So, this is the lumen of the sarcoplasma ticulum, this is the membrane of the sarcoplasmarticulum and this is the cytoplasm of the muscle cell."}, {"title": "P-Type ATPases .txt", "text": "So we have a high concentration on the lumen side, a low concentration of calcium on the cytoplasmic side."}, {"title": "P-Type ATPases .txt", "text": "So this is our ptype Atpas."}, {"title": "P-Type ATPases .txt", "text": "In this case it's the calcium Atpas."}, {"title": "P-Type ATPases .txt", "text": "And notice it exists in a specific type of conformation."}, {"title": "P-Type ATPases .txt", "text": "And the conformation basically allows the movement of these calcium ions into this region of that transmembrane protein."}, {"title": "P-Type ATPases .txt", "text": "Once the calcium moves in, this uses ATP, it hydrolyzes ATP that creates a conformational change."}, {"title": "P-Type ATPases .txt", "text": "And now it traps that calcium and it opens up to the other side."}, {"title": "P-Type ATPases .txt", "text": "And the calcium can now move onto this side, the other side of that membrane."}, {"title": "P-Type ATPases .txt", "text": "And so in this way, these types of ptype ATPases can basically couple ATP."}, {"title": "P-Type ATPases .txt", "text": "So use ATP, the energy stored in ATP, and then drive the movement of these molecules to store that energy in the existence of this electrochemical gradient."}, {"title": "P-Type ATPases .txt", "text": "Now, this is the general diagram of how these actually work."}, {"title": "P-Type ATPases .txt", "text": "But what exactly is the structure of the calcium ATPA?"}, {"title": "P-Type ATPases .txt", "text": "So this is what it looks like."}, {"title": "P-Type ATPases .txt", "text": "So, we have four main regions."}, {"title": "P-Type ATPases .txt", "text": "We have a transmembrane domain and the transmembrane domain basically is found within that membrane."}, {"title": "P-Type ATPases .txt", "text": "And we also have these three other domains which are found on the cytoplasm side of that particular molecule."}, {"title": "P-Type ATPases .txt", "text": "So we have a domain which is this purple one."}, {"title": "P-Type ATPases .txt", "text": "We have the P domain which is this blue one."}, {"title": "P-Type ATPases .txt", "text": "We have the end domain which is this green one."}, {"title": "P-Type ATPases .txt", "text": "Now, the end domain is called the end domain because it is actually responsible for binding that ATP nucleotide."}, {"title": "P-Type ATPases .txt", "text": "So nucleotide begins with N and that's why we call it the end domain."}, {"title": "P-Type ATPases .txt", "text": "Then we have the blue domain."}, {"title": "P-Type ATPases .txt", "text": "The blue domain accepts that phosphoryl group when that ATP is hydrolyzed into ADP."}, {"title": "P-Type ATPases .txt", "text": "And so that's why we call it the P domain."}, {"title": "P-Type ATPases .txt", "text": "And the A domain actually links that conformational change in these two domains to the conformational change in the transmembrane domain."}, {"title": "P-Type ATPases .txt", "text": "So the A domain is responsible for stimulating the conformational change, as we'll see in just a moment."}, {"title": "P-Type ATPases .txt", "text": "So let's actually take a look at the details of how the calcium Atph actually works."}, {"title": "P-Type ATPases .txt", "text": "And notice we have six different diagrams and this basically cycles back and forth."}, {"title": "P-Type ATPases .txt", "text": "So let's begin with the starting point, this diagram here."}, {"title": "P-Type ATPases .txt", "text": "So this is known as the e one state of this protein."}, {"title": "P-Type ATPases .txt", "text": "So this is the calcium Atpas, the lumen side of the sarcoplas reticulum, the cytoplasm side of the sarcoplas reticulum."}, {"title": "P-Type ATPases .txt", "text": "Now, in the e one stage in the e one state, notice that this structure basically is open to this side of the cytoplasm."}, {"title": "P-Type ATPases .txt", "text": "And two, not one, but two calcium ions can move into this pocket of the transmembrane domain."}, {"title": "P-Type ATPases .txt", "text": "So it's the transmembrane domain that is responsible for actually binding those calcium ions."}, {"title": "P-Type ATPases .txt", "text": "And it's two calcium ions per one ATP that is actually pumped to the other side of that particular membrane."}, {"title": "P-Type ATPases .txt", "text": "So in the e one state, we see that the ATP isn't actually bound and these calcium ions can move into the transmembrane domain, as shown here."}, {"title": "P-Type ATPases .txt", "text": "And that's what happens when going from the E one stage to the E one calcium two stage."}, {"title": "P-Type ATPases .txt", "text": "So now we have the two calcium ions inside the transmembrane domain."}, {"title": "P-Type ATPases .txt", "text": "And now the ATP can actually go in and bind and interact with this green domain, the end domain."}, {"title": "P-Type ATPases .txt", "text": "So remember, the end domain binds that ATP nucleotide to this section."}, {"title": "P-Type ATPases .txt", "text": "And so now we go from this stage to the e one calcium to ATP stage."}, {"title": "P-Type ATPases .txt", "text": "And as soon as the ATP binds onto this green section, it creates a localized conformational change in the green structure, the blue structure, and this purple structure."}, {"title": "P-Type ATPases .txt", "text": "And what that does is it seals off, it blocks off this entrance here and also exits."}, {"title": "P-Type ATPases .txt", "text": "And so now these calcium ions are trapped inside this pocket, inside that transmembrane domain."}, {"title": "P-Type ATPases .txt", "text": "Now, notice this transmembrane domain didn't actually undergo a conformational change."}, {"title": "P-Type ATPases .txt", "text": "Only these three domains underwent the transformational change."}, {"title": "P-Type ATPases .txt", "text": "And that's what sealed off that exit."}, {"title": "P-Type ATPases .txt", "text": "Now, in the next stage, we hydrolyze that ATP into an ADP."}, {"title": "P-Type ATPases .txt", "text": "And that phosphoryl group is basically transferred onto the blue section."}, {"title": "P-Type ATPases .txt", "text": "So this P domain and so that P basically goes onto this blue section."}, {"title": "P-Type ATPases .txt", "text": "The ADP remains attached onto the green section."}, {"title": "P-Type ATPases .txt", "text": "And this stage is known as the E one P, where P is the first world calcium two ADP."}, {"title": "P-Type ATPases .txt", "text": "Now, in the next stage, as the ADP begins to exit, so the ADP detaches."}, {"title": "P-Type ATPases .txt", "text": "As it detaches, that creates a conformational change in the structure of that domain."}, {"title": "P-Type ATPases .txt", "text": "And so what happens?"}, {"title": "P-Type ATPases .txt", "text": "That domain basically inverts."}, {"title": "P-Type ATPases .txt", "text": "It opens up to the other side of the membrane and that allows these calcium ions to actually exit that particular transmembrane region."}, {"title": "P-Type ATPases .txt", "text": "And so now the calcium ions end up on the other side, on the lumen side of the membrane."}, {"title": "P-Type ATPases .txt", "text": "And notice we still have that phosphoryl group attached onto the blue domain."}, {"title": "P-Type ATPases .txt", "text": "And so that P domain."}, {"title": "P-Type ATPases .txt", "text": "And so this stage is known as the E two P. And notice it's called E two and not E one."}, {"title": "P-Type ATPases .txt", "text": "So here we have E one, E one, e one and E one, because essentially this confirmation is still open to the cytoplasmic side of that membrane."}, {"title": "P-Type ATPases .txt", "text": "But the E two means it is open to the other side, the lumen side of that membrane."}, {"title": "P-Type ATPases .txt", "text": "So here we have this conformation, but here we have this confirmation."}, {"title": "P-Type ATPases .txt", "text": "That's why we have the E two."}, {"title": "P-Type ATPases .txt", "text": "Now, in the final step, or I shouldn't say the final step, but in the next step, we basically use a water molecule to actually hydrolyze and remove this phosphoryl group from the P domain."}, {"title": "P-Type ATPases .txt", "text": "And as removes as it is removed, we basically form this e two stage."}, {"title": "P-Type ATPases .txt", "text": "And in the last step of this process, what happens is as soon as that phosphorus is removed, this interconverts back into the e one stage."}, {"title": "P-Type ATPases .txt", "text": "And so now, instead of being open this side, it is open to this side."}, {"title": "P-Type ATPases .txt", "text": "When that takes place, this entire section basically opens up."}, {"title": "P-Type ATPases .txt", "text": "And now these calcium ions can once again go into the transmembrane domain and the cycle can basically restart itself."}, {"title": "P-Type ATPases .txt", "text": "So we see that what the ptype Atpas does, what the calcium Atpas does is it moves two of these calcium ions against the electrochemical gradient from a low to a high concentration."}, {"title": "P-Type ATPases .txt", "text": "And the way that it does this is by using the energy that is stored in these ATP molecules."}, {"title": "P-Type ATPases .txt", "text": "So that's exactly why these membrane pumps are energy transducers."}, {"title": "P-Type ATPases .txt", "text": "They essentially take one form of energy."}, {"title": "P-Type ATPases .txt", "text": "In this case, it's the energy stored in the ATP molecules."}, {"title": "P-Type ATPases .txt", "text": "And then they transfer that energy and store it in the energy that exists as a result of this electrochemical gradient between the two sides of the."}, {"title": "Posterior Pituitary Gland.txt", "text": "Previously we discussed the pituitary gland and we said that the pituitary gland, also known as the hypothesis, consists of two sections the frontal section, known as the anterior pituitary section, and the back section, known as the polesthere pituitary section."}, {"title": "Posterior Pituitary Gland.txt", "text": "So previously, we focused on only the anterior pituitary gland and we said that the anti anterior your pituitary gland releases and produces six different types of hormones."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the human growth hormone ACTH, also known as the adrenocorticotropic hormone, it produces the thyroid stimulating hormone, it produces our prolactin, the follicle stimulating protein, as well as the luteinizing protein."}, {"title": "Posterior Pituitary Gland.txt", "text": "So all these six different proteins are produced in the endocrine cells in the anterior pituitary gland and they're basically controlled by the hormones produced in the hypothalamus, the region in the brain found in the forebrain."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the hypothalamus basically produces a set of hormones of its own that ultimately are injected into the capillary bat system found within this region."}, {"title": "Posterior Pituitary Gland.txt", "text": "This entire capillary vein artery system is known as our hypothesial portal system and it basically connects the hypothalamus to the anterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the hormones in the hypothalamus are released into the portal system and they control the release of these hormones in the endocrine cells of the anterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, let's discuss the functionality and the purpose of the posterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "This section, this gland found in the back."}, {"title": "Posterior Pituitary Gland.txt", "text": "So we have the hypothalamus, we have the posterior, the anterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "And this funnel section that connects these two regions is known as our infidibulum."}, {"title": "Posterior Pituitary Gland.txt", "text": "So basically, instead of having this system of capillary beds that connects the hypothalamus to our posterior pituitary gland, we have a set of neurons."}, {"title": "Posterior Pituitary Gland.txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Posterior Pituitary Gland.txt", "text": "So instead of actually synthesizing any type of hormone inside the posterior pituitary gland, the posterior pituitary gland does not actually produce any hormone of its own."}, {"title": "Posterior Pituitary Gland.txt", "text": "What happens is the two hormones that are used by the posterior pituitary gland and we'll see what they are in just a moment, are both synthesized in the cell bodies of the neurons found in the hypothalamus."}, {"title": "Posterior Pituitary Gland.txt", "text": "And these neurons, their axons basically begin in the hypothalamus and they all extend and end up ending in the posterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "So once we synthesize our hormones, they are then secreted and traveled through the axon and are basically stored inside the posterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "So even though this posterior pituitary gland does store two hormones, it doesn't actually produce those hormones they're produced in the hypothalamus."}, {"title": "Posterior Pituitary Gland.txt", "text": "So in the hypothalamus, we have three sections of nuclei neurons."}, {"title": "Posterior Pituitary Gland.txt", "text": "We have the supraoptic nuclei."}, {"title": "Posterior Pituitary Gland.txt", "text": "Supra simply means in front of or above, we have the paraventricular nuclei and the neurosecratory nuclei."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the two types of hormones that are produced in the hypothalamus and which are stored inside the posterior pituitary gland is the antidiauretic hormone ADH, also known as vasopressin, as well as oxytocin."}, {"title": "Posterior Pituitary Gland.txt", "text": "And both of these proteins are small polypeptides and that means they are both synthesized in the rough endoplasmic reticulum of the cell nuclei, in the cell bodies of these nuclei, in the hypothalamus."}, {"title": "Posterior Pituitary Gland.txt", "text": "So let's discuss how they are actually produced and what their functionality is and when they are released."}, {"title": "Posterior Pituitary Gland.txt", "text": "And let's begin with the antidiauretic hormone also known as ADH."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the antiduretic hormone also known as vasopressin."}, {"title": "Posterior Pituitary Gland.txt", "text": "And we'll see why it's given this name in just a moment."}, {"title": "Posterior Pituitary Gland.txt", "text": "This hormone is produced in the cell bodies, in the rough endoplasmaticulum of the cell bodies of the supraoptic nuclei."}, {"title": "Posterior Pituitary Gland.txt", "text": "And once we produce them, we package them into special secretary vesicles and they travel through the axon all the way to the posterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "And once they arrive in the posterior pituitary gland, we store them in specialist secretary vesicles known as the herring bodies."}, {"title": "Posterior Pituitary Gland.txt", "text": "And we store them until they are released, until a certain type of stimulation takes place."}, {"title": "Posterior Pituitary Gland.txt", "text": "The question is what stimulates the release of our ADH of the vasopressin?"}, {"title": "Posterior Pituitary Gland.txt", "text": "So the vasopressin, our antidiaretic hormone, is basically stimulated by the following."}, {"title": "Posterior Pituitary Gland.txt", "text": "When we basically have an increase in the osmolarity of our blood, meaning the blood volume decreases, the amount of fluid, the amount of water in the blood decreases at the same time the amount of solute increases."}, {"title": "Posterior Pituitary Gland.txt", "text": "This is what stimulates the release of ADH from the post sphere pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "So basically, it is released into this network of vessels, blood vessels, and they basically leave and exit the vein."}, {"title": "Posterior Pituitary Gland.txt", "text": "So these three endings are the hypothesical veins."}, {"title": "Posterior Pituitary Gland.txt", "text": "So they are released into the blood and they eventually, the ADH eventually ends up in the kidneys and it basically influences the collecting ducts found in our kidneys."}, {"title": "Posterior Pituitary Gland.txt", "text": "It causes our collecting ducts to basically become more permeable to water."}, {"title": "Posterior Pituitary Gland.txt", "text": "So the collecting ducts end up absorbing more water back into our body, back into our blood vessels, and that increases the water volume found inside our blood."}, {"title": "Posterior Pituitary Gland.txt", "text": "It also decreases the blood osmolarity and it basically increases our blood pressure."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, our ADH also increases blood pressure by constricting our blood vessels."}, {"title": "Posterior Pituitary Gland.txt", "text": "And this is known as vasoconstriction."}, {"title": "Posterior Pituitary Gland.txt", "text": "And that's exactly why ADH is also known as vastopressin, because it presses on those vessels and that's why we have vassal constriction."}, {"title": "Posterior Pituitary Gland.txt", "text": "So once again, ADH is released when blood osmolarity increases."}, {"title": "Posterior Pituitary Gland.txt", "text": "That means our solid concentration increases and our volume, amount of water decreases in the blood."}, {"title": "Posterior Pituitary Gland.txt", "text": "So ADH affects the permeability of the collecting dusts in our kidneys to water."}, {"title": "Posterior Pituitary Gland.txt", "text": "It increases the amount of water that is absorbed back into the blood vessels."}, {"title": "Posterior Pituitary Gland.txt", "text": "And that means it decreases the amount of water that is released in the urine."}, {"title": "Posterior Pituitary Gland.txt", "text": "It increases the concentration of the solute in our urine that is expelled."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, this in turn increases the amount of water, the volume of the blood, and that increases the blood pressure."}, {"title": "Posterior Pituitary Gland.txt", "text": "And ADH also increases blood pressure by constricting by pressing down on those blood vessels."}, {"title": "Posterior Pituitary Gland.txt", "text": "And this is known as vasoconstriction."}, {"title": "Posterior Pituitary Gland.txt", "text": "So this is ADH."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, what about oxytocin?"}, {"title": "Posterior Pituitary Gland.txt", "text": "Well, oxytocin is also produced in the cell bodies of our neurons."}, {"title": "Posterior Pituitary Gland.txt", "text": "They're produced in the cell bodies of the parabentricular nuclei as well as the supra optic nuclei."}, {"title": "Posterior Pituitary Gland.txt", "text": "And once we produce oxytocin they travel down the axon in these secretory vesicles and just like in this case they are stored in special vesicles on the axon of these neurons known as herring bodies."}, {"title": "Posterior Pituitary Gland.txt", "text": "And when stimulation takes place, these hormones the oxytocin is released into this bed of capillaries into the network of capillaries and eventually exits through our veins known as our hypothesial vein."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, by the way, this is the superior hypothesial artery."}, {"title": "Posterior Pituitary Gland.txt", "text": "This is the inferior superior means on top of an inferior means on the bottom of."}, {"title": "Posterior Pituitary Gland.txt", "text": "So these two arteries essentially bring the oxygenated blood as well as the nutrients to the hypothalamus portion as well as to this portion the posterior pituitary portion of our gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "Now, the question is when exactly do we release our oxytocin and what effect does the oxytocin hormone have on our body?"}, {"title": "Posterior Pituitary Gland.txt", "text": "Well, basically oxytocin is released during childbirth in the female human and this basically causes the contraction of smooth muscles in our uterus and that basically helps move our child out of the body."}, {"title": "Posterior Pituitary Gland.txt", "text": "And what the oxytocin also does post childbirth is it basically stimulates the secretion the ejection of our milk found in the glands in the breast."}, {"title": "Posterior Pituitary Gland.txt", "text": "So basically, this is the function of oxytocin while this is the function of the antidiaretic hormone."}, {"title": "Posterior Pituitary Gland.txt", "text": "Both of these hormones are not actually produced in the posterior pituitary gland."}, {"title": "Posterior Pituitary Gland.txt", "text": "They are produced in the cell bodies of the neurons found in the hypothalamus."}, {"title": "Posterior Pituitary Gland.txt", "text": "But once produced, they are released and stored in the herring bodies in the region of our posterior pituitary gland as shown in this region."}, {"title": "Neurulation .txt", "text": "Gastrielation is the process by which the three different germ layers are formed within that developing human embryo."}, {"title": "Neurulation .txt", "text": "And as soon as the germ layers are formed, they can begin producing the different types of structures, organs and systems found within that human adult organism."}, {"title": "Neurulation .txt", "text": "Now, the first type of system that is produced during embryological development is the nervous system."}, {"title": "Neurulation .txt", "text": "And the process says by which the ectoderm germ layer forms."}, {"title": "Neurulation .txt", "text": "The nervous system is known as neuralization."}, {"title": "Neurulation .txt", "text": "And this will be the focus of this lecture."}, {"title": "Neurulation .txt", "text": "Now, neuralization takes place as soon as gastrolation takes place."}, {"title": "Neurulation .txt", "text": "So let's begin by supposing."}, {"title": "Neurulation .txt", "text": "We have a cross section of the gastrial stage of embryological development which is shown in the following diagram."}, {"title": "Neurulation .txt", "text": "So we take a cross section and we see the following different types of cells."}, {"title": "Neurulation .txt", "text": "The purple cells are the cells that make up the trophy blast."}, {"title": "Neurulation .txt", "text": "And the trophy blast eventually forms the coriane as well as the placenta."}, {"title": "Neurulation .txt", "text": "Now, these are the three different germ layers."}, {"title": "Neurulation .txt", "text": "We have the green cells that make up the endoderm."}, {"title": "Neurulation .txt", "text": "We have these red cells that make up the mesoderm and we have these blue cells that make up our actoderm."}, {"title": "Neurulation .txt", "text": "Now, the endoderm is the germ layer that eventually forms the epithelial layer of our digestive tract as well as the lungs, our liver and our pancreas and other structures such as the thyroid and parathyroid glands and the thymus."}, {"title": "Neurulation .txt", "text": "The mesoderm forms the muscular and the skeletal system as well as the cardiovascular system, the excretory system and the reproductive system while the ectoderm is what forms the skin as well as the nervous system."}, {"title": "Neurulation .txt", "text": "Now, before these blue cells can actually organize themselves and arrange themselves and differentiate into the cells that ultimately make up the central and the peripheral nervous system of our body, what must happen is a structure known as the noticort must actually form."}, {"title": "Neurulation .txt", "text": "And the noticort is formed from the cells found in the Masodum germ layer."}, {"title": "Neurulation .txt", "text": "So the Masodermal cells basically form a structure known as the noticord."}, {"title": "Neurulation .txt", "text": "And a noticor is a cylindrical collection."}, {"title": "Neurulation .txt", "text": "It's a cylindrical rod of cells that runs all the way along the entire length of that developing embryo."}, {"title": "Neurulation .txt", "text": "So in this diagram, we form the noticored from these red mesodermal cells."}, {"title": "Neurulation .txt", "text": "So if we zoom in on the following diagram, we get the following picture."}, {"title": "Neurulation .txt", "text": "And this structure here is the notice."}, {"title": "Neurulation .txt", "text": "Or it goes into the board and it comes out of the board and it runs along the entire length of that developing organism."}, {"title": "Neurulation .txt", "text": "Because remember, this is only a cross section of that entire developing organism."}, {"title": "Neurulation .txt", "text": "That's why the noticort looks like a circle."}, {"title": "Neurulation .txt", "text": "Now, what exactly is the point of the noticort?"}, {"title": "Neurulation .txt", "text": "Well, the cells found in the noticort are responsible for stimulating and inducing the thickening of the actoderm region, this section here to produce a structure known as the neural plate."}, {"title": "Neurulation .txt", "text": "And it's the actodermal cells of the neural plate that eventually give rise to the central and the peripheral nervous system."}, {"title": "Neurulation .txt", "text": "So what the noticore does is it stimulates the outward motion, the outward movement, the imagination of the neural plate of this section here towards the noticord."}, {"title": "Neurulation .txt", "text": "And what we begin to produce is something called the neural groove."}, {"title": "Neurulation .txt", "text": "And these two folds we call the neural fold."}, {"title": "Neurulation .txt", "text": "So these are the two neural folds."}, {"title": "Neurulation .txt", "text": "And this is a neural groove that is produced as a result of that outward motion of this central portion of the neural plate."}, {"title": "Neurulation .txt", "text": "Now the continual outward motion of that neural plate eventually brings these two neural folds together."}, {"title": "Neurulation .txt", "text": "So this should be neural neural folds."}, {"title": "Neurulation .txt", "text": "So it brings the two neural folds together."}, {"title": "Neurulation .txt", "text": "And when it folds, when these two touch they basically form this cylindrical structure known as the neural tube."}, {"title": "Neurulation .txt", "text": "And we also have these two tiny extensions known as the neural crest."}, {"title": "Neurulation .txt", "text": "Now the neural tube eventually forms the brain and the spinal cord."}, {"title": "Neurulation .txt", "text": "So it's the neural tube that eventually forms the central nervous system."}, {"title": "Neurulation .txt", "text": "On the other hand, it's these two neural crests that give rise to the peripheral nervous system so they give rise to the ganglia that is found outside the brain and the spinal cord."}, {"title": "Neurulation .txt", "text": "And this process by which we form the neural tube and the neural crest and eventually they give rise to the central nervous system and the peripheral nervous system."}, {"title": "Neurulation .txt", "text": "This process is known as neuralization."}, {"title": "Neurulation .txt", "text": "And it takes place as soon as we form the ectoderm layer during the process of gastric relation."}, {"title": "Human Gestation and Birth.txt", "text": "So now that we know the details of how the embryo and the fetus actually develops inside the uterus of the mother let's focus on the overall picture."}, {"title": "Human Gestation and Birth.txt", "text": "Let's discuss how the pregnancy actually takes place from beginning to end."}, {"title": "Human Gestation and Birth.txt", "text": "And then let's discuss the birth period, the birth process."}, {"title": "Human Gestation and Birth.txt", "text": "So the human gestation period begins with the last menstrual cycle of that woman before she undergoes sexual intercourse and then ends with the birth of that fetus."}, {"title": "Human Gestation and Birth.txt", "text": "And normally, it's about 280 days which is equivalent to 40 weeks."}, {"title": "Human Gestation and Birth.txt", "text": "Now, the human gestation period can be broken down into three sections, into three stages or three trimesters."}, {"title": "Human Gestation and Birth.txt", "text": "So we have trimester one, we have the second trimester and we have the third trimester."}, {"title": "Human Gestation and Birth.txt", "text": "And within each one of these trimesters, something important takes place as we'll see in just a moment."}, {"title": "Human Gestation and Birth.txt", "text": "And following the third trimester, we have the process of birth, also known as parturition."}, {"title": "Human Gestation and Birth.txt", "text": "So let's begin by discussing what takes place within the first trimester."}, {"title": "Human Gestation and Birth.txt", "text": "So let's suppose that sexual intercourse did not yet take place and the menstrual cycle of that woman begins."}, {"title": "Human Gestation and Birth.txt", "text": "Now, following sexual intercourse the sperm is deposited into the vaginal tract."}, {"title": "Human Gestation and Birth.txt", "text": "It then travels into the uterus and it travels up into the fallopian tube."}, {"title": "Human Gestation and Birth.txt", "text": "And eventually, it reaches and combines with the egg cell."}, {"title": "Human Gestation and Birth.txt", "text": "And once this process takes place, known as fertilization we form the zygote."}, {"title": "Human Gestation and Birth.txt", "text": "So as soon as we form that zygote that zygote begins to move along the cilia along the cilia of the fallopian tube and towards the uterine cavity."}, {"title": "Human Gestation and Birth.txt", "text": "And eventually, as it moves along the fallopian tube it begins a process known as cleavage."}, {"title": "Human Gestation and Birth.txt", "text": "Now, once it reaches the cavity of the uterus it undergoes a process known as blastulation to form a blastocyst."}, {"title": "Human Gestation and Birth.txt", "text": "And about seven days after fertilization took place that blastocyst will implant itself onto the endometrium onto the lining of the uterus of that individual woman."}, {"title": "Human Gestation and Birth.txt", "text": "And once implantation takes place, we begin to form the placenta."}, {"title": "Human Gestation and Birth.txt", "text": "Remember, the placenta is the organ that eventually begins the exchange of nutrients and gases between the mother and that fetus."}, {"title": "Human Gestation and Birth.txt", "text": "Now, once implantation takes place, we also begin the process of gastrelation."}, {"title": "Human Gestation and Birth.txt", "text": "Now remember, gastrolation is the process by which we form the three different germ layers."}, {"title": "Human Gestation and Birth.txt", "text": "And these three different germ layers eventually give rise to the different tissues, organs and systems that are found within that adult individual."}, {"title": "Human Gestation and Birth.txt", "text": "Now, this all takes place within the first trimester."}, {"title": "Human Gestation and Birth.txt", "text": "In fact, it takes place within the first several weeks following fertilization."}, {"title": "Human Gestation and Birth.txt", "text": "Now, we also have neuralation take place."}, {"title": "Human Gestation and Birth.txt", "text": "And neuralation is basically when we form the noticord."}, {"title": "Human Gestation and Birth.txt", "text": "The notrecord eventually goes on to form the neural folds as well as the neural plate."}, {"title": "Human Gestation and Birth.txt", "text": "The neural plate then forms the neural tube as well as these tiny neural crests."}, {"title": "Human Gestation and Birth.txt", "text": "And the neural crests give rise to the peripheral nervous system while the neural tube gives rise to the central nervous system the brain as well as the spinal cord."}, {"title": "Human Gestation and Birth.txt", "text": "So we see that the nervous system begins to form during the first trimester."}, {"title": "Human Gestation and Birth.txt", "text": "Now, we also have many other organs begin to form."}, {"title": "Human Gestation and Birth.txt", "text": "For example, we begin the formation of the heart and we begin the formation of the lungs."}, {"title": "Human Gestation and Birth.txt", "text": "We also begin to form our digestive system."}, {"title": "Human Gestation and Birth.txt", "text": "And the digestive system begins to basically form these outgrowths, which eventually form the liver."}, {"title": "Human Gestation and Birth.txt", "text": "That eventually forms the pancreas as well as the gallbladder."}, {"title": "Human Gestation and Birth.txt", "text": "And the limbs also begin to develop."}, {"title": "Human Gestation and Birth.txt", "text": "In fact, we also develop the gonads."}, {"title": "Human Gestation and Birth.txt", "text": "So by the end of the first trimester we basically know exactly what the sex of that fetus is because the gonads are essentially formed."}, {"title": "Human Gestation and Birth.txt", "text": "So if it's a female, we'll have ovaries."}, {"title": "Human Gestation and Birth.txt", "text": "If it's a male, we'll have testes."}, {"title": "Human Gestation and Birth.txt", "text": "Now let's move on to the second trimester."}, {"title": "Human Gestation and Birth.txt", "text": "By the way, the first trimester begins with that last period, with that last menstrual cycle and ends at the 13th week following fertilization, essentially."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what about the second trimester?"}, {"title": "Human Gestation and Birth.txt", "text": "Well, this begins at the 14th week and ends at the 27th week."}, {"title": "Human Gestation and Birth.txt", "text": "And this is when the heart begins to develop even further."}, {"title": "Human Gestation and Birth.txt", "text": "Now, in the first trimester, the heart beats relatively slowly."}, {"title": "Human Gestation and Birth.txt", "text": "It makes about 60 beats per minute."}, {"title": "Human Gestation and Birth.txt", "text": "But in the second trimester, the beat of that heart basically speeds up."}, {"title": "Human Gestation and Birth.txt", "text": "Here, it beats about 100 beats every single minute."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what also happens is that fetus begins to actually move."}, {"title": "Human Gestation and Birth.txt", "text": "And now this movement can be felt by that mother."}, {"title": "Human Gestation and Birth.txt", "text": "Now, the eyes, the ears, the nose and the face also begins to form and it basically resembles the human being."}, {"title": "Human Gestation and Birth.txt", "text": "So it begins to look normal, like a normal individual."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what happens during the third trimeth?"}, {"title": "Human Gestation and Birth.txt", "text": "So this essentially begins at the 28th week and ends at the birth process."}, {"title": "Human Gestation and Birth.txt", "text": "So we'll talk about the birth in just a moment."}, {"title": "Human Gestation and Birth.txt", "text": "So what happens during the third trimester?"}, {"title": "Human Gestation and Birth.txt", "text": "So this is when the fetus begins to grow very rapidly and quickly, they actually increase in size."}, {"title": "Human Gestation and Birth.txt", "text": "So this is when the final differentiation of all the organs begin to take place."}, {"title": "Human Gestation and Birth.txt", "text": "For example, the cerebral found in the central nervous system begins to fully differentiate as well as it develops those convolutions that we see on the brain."}, {"title": "Human Gestation and Birth.txt", "text": "So we have different types of reflexes become apparent."}, {"title": "Human Gestation and Birth.txt", "text": "For example, we have grasping and suckling."}, {"title": "Human Gestation and Birth.txt", "text": "And this is when that fetus begins to actually suck on their thumb."}, {"title": "Human Gestation and Birth.txt", "text": "And finally, the hair also may or may not grow."}, {"title": "Human Gestation and Birth.txt", "text": "So these three trimesters basically divide the three different stages of the gestation period, the period during which that female individual is pregnant."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what about the birth process?"}, {"title": "Human Gestation and Birth.txt", "text": "Well, the birth process, also known as parteration, can also be broken down into three stages."}, {"title": "Human Gestation and Birth.txt", "text": "We have stage number one, which lasts about 12 hours."}, {"title": "Human Gestation and Birth.txt", "text": "We have stage number two, which lasts from anywhere from 20 minutes to 1 hour."}, {"title": "Human Gestation and Birth.txt", "text": "And then we have stage three, which lasts about ten to 15 minutes."}, {"title": "Human Gestation and Birth.txt", "text": "So let's begin with stage one."}, {"title": "Human Gestation and Birth.txt", "text": "So in stage one is when special hormones are released by the body and they stimulate the contraction of the walls of that uterus."}, {"title": "Human Gestation and Birth.txt", "text": "Remember, the wall of the uterus not only has that endometrium, but it also contains smooth muscle."}, {"title": "Human Gestation and Birth.txt", "text": "And that smooth muscle is capable of contracting."}, {"title": "Human Gestation and Birth.txt", "text": "And so in the first stage of the birthing process, also known as labor, this is when the contraction of that uterus begins."}, {"title": "Human Gestation and Birth.txt", "text": "And as a result of these contractions, that fetus, the head of the fetus, begins to position and begins to move towards the cervix."}, {"title": "Human Gestation and Birth.txt", "text": "So remember, the cervix is that section between the uterus and the tract of the vagina."}, {"title": "Human Gestation and Birth.txt", "text": "What also happens is the cervix is normally very rigid."}, {"title": "Human Gestation and Birth.txt", "text": "And what happens is it begins to relax, it dilates and it flattens out."}, {"title": "Human Gestation and Birth.txt", "text": "And this is important because that is essentially what allows the head of that fetus to make its way into the tract of the vagina."}, {"title": "Human Gestation and Birth.txt", "text": "Now, eventually, towards the end of stage one, we have the amnion that ruptures."}, {"title": "Human Gestation and Birth.txt", "text": "So the AMN is that sac, the fluid filled sac that contains that developing embryo and that developing fetus."}, {"title": "Human Gestation and Birth.txt", "text": "And so what happens towards the end is it ruptures, releasing about one liter of amniotic fluid through the vaginal cavity and into the outside environment."}, {"title": "Human Gestation and Birth.txt", "text": "And so this is when that woman knows she's at the end of stage one."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what about stage two?"}, {"title": "Human Gestation and Birth.txt", "text": "Well, stage two is the actual birthing process."}, {"title": "Human Gestation and Birth.txt", "text": "This is when the woman actually pushes."}, {"title": "Human Gestation and Birth.txt", "text": "And so when she pushes, what she does is she contracts her abdominal muscles."}, {"title": "Human Gestation and Birth.txt", "text": "And along with the contraction of the uterine muscles, the combination of these two types of forces, these two types of muscles, basically push that fetus through the cervix, through the vaginal cavity and eventually to the outside environment."}, {"title": "Human Gestation and Birth.txt", "text": "And then that individual, that fetus, is born."}, {"title": "Human Gestation and Birth.txt", "text": "And we call that fetus a neonate."}, {"title": "Human Gestation and Birth.txt", "text": "Now, what about stage three?"}, {"title": "Human Gestation and Birth.txt", "text": "Well, stage three lasts about ten to 15 minutes and this is known as after birth."}, {"title": "Human Gestation and Birth.txt", "text": "So the uterus basically continues to contract."}, {"title": "Human Gestation and Birth.txt", "text": "Why does the uterus continue to contract?"}, {"title": "Human Gestation and Birth.txt", "text": "Well, because at this stage, the placental membrane is still attached to the wall of that uterus."}, {"title": "Human Gestation and Birth.txt", "text": "And so the uterus has to continue to contract to basically loosen that placental membrane and eventually expel that membrane to the outside environment."}, {"title": "Human Gestation and Birth.txt", "text": "So eventually the physicians basically tie up the umbilical cord and then they make the cut."}, {"title": "Human Gestation and Birth.txt", "text": "And finally, the uterus, the endometrium or the wall of that uterus, begins to regenerate itself and eventually the menstrual cycle will begin once again."}, {"title": "Human Gestation and Birth.txt", "text": "And by the way, the menstrual cycle does not take place during the pregnancy period."}, {"title": "Human Gestation and Birth.txt", "text": "And that's because we don't want to actually get rid of the lining of the endometrium because we have a growing embryo and a growing fetus within that endometrium."}, {"title": "Human Gestation and Birth.txt", "text": "So we see that the human gestation period can be broken down into three stages."}, {"title": "Human Gestation and Birth.txt", "text": "We have the first trimester, the second trimester and the third trimester."}, {"title": "Human Gestation and Birth.txt", "text": "And then following these trimesters."}, {"title": "Human Gestation and Birth.txt", "text": "We have the process of birth take place, and that can also be broken down into three stages."}, {"title": "Human Gestation and Birth.txt", "text": "So this actually takes place before the actual birth process."}, {"title": "Human Gestation and Birth.txt", "text": "This is during the birth process when that woman expels and propels that fetus to the outside environment."}, {"title": "Human Gestation and Birth.txt", "text": "And we have the after birth stage three, which takes about ten to 15 minutes to actually take place."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So in biochemistry, instead of using either one of those equations, we use this equation here."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "But basically it's the same exact equation, just it's in a slightly different form."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So this is Faraday's constant."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So it's 96,500."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And what it basically tells us is it's the amount of charge that exists on 1 mol of electrons as they move move along that particular cell membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "Now, Z, what Z is it's basically the value of the charge on that particular ion."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So if the charge, let's say we're dealing with sodium ions, the Z value is plus one."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "If we're dealing with chloride ions, the Z value is negative one."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "If we're dealing with, let's say potassium has a positive one, it's also positive one, and so forth."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So basically, Z is the charge on the ion."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "It could be positive negative one, positive negative two, positive negative three."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "Now, if we're dealing with an uncharged neutral molecule, z is zero."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so the delta G is zero, because that neutral charge will not feel any type of electric force within that voltage difference."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So essentially, this is the equation that we can basically use to tell us how much energy we have to input."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "We have to give a charged molecule or ion to basically move it across that particular voltage difference."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And by the same exact reasoning, if this is zero, that means it will not move in any direction if it is negative."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "What that basically means is as it moves, it releases energy."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so no work must be done."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And if this is negative, what that means is the process is a passive process."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "It involves passive transport."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "If this is positive, that involves active transport actually using energy."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So doing work on that charged species to move it across that particular membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So, by the way, delta V is simply the difference in the voltage between this side of the membrane and the other side of the membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So this is the voltage difference, the electrical potential difference, what we call the electrical gradient."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So delta G describes the amount of energy that must be transferred into the molecule or the molecule releases into the environment to basically move between the two sides of the membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And to demonstrate how we can use this particular equation, let's take a look at the following diagram."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So, let's suppose we have a cell membrane, and in that cell membrane we have an open channel."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And the channel basically allows the movement of these sodium ions."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And notice in this case, we didn't have to consider the channel because we were looking at these non polar molecules and they can simply diffuse across that membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So let's take a look at this particular case."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So let's suppose that the resting potential so the electrical potential difference between the two sides of the membrane in this particular case is negative 45 millivolts millivolts."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And what that basically means is this quantity here is more negative than this quantity here, as we show in this particular case."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "Now, we know that on the outside, we're going to have a larger concentration of sodium ions than on the inside."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And before we actually calculate anything, the question is, will these sodium ions actually move from this side to this side of that cell membrane?"}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So what we see is, because we have a higher positive charge on this side, these ions will tend to move into that cell."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So in this direction."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And what that means is this number has to be negative for that to actually be true."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "Because if we open up the channel, these ions will want to spontaneously move down their electrical gradient from a high electric potential to a low electric potential."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so if we calculate Delta G, we see that the z value is positive one, the F is 96,500 coulombs per mole."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And we see that this quantity, so Delta V is so we have to use V, not milliv."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so it's negative zero point 45."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And we multiply these out and we get a negative quantity."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So Delta G is equal to negative 4342 joules per mole."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so we see that once we open up the channel, because there exists this electrical gradient."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So we have a high electrical potential on this side, a low electrical potential on the other side."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "There will be a movement, so a spontaneous movement from the outside to the inside of that cell."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And that's exactly what the negative Delta G actually tells us."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So if the Delta G is positive, energy must be inputted to actually move the chart species across that particular cell membrane."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So if instead we wanted to basically move the sodium from this side to this side, this value would have been positive."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so a Delta G in this case would have been positive."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "But because our Delta G is negative, we're basically moving from this side to this side."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And that means no energy must be inputted into that molecule to move it in that direction."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So what that means is this will be passive transport, not active transport."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And finally, now that we know what concentration gradient is and electro gradient is, we can basically combine these two concepts into a single concept."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So we combine this equation with this equation."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And so what that gives us is the following equation."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And this equation is the equation that we can basically use to quantify and measure how much energy exists between the two sides of the membrane for molecules that have unequal distribution along the two membranes, as well as an unequal charge distribution."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "So if the charge distribution is the same, then that means this will be zero."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "But if the concentration distribution is the same, what that means is this quality is zero."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "But if neither the concentration distribution is the same, nor is the charge distribution the same, that means these two quantities are not zero."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And we have to use both of them to actually calculate what that Delta G is."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "And once again, when that Delta G is positive, the process will be an active transport process."}, {"title": "Measuring the Electrochemical Gradient .txt", "text": "If it's negative, it will be a passive transport, because that doesn't require energy for that molecule to move down its electrochemical gradient."}, {"title": "Compliance of Blood Vessels.txt", "text": "Previously we discussed the concept of blood pressure and we said that inside arteries we have a much higher blood pressure than inside our veins."}, {"title": "Compliance of Blood Vessels.txt", "text": "And this is because of a difference in structure of the two different types of blood vessels."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now, blood pressure is not the only measurement that we can use to describe the properties and the behavior of the different types of blood vessels."}, {"title": "Compliance of Blood Vessels.txt", "text": "We can also use a measurement known as compliance to describe the behavior properties of blood vessels."}, {"title": "Compliance of Blood Vessels.txt", "text": "So let's begin by defining what compliance is."}, {"title": "Compliance of Blood Vessels.txt", "text": "So compliance, loosely speaking, describes how easy it is to actually expand a given blood vessel."}, {"title": "Compliance of Blood Vessels.txt", "text": "So if we take a blood vessel and we try to expand that blood vessel by increasing its crosssectional area and if that blood vessel is able to resist it and recall back into its original position then in this case we say that the blood vessel has a low compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "On the other hand, if by trying to expand that blood vessel the blood vessel remains in that expanded state and doesn't recoil back into place well, in this case we say the blood vessel has a high compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "So high compliance means we have to apply a low pressure to expand it."}, {"title": "Compliance of Blood Vessels.txt", "text": "But low compliance means we have to apply a high pressure to expand it even by a tiny amount."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now let's discuss arteries."}, {"title": "Compliance of Blood Vessels.txt", "text": "So let's recall that the structure of arteries consists of three different layers and for arteries, the middle layer known as the tunica media contains a thick layer of smooth muscle."}, {"title": "Compliance of Blood Vessels.txt", "text": "And as a result of this thick layer of smooth muscle it gives arteries the ability to recoil when we actually try to expand them."}, {"title": "Compliance of Blood Vessels.txt", "text": "So what this means is when the blood actually flows through these arteries and when the blood applies a force and a pressure on the walls of those arteries as a result of that smooth muscle the walls can exert a force back on that blood and resist that expansion."}, {"title": "Compliance of Blood Vessels.txt", "text": "So that is what we mean by recoiling back into place."}, {"title": "Compliance of Blood Vessels.txt", "text": "So once again, arteries have a thick layer of smooth muscle which gives them the ability to recoil during expansion."}, {"title": "Compliance of Blood Vessels.txt", "text": "This means that when the blood pushes against the walls of these arteries they can push right back."}, {"title": "Compliance of Blood Vessels.txt", "text": "Therefore, when the blood fills these arteries and it tries to expand them the expansion doesn't actually take place or it takes place but only a very small percentage of expansion actually takes place."}, {"title": "Compliance of Blood Vessels.txt", "text": "So for relatively large arteries such as our femoral artery, the femoral artery it only expands by about 10%."}, {"title": "Compliance of Blood Vessels.txt", "text": "So in diagram A we have the relaxed state of our artery and no blood actually flows across."}, {"title": "Compliance of Blood Vessels.txt", "text": "But when blood actually fills the arteries the fluid, the blood pushes against the walls but the walls push right back and so it expands only by a tiny amount and that means that arteries have a low compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "A very, very high force is actually needed."}, {"title": "Compliance of Blood Vessels.txt", "text": "A very high pressure is needed to actually expand our arteries."}, {"title": "Compliance of Blood Vessels.txt", "text": "So arteries can withstand high pressures without increasing in volume by too much, meaning they have a low compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now, what about veins?"}, {"title": "Compliance of Blood Vessels.txt", "text": "Well, recall that veins have a slightly different structure."}, {"title": "Compliance of Blood Vessels.txt", "text": "They also consist of the same three layers."}, {"title": "Compliance of Blood Vessels.txt", "text": "But the tunica media and veins is relatively thin."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that's because they have a thin layer of smooth muscle."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that's exactly why veins behave slightly differently."}, {"title": "Compliance of Blood Vessels.txt", "text": "They have different properties."}, {"title": "Compliance of Blood Vessels.txt", "text": "So what happens when blood actually injures our veins?"}, {"title": "Compliance of Blood Vessels.txt", "text": "Well, when blood flows through our veins, the blood exerts a pressure on the walls of the veins."}, {"title": "Compliance of Blood Vessels.txt", "text": "But the walls of the veins cannot actually push back the same way that the arteries can."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that's exactly why when the blood flows through the veins, that increases the volume of our vein and the veins can actually push back."}, {"title": "Compliance of Blood Vessels.txt", "text": "They cannot recoil back."}, {"title": "Compliance of Blood Vessels.txt", "text": "And so we say that veins have a high compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "So veins behave very differently than arteries."}, {"title": "Compliance of Blood Vessels.txt", "text": "When they experience blood flow, the blood pushes on the walls, but the walls cannot actually push back as well."}, {"title": "Compliance of Blood Vessels.txt", "text": "And so what happens is this increases and expands the cross sectional area of our vein and therefore increases the amount of volume that can pass along that given vein."}, {"title": "Compliance of Blood Vessels.txt", "text": "It also ensures that there isn't a build up of pressure within our veins."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that's exactly why in arteries we have a high pressure because the walls can easily push back."}, {"title": "Compliance of Blood Vessels.txt", "text": "But in veins, the walls cannot push back."}, {"title": "Compliance of Blood Vessels.txt", "text": "So we have expansion taking place and the pressure remains at a relatively low value."}, {"title": "Compliance of Blood Vessels.txt", "text": "So in A, we have a relaxed vein, but in this diagram, let's call it B when the blood flows and easily pushes against, it expands, but the walls cannot push back and so it remains expanded and the volume increases."}, {"title": "Compliance of Blood Vessels.txt", "text": "In this case, we have an increase by 10%."}, {"title": "Compliance of Blood Vessels.txt", "text": "In this case, we can have an increase by, let's say, 200%."}, {"title": "Compliance of Blood Vessels.txt", "text": "So it doubles in its size."}, {"title": "Compliance of Blood Vessels.txt", "text": "And as a result, our veins can actually store much more of the blood volume than our arteries can."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now, this is a qualitative discussion."}, {"title": "Compliance of Blood Vessels.txt", "text": "What about a quantitative discussion?"}, {"title": "Compliance of Blood Vessels.txt", "text": "Is their formula that describes the compliance of our blood vessels?"}, {"title": "Compliance of Blood Vessels.txt", "text": "And the answer is yes."}, {"title": "Compliance of Blood Vessels.txt", "text": "So this is basically a linear equation that describes our compliance where C is the compliance of that given blood vessel."}, {"title": "Compliance of Blood Vessels.txt", "text": "The change in volume is by how much volume it increases."}, {"title": "Compliance of Blood Vessels.txt", "text": "And delta p is basically the change in pressure, the difference in pressure between the inside portion of the blood vessel and the outside portion of our blood vessel."}, {"title": "Compliance of Blood Vessels.txt", "text": "So if we change around this equation and if we bring the delta p to this side we get a linear function, we get delta v is equal to the product of c multiplied by delta p and we can easily plot this equation on the XY plot."}, {"title": "Compliance of Blood Vessels.txt", "text": "So let's take a look at what that actually looks like."}, {"title": "Compliance of Blood Vessels.txt", "text": "So let's plot this four arteries."}, {"title": "Compliance of Blood Vessels.txt", "text": "So the y axis is the relative increase in volume given to us in percentage where 100% basically means the blood vessel is fully relaxed."}, {"title": "Compliance of Blood Vessels.txt", "text": "It contains 100% of that blood."}, {"title": "Compliance of Blood Vessels.txt", "text": "So our x axis describes the pressure in millimeters of mercury."}, {"title": "Compliance of Blood Vessels.txt", "text": "So we have 5100, 100 and 5200 and so forth."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now, the line, the slope of this line designates our value for our C, which is the compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "So if we bring this over to this side, the C will basically describe our compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "And the higher the slope is, the greater the value of C compliance is."}, {"title": "Compliance of Blood Vessels.txt", "text": "Now, this is the same exact graph except here we're using our veins."}, {"title": "Compliance of Blood Vessels.txt", "text": "And right away notice that the slope for our artery is much lower than the slope of our vein."}, {"title": "Compliance of Blood Vessels.txt", "text": "Why is that?"}, {"title": "Compliance of Blood Vessels.txt", "text": "Well, that's because we have to apply a very high pressure to actually increase the volume of our artery."}, {"title": "Compliance of Blood Vessels.txt", "text": "But in the case of our vein, we can apply a time pressure to actually increase the volume because they can't actually push back on that blood very well."}, {"title": "Compliance of Blood Vessels.txt", "text": "So for arteries, the slope is small, as shown here."}, {"title": "Compliance of Blood Vessels.txt", "text": "And so that means compliance is small as well."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that means that they can resist high pressures without actually really increasing in volume by that much."}, {"title": "Compliance of Blood Vessels.txt", "text": "On the other hand, a very tiny change in pressure, if we even apply the slightest pressure to our veins, they will easily expand by a great percentage."}, {"title": "Compliance of Blood Vessels.txt", "text": "So even a small application, let's say 25 mercury will increase it by that 400% versus in this case, a 25% increase in pressure does not actually increase it by that much."}, {"title": "Compliance of Blood Vessels.txt", "text": "So for veins, the slope is very large, the compliance is large."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that means that they change in volume even when there is a timing change in our pressure."}, {"title": "Compliance of Blood Vessels.txt", "text": "And this means we can expand them very well."}, {"title": "Compliance of Blood Vessels.txt", "text": "We can distend them very well."}, {"title": "Compliance of Blood Vessels.txt", "text": "Distant simply means expand."}, {"title": "Compliance of Blood Vessels.txt", "text": "And so that's exactly why in our body, veins are used to store a lot of that blood."}, {"title": "Compliance of Blood Vessels.txt", "text": "So veins store much more of that blood volume than do our arteries for this specific reason."}, {"title": "Compliance of Blood Vessels.txt", "text": "So arteries have a low compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "They can easily resist and recoil while our veins do not easily resist and recoil."}, {"title": "Compliance of Blood Vessels.txt", "text": "And that means we can easily expand them."}, {"title": "Compliance of Blood Vessels.txt", "text": "And so they have a high compliance."}, {"title": "Compliance of Blood Vessels.txt", "text": "For arteries, the slope is low because our compliance is low."}, {"title": "Compliance of Blood Vessels.txt", "text": "But for veins, the slope is much higher because the compliance is much higher."}, {"title": "Exchange Across Capillaries .txt", "text": "Our systemic capillaries are specialized blood vessels whose function is to exchange and allow the movement of nutrients and waste products between the tissue side and the blood plasma side of our capillaries."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, things like water molecules, proteins, gases, nutrients and waste products, hormones and electrolytes, all these things dissolved in their blood plasma, must be able to move across the wall of our capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "The question is, how does this movement actually take place?"}, {"title": "Exchange Across Capillaries .txt", "text": "Well, recall that our capillary wall is very, very thin."}, {"title": "Exchange Across Capillaries .txt", "text": "In fact, it's so thin that it only consists of a single endothelial layer."}, {"title": "Exchange Across Capillaries .txt", "text": "And between the endothelial cells of our capillary wall, we have very tiny junctions, very tiny slits."}, {"title": "Exchange Across Capillaries .txt", "text": "And these slits and junctions act as pores and allow the movement of the fluid, the blood plasma, along with the molecules dissolved inside the blood plasma across the wall of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, because of the limited size of these pores, we basically prevent the movement of larger things such as red blood cells across the wall of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "So we see that the wall of the capillary is in fact a semipermeable membrane."}, {"title": "Exchange Across Capillaries .txt", "text": "So now we know how this movement actually takes place."}, {"title": "Exchange Across Capillaries .txt", "text": "It takes place through these tiny pores and holes we call junctions and slits that exist between our endothelial cells of the capillary wall."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, the next question is what causes this movement of blood plasma across the wall of the capillary?"}, {"title": "Exchange Across Capillaries .txt", "text": "And in what direction does this fluid actually move?"}, {"title": "Exchange Across Capillaries .txt", "text": "Does it move out of the capillary or into our capillary?"}, {"title": "Exchange Across Capillaries .txt", "text": "Or does it move in both directions?"}, {"title": "Exchange Across Capillaries .txt", "text": "So, to answer this question, we have to discuss the pressure that exists between the inside of the capillary and the outside, the tissue side of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "Because ultimately, it's a difference in pressure that allows the movement of our fluid from point A to point B."}, {"title": "Exchange Across Capillaries .txt", "text": "And the two types of pressures we have discussed are hydrostatic pressure as well as osmotic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "So let's begin with hydrostatic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "So as our blood plasma, as our fluid moves along our blood vessel, along the capillary, that fluid exerts a force and it pushes against the walls of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "And this is what we call the hydrostatic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "Hydro simply means water, because our blood plasma is predominantly water."}, {"title": "Exchange Across Capillaries .txt", "text": "And static simply means we have these forces."}, {"title": "Exchange Across Capillaries .txt", "text": "So hydrostatic means the force as a result of that fluid that moves along our capillary system."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, let's take a look at the following diagram that describes our blood vessel."}, {"title": "Exchange Across Capillaries .txt", "text": "So these are the cells, the endothelial cells, of our capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "And this is the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "These are the junctions, the slits found in between our endothelial cells."}, {"title": "Exchange Across Capillaries .txt", "text": "And this is where the movement actually takes place."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, we know that capillaries actually connect our arterioles to our vanills."}, {"title": "Exchange Across Capillaries .txt", "text": "So this is the arterial side of the capillary and this is the Venuel side of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, recall in our discussion on the circulation system, we said that it's the heart that actually creates the hydrostatic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "And it allows the movement of fluid of blood plasma inside our blood vessels."}, {"title": "Exchange Across Capillaries .txt", "text": "And because the arterial end of the capillary is closer to the heart than the Venuel end of the capillary, what that means is the arterial end of the capillary will have a greater hydrostatic pressure than the Venuel side."}, {"title": "Exchange Across Capillaries .txt", "text": "So the hydrostatic pressure that is exerted on the walls of the capillary on the arterial end is about 41.3 Mercury."}, {"title": "Exchange Across Capillaries .txt", "text": "But on the venue end, it's about 21.3 mmhg."}, {"title": "Exchange Across Capillaries .txt", "text": "And we'll see what that means in just a moment."}, {"title": "Exchange Across Capillaries .txt", "text": "Now let's move on to the osmotic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "So, osmotic pressure, also known as oncotic pressure, and we'll see why in just a moment, is the pressure that exists between the two sides of a semi permeable membrane as a result of a difference in solute concentration between the two sides of that semipermeable membrane."}, {"title": "Exchange Across Capillaries .txt", "text": "In this case, our semipermeable membrane is the wall of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "So, if we examine the following diagram, we see that inside our capillary, the blood plasma actually contains a higher concentration of solute molecules."}, {"title": "Exchange Across Capillaries .txt", "text": "It contains more proteins, it contains more ions, and so forth."}, {"title": "Exchange Across Capillaries .txt", "text": "And as a result, it has a greater concentration of solute."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, recall that water always naturally moves from a lower solute concentration to a higher solute concentration."}, {"title": "Exchange Across Capillaries .txt", "text": "Water always moves from a high osmotic potential to a low asthmatic potential."}, {"title": "Exchange Across Capillaries .txt", "text": "And because a greater solid concentration means a lower osmotic potential, water will always move from the tissue side to the blood plasma side of our capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "So, in the same exact way that objects always travel from a higher gravitational potential to a lower gravitational potential, water will always move from a higher osmotic potential in the tissue to a lower osmotic potential inside our blood vessel."}, {"title": "Exchange Across Capillaries .txt", "text": "And that's why water moves along this direction into our capillaries."}, {"title": "Exchange Across Capillaries .txt", "text": "So, due to the high level of proteins, ions and other solute molecules in the blood, the blood plasma has a greater solute concentration than the tissue of the membrane, and that means it has a lower osmotic potential."}, {"title": "Exchange Across Capillaries .txt", "text": "Therefore, water will move from the tissue and into the blood plasma from a high to a low osmotic potential, in the same way that objects move from a higher to a lower gravitational potential."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, because inside the blood plasma, the relative concentration of these solute molecules remains the same, that means the zmodic pressure along the entire capillary will also remain the same."}, {"title": "Exchange Across Capillaries .txt", "text": "It will be equal to about 28 Mercury."}, {"title": "Exchange Across Capillaries .txt", "text": "So it's the same here as it is the same on the other side, the manual side of our capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, the question is, how exactly do these two different pressures influence the movement of our blood plasma across the wall of the capillary?"}, {"title": "Exchange Across Capillaries .txt", "text": "Well, to find the net pressure and the net fluid flow, we have to basically add up these two different pressures."}, {"title": "Exchange Across Capillaries .txt", "text": "So let's begin on the arterial end, of the capillary."}, {"title": "Exchange Across Capillaries .txt", "text": "We know that the hydrostatic pressure points outward, but the osmotic pressure points inward."}, {"title": "Exchange Across Capillaries .txt", "text": "So they point in opposite directions."}, {"title": "Exchange Across Capillaries .txt", "text": "And that means to find the net pressure, we have to have these two values up."}, {"title": "Exchange Across Capillaries .txt", "text": "So the P hydrostatic minus the P osmotic."}, {"title": "Exchange Across Capillaries .txt", "text": "So we choose this to be the positive pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "And this to be the negative pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "And so 41.3 Mmhg -28 mmhg gives us positive 13.3 Mmhg."}, {"title": "Exchange Across Capillaries .txt", "text": "The fact that this is positive basically means that the net fluid flow on the arterial end of the capillary will be out of that capillary and into the tissues of our body."}, {"title": "Exchange Across Capillaries .txt", "text": "And so this is where the nutrients, for example, the glucose and Oxygen will flow into the tissues of our body."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, what about the Venuel side?"}, {"title": "Exchange Across Capillaries .txt", "text": "Well, we follow the same exact procedure, but now notice the hydrostatic pressure is less."}, {"title": "Exchange Across Capillaries .txt", "text": "In fact, because it's less than osmotic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "When we take the sum, we get negative 6.7 Mercury."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, what that basically means is because it's negative, there will be a net fluid flow of our blood plasma into the capillaries from the tissue."}, {"title": "Exchange Across Capillaries .txt", "text": "And this is when the waste products, for example, ammonia and Carbon dioxide, will flow into the blood plasma."}, {"title": "Exchange Across Capillaries .txt", "text": "And then they will ultimately travel to the kidneys and other organs of our body that are responsible for excreting those different types of wasteful."}, {"title": "Exchange Across Capillaries .txt", "text": "Byproducts now, because we have a difference in pressure, because the pressure that pushes into the tissue on the arterial side is greater than the pressure that pushes inward into the capillary, we see that there's going to be a net loss of fluid to the tissues."}, {"title": "Exchange Across Capillaries .txt", "text": "In fact, there is a net loss of about 10% of the fluid that exists that takes place and that extra fluid, the 10% of the fluid that leaves our capillaries into our Lymphatic system."}, {"title": "Exchange Across Capillaries .txt", "text": "And the Lymphatic system ultimately returns that fluid to our blood circulating throughout our circulation system."}, {"title": "Exchange Across Capillaries .txt", "text": "And we'll talk much more about what the Lymphatic system is in a future lecture."}, {"title": "Exchange Across Capillaries .txt", "text": "So we see that the exchange in our fluid between the wall of the capillary takes place due to these junctions and slits between the endothelial cells."}, {"title": "Exchange Across Capillaries .txt", "text": "Now, the reason it takes place, the reason we have a net fluid flow is because of a difference in pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "On the arterial side, we have a greater hydrostatic pressure than azmodic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "So we have have a net movement of out of the capillary into our tissue."}, {"title": "Exchange Across Capillaries .txt", "text": "But on the Venuel side, the opposite is true."}, {"title": "Exchange Across Capillaries .txt", "text": "The hydrostatic pressure is less than asthmatic pressure."}, {"title": "Exchange Across Capillaries .txt", "text": "So there is a net movement of fluid from the tissue and into the capillaries of our body."}, {"title": "Neuroglia .txt", "text": "The nervous system is made up of a functional unit known as the neuron."}, {"title": "Neuroglia .txt", "text": "And the neuron is a specialized type of cell that is capable of accepting, generating and sending electrical signals to other cells in the body."}, {"title": "Neuroglia .txt", "text": "And this is a very effective and efficient way of communicating between cells."}, {"title": "Neuroglia .txt", "text": "Now, the question is, are there any other cells found inside inside our nervous system, inside the body aside from these neurons?"}, {"title": "Neuroglia .txt", "text": "And the answer is yes."}, {"title": "Neuroglia .txt", "text": "In fact, we have many more of these other cells found inside our nervous system than our neurons."}, {"title": "Neuroglia .txt", "text": "Now, all these other cells fall into a category that we call neuroglia."}, {"title": "Neuroglia .txt", "text": "So neuroglia, also known as glial cells, are all the other cells aside from the neuron found inside our nervous system."}, {"title": "Neuroglia .txt", "text": "And the purpose of these other cells, the purpose of neuronglia is to basically increase the effectiveness and functionality of these neurons found inside our nervous system and to support these neurons in different ways."}, {"title": "Neuroglia .txt", "text": "So that's exactly why neuroglia, or glial cells, are commonly known as the support cells of the nervous system."}, {"title": "Neuroglia .txt", "text": "Now, generally speaking, our nervous system can be broken down into two divisions."}, {"title": "Neuroglia .txt", "text": "We have the central nervous system, which includes the brain and the spinal cord and we have the peripheral nervous system, which includes everything else."}, {"title": "Neuroglia .txt", "text": "And these two divisions themselves contain their own different types of neuroglia."}, {"title": "Neuroglia .txt", "text": "So let's discuss the different types of neuroglia in the central nervous system as well as in the peripheral nervous system."}, {"title": "Neuroglia .txt", "text": "So within the central nervous system, we have four major types."}, {"title": "Neuroglia .txt", "text": "We have astrocytes, we have appendimal cells, we have oligodendrocytes and we have microglia."}, {"title": "Neuroglia .txt", "text": "Within our peripheral nervous system, we have satellite cells and schwann cells."}, {"title": "Neuroglia .txt", "text": "So let's discuss the functionality and the structure of each one of these cells."}, {"title": "Neuroglia .txt", "text": "And let's begin with the astrocyte."}, {"title": "Neuroglia .txt", "text": "So the astrocyte contains the cell body as shown."}, {"title": "Neuroglia .txt", "text": "It contains the nucleus, shown in blue and it contains other organelles not shown."}, {"title": "Neuroglia .txt", "text": "It also contains these extensions."}, {"title": "Neuroglia .txt", "text": "And these extensions basically wrap around and connect to our neuron as well as blood vessels and they connect via gap junctions."}, {"title": "Neuroglia .txt", "text": "So basically the oxygen and the nutrients such as our glucose that is traveling through our blood can actually get to the neuron via these astrocytes."}, {"title": "Neuroglia .txt", "text": "On top of that, the astrocytes are also capable of actually providing physical support to the neurons and they maintain the nutrient and ion concentration in and around our neuron."}, {"title": "Neuroglia .txt", "text": "So let's move on to the second type of glial cell in a central nervous system known as our appendomyl cell."}, {"title": "Neuroglia .txt", "text": "Now, the pandemic cells are basically those cells that line the spinal cord as well as are found in certain sections of the brain."}, {"title": "Neuroglia .txt", "text": "And the entire purpose of these appendyl cells is to help generate the cerebral spinal fluid."}, {"title": "Neuroglia .txt", "text": "In fact, they use the cilia."}, {"title": "Neuroglia .txt", "text": "And these cilia move in a wavelike fashion as shown in the diagram."}, {"title": "Neuroglia .txt", "text": "So these are our appendomal cells."}, {"title": "Neuroglia .txt", "text": "So they contain the cilia that move."}, {"title": "Neuroglia .txt", "text": "And the movement of the cilia helps move our cerebral spinal fluid around our body."}, {"title": "Neuroglia .txt", "text": "So let's move on to the third type of support cell of the nervous system in a central nervous system known as oligodendrocytes."}, {"title": "Neuroglia .txt", "text": "Now let's recall the structure of the neuron."}, {"title": "Neuroglia .txt", "text": "So the neuron contains the dendrites which accept our signal."}, {"title": "Neuroglia .txt", "text": "We have the cell body which contains the nucleus and the organelles."}, {"title": "Neuroglia .txt", "text": "We have the exxon hillock which generates the electric signal and we have the exxon."}, {"title": "Neuroglia .txt", "text": "We also have the exxon terminal."}, {"title": "Neuroglia .txt", "text": "Now, the exxon usually contains myelination."}, {"title": "Neuroglia .txt", "text": "And what the myelin is, it is basically a special type of substance that's composed of protein and fats."}, {"title": "Neuroglia .txt", "text": "And these myelin sheaths or simply myelin, help insulate our axon."}, {"title": "Neuroglia .txt", "text": "And that means that increases the speed of propagation of the action potential along our axon."}, {"title": "Neuroglia .txt", "text": "Now, within our central nervous system the cells responsible for actually creating the myelin around the axon are the liga denticides."}, {"title": "Neuroglia .txt", "text": "So they use these extensions to wrap around specific regions of the axon and actually create those myelin."}, {"title": "Neuroglia .txt", "text": "So let's move on to the fourth type known as microglia."}, {"title": "Neuroglia .txt", "text": "So microglia are those cells that differentiate from monocides found inside the bone marrow."}, {"title": "Neuroglia .txt", "text": "So inside the bone marrow we have monocides."}, {"title": "Neuroglia .txt", "text": "They become microglia and then the microglia travels to the brain and they basically function as macrophages."}, {"title": "Neuroglia .txt", "text": "And that means they basically engulf different harmful types of things such as some type of harmful debris."}, {"title": "Neuroglia .txt", "text": "So if this is our debris floating around our neuron, the microglia basically eats up a debris and breaks it down so that it doesn't harm our neuron in any way."}, {"title": "Neuroglia .txt", "text": "So these are the four major types of neuronglia glial cells, support cells found within our central system."}, {"title": "Neuroglia .txt", "text": "Let's move on to our peripheral nervous system."}, {"title": "Neuroglia .txt", "text": "So basically we have satellite cells and Schwann cells."}, {"title": "Neuroglia .txt", "text": "Now, the function of satellite cells is very similar to the function of astrocytes but the structure of satellite cells is somewhat different."}, {"title": "Neuroglia .txt", "text": "So the satellite cells actually cover the outside surface of the neurons and they basically provide a supply of nutrients and other things into our cells, into our neurons."}, {"title": "Neuroglia .txt", "text": "On top of that, they also give structure and support to our neurons and they protect and cushion those neurons so that they aren't damaged in any way."}, {"title": "Neuroglia .txt", "text": "Now, Schwann cells are very similar to oligodendrocytes in a sense that they create the myelin on the neurons found in the peripheral nervous system."}, {"title": "Neuroglia .txt", "text": "So these Schwann cells basically attach physically attached to our sections on our axon and then they secrete that myelin material onto our axon."}, {"title": "Neuroglia .txt", "text": "So these are the Schwann cells."}, {"title": "Neuroglia .txt", "text": "So notice that they're different from oligodentrocytes which are separated from the axon."}, {"title": "Neuroglia .txt", "text": "So this is the body of the ligamentrocyte while this is the body actually attached onto the axon of that neuron."}, {"title": "Neuroglia .txt", "text": "So these are the four different types of glial cells found in the central nervous system and these are the two different types types of cells found within our peripheral nervous system."}, {"title": "Neuroglia .txt", "text": "So all these different types of cells are known as neuroglia glial cells or support cells of the neurons found in the nervous system of our body."}, {"title": "Ion Exchange Chromatography.txt", "text": "Another property that we can use to separate or purify a mixture of proteins is their net charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "So why do proteins have a net charge?"}, {"title": "Ion Exchange Chromatography.txt", "text": "So, remember, proteins are composed of 20 different types of amino acids, and these different types of amino acids differ from one another based on their side chain group."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, some of these side chain groups have a positive charge, such as Lysine and and arginine, while others have a neutral charge, for example, glycine and valine and so forth."}, {"title": "Ion Exchange Chromatography.txt", "text": "And yet other amino acids have a full negative charge, for example, glutamate and aspartate."}, {"title": "Ion Exchange Chromatography.txt", "text": "So we have different types of amino acids."}, {"title": "Ion Exchange Chromatography.txt", "text": "And because proteins are composed of a variation of these different amino acids, the ones that have more side chain groups that are positively charged end up having a net positive charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "While the ones have equal amounts, they have a net neutral charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "And those that have more negatively charged side chains, those have a net negative charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, because certain proteins differ from one another based on their net charge, this is another property that we can use to separate and purify proteins."}, {"title": "Ion Exchange Chromatography.txt", "text": "And the technique, the method that we use to separate proteins based on the net charge is called ion exchange chromatography, or simply ion chromatography."}, {"title": "Ion Exchange Chromatography.txt", "text": "So the setup in ion exchange chromatography is very similar to that of gel filtration chromatography."}, {"title": "Ion Exchange Chromatography.txt", "text": "So it looks something like this."}, {"title": "Ion Exchange Chromatography.txt", "text": "So we have two types of setups, and in each setup, we have a funnel that is placed on top of a long column, and inside that column, we have special gel beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, in this particular case, the gel beads are made so that they have a positive charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "And in this case, the gel beads are made so that they have a negative charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "For example, the gel bead can be made from a sugar polymer cellulose, and we can add special side groups onto the cellulose that make them negatively charged, as shown in the following diagram."}, {"title": "Ion Exchange Chromatography.txt", "text": "So this is a single bead that is found inside this column here."}, {"title": "Ion Exchange Chromatography.txt", "text": "So the setup in inexchange chromatography consists of a funnel placed on top of a narrow column."}, {"title": "Ion Exchange Chromatography.txt", "text": "The column is packed with these charge gel beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And depending on the proteins that we actually want to separate, we can make those beads either positively charged, as in this case, or negatively charged, as in this particular case."}, {"title": "Ion Exchange Chromatography.txt", "text": "So red means positively charged, and blue means negatively charged."}, {"title": "Ion Exchange Chromatography.txt", "text": "And these beads are usually made from some type of carbohydrate polymer, such as cellulose."}, {"title": "Ion Exchange Chromatography.txt", "text": "Okay, so in this lecture, we're going to focus on this setup."}, {"title": "Ion Exchange Chromatography.txt", "text": "So let's zoom in on one of these, or let's zoom in on a small section of our column."}, {"title": "Ion Exchange Chromatography.txt", "text": "We get the following diagram."}, {"title": "Ion Exchange Chromatography.txt", "text": "So, these blue beads are our negatively charged cellulose beads, as shown in the following diagram."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, let's suppose we want to separate a mixture of three different proteins, and these proteins differ from one another based on their net charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "So one of these proteins we're going to call protein number one, has a net positive charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "So we have three of these charges, which make it very positive."}, {"title": "Ion Exchange Chromatography.txt", "text": "The second protein, showed in a brown, contains two positive charges and one negative charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so the net charge is positive one."}, {"title": "Ion Exchange Chromatography.txt", "text": "So the net charge here is positive three."}, {"title": "Ion Exchange Chromatography.txt", "text": "The net charge here is positive one."}, {"title": "Ion Exchange Chromatography.txt", "text": "So this is only slightly positive."}, {"title": "Ion Exchange Chromatography.txt", "text": "The final protein is shown in green, and this contains one positive charge and two negative charges."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so the net charge in this case is negative one."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so that makes this last protein unnegatively charged protein, contains a net negative charge of negative one."}, {"title": "Ion Exchange Chromatography.txt", "text": "So the question is, when we place the mixture of proteins into the column that contains these negatively charged cellulose beets, what exactly will happen?"}, {"title": "Ion Exchange Chromatography.txt", "text": "What will be the rate of movement of each of one of these proteins?"}, {"title": "Ion Exchange Chromatography.txt", "text": "Well, as you might know, the positively charged proteins will be attracted to the negatively charged beats beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And the more positive charge we have, we know by Coulomb's law, the greater that attraction will be."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so what that means is these very positive, these proteins that have a very large net positive charge will be attracted to those beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "The ones that are slightly positive will be attractive, but not as much."}, {"title": "Ion Exchange Chromatography.txt", "text": "The attraction will be less."}, {"title": "Ion Exchange Chromatography.txt", "text": "And these negatively charged will not be attractive, they will be repelled."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so what that means is these negatively charged proteins will travel the quickest in this column that contains these negatively charged beats, while these very positive proteins will essentially not travel at all, because they will be stuck."}, {"title": "Ion Exchange Chromatography.txt", "text": "They will be attractive to those negatively charged beats as a result of the electric attraction between positive charges and negative charges."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, one analogy I can give is the following."}, {"title": "Ion Exchange Chromatography.txt", "text": "Let's suppose we have two kids."}, {"title": "Ion Exchange Chromatography.txt", "text": "One of these kids loves chocolate chip cookies, and the other one hates chocolate chip cookies."}, {"title": "Ion Exchange Chromatography.txt", "text": "In fact, the second one is allergic to chocolate chip cookies."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, let's suppose we asked these two kids to walk down a road, and in the middle of the road, we have a table."}, {"title": "Ion Exchange Chromatography.txt", "text": "On that table, we have chocolate chip cookies."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, as the two kids walk along the pathway, the kid that loves those chocolate chip cookies will stop at the table to actually eat those cookies, while the kid that doesn't like them will keep on walking."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so, basically, the kid that makes it to the end of the pathway is the kid that is not attracted to those chocolate chip cookies."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so, in the same analogous way, because this negatively charged protein isn't attracted to the negatively charged beads, it will make it down to that pathway the fastest."}, {"title": "Ion Exchange Chromatography.txt", "text": "It will be collected at the bottom the fastest as compared to the other proteins."}, {"title": "Ion Exchange Chromatography.txt", "text": "So, to see exactly how we can basically carry out this experiment with these three proteins."}, {"title": "Ion Exchange Chromatography.txt", "text": "Let's take a look at the following diagram."}, {"title": "Ion Exchange Chromatography.txt", "text": "So we have diagram A through E, and let's begin with diagram A."}, {"title": "Ion Exchange Chromatography.txt", "text": "So in diagram A, we take our solution of three proteins and we pour it into our funnel in diagram B."}, {"title": "Ion Exchange Chromatography.txt", "text": "That protein mixture, at the initial moment that we pour it in, basically collects at the top of the column and it has not separated yet."}, {"title": "Ion Exchange Chromatography.txt", "text": "So this is our protein mixture that consists of three proteins."}, {"title": "Ion Exchange Chromatography.txt", "text": "Protein one, protein two and protein three."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, after we wait some time, what happens is the gravitational force will basically pull on those molecules and the protein that has the least positive charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "So protein three with the negative charge will basically be pulled and it will repel those negatively charged beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so it will travel the fastest down our column."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so it will end up all the way at the bottom first."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so this is protein three."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, the slightly positive protein will be attracted to those beads, but it will also be pulled down by the force of gravity."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so, because the traction isn't that great, it will end up somewhere in the middle, below protein One, which will be at the top, because it has that very strong electric attraction to those beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so, over time, when this protein Three ends up at the bottom, it will end up at the bottom first."}, {"title": "Ion Exchange Chromatography.txt", "text": "We can open our knob and collect that protein in a test tube."}, {"title": "Ion Exchange Chromatography.txt", "text": "And likewise, we can wait longer period of time, and then we can collect protein number two in our second test tube."}, {"title": "Ion Exchange Chromatography.txt", "text": "Now, the problem with protein One is we have to wait a very, very long time."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so, to speed up the process, we can basically look at diagram E. And in diagram E, what we do is we essentially pour a salt solution into our mixture."}, {"title": "Ion Exchange Chromatography.txt", "text": "And what the salt solution does is, so the salt solution, for example, can contain sodium chloride ions."}, {"title": "Ion Exchange Chromatography.txt", "text": "And what happens is the sodium and the chloride ions dissociate in our solution, and those positively charged sodium ions will begin to interact with these negatively charged beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so what that will do is that will disrupt those electric interactions between protein One and these negatively charged beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so by pouring our solid solution, we're breaking the electric interactions between the protein and the negatively charged beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so now gravity can basically overcome that electric force, and this protein will begin to move down and eventually it will elude and we can collect it in another test tube."}, {"title": "Ion Exchange Chromatography.txt", "text": "So let's suppose this is our test tube that contains that protein number one that we wanted to actually isolate in the first place."}, {"title": "Ion Exchange Chromatography.txt", "text": "So we can see ion exchange chromatography is actually only helpful if there is a big difference between the net charges on our protein."}, {"title": "Ion Exchange Chromatography.txt", "text": "We cannot use ion exchange chromatography to purify proteins."}, {"title": "Ion Exchange Chromatography.txt", "text": "If all the proteins in our mixture have the same exact type of net charge."}, {"title": "Ion Exchange Chromatography.txt", "text": "For example, if all the proteins have a net neutral charge, then that means none of them will be attracted to those charged beads."}, {"title": "Ion Exchange Chromatography.txt", "text": "And so what that means is the rate at which they actually move along our column will be exactly the same."}, {"title": "Ion Exchange Chromatography.txt", "text": "And that is not useful, because that means we cannot separate them and collect them into these separate beakers, as shown in the following diagram."}, {"title": "Dihybrid Cross Part II.txt", "text": "But we have short because we have two recessive t. So green and short, that gets one."}, {"title": "Dihybrid Cross Part II.txt", "text": "Now, once again we have green and tall, we have green and short, right, because this is still dominant over the lowercase g, but we have two recessive here."}, {"title": "Dihybrid Cross Part II.txt", "text": "So we'll have short here we have green and we have tall."}, {"title": "Dihybrid Cross Part II.txt", "text": "Once again, green and tall here."}, {"title": "Dihybrid Cross Part II.txt", "text": "Now we have yellow, yellow and tall, so one here."}, {"title": "Dihybrid Cross Part II.txt", "text": "Once again, we have yellow and tall here we have tall and green, so we have one more here."}, {"title": "Dihybrid Cross Part II.txt", "text": "Here we have green and short, so we have green and short here we have yellow and short."}, {"title": "Dihybrid Cross Part II.txt", "text": "And finally we have yellow here we have yellow and tall, and here we have yellow and short."}, {"title": "Dihybrid Cross Part II.txt", "text": "So we see that we have nine here, nine total here."}, {"title": "Dihybrid Cross Part II.txt", "text": "We have three total here, three total here, and we have a one total here."}, {"title": "Dihybrid Cross Part II.txt", "text": "So we see that the ratio is nine to three to three to three."}, {"title": "Dihybrid Cross Part II.txt", "text": "This is the ratio of the four different types of phenotypes of our offspring."}, {"title": "Dihybrid Cross Part II.txt", "text": "So we have four potential phenotypes and these are the ratios."}, {"title": "Dihybrid Cross Part II.txt", "text": "Now, if we want to talk in terms of probability, we can also talk in terms of probability."}, {"title": "Dihybrid Cross Part II.txt", "text": "So remember, the probability of each one of these gametes forming is one four, because out of the four, we have four different possibilities."}, {"title": "Dihybrid Cross Part II.txt", "text": "So each one of these has a probability of taking place with this fraction."}, {"title": "Dihybrid Cross Part II.txt", "text": "And here we have the same exact situation one fourth, one fourth, one fourth."}, {"title": "Dihybrid Cross Part II.txt", "text": "And so every time we cross this, each one of these has a probability of 116."}, {"title": "Dihybrid Cross Part II.txt", "text": "So 116 for each one of these."}, {"title": "Dihybrid Cross Part II.txt", "text": "Let's pretend that each one of these has one 16th to save time."}, {"title": "Dihybrid Cross Part II.txt", "text": "And if we actually tally up here, we have nine of them."}, {"title": "Dihybrid Cross Part II.txt", "text": "And if we add up nine of these, one 16th values, nine times 116 gives us nine over 16."}, {"title": "Dihybrid Cross Part II.txt", "text": "Here it's three over 16."}, {"title": "Dihybrid Cross Part II.txt", "text": "Here's three over 16, and here's one over 16."}, {"title": "Dihybrid Cross Part II.txt", "text": "So these are the probabilities."}, {"title": "Dihybrid Cross Part II.txt", "text": "So there is a nine out of 16 chance that the offspring that will be produced will be green and tall."}, {"title": "Dihybrid Cross Part II.txt", "text": "There's a three 16th chance that three 16th chance that our offspring will be green and short."}, {"title": "Dihybrid Cross Part II.txt", "text": "316 chance that it will be yellow and tall."}, {"title": "Dihybrid Cross Part II.txt", "text": "And only one out of 16th probability that it will be yellow and short."}, {"title": "Dihybrid Cross Part II.txt", "text": "So this is what we mean by Dye hybrid cross."}, {"title": "Dihybrid Cross Part II.txt", "text": "A dihybrid cross is simply a cross in which we're considering not one, but two different traits for that individual, for that offs, or for that plant, or for that organism."}, {"title": "Glycolipids and Cholesterol .txt", "text": "The cell membranes of eukaryotic cells."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And some bacterial cells contain three different types of lipid molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So phospholipids, glycolipids and cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, previously we focused on phospholipids and we said that phospholipids come in two types."}, {"title": "Glycolipids and Cholesterol .txt", "text": "We have phosphoglycerides and we also have spingolipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now in, in this lecture we're going to focus on glycolipids and cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So let's begin with glycolipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "What exactly are glycolipids?"}, {"title": "Glycolipids and Cholesterol .txt", "text": "Well, Glycolipids are biological molecules that contain a lipid molecule attached via glycosetic bond to a sugar moiety."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And that sugar moie can be a single sugar or it can be some type of polysaccharide many sugars."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, glycolipids actually resemble a type of phospholipid we call the spingolipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And that's because glycolipids also contain the sphingocene molecule, just like spingolipids do."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this is the general way that we represent a glycolipid."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So this is using boxes and this is using a slightly different format."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And we actually use this pictorial representation in just a moment."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So basically, the brown structure is the sphingosine, this is the fatty acid and this is the sugar moiety."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, based on this representation, we see that the spinocine actually acts as that backbone."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And what that means, it connects the fatty acid and it connects that sugar molecule."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, this entire fatty acid spinocine molecule is predominantly nonpolar."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And so this is the hydrophobic section that will be found inside the cell interacting with the hydrophobic tails of the other phospholipid molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So we see that the spinocine acts as the backbone of attachment for the fatty acid and the carbohydrate component and the spongesine fatty acid component is hydrophobic."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And that basically means it stretches across the cell membrane, interacting with the non polar tails of those nearby phospholipids, as we'll see in just a moment in this diagram."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, the sugar molecule contains the hydroxyl groups and that makes it polar."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So that means the sugar molecule will interact with the hydrophilic sections of those phospholipids, the heads, and it will point to the aqueous extracellular environment."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So the carbohydrate moiety of this glycolipid will interact with the aqueous extracellular environment."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, let's give an example of the simplest type of glycolipid shown in this diagram."}, {"title": "Glycolipids and Cholesterol .txt", "text": "This is known as a cerebral side."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So in a cerebral side, the sugar molecule is either glucose or a galactose."}, {"title": "Glycolipids and Cholesterol .txt", "text": "The point is, we only have a single sugar moody, a single sugar molecule."}, {"title": "Glycolipids and Cholesterol .txt", "text": "The sugar molecule is attached in this carbon position to this oxygen, the primary alcohol of this finocene shown in brown."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So this is the primary alcohol group, this is a secondary alcohol group, and it's the primary alcohol that is attached via this glycosytic bond to this sugar molecule."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, this entire long unsaturated hydrocarbon chain is that non polar region of that fingersene molecule."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And notice we also have a double bond that means it is unsaturated."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this nitrogen here is basically attached onto the carbon of the carboxylic acid that is part of that fatty acid."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And so these two chains basically extend along this direction, as shown in this pictorial representation."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this is a region that will be found deep inside that cell membrane interacting with the non polar regions of those nearby phospholipid molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this is a section that will basically interact with the aqueous environment and with the heads, the hydrophilic heads of those nearby phospholipid molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, let's move on to cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So, cholesterol molecules actually have a very special shape and that's because cholesterol molecules are actually steroid molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And what that means is they contain a four ring structure as shown in the following diagram."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So cholesterol is a steroid, which means it is composed of four fused hydrocarbon rings."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, on one side of those four rings, we basically have a tail that is hydrophobic."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So this hydrocarbon chain, on the other side, we have a polar group."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this is the hydroxyl group that makes this molecule very, very slightly polar."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So the predominant region of this cholesterol is in fact nonpolar."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this entire section will be found inside that membrane."}, {"title": "Glycolipids and Cholesterol .txt", "text": "But this tiny region will point to the aqueous environment and it will interact with the nearby heads of those phospholipid molecules because the heads consist of the phosphate groups and sometimes the alcohol molecules that contain those polar regions."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So the hydroxyl group, being a polar region, basically interacts with the hydrophobic heads of the phospholipids in that cell membrane and therefore it points towards the aqueous environment."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And the rest of the cholesterol molecule, the four fuse rings, as well as this hydrocarbon chain."}, {"title": "Glycolipids and Cholesterol .txt", "text": "The tail will basically lie inside the membrane and will be parallel with respect to the nonpolar tails of those phospholipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, to see what we mean by all that, let's take a look at the following diagram."}, {"title": "Glycolipids and Cholesterol .txt", "text": "A two dimensional image of our cell membrane, found typically, let's say, in eukaryotic cells, such as our own cells of the body."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, all these blue molecules, so these blue molecules with these two purple regions, these are the phospholipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So we have the phosphate group, showed in blue."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And these purple regions are basically those fatty acids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, these guys here are basically our glycolipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So some glycolipids, let's say, contain two sugar molecules, others contain more sugar molecules, as shown here."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So the, this is the sugar moiety of this glycolipid."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And one of these is basically that fatty acid chain."}, {"title": "Glycolipids and Cholesterol .txt", "text": "The other one is this hydrocarbon chain of that fingosine molecule as shown here in brown."}, {"title": "Glycolipids and Cholesterol .txt", "text": "These are basically our cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "This is, let's say, some type of integral transmembrane protein."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And this is a peripheral protein that contains a carbohydrate component."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So this is an example of glycoprotein."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So we have a glycoprotein, a transmembrane protein."}, {"title": "Glycolipids and Cholesterol .txt", "text": "We have these phospholipids, in which case we have two types of phospholipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "We have those phosphoglycerides as well as finolipids, which we spoke of previously."}, {"title": "Glycolipids and Cholesterol .txt", "text": "We have the glycolipid, which we spoke about here, and we also have these cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So notice that the hydroxyl group shown in orange basically interacts with these blue heads of the nearby phospholipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "And these hydroxyl groups basically points toward the aqueous environment either into the cell or out of the cell."}, {"title": "Glycolipids and Cholesterol .txt", "text": "In the case of these glycolipids, these sugar molecules also interact with these nearby blue heads of the nearby phospholipid molecules, and they also point toward the extracellular aqueous environment towards the outside of the cell, as shown here."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Now, the final note that I'd like to add about cholesterol molecules is the following."}, {"title": "Glycolipids and Cholesterol .txt", "text": "Even though even though some bacterial cells, for instance, the mycoplasma, contain cholesterol, cholesterol molecules are actually predominantly eukaryotic membrane lipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "In fact, in certain cells of our body, for instance, nerve cells, we have as much as 25% of the membrane of the cell that consists of cholesterol molecules."}, {"title": "Glycolipids and Cholesterol .txt", "text": "So we find cholesterol predominantly in eukaryotic cells, more specifically in animal cells, but in bacteria, we commonly find phospholipids and glycolipids."}, {"title": "Glycolipids and Cholesterol .txt", "text": "But only a few bacteria actually have the cholesterol within their cell membrane."}, {"title": "Development and Function of Placenta .txt", "text": "The placenta is a very important organ that exists during the development process of the embryo."}, {"title": "Development and Function of Placenta .txt", "text": "Now, there are many important functions of the placenta, but before we discuss the functionality of the placenta, let's actually focus on how the placenta is developed."}, {"title": "Development and Function of Placenta .txt", "text": "So, during early embryological development, we have a process known as implantation take place."}, {"title": "Development and Function of Placenta .txt", "text": "And during that process, the blastocyst actually implants itself onto the endometrium, the lining of the uterus."}, {"title": "Development and Function of Placenta .txt", "text": "Now, as soon as implantation takes place, the Trophy blast cells of that blastocyst begin to produce digestive enzymes."}, {"title": "Development and Function of Placenta .txt", "text": "And these digestive enzymes are released into the surrounding tissue of the endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "And what those digestive enzymes do is they begin to break down and digest the vascular and connective tissue found inside that endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "And that not only allows the embryo to make its way entirely into the endometrium, but it also forms these tiny extensions, tiny projections known as the Corianic villi."}, {"title": "Development and Function of Placenta .txt", "text": "So the purple section is the Coriane that develops from the Trophy blast of that blastocyst that implants itself onto the endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "And these Corianic extensions are known as Coryonic villi, and they basically form a structure that looks like a capillary bed."}, {"title": "Development and Function of Placenta .txt", "text": "So as the circulatory system, as the cardiovascular system of that growing embryo develops, these Corianic extensions begin to become populated with the blood vessels."}, {"title": "Development and Function of Placenta .txt", "text": "And so inside these Corianic villi, if we take a cross section, we'll see this population of blood vessels."}, {"title": "Development and Function of Placenta .txt", "text": "And these embryonic blood vessels eventually connect to the umbilical arteries and the umbilical veins found inside the umbilical cord."}, {"title": "Development and Function of Placenta .txt", "text": "And those structures, those blood vessels eventually directly connect to the circulatory system of that fetus."}, {"title": "Development and Function of Placenta .txt", "text": "Now, once those digestive enzymes begin to break down the endometrium, the connective tissue, they also actually break down the vascular tissue."}, {"title": "Development and Function of Placenta .txt", "text": "And that means those digestive enzymes released by the Corian eventually break down the maternal blood vessels found within the endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "And as soon as we rupture these blood vessels, the blood of the mother actually oozes out and leaks out into the endometrium, into the area surrounding these Corianic villi."}, {"title": "Development and Function of Placenta .txt", "text": "And so we have the pooling of the mother's blood shown in the diagram as this light purple section."}, {"title": "Development and Function of Placenta .txt", "text": "And what that allows is it allows the exchange of nutrients and waste products and minerals and oxygen, carbon dioxide between the blood of that fetus and the blood of the mother, as we'll see in just a moment."}, {"title": "Development and Function of Placenta .txt", "text": "So this entire diagram basically describes the components of our placenta."}, {"title": "Development and Function of Placenta .txt", "text": "We have the Coriane that comes from the Trophy blast."}, {"title": "Development and Function of Placenta .txt", "text": "We have these Corianic villi which are in contact with the mother's blood."}, {"title": "Development and Function of Placenta .txt", "text": "And we have these maternal blood vessels, which essentially have ruptured and created the pooling of that blood within the endometrium in our placenta."}, {"title": "Development and Function of Placenta .txt", "text": "Now, we also have the Biblical cord, which contains those two blood vessels, the two types of blood vessels."}, {"title": "Development and Function of Placenta .txt", "text": "We have the umbilical vein, and we have the umbilical artery."}, {"title": "Development and Function of Placenta .txt", "text": "And the umbilical cord also actually contains two types of extra embryonic membranes."}, {"title": "Development and Function of Placenta .txt", "text": "It contains the lantos and it also contains the umbilical vesicle, also known as the yolksac."}, {"title": "Development and Function of Placenta .txt", "text": "And the corian is the third type of extra embryonic membrane."}, {"title": "Development and Function of Placenta .txt", "text": "Now, the next question is what exactly is the function?"}, {"title": "Development and Function of Placenta .txt", "text": "What is the purpose of the placenta?"}, {"title": "Development and Function of Placenta .txt", "text": "So the placenta has several important functions."}, {"title": "Development and Function of Placenta .txt", "text": "So let's begin with the endocrine function of the placenta."}, {"title": "Development and Function of Placenta .txt", "text": "So as soon as implantation takes place the cells of the trophy blast that eventually become the placenta begin to release a hormone known as the human corianic gonadotropin hormone."}, {"title": "Development and Function of Placenta .txt", "text": "So HCG and what the human corianic gonadotropin does is it goes on to the corpus luteum found in the ovaries and it causes the corpus luteum to continue to release progesterone and estrogen because these two hormones are needed to actually maintain the thickening of that endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "Now eventually, when the placenta actually forms, that placenta will stop releasing human coryonic natural and it will begin to release its own estrogen and its own supply of progesterone and that will ultimately allow the maintenance of that endometrium."}, {"title": "Development and Function of Placenta .txt", "text": "So these are the three hormones released by the placenta."}, {"title": "Development and Function of Placenta .txt", "text": "Not only that, it actually also releases a fourth hormone at the end of the pregnancy."}, {"title": "Development and Function of Placenta .txt", "text": "So towards the end of the pregnancy, the placenta also releases a hormone known as the corticotropic releasing hormone or CRH."}, {"title": "Development and Function of Placenta .txt", "text": "Now, what the corticotropic releasing hormone does is it goes on to the pituitary gland found in the brain and it stimulates the pituitary gland to release a hormone known as ACTH."}, {"title": "Development and Function of Placenta .txt", "text": "And ACTH goes down to the adrenal gland and it causes the adrenal gland to produce the precursor molecule that then goes down into the placenta."}, {"title": "Development and Function of Placenta .txt", "text": "And the placenta uses that precursor molecule to form even more estrogen."}, {"title": "Development and Function of Placenta .txt", "text": "And the rising level of estrogen ultimately causes the contraction of the smooth muscle found inside the uterus and that eventually leads to the process of childbirth."}, {"title": "Development and Function of Placenta .txt", "text": "So one of the functions of the placenta is to act as an endocrine gland and it basically produces these four different types of hormones."}, {"title": "Development and Function of Placenta .txt", "text": "Now the second and probably the primary purpose and the primary function of placenta is to act in gas exchange and nutrient exchange."}, {"title": "Development and Function of Placenta .txt", "text": "So the placenta provides nutrients and exchanges gas between the blood of the mother and the blood of the fetus."}, {"title": "Development and Function of Placenta .txt", "text": "And this takes place within the corianic villi."}, {"title": "Development and Function of Placenta .txt", "text": "So these corianic villi contain the network of blood vessels that are part of the circulatory system of that developing embryo."}, {"title": "Development and Function of Placenta .txt", "text": "And notice that the corianic villi are actually surrounded by a semipermeable membrane."}, {"title": "Development and Function of Placenta .txt", "text": "So note that the maternal and the fetal blood do not actually mix because we have this semipermeable membrane."}, {"title": "Development and Function of Placenta .txt", "text": "So certain things are allowed to pass across the membrane but things like blood red blood cells and bacterial cells and large molecules cannot actually pass across this semipermeable placental membrane."}, {"title": "Development and Function of Placenta .txt", "text": "So the placental membrane found within the coryonic villi creates a semipermeable membrane that acts as a barrier for relatively large substances such as bacterial cells and red blood cells."}, {"title": "Development and Function of Placenta .txt", "text": "So that allows us to jump directly to the immune protection of that placenta."}, {"title": "Development and Function of Placenta .txt", "text": "It basically not only protects that blood system of that fetus from acquiring the same type of bacterial cells and infected cells found within that mother, but it also allows the movement of tiny antibodies called immunoglobulin g. So one type of antibody known as IgG or immunoglobulin G can easily make its way across the membrane and into the blood system of that fetus."}, {"title": "Development and Function of Placenta .txt", "text": "And the immunoglobulin g protects that fetus from different types of pathogens that can infect that growing embryo."}, {"title": "Development and Function of Placenta .txt", "text": "So we see that the placenta, as a result of allowing the movement of immunoglobigging gives that growing embryo passive immunity because when the embryo grows the immune system of that embryo is not fully developed."}, {"title": "Development and Function of Placenta .txt", "text": "So function number one is as an endocrine gland."}, {"title": "Development and Function of Placenta .txt", "text": "Function number two is it provides a route by which there's an exchange between the nutrients such as glucose, water, minerals, so salts as well as amino acids between the blood of that mother and the blood of that fetus."}, {"title": "Development and Function of Placenta .txt", "text": "Gas exchange also takes place."}, {"title": "Development and Function of Placenta .txt", "text": "And that's important because as the fetus is developing the lungs of that fetus do not actually form until after birth takes place."}, {"title": "Development and Function of Placenta .txt", "text": "And so the placenta acts as a system where gas exchange takes place."}, {"title": "Development and Function of Placenta .txt", "text": "Oxygen goes into the blood and carbon dioxide is expelled as a waste product."}, {"title": "Development and Function of Placenta .txt", "text": "And so that leads us directly into function three, waste product removal or function four, waste product removal."}, {"title": "Development and Function of Placenta .txt", "text": "What that basically means is not only carbon dioxide is removed by the placenta from the blood of that embryo but also other byproducts wasteful byproducts such as urea."}, {"title": "Development and Function of Placenta .txt", "text": "Uric, acid and creepine are all released by the blood of that fetus and into the blood of the mother."}, {"title": "Development and Function of Placenta .txt", "text": "And the blood of the mother eventually dumps those waste products into the kidneys where the kidneys essentially recycle and excrete those waste products to the outside environment."}, {"title": "Development and Function of Placenta .txt", "text": "So these are the many important functions of the placenta."}, {"title": "Development and Function of Placenta .txt", "text": "And the placenta only exist during the process of embryological development of that fetus which takes is placed inside the uterus of that individual."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So far in our discussion on genetics, we focused on those traits that only have two different types of alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "For example, in our discussion on Pea plants, we said that there are two different types of colors for the seeds."}, {"title": "Multiple Alleles and Codominance.txt", "text": "In Pea plants, we can either have green seeds or we can have yellow seeds."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And what that means is we have two different types of alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Possible."}, {"title": "Multiple Alleles and Codominance.txt", "text": "We have the allelat codes for the color green or we can have the allelat codes for the color yellow."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So this particular trait, the color trait for seed color and Pea plants comes in two different alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So we have the green allele and we have the yellow allele."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, sometimes we also have those traits that can have three or more different types of alleles for that particular trait."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And in such a case, whenever we have a trait that contains three or more different types of alleles, that trait is said to have multiple alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And one particularly common example in which a trait has multiple alleles in humans is the human Abo blood group traits."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So there are three different types of alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "For the blood group traits, we have allele given by uppercase I with the A SuperScript."}, {"title": "Multiple Alleles and Codominance.txt", "text": "We have allele that is given by uppercase I with the B SuperScript, or we have lowercase I."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, what this means is at this particular locus on the chromosome, we have a specific sequence of nucleotides that codes for a special protein we're going to call protein A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And protein A will be found on the membrane of red blood cells."}, {"title": "Multiple Alleles and Codominance.txt", "text": "For this particular case, at this same locus, instead of having this sequence shown in red, we have a slightly different sequence of nucleotide shown in blue that codes for a different protein."}, {"title": "Multiple Alleles and Codominance.txt", "text": "We're going to call protein B that will be found on the membrane of the red blood cells."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And the third allele basically means at the locus, we have a sequence of nucleotides that doesn't code for either one of these proteins."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so lowercase I is the allele that expresses neither protein A or protein B on the membrane of red blood cells."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So we have phenotype A or protein A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "We have phenotype protein B and we have a phenotype in which neither of the proteins are actually expressed."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, remember, in diploid organisms, every single chromosome comes with a homologous pair."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so what that means is we're going to have two different types of alleles in any given individual for this particular trait, the Abo blood group traits."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, the question is, if we have a male individual with one blood group type and a female individual with a second blood group type, and these two individuals decide to make to produce an offspring, the question is, what exactly is the mode of inheritance of this particular trait?"}, {"title": "Multiple Alleles and Codominance.txt", "text": "Does it follow the dominant or the complete dominance mode?"}, {"title": "Multiple Alleles and Codominance.txt", "text": "Does it follow the incomplete dominance mode or does it follow something else."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So in this particular case, we have a mode of inheritance known as codominance."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So these three alleles that make up the Abo blood group trait in humans follow a mode of inheritance we called codominance."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, what exactly do we mean by codominance?"}, {"title": "Multiple Alleles and Codominance.txt", "text": "Well, in codominance, neither allele is dominant over the other one."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And what that means is in heterozygous individuals, heterozygous individuals will basically express both types of phenotypes."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And to see what we mean, let's consider the following example."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Let's suppose we have an individual, let's say a male individual that has both alleles for this particular allele."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And the female individual has both alleles for this particular allele."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so when those two individual mates, they basically produce a Zygote and offspring that contains the following homologous pair."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so what that means is one chromosome will contain this gene, this allele, and the other chromosome will contain this allele."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And in this particular heterozygous individual, because the mode of inheritance is codominance, what that means is both protein A and protein B will be expressed, will be produced and will be found on the membrane of red blood cells."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, the next question is this is only one of many different types of Zygotes that we can produce."}, {"title": "Multiple Alleles and Codominance.txt", "text": "What are all the different types of possibilities of the genotypes?"}, {"title": "Multiple Alleles and Codominance.txt", "text": "Well, to answer that question, we have to carry out the following Punnett square."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So on this row, in this row, we have the three different types of alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "In this column, we have the three different types of alleles."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So these alleles can come from the male parent and these alleles can come from the female parent."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so if we carry out the Punnett square, these are the nine different types of possibilities."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So in this particular case, both of those chromosomes contains the alleles that code for protein A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "In these two cases, one of the chromosomes contains that allele that doesn't code for anything, but the other one contains the allele that codes for protein A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so this case, this case and this case will always produce only protein A on the membrane of red blood cells."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And this is known as blood group A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, let's take a look at these two cases."}, {"title": "Multiple Alleles and Codominance.txt", "text": "In these two cases, both of the alleles are found on each of one of the two chromosomes, or not both of them."}, {"title": "Multiple Alleles and Codominance.txt", "text": "But I should say one is found on one chromosome and the other one is found on the other chromosome."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so in such a case, this is what we have."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And this type of blood group is known as blood group AB."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So an individual that has blood group AB, what that means is they have both of these alleles that code for these two proteins."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Now, what about this particular case?"}, {"title": "Multiple Alleles and Codominance.txt", "text": "Well, in this particular case, in this case, both of those chromosomes contain one of these alleles each."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so the only type of protein that will be expressed is protein B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "In this case, one of the alleles doesn't code for anything and the other allele codes for protein B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so in these three cases, we're going to have blood group B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And finally, this is the only case in which neither of the proteins will actually be expressed because both of those chromosomes contain this particular allele that doesn't code for either of the two proteins."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So now that we know what Codominance is, and the fact that Abo blood group tray follows this mode of inheritance we call Codominance, let's take a look at the following example."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So, what are the distribution of the phenotypes of an offspring when we mate a male individual that contains blood group AB with a female individual that contains this blood group type."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So basically, this male individual can produce one of two different types of sperm cells, either the IA sperm cell or a sperm cell that contains IA chromosome, or it can contain the IB chromosome."}, {"title": "Multiple Alleles and Codominance.txt", "text": "This can produce X cells that contains either the IB chromosome or the lowercase I chromosome."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So if we carry out the punitive square, we get the following distribution of phenotypes."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So in this or the following genotypes, in this particular genotype, we produce the AB group."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So the AB phenotype in this particular case, one is lowercase I, the other one is lowercase B, or a lowercase a upper case I A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And what that means is we're going to produce the protein A."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And so the phenotype will be group A in this particular case."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And in this particular case, we're going to have group B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So in this particular case, we're going to have both of the chromosomes that contain the allele that codes for protein B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "But in this case, we're only going to have one of the two chromosomes that contains that allele that codes for protein B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So these are the three different types of phenotypes of the offspring."}, {"title": "Multiple Alleles and Codominance.txt", "text": "The offspring can either be blood group A B in this case, blood group A as in this case, or blood group B, as in these two cases."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So there is a 50% chance of having a child that is blood group B."}, {"title": "Multiple Alleles and Codominance.txt", "text": "There is a 25% chance of having blood group A and a 25% chance of having the individual that is blood group AB."}, {"title": "Multiple Alleles and Codominance.txt", "text": "So this is what we mean by code dominance in Codominance."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Neither of the traits is dominant over the other one."}, {"title": "Multiple Alleles and Codominance.txt", "text": "And in heterozygous individuals like this one here, both of those genes are actually expressed."}, {"title": "Multiple Alleles and Codominance.txt", "text": "Both proteins are expressed."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Previously we said that if we purify our protein that we want to study and we don't know anything about that protein, then the first step is to basically determine what the composition of amino acids is inside that protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And that involves determining not only what types of amino acids we have, but also how many of each amino acid we have inside our protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, once we know that information, what is the next logical step?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, the next step is to basically determine exactly what the order is of our amino acid inside that protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And what that means is we want to sequence those amino acids inside that protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, what is the first step in sequencing our amino acids?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, the first step is to basically determine what that first amino acid is in that specific sequence in that protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And the procedure that allows us to basically determine what that first amino acid is, is known as the Edmund degradation."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, to demonstrate how the Edmond degradation actually works, we're going to begin by assuming we know what the sequence of amino acids is."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "But in your protein that you're going to be studying, you don't know what that amino acid sequence is."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And that's exactly why you want to use the admin degradation process."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So in our hypothetical example, we're going to use the same exact protein that we used previously."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So, Alanine, arginine, phenylalalanine, glycine, aspartate and glycine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So once again, I give you the exact sequence to basically demonstrate how this procedure works."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "But normally you're not going to know the sequence of your proteins."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So let's begin with step one."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So, in the first step of the evidengration, we want to basically label that first amino acid."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And the way that we label that first amino acid is by reacting it with a special molecule known as pheny, or phenyl isothiocyanate."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, the structure of phenol isotiocyanate is this structure here."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, what's so special about this molecule?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, it turns out that if you react this molecule with our polypeptide and the alpha amino group does not have a positive charge, then this will react with it to basically form a bond."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "It will attach to this uncharged terminal alpha amino group."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So if we draw the structure of our six amino acid polypeptide, this is what we get."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we have Alamine, we have arginine, we have phenylalanine, we have glycine, we have aspartate, and we have glycine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So this is the beginning and this is our end."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So if this nitrogen is not charged, then the phenol isotherthionate will react with this and bind to it, and this will label it."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So the reaction basically forms this product, as shown."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, if you want to know what the reaction mechanism is in this particular reaction, I'll link you above and you can check that reaction mechanism out."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So what's the entire point of step one?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, we want to label that initial amino acid."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Why do we want to label it?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, because in the second step, what we're going to do is we're going to basically cleave this peptide bond that is holding this Allen amino acid and this Arginine amino acid."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And by cleaving it, we're going to separate it from the rest of the polypeptide."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And once we separate it, we want to have a means of separating this amino acid that was cleaved, that was separated and the rest of that polypeptide."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And that's why we label it with this phenol ISO thiosyanate molecule."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So once again, the bond that we're about to break or that we want to break is this bond."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, the difficult question is, how do we break this specific peptide bond and at the same time not break any other of these peptide bonds."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we want to create a procedure in which we only somehow break this peptide bond here between this first and second amino acid."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "But at the same time, we want to keep the remaining peptide bonds intact."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, the way that we can do it is we can simply take this molecule here and place it under mildly acidic conditions."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And if we place it under mildly acidic conditions, what happens is this peptide bond will hydrolyze, it will break, it will rearrange."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So this entire molecule will rearrange to basically form this molecule here."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And this is known as PTH amino acid, where in this particular case, because this amino acid is Alanine, then that means this is PTH Alamine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "If this amino acid was something else, let's say Glycine, then this would be PTH, glycine and so forth."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So in the second step, we were able to break that first peptide bond while keeping the other peptide bonds intact."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And so now we have this labeled amino acid, the PTH Allamine, and this remaining polypeptide that now consists of five amino acids."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And by using a chromatography technique and because this is labeled, we can separate this and then determine what this amino acid actually is."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So the admin degradation process is very useful because it gives us a systematic approach to basically cleaving that first peptide bond and no other peptide bonds are cleaved within that polypeptide chain."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now the admin degradation process is even more useful."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "How?"}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Well, let's take a look at the following two molecules."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So once we isolate this molecule and remove it, we have this peptide bond left."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, we don't know what the sequence is of these other amino acids."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And so what we can actually do is if the polypeptide isn't too long as it is in this case, so if it's about 50 amino acids or less, we can actually continue that Edmund degradation process."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "We can repeat it over and over and over until we get every one of these amino acids."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So if we take this five amino acid polypeptide and we repeat the Edmund degradation process again, then we'll be able to remove this amino acid here, which is arginine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we know that this is Alanine, and then we repeat it a second time."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And now we know it is Arginine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And after we repeat a second time, we're going to get this peptide that contains four amino acids, and we continue it over and over until we get all those amino acids."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And this is shown in the following diagram."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So once we carry out the admin degradation process the first time, we can repeat this procedure four more times to basically determine the entire sequence of amino acids."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And this is shown here."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So this peptide here is this peptide here."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we have arginine, we have phenylalanine, we have glycine, we have aspartate, and we have glycine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we take this, we mix it with our phenol isotiocyanate, we label it in step one, and in step two, we remove it."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So we basically form the PTH arginine."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And then we isolate that and determine what that amino acid is."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And then we take this four membered amino acid polypeptide, and then we repeat the admin degradation process a third time, then a fourth time and a fifth time."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And at the end, we basically know exactly what that sequence of amino acid is in our polypeptide chain."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So this process is a very, very useful process because it gives us a systematic approach to cleaving a specific peptide bond and thereby determining exactly what that sequence is."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "Now, the edgeman degradation process is only useful up to a certain size of that protein."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "For instance, if our number of amino acids is, let's say, 1000, this is not a very useful process."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "And we'll see exactly why in the next lecture."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "In the next lecture, we're going to see how we can basically determine the sequence of amino acids of larger proteins."}, {"title": "Sequencing Amino Acids and Edman Degradation .txt", "text": "So the Edmond degradation process usually works on those proteins that are about 50 amino acids in length or less."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "The process of aerobic cell respiration is a very complicated and a very intricate process because it actually consists of many individual processes in many individual steps."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So, so far we discussed glycolysis, pyruvate carboxylation and the citric acid cycle."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, the final process of aerobic cell respiration, the culmination of aerobic cell respiration, is a process process we call oxidative phosphorylation, that takes place on the electron transfer chain of the inner membrane of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this is what we're going to introduce in this lecture."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "But before we focus on the electron transport chain and oxidative phosphorylation, let's remember what happened in glycolysis, pyruvate carboxylation and the citric acid cycle."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So in glycolysis, we broke down glucose into pyruvate molecules and we also formed NADH molecules and a few ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this took place in the cytoplasm of the cell."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, in the presence of oxygen, the pyruvate molecules will be moved into the matrix of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And in the matrix, we're going to prepare the pyruvate molecules for the citric acid cycle by a process called pyruvate carboxylation."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we form acetylco enzyme A molecules, and those acetyl coenzyme A molecules are then moved into the citric acid cycle, which also takes place in the matrix of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So in the cytoplasm, we have glycolysis, but inside the matrix, we have the citric acid cycle and pyruvate carboxylation."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, the entire point of the citric acid cycle is to actually further oxidize the glucose derivative molecules so that we can extract those high energy electrons and place those high energy electrons onto special calorie molecules we call NAD plus an fad."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, what's the point of extracting these high energy electrons?"}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Well, the point of extracting these high energy electrons is to use the high energy electrons to basically oxidatively phosphorylate ADP molecules into ATP molecules along the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we ultimately use the NADH molecules and the fadh, two molecules produced in glycolysis and the citric acid cycle, to actually generate those high energy ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this takes place in the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the culmination of aerobic cell respiration is oxidative aspiration along the proteins of the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the NADH molecules form in glycolysis, which takes place in a cytoplasm."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And the NADH and the fadh, two molecules formed in the citric acid cycle, which takes place in the matrix of the mitochondria, are basically used to ultimately reduce diatomic oxygen molecules to form water, in the process also generating high energy ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this is shown summarized in the following diagram."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So this is a single mitochondrion."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "In the mitochondrion, we have several compartments."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "We actually have two different membranes."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "We have an outer mitochondrial membrane and the inner mitochondrial membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this electron transport chain is found on the inner mitochondrial membrane that consists this folding pattern known as Christie that we're going to focus on in just a moment."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So let's zoom in on a small section of the inner mitochondrial membrane, this is what we're going to find."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So this is the matrix, this portion, and this is the intermembrane space, this space between the inner membrane and the outer membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the outer membrane is somewhere right here."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So, as we can see from the diagram, our electron transport chain is located on the inner mitochondrial membrane and it consists of these special types of proteins as we'll discuss in a future lecture."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we have protein complex one, protein complex two, protein complex three and four, as well as other proteins, as we'll see in a future lecture."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And we have this final protein molecule known as ATP synthase."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So ultimately, what happens is protein complex one is responsible for accepting those high energy electrons from NADH molecules produced in glycolysis and the citric acid cycle."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And we extract these high energy electrons into this area here."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "At the same time, we also regenerate those NAD plus molecules needed for glycolysis and the citric acid cycle to actually continue taking place."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, the Fadh two molecules produced in the citric acid cycle are actually taken by protein complex two."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, once these high energy electrons are extracted, they begin to move along the proteins of the inner membrane of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And from basic physics, we know that whenever electrons flow from .1 to .2, the flow of that electron or the flow of the electrons creates an electrical current."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that electrical current can be used to carry out some process."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So what process are we ultimately carrying out?"}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Well, as these high energy electrons are moving along the proteins of the electron transport chain, that allows some of these proteins to actually act as proton pumps and pump H plus ions from the matrix of the mitochondria to the intermembrane space."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So protein complex one, three, and four actually allow the movement of these H plus ions."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the movement of this electric current allows us to actually pump these H plus ions to the intermembrane space of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And once these electrons end up on protein complex four, this is where we actually use those electrons to actually reduce the diatomic oxygen, the same oxygen that we breathe in from the environment to form the water molecules in the process."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Once we generate this proton gradient across the two sides of the membrane, we use another protein complex known as ATP synthase to actually generate those ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So ultimately, we establish a proton gradient in which we have a high proton concentration here and a low proton concentration here."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this ATP synthase basically uses that established electrochemical gradient of H plus ions, moves these H plus ions down that established electrochemical gradient from a high to a low electrochemical potential."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that allows the ATP synthase to actually phosphorylate ADP to ATP."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that's why we call it oxidative phosphorylation because we actually use an oxygen on the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So, remember, the citric acid cycle doesn't actually require oxygen itself, but the electron transport chain does."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And we need the citric acid cycle to generate the majority of the NADH molecules and these Fadh two molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the electron transport chain is a series of proteins that receive these high energy electrons from NADH molecules and Fadh two molecules and they move these electrons along the inner membrane of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And the final acceptor of these electrons is oxygen."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we reduce oxygen to form the H 20 molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, we know from physics that as these electrons flow, they create an electrical current and that basically allows us to carry out some type of process to do work."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And so we are able to actually pump these protons to establish a proton gradient."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that proton is gradient is then used by ATP synthase to actually generate those ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we can summarize these four steps in the following four."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So one, two, three and four."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "In one, those high energy electrons are extracted from these high energy electron carrier molecules synthesized in the citric acid cycle and glycolysis."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And once these electrons are extracted, they move along the proteins, the enzymes of the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that ultimately allows some of these proteins to actually pump the H plus ions to the intermembrane space, the space between the inner and the outer membrane of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this establishes an electrochemical gradient for the hydrogen ions."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So this takes place here, here and here."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Then the electrons are ultimately accepted by that diatomic oxygen to form water molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And in the final step of the electron transport chain, the fact that we have an unequal distribution of H plus ions basically means we have an electrochemical potential difference between the two sides of our membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that allows the ATP synthase to actually use that energy that is stored in that proton gradient to generate these ATP molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we conclude the following the oxidation of the fuel molecules in glycolysis and the citric acid cycle is actually coupled to the oxidative phosphorylation of the ADP to ATP by using this oxygen in protein complex four, by the establishment of this hydrogen ion gradient on the electron transport chain."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So what we're ultimately doing in aerobic cell respiration is we're transforming one form of energy into a different form of energy, into a form that we can actually use by the cells of our body."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So we basically transform the energy that is stored in the movement of electrons into the energy that is stored in the gradient that exists between the two sides as a result of the unequal distribution of H plus ions."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And then we ultimately transform that energy into the energy that is stored in the chemical bonds of the ATP molecules because it's the ATP molecules which can be used by ourselves to carry out a variety of different types of processes."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the final thing that I'd like to focus on in this lecture is some facts that you should know about the mitochondrion found inside our cells."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So, as I mentioned in the beginning, the mitochondrion actually consists of two different types of membranes."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "We have the outer membrane and the inner membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the innermost compartment of the mitochondrion is known as the mitochondrial matrix."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And the space between the two membranes is called the intermembrane space."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And this is found entirely in the inner mitochondrial membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, there are several important differences between these two membranes."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "First of all, notice that the inner membrane actually consists these folding patterns."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And the folding patterns create something called the Christy."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, Christy are these inner foldings that greatly increases the surface area on which the electron transport chain can actually lie."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And so we have a greater surface area as a result of these inner foldings."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And so that means we can have many more of these electron transport chains and that greatly increases our cells ability to actually undergo oxidative phosphorylation."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, the second important difference between the two membranes is the fact that the outer mitochondrial membrane contains these special mitochondrial pores, these special mitochondrial proteins called porns mitochondrial porins, also known as VDAC, where VDAC basically stands for voltage dependent and ionic complexes."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And so what happened is these mitochondrial porins found on the outer membrane basically allowed the movement of anion molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So small molecules, which are anions."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So things like chloride ions, things like ATP molecules, can actually move across the outer mitochondrial membrane from the cytoplasm into the intermembrane space without much difficulty."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "But the inner membrane doesn't actually contain these mitochondrial porns."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So that means it is impermeable to charged molecules and it's impermeable to polar molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So molecules such as citrate molecules or pyruvate molecules or ATP molecules actually depend on special protein membranes or membrane proteins to actually shuttle those molecules across the matrix, across the matrix and into the intermembrane space."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So the outer membrane is permeable to the majority of small molecules and anions due to the presence of voltage gated channels we call mitochondrial porns or VDAC."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "It allows the movement of anionic metabolites, such as chloride molecules and ATP molecules and so forth."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "But the inner membrane lacks these mitochondrial porns, and so it's impermeable to ions and polar molecules."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So metabolites such as pyruvate molecules or ATP molecules or citrate molecules actually depend on special protein transporters to move across the two sides of the membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, if we examine, if we take a small section of this region here, this is what we're going to get."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "So this is the outer and the inner membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Now, the inner membrane, on the matrix side, we have a negative charge."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "On the intermembrane space side, we have a positive charge."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And that's why this side of the membrane is called the N side, n for negative, and this side is called the pside P for positive."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "Likewise, this N side is also sometimes called the matrix side, while this side is sometimes called the cytoplasmic side, because the intermembrane space is pretty much connected to the cytoplasm via these mitochondrial porins found in the outer membrane of the mitochondria."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "And as I mentioned just a moment ago, the folding pattern of the inner membrane."}, {"title": "Introduction to Oxidative Phosphorylation .txt", "text": "This structure here consist of these christi, which greatly increase the surface area on which oxidative phosphorylation can actually take place."}, {"title": "Leukocytes of Immune System .txt", "text": "Leukocytes, also known as white blood cells, are the cells of our immune system that function to protect and defend our body cells from different types of pathogens, for example, bacterial cells as well as viral agents."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, just like red blood cells, our white blood cells also come from the same exact stem cell found in the bone marrow of our body."}, {"title": "Leukocytes of Immune System .txt", "text": "And the stem cells cells are known as hematopoietic stem cells."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, all white blood cells, or generally speaking, white blood cells, can actually differentiate into many different types of specialized white blood cells, as we'll see in just a moment."}, {"title": "Leukocytes of Immune System .txt", "text": "And all these specialized white blood cells have their own unique purpose and function."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's begin by taking a look at the following flowchart, which basically describes the different types of categories of leukocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "So generally, we can divide leukocytes into these three categories."}, {"title": "Leukocytes of Immune System .txt", "text": "We have granulocytes, agranulocytes and megacaryocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "And then we can even further subdivide all these categories and we'll discuss that in just a moment."}, {"title": "Leukocytes of Immune System .txt", "text": "So leukocytes, the white blood cells, are found circulating in the blood plasma in our lymph system and also inside our tissue."}, {"title": "Leukocytes of Immune System .txt", "text": "And actually, leukocytes are amoebilike cells."}, {"title": "Leukocytes of Immune System .txt", "text": "And what that means is leukocides can actually move independently of other cells and other structures inside our body."}, {"title": "Leukocytes of Immune System .txt", "text": "In fact, leukocytes can move against the flow of blood and the flow of lymph in our vessels, blood vessels and lymph vessels of our body."}, {"title": "Leukocytes of Immune System .txt", "text": "And that's important because leukocytes must be able to move from one location to different locations where that infection is actually taking place."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, the way that the leukocytes actually move across the capillaries from the blood plasma to the tissue or in reverse, is via a process known as diapedesis."}, {"title": "Leukocytes of Immune System .txt", "text": "And what diapedesis is, it's the movement, it's the squeezing of these leukocides through the tiny slits and crevices found between the endothelial cells of our capillaries."}, {"title": "Leukocytes of Immune System .txt", "text": "So our capillaries consist of this tiny layer of endothelial cells and between these cells we have very tiny holes."}, {"title": "Leukocytes of Immune System .txt", "text": "And that's where the leukocytes actually move through via the process of diabetesis."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, let's begin by taking a look at granular sites."}, {"title": "Leukocytes of Immune System .txt", "text": "Question number one is why do we call them granular sites?"}, {"title": "Leukocytes of Immune System .txt", "text": "Well, if we take a granular side and we have three different types of granular sites, each one of the granular side will look very similar under the microscope."}, {"title": "Leukocytes of Immune System .txt", "text": "This cytoplasm will contain many of these tiny granules as we see in the following diagram."}, {"title": "Leukocytes of Immune System .txt", "text": "And what these granules are, they're tiny vesicles that contain special chemicals and molecules that are responsible for initiating and carrying out the process of inflammation, which is a process that exists in our innate or nonspecific immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "And we'll see exactly what that means in just a moment."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's go."}, {"title": "Leukocytes of Immune System .txt", "text": "And also if we examine the nucleus, notice that the nucleus has a shape of a lobe and that is a distinct characteristic of granular sides which distinguishes granular sides from a granular side as we'll see in just a moment."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's take a look at the different divisions of granulocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "We have three different cell types."}, {"title": "Leukocytes of Immune System .txt", "text": "We have neutrophils, we have yassinophils and we have basic fields."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's begin with neutrophils."}, {"title": "Leukocytes of Immune System .txt", "text": "Neutrophils are phagocytic cells that can actually seek out, engulf and destroy different types of pathogens."}, {"title": "Leukocytes of Immune System .txt", "text": "For example, Arabacterial cells."}, {"title": "Leukocytes of Immune System .txt", "text": "Now?"}, {"title": "Leukocytes of Immune System .txt", "text": "What about Eosinophils?"}, {"title": "Leukocytes of Immune System .txt", "text": "Eosinophils are essentially those cells, those granulocytes that are involved not only in allergic reactions, but also in destroying and killing off parasites and dealing with parasitic infections."}, {"title": "Leukocytes of Immune System .txt", "text": "And finally, we also have basicils."}, {"title": "Leukocytes of Immune System .txt", "text": "Now basicils contain special chemicals."}, {"title": "Leukocytes of Immune System .txt", "text": "For example, histamines found within those granules, the secretary vesicles, inside the cytoplasm."}, {"title": "Leukocytes of Immune System .txt", "text": "And these histamines are involved in initiating the process of inflammation, a type of protection that we have in our innate immune system, in the non specific immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, our basic film is also contain an anticlotting agent known as Heparin."}, {"title": "Leukocytes of Immune System .txt", "text": "And heparin is very important for basically creating a very continuous flow of blood in our blood vessels."}, {"title": "Leukocytes of Immune System .txt", "text": "So we see that granulocytes are not only involved in the process of inflammation, they're also involved in protecting us from parasitic infections as well as contain special cells, the basic pills that contain the anticlotting agent heparin."}, {"title": "Leukocytes of Immune System .txt", "text": "Now let's move on to megacaryocides."}, {"title": "Leukocytes of Immune System .txt", "text": "So this is what the megacaryocide actually looks like and megacarasites differentiate into these tiny structures we call platelets."}, {"title": "Leukocytes of Immune System .txt", "text": "And platelets are also known as Thrombicides."}, {"title": "Leukocytes of Immune System .txt", "text": "So Thrombocides."}, {"title": "Leukocytes of Immune System .txt", "text": "Now these megacaria sides, the cytoplasm, as well as a tiny portion of our membrane of the megacary sides, essentially break down into these very tiny pieces that we see in the following diagram."}, {"title": "Leukocytes of Immune System .txt", "text": "So essentially, tiny pieces of the megacaraside break down into these platelets and these are the platelets that we are describing."}, {"title": "Leukocytes of Immune System .txt", "text": "And basically what the platelets have is nothing but cytoplasm."}, {"title": "Leukocytes of Immune System .txt", "text": "They don't actually have any nucleus."}, {"title": "Leukocytes of Immune System .txt", "text": "So when pieces of megacaria sides break off, they form structures called platelets or thrombicide."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, what exactly is the function of our platelet?"}, {"title": "Leukocytes of Immune System .txt", "text": "Well, as the platelets actually move along our blood vessel, if some type of cut develops inside our blood vessel, these platelets essentially bind to that cut and they begin to aggregate."}, {"title": "Leukocytes of Immune System .txt", "text": "And in a matter of five minutes they essentially form a temporary patch."}, {"title": "Leukocytes of Immune System .txt", "text": "And they also create different types of chemicals."}, {"title": "Leukocytes of Immune System .txt", "text": "They release chemicals that ultimately call other cells into that location and that helps to patch up that cell that cut within our blood plasma."}, {"title": "Leukocytes of Immune System .txt", "text": "Now let's move on to a granular side."}, {"title": "Leukocytes of Immune System .txt", "text": "So the big distinction between granular sites and agranulocides is that agranulocytes don't actually have those vesicles, don't actually have those granules and they also have a spherical or a kidney shape for the nucleus."}, {"title": "Leukocytes of Immune System .txt", "text": "So we see these are the two main differences between a granular side and granulocides that we might see under the microscope."}, {"title": "Leukocytes of Immune System .txt", "text": "So these cells lack granules and have spherical or kidney shaped nuclei."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, we can subdivide a granule size into two types."}, {"title": "Leukocytes of Immune System .txt", "text": "We have monocides and we have lymphocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's begin by focusing on monocides."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, monocides ultimately differentiate into macrophages."}, {"title": "Leukocytes of Immune System .txt", "text": "And macrophages are the largest white blood cells of our body."}, {"title": "Leukocytes of Immune System .txt", "text": "They are very, very large phagocytic cells and these scavenger cells essentially move around our tissue and they seek out different types of harmful agents pathogens, bacterial cells and so forth."}, {"title": "Leukocytes of Immune System .txt", "text": "They engulfed them and then they essentially destroyed them."}, {"title": "Leukocytes of Immune System .txt", "text": "So monocides enter tissue and develop into macrophages which are large scavenger cells that engulf pathogens via phagocytosis."}, {"title": "Leukocytes of Immune System .txt", "text": "So the two type of phagocytitic cells, phagocytic cells inside our immune system are macrophages as well as neutrophils."}, {"title": "Leukocytes of Immune System .txt", "text": "But macrophages are much, much larger than the neutrophils."}, {"title": "Leukocytes of Immune System .txt", "text": "Now let's move on to our lymphocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "So lymphocytes are those specialized wide blood cells that make up our specific immune system, our acquired or adapted immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "So remember, we have three different types of lymphocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "We not only have B lymphocytes and T lymphocytes but we also have natural killer cells which basically looks something like this."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, natural killer cells are those cells that essentially bind to antigens on other cells and they can either kill off infected cells or they can kill off cancer cells."}, {"title": "Leukocytes of Immune System .txt", "text": "So we see that natural killer cells seek out and destroy infected cells that have been infected by, let's say, some type of virus and they also kill off cancer cells."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, what about B lymphocytes and T lymphocytes?"}, {"title": "Leukocytes of Immune System .txt", "text": "Let's begin with B lymphocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "B lymphocytes are those cells of our antibody mediated response system of our adaptive required immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "So these B lymphocytes are essentially responsible for creating antibodies, these proteins that essentially travel inside our blood system and which help play an important role in actually protecting us from infection."}, {"title": "Leukocytes of Immune System .txt", "text": "So belymphasize, our cells that are part of the antibody mediator response system they further differentiate into plasma cells as well as memory cells."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, plasma cells are those B lymphocytes that produce the antibodies and the memory cells are those cells that essentially store those antibodies and help us protect us from reinfection."}, {"title": "Leukocytes of Immune System .txt", "text": "So if some bacterial cell infected us once it's the memory cells that essentially protect us the second time."}, {"title": "Leukocytes of Immune System .txt", "text": "Those same cell types will infect us."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, what about the T lymphocytes?"}, {"title": "Leukocytes of Immune System .txt", "text": "So B lymphocytes and T lymphocytes basically look something like this."}, {"title": "Leukocytes of Immune System .txt", "text": "We have our membrane and on the membrane we have these different types of proteins that act as receptors for antigens."}, {"title": "Leukocytes of Immune System .txt", "text": "They can actually bind onto antigens found on cell membranes of bacterial cells or infected cells and that can essentially destroy those pathogens when these cells bind onto them."}, {"title": "Leukocytes of Immune System .txt", "text": "So we have four different types of T lymphocytes or T cells."}, {"title": "Leukocytes of Immune System .txt", "text": "So we have helper T cells, killer T cells, memory T cells and suppressor T cells."}, {"title": "Leukocytes of Immune System .txt", "text": "So let's begin with the helper T cells."}, {"title": "Leukocytes of Immune System .txt", "text": "So helper T cells basically release special types of chemicals into the surrounding blood or the surrounding lymph and they help other cells, other immune cells, actually mature into their specialized form and we'll talk more about that in the next several lectures."}, {"title": "Leukocytes of Immune System .txt", "text": "We also have killer T cells, not to be confused with natural killer cells."}, {"title": "Leukocytes of Immune System .txt", "text": "These two cells are two different types of cells."}, {"title": "Leukocytes of Immune System .txt", "text": "So killoty cells are responsible for using their protein, their membrane bound protein found on the cell membrane to basically seek out specific types of pathogens and kill off those pathogens by releasing a special type of chemical into those pathogen cells."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, what about memory T cells?"}, {"title": "Leukocytes of Immune System .txt", "text": "Well, memory T cells basically function the same way that memory B cells function."}, {"title": "Leukocytes of Immune System .txt", "text": "They help protect us from reinfection."}, {"title": "Leukocytes of Immune System .txt", "text": "And finally, we have suppressor cells and these suppressor cells are responsible for suppressing and regulating our immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "And we'll discuss how this actually takes place in the next several lectures."}, {"title": "Leukocytes of Immune System .txt", "text": "So this is a brief introduction to different types of white blood cells found inside our immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "We also actually have other types of white blood cells."}, {"title": "Leukocytes of Immune System .txt", "text": "For example, we have mass cells and we have dendritic cells and we're going to focus on these in the next several lectures."}, {"title": "Leukocytes of Immune System .txt", "text": "So once again, we have three different types of categories of leukocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "We have granulocytes, a granulocytes and megacariocytes."}, {"title": "Leukocytes of Immune System .txt", "text": "Megacariocytes are responsible are responsible for actually clotting those cuts that we find in our blood vessels and they also initiate other blood clotting responses."}, {"title": "Leukocytes of Immune System .txt", "text": "Granulocytes are involved in our inflammation process."}, {"title": "Leukocytes of Immune System .txt", "text": "They're responsible for also killing off parasitic infections and they're responsible for producing the anticlotting agent known as heparin."}, {"title": "Leukocytes of Immune System .txt", "text": "So these are the cells involved in our innate immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "Now, if we look at the agranulocytes, we have the lymphocytes that essentially makeup our acquired or adaptive specific immune system."}, {"title": "Leukocytes of Immune System .txt", "text": "And we also have the monocides, which create the largest types of phagocytic cells in our body known as macrophages."}, {"title": "Glycogen Synthase Regulation .txt", "text": "The key enzyme that is needed for glycogenesis the building of glycogen molecules is glycogen synthase."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So this is the enzyme that basically catalyzed the formation of alpha one four glycosytic bonds."}, {"title": "Glycogen Synthase Regulation .txt", "text": "It basically connects the glucose molecules within the glycogen."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So it extends and elongates the glycogen polymer chain."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now this enzyme enzyme is not only actually used to build up the glycogen chain it is also actually used to control the rate at which glycogen synthesis actually takes place."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So we can actually turn off the glycogen synthase enzyme and that in turn turns off the process of glycogenesis."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So once again, glycogen synthase catalyzes the elongation of glycogen."}, {"title": "Glycogen Synthase Regulation .txt", "text": "It attaches the glucose monuments by forming alpha one four glycocitic bonds."}, {"title": "Glycogen Synthase Regulation .txt", "text": "But this important enzyme also happens to be a key regulatory protein in glycogenesis."}, {"title": "Glycogen Synthase Regulation .txt", "text": "In building the glycogen molecule it helps control the rate of glycogen synthesis."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So this enzyme, glycogen synthase, actually exists in two different forms."}, {"title": "Glycogen Synthase Regulation .txt", "text": "We have glycogen synthase A and glycogen synthase B."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now the only difference between these two enzymes is the fact that glycogen synthase B is simply the phosphorylated version of glycogen synthase A."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now glycogen synthase A always exists in the fully active form."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now glycogen synthase B is predominantly in the inactive form but under certain molecules."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So certain molecules that we'll talk about in just a moment can actually act as allosteric activators of glycogen synthase B."}, {"title": "Glycogen Synthase Regulation .txt", "text": "And by binding to glycogen synthase B they can actually make it an active molecule."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now to go from glycogen synthase E the fully active molecule that basically stimulates glycogen synthesis into glycogen synthase B the inactive molecule we have to actually use ATP molecules to phosphorylate glycogen synthase A."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now Glycogen synthase A contains several sites where phosphorylation can actually take place and glycogen synthase A also basically responds to a number of different types of protein kinases."}, {"title": "Glycogen Synthase Regulation .txt", "text": "But two important protein kinases which basically deactivate glycogen synthase A by phosphorylating it are protein kinase A, PKA and an enzyme known as glycogen synthase kinase or GSK."}, {"title": "Glycogen Synthase Regulation .txt", "text": "More specifically, it's glycogen synthase kinase three."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So glycogen synthase is affected by several kinases and contains different phosphorylating sites."}, {"title": "Glycogen Synthase Regulation .txt", "text": "However, two very important kinases that are able to actually turn off glycogen synthase A are protein kinase A and glycogen synthase kinase."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now remember that protein kinase A is actually stimulated by cyclic Amp."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So if some type of signal transduction pathway takes place that increases the concentration of cyclic Amp within our cell that in turn stimulates PKA."}, {"title": "Glycogen Synthase Regulation .txt", "text": "And one of the target proteins of PKA is glycogen synthase A."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So upon the stimulation of PKA that essentially promotes the transformation of glycogen synthase A into glycogen synthase B."}, {"title": "Glycogen Synthase Regulation .txt", "text": "In addition, we also have this other kinase the glycogen synthase kinase that also stimulates the transformation of glycogen synthase A into glycogen synthase B."}, {"title": "Glycogen Synthase Regulation .txt", "text": "Now, once we go from this enzyme to this enzyme this enzyme exists predominantly in the inactive form."}, {"title": "Glycogen Synthase Regulation .txt", "text": "And what that means is glycogen synthesis will not take place when the enzyme is in this particular form."}, {"title": "Glycogen Synthase Regulation .txt", "text": "However, there is an allosteric activator molecule that can actually influence this to become much more active, and that is glucosex phosphate."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So if inside our body, if inside our cell, we have a build up of glucosex phosphate molecules, what that means is we don't want to keep the glucose phosphate in that state."}, {"title": "Glycogen Synthase Regulation .txt", "text": "We want to store them in some other form."}, {"title": "Glycogen Synthase Regulation .txt", "text": "That is, we want to form glycogen."}, {"title": "Glycogen Synthase Regulation .txt", "text": "And so when we have a build up of glucosex phosphates, the glucose phosphate can actually bind to regulatory sites on glycogen synthase B, and that will stimulate it."}, {"title": "Glycogen Synthase Regulation .txt", "text": "It will transform it into its active form."}, {"title": "Glycogen Synthase Regulation .txt", "text": "So glycogen synthase B in the active form, and in that particular case, glycogen synthase B in the active form will stimulate glycogen synthesis, just like glycogen synthase A always stimulates the process of glycogen formation."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Monosaccharides have a choice."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "They can either exist in the open change form or in the cyclic form."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And because the cyclic form is more stable and lower in energy, it's the cyclic form of the sugar that will predominate."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So let's take a look at glucose."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Glucose is an example of an aldohexose."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And what that means is it contains an alkali group on one end, and it contains six carbon atoms, confirmed 12345 and six."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So the D glucose will predominate in the cyclic form."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And because this is the open chain form, it will have to undergo an intramolecular nucleophilic addition reaction to form the cyclic conformation."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And so what happens is the blue hydroxyl group attached to carbon number five attacks this carbon, the electrophile of this aldehyde group."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And we form a bond between this oxygen and this carbon."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And this bond is shown in purple in this diagram."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So this is the bond formed between the blue oxygen and the green carbon."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, this basically becomes a hydroxyl group shown here."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So this is carbon number two."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "This is carbon number two."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "This is carbon number three, carbon number 3456 and so forth."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, notice that we actually have a mixture of two types of isomers, and we form this mixture of two types of isomers we call atomers, the alpha atomer and the beta atomer."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Because this nucleophile can attack the carbon either from the top side or from the bottom side."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "When it attacks from the top side, it forms one of these."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "When it talks from the bottom side, it forms the other isomer."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, what is the difference between these two animals, these two isomers?"}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Well, if we examine the stereochemistry of carbon number one, we'll see that the stereochemistry of carbon number one is different in these two cases."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So all the other atoms are arranged in the same exact way."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "But the atoms on carbon number one are arranged differently in alpha beta atomers."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "In the alpha case, we have this hydroxyl group points down in the opposite direction with respect to this group attached to carbon number five, while in the beta anamar case, in the beta g glucopyronose, this hydroxyl group is attached basically points up and points in the same direction as this group attached to carbon number five."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So less than 1% of this mixture will exist in the open chain form and the remaining will exist as a mixture of these two cyclic forms."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, it turns out that about two thirds will exist in the beta animal form and one third will exist in the alpha animal form."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So the question that I'd like to answer this question is why is it that the beta animer form of glucose predominates?"}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "What makes this molecule predominate over this molecule here?"}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And the answer lies in examining the chair confirmation of these two molecules."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So remember from organic chemistry that anytime we have a six membered ring, so a ring structure that contains six atoms, that ring structure will take on the chair confirmation because it's the chair confirmation that is the most stable type of arrangement of atoms."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "All these atoms in a chair confirmation are as far away from one another as possible."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And that basically decreases the energy of that chair confirmation."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, in any chair confirmation, we have two types of positions."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "We have the axial position and the equatorial position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So the axial bonds are nearly perpendicular with respect to the plane of that molecule, while the equatorial bonds are nearly parallel, so they point away from the plane of that cyclic molecule."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, remember that it is energetically favorable for large groups to be found on the equatorial position rather than the exile position, because it's the equatorial position that points away from the general structure of that cyclic molecule, and it points away from the other groups."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And so what that means is, because the groups point as far away from one another as possible, when all the groups lie along the equatorial position, that will create the least amount of steric hindrance."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And what steric hindrance means is it will create the least amount of electric repulsion."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, for instance, if we examine the following hypothetical cyclohexane molecule, in which the first carbon and the third carbon contain these large green groups that point along the axial position, because these point along the axial position, they will essentially bump with one another, their electron densities will slightly coincide."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And these electron densities, because they both have negative charge, will basically create electric repulsion."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And that electric repulsion will increase the energy of this molecule compared to the case when these two groups would point along the equatorial position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, with that in mind, let's compare the alpha D Glucopyronose and the beta D Glucopyronose in their chair confirmations."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, let's begin with the alpha D glucose."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So how many carbon atoms?"}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So we have 1234 carbon atoms within no, we have 12345 carbon atoms within this six membrane ring."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Five of these carbon atoms contain the large groups that point or, I'm sorry, four of these five carbon atoms contain these large groups that point along the more stable equatorial position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "But along the carbon number one, this hydroxyl group points along the axial position, which is, as we said just a moment ago, the higher in energy position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And if we examine the beta case, we'll see that the stereo chemistry and carbon number one of the beta anomer is the opposite."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And this hydroxyl group actually points along the equatorial position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, in the beta D Glucopyrenose, all these large groups, this one here, this one here, this one here, this one here, and this one here, they all point along that more stable, lower in energy equatorial position."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And that's exactly why it's the beta animal that is lower in energy and more stable than that alpha animal."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, this is the energy diagram."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "As we go higher up, the energy increases."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And because in this particular case, this hydroxyl group points along the axial position, this molecule will have a higher energy and so will be slightly less stable."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And that's exactly why this will predominate over this alpha animal."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So, generally speaking, in six member sugar molecules, it's the beta animmer for the glucose that will predominate over the alpha one because of what we just discussed."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So the beta anniversary of glucose is favored because all the groups lie along the less hindered equatorial side."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, we not only have six memory rings in our body, we also have five member rings."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And so we have fructose molecules that exist as five member rings."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "We also have ribose molecules."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And ribose are very important because they're constituents of nucleic acids, DNA and RNA molecules."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And if you studied DNA molecules and RNA molecules, you know that ribose exist as a five membered ring."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So in fact, ribose is appendose."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And what that means is it consists of five carbon atoms."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So this is the open chain form of our ribose molecules."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So we have carbon number 1234 and five."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And notice, just like the glucose, ribose is an aldose, it contains an aldehyde."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And so what happens is we have that same type of intramolecular nucleophilic."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Additional reaction take place and this attacks this electrophile nucleophilically, forming a purple bond that is shown here."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, this is an example of the beta Dribribribe."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "We can also have the alpha D ribofiorness, but only the beta Dribor nose is shown for simplification purposes."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Now, unlike six member rings, which exist in the chair confirmation form, five member rings, five member sugar molecules exist in a puckered form we call the envelope form."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So why we call it the envelope form?"}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "Well, simply because it looks like a simple envelope."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So on an envelope, the four corners lie along the same plane."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So these coroners are known as coplaner."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "They lie along the same plane."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And by the same exact analogy, if we examine the five membered ring of ribose, four of these atoms will lie along the same plane."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So there are two types of conformations."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "We have either the C two endo or the C three endo."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "In the C two endo, it's the second carbon that is puckered."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So we have carbon number one, carbon number two, carbon number three."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "This is, let's say, our oxygen."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And this is the last carbon number five."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "That is essentially this is the carbon number four that is puckered."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So in this particular case, it's this carbon number two that is puckered."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So this is the carbon number two that we have in this diagram and these other atoms."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So this carbon here, this carbon here, this carbon here, and this oxygen here, these lie along the same exact plane."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And likewise, in the other type of conformation, c three endo, where the third carbon is puckered, this becomes the third carbon."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And so now this carbon number one, two for this oxygen will lie along the same plane."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And carbon number three is the one that is puckered."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "So we see that inside our body it's the ring structure, the sugars that predominate."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "In the case of six member rings, we have the chair confirmation."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And in the case of the five member rings we have this envelope form, this puckered form that will basically exist."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "And we either have the C two endo or the C three endo."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "In the C two endo it's a second carbon."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "It's a second carbon that ends up being puckered."}, {"title": "Stability of Glucose Anomie\u2019s .txt", "text": "In a C three endo it's the third car, and that ends up being puckered."}, {"title": "Fetal Circulation.txt", "text": "The way that blood moves inside the circulatory system of developing fetus is quite different than the way that blood moves inside the fully functional adult individual."}, {"title": "Fetal Circulation.txt", "text": "And in this lecture, we're going to focus on the former."}, {"title": "Fetal Circulation.txt", "text": "We're going to discuss the way that blood moves inside the developing circulatory system of the fetus."}, {"title": "Fetal Circulation.txt", "text": "So let's begin inside the placenta."}, {"title": "Fetal Circulation.txt", "text": "Inside the placenta."}, {"title": "Fetal Circulation.txt", "text": "And so we have an exchange taking place."}, {"title": "Fetal Circulation.txt", "text": "Oxygen and nutrients are picked up by the blood of that fetus, while carbon dioxide and other waste products are deposited into the blood of that mother."}, {"title": "Fetal Circulation.txt", "text": "And once this exchange takes place inside the placenta, a special type of blood vessel carries the oxygenated and nutrient filled blood away from the placenta and towards the heart of that developing fetus."}, {"title": "Fetal Circulation.txt", "text": "And this blood vessel is known as dambilical vein."}, {"title": "Fetal Circulation.txt", "text": "So just like any vein always carries blood to the heart, umbilical vein always carries blood to that heart."}, {"title": "Fetal Circulation.txt", "text": "Now, as dambilical vein shown in red, actually carries the oxygenated and nutrient filled blood to the heart, eventually it comes in close proximity with the liver, and there is a tiny blood vessel that goes into that liver."}, {"title": "Fetal Circulation.txt", "text": "Now, the problem with the liver in the fetus is the liver is underdeveloped."}, {"title": "Fetal Circulation.txt", "text": "It is not fully functional."}, {"title": "Fetal Circulation.txt", "text": "And what that means is we should not waste that oxygen and nutrients onto the liver, because the liver doesn't yet function the same way does in the adult individual."}, {"title": "Fetal Circulation.txt", "text": "And so what the fetal circulatory system does is it conserves some of that oxygen and the nutrients inside the blood by shunting or redirecting that blood away from that liver and directly into thin fear venecava."}, {"title": "Fetal Circulation.txt", "text": "And this takes place as a result of the presence of a special type of duct within the circulatory system of that fetus known as the ductus venosis."}, {"title": "Fetal Circulation.txt", "text": "So the ductus venosis is a small type of blood vessel that creates a pathoge way that allows the oxygenated and nutrient filled blood to bypass the liver and go directly into the inferior venecaiva."}, {"title": "Fetal Circulation.txt", "text": "So this is the inferior venecrava."}, {"title": "Fetal Circulation.txt", "text": "And notice, the inferior venecaiva carries the deoxygenated blood from the organs and tissues found at the bottom of that developing fetus."}, {"title": "Fetal Circulation.txt", "text": "And when we have this intersection taking place, we have the mixing of the oxygenated and nutrient filled blood with the deoxynated blood."}, {"title": "Fetal Circulation.txt", "text": "And so we form a partially oxygenated blood."}, {"title": "Fetal Circulation.txt", "text": "And that's why we use a light purple color for the partially oxygenated blood."}, {"title": "Fetal Circulation.txt", "text": "So this is essentially the inferior venecaba that eventually connects with a superior venecrava."}, {"title": "Fetal Circulation.txt", "text": "And when this connection takes place, we have a further mixing of the oxygenated and deoxyted blood to form an even less partially oxygenated blood."}, {"title": "Fetal Circulation.txt", "text": "And all that blood eventually reaches the right atrium of the heart."}, {"title": "Fetal Circulation.txt", "text": "So, once again, oxygenated blood from the placentae is carried via the umbilical vein, this entire structure here."}, {"title": "Fetal Circulation.txt", "text": "And notice we call it a vein and not an artery, because a vein, by definition, always carries blood towards the heart, while the artery always carries blood away from the heart."}, {"title": "Fetal Circulation.txt", "text": "Now, as it travels past the underdeveloped liver of the fetus, the blood bypasses the liver via blood duct called the ductus Venosis, as shown in this diagram and as shown in this diagram here."}, {"title": "Fetal Circulation.txt", "text": "So this structure here is our ductus Venosis."}, {"title": "Fetal Circulation.txt", "text": "It connects the umbilical vein to that inferior Venecaiva and allows the blood to bypass the liver."}, {"title": "Fetal Circulation.txt", "text": "So the ductus Venosis, that should be Venosis, the ductus Venosis, connects with the inferior Venecaa, which mixes the oxygenated and the deoxygenated blood and the mixed blood."}, {"title": "Fetal Circulation.txt", "text": "The partially oxygenated blood is shown in light purple and eventually travels to the right atrium of the heart."}, {"title": "Fetal Circulation.txt", "text": "So this should be ductus Venosis."}, {"title": "Fetal Circulation.txt", "text": "Okay?"}, {"title": "Fetal Circulation.txt", "text": "Now let's move on to the right atrium of the heart, and let's see what takes place within our right atrium."}, {"title": "Fetal Circulation.txt", "text": "Now, before we move on to the right atrium, let's focus on the lungs."}, {"title": "Fetal Circulation.txt", "text": "So what happens in the lungs of the fetus?"}, {"title": "Fetal Circulation.txt", "text": "So, just like the liver is not yet fully functional, the lungs inside the fetus are also not functional."}, {"title": "Fetal Circulation.txt", "text": "And that's because the alveoli of the lungs are completely filled with fluid."}, {"title": "Fetal Circulation.txt", "text": "And what that means is there is no oxygen exchange actually taking place within the lungs."}, {"title": "Fetal Circulation.txt", "text": "Remember, all the oxygen and carbon dioxide is exchanged inside the placenta of that developing fetus."}, {"title": "Fetal Circulation.txt", "text": "So because the lungs are filled with fluid, what that means is there is a high resistance inside that fluid, inside the lungs, and that creates a high pressure."}, {"title": "Fetal Circulation.txt", "text": "Now, we know that blood, as any other fluid, will always flow from a high pressure to a low pressure."}, {"title": "Fetal Circulation.txt", "text": "So because the lungs have a high pressure, that creates a high pressure in the pulmonary trunk, and it also creates a high pressure in the right ventricle and the right atrium."}, {"title": "Fetal Circulation.txt", "text": "Now, because of the high pressure in the lungs, the blood inside the right atrium does not actually want to flow into those lungs."}, {"title": "Fetal Circulation.txt", "text": "And so what happens is once again, we have redirection and shunting taking place."}, {"title": "Fetal Circulation.txt", "text": "But this time, instead of using this pathogeway called the Doctor's Venosis, we use another passageway known as the Foray Mino valley."}, {"title": "Fetal Circulation.txt", "text": "And what the foray Mino Valley is."}, {"title": "Fetal Circulation.txt", "text": "It's a small door."}, {"title": "Fetal Circulation.txt", "text": "It's a small hole that exists inside the wall between the right atrium and the left atrium."}, {"title": "Fetal Circulation.txt", "text": "So the right atrium has its own wall, and the left atrium also has its own wall."}, {"title": "Fetal Circulation.txt", "text": "And there are two tiny holes, one in the right atrium and one in the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And that creates this door like structure that essentially opens one way, and it opens from the right atrium to the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And that's because inside the right atrium, we have a higher pressure than inside the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And so, because there is a higher pressure inside the right atrium, then inside the left atrium, blood will naturally and spontaneously move from the right atrium into the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And this is the shunting of blood that takes place between the two atrium of the fetal heart."}, {"title": "Fetal Circulation.txt", "text": "Now, a small portion of the blood will still leak into the right ventricle and then will pass into the pulmonary trunk."}, {"title": "Fetal Circulation.txt", "text": "So this is the pulmonary trunk that connects to the right and the left pulmonary arteries."}, {"title": "Fetal Circulation.txt", "text": "Now, those pulmonary arteries at the pulmonaire trunk we have yet another connection between the pulmonary trunk and our aorter."}, {"title": "Fetal Circulation.txt", "text": "So this is our A order."}, {"title": "Fetal Circulation.txt", "text": "And between the aorta and the pulmonary trunk we have another type of passageway that allows the redirecting and the rerouting of that blood, but this time from the pulmonary trunk and directly into our order."}, {"title": "Fetal Circulation.txt", "text": "So we have these three different shunting processes that take place within the circulatory system of the fetus."}, {"title": "Fetal Circulation.txt", "text": "One takes place between the umbilical vein and the inferior venecrava."}, {"title": "Fetal Circulation.txt", "text": "The second one takes place between the right atrium and the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And the third one takes place between the pulmonary trunk and between our aorter."}, {"title": "Fetal Circulation.txt", "text": "So once again, if we examine this diagram here, the deoxygenated blood coming from the superior venecave is further mixed with the oxygenated blood that is coming from the inferior venecrava."}, {"title": "Fetal Circulation.txt", "text": "So we have these two different types of blood coming in and they mix and they enter the right atrium."}, {"title": "Fetal Circulation.txt", "text": "Now, once they enter the right atrium, there is a high pressure inside the right atrium as a result of the high pressure inside the lungs."}, {"title": "Fetal Circulation.txt", "text": "So since the fetal lungs are filled with fluid, they contain a high resistance to flow and that creates a high pressure."}, {"title": "Fetal Circulation.txt", "text": "And as a result, the blood is rerouted and moves to the lower pressure left atrium via the four men ovaly."}, {"title": "Fetal Circulation.txt", "text": "So there is this tiny one way door that opens as a result of that push, as a result of that difference in pressure."}, {"title": "Fetal Circulation.txt", "text": "And so as the blood moves from the high pressure into the low pressure, this forayman O'Valley opens up and the blood travels into the left atrium and from the left atrium, it passes into the left ventricle and then it moves into our aorter."}, {"title": "Fetal Circulation.txt", "text": "Now, of course, a small portion of that blood will leak from the right atrium and into the right ventricle and then will pass into the pulmonary trunk."}, {"title": "Fetal Circulation.txt", "text": "Now, in the pulmonary trunk, remember, we don't want to waste any of that oxygen and nutrients on the lungs because the lungs inside that fetal individual are not yet developed."}, {"title": "Fetal Circulation.txt", "text": "And so that means they cannot exchange any of that oxygen for carbon dioxide."}, {"title": "Fetal Circulation.txt", "text": "And so we need another duct."}, {"title": "Fetal Circulation.txt", "text": "And this duct is called the ductus arteriosis."}, {"title": "Fetal Circulation.txt", "text": "So the ductus arteriosis connects the pulmonary trunk directly to our order."}, {"title": "Fetal Circulation.txt", "text": "And so as that blood fills the pulmonary trunk, some of it actually leaves or most of it leaves this section, the pulmonary artery and enters our aorter."}, {"title": "Fetal Circulation.txt", "text": "Now, of course, a small amount of that oxygenated and nutrient filled blood will actually leave and enter the left and right pulmonary artery."}, {"title": "Fetal Circulation.txt", "text": "And so they will carry the oxygen to the lungs."}, {"title": "Fetal Circulation.txt", "text": "And that's okay because the lungs do need a small amount of oxygen to actually develop further."}, {"title": "Fetal Circulation.txt", "text": "So once our partially oxygenated blood travels into our order, what happens is it begins to move into the tissues and organs found in the upper portion of that fetus and the lower portion of that fetus."}, {"title": "Fetal Circulation.txt", "text": "Eventually, that deoxygenated blood will enter these internal iliac arteries and they will connect with these umbilical, arteries, and that will carry the deoxynated blood back into the placenta."}, {"title": "Fetal Circulation.txt", "text": "And once again, inside the placenta, we have the oxygenation of that blood and the nutrients flow into that blood once again."}, {"title": "Fetal Circulation.txt", "text": "And so the fetal blood now contains the oxygen nutrients, and the cycle can basically start over again."}, {"title": "Fetal Circulation.txt", "text": "So this is the way that blood circulates inside that developing fetus before the birth of that fetus."}, {"title": "Fetal Circulation.txt", "text": "So we have three important shunting processes taking place."}, {"title": "Fetal Circulation.txt", "text": "And the reason we need the shunting processes is because the liver and the lungs are not functional in that developing fetus."}, {"title": "Fetal Circulation.txt", "text": "So to redirect the blood and conserve that oxygen nutrients, we have the Ductus Venus that redirects the blood and bypasses the liver."}, {"title": "Fetal Circulation.txt", "text": "And the blood enters the inferior veneca."}, {"title": "Fetal Circulation.txt", "text": "Now, between the right atrium and the left atrium, we have this small door like structure known as the forayman O'Valley."}, {"title": "Fetal Circulation.txt", "text": "And what that allows us to do is it allows us to basically shunt and bypass the lungs."}, {"title": "Fetal Circulation.txt", "text": "And so the blood flows from a high pressure, the right atrium to the low pressure, the left atrium."}, {"title": "Fetal Circulation.txt", "text": "And the high pressure is created as a result of the high resistance and high pressure inside the fluid filled lungs."}, {"title": "Fetal Circulation.txt", "text": "And finally, because a tiny portion of that oxygen blood will into the right ventricle and eventually into the pulmonary trunk, what happens is we have yet another passageway that allows the bypassing of those lungs."}, {"title": "Fetal Circulation.txt", "text": "And this passageway is known as the Ductus arteriosis."}, {"title": "Fetal Circulation.txt", "text": "It allows us to actually bypass the lungs by connecting the pulmonary trunk directly to the order of that developing Circle toy system."}, {"title": "Determining Gene Order .txt", "text": "Gene mapping is the process by which we determine what the position is of the genes along any given chromosome."}, {"title": "Determining Gene Order .txt", "text": "Now part of gene mapping involves determining what the order is of the genes along the chromosome."}, {"title": "Determining Gene Order .txt", "text": "But to determine what the order of the genes is, we have to determine, we have to know what the percent of recombination is between each pair of gene along along that chromosome."}, {"title": "Determining Gene Order .txt", "text": "So to demonstrate how we can use the percent recombination between each gene pair to calculate or to determine what the gene order is, let's take a look at the following example."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose on a given chromosome we have three different genes."}, {"title": "Determining Gene Order .txt", "text": "Gene A given in red, gene B given in purple and gene C given in blue."}, {"title": "Determining Gene Order .txt", "text": "Now all these three genes are linked with respect to one another and that simply means they are located on the same chromosome."}, {"title": "Determining Gene Order .txt", "text": "So let's begin with part A."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose in part A we know that the percent recombination between gene A and B is 5%."}, {"title": "Determining Gene Order .txt", "text": "The percent recombination between B and C is 3% and that between A and C is 8%."}, {"title": "Determining Gene Order .txt", "text": "So knowing what the percent recombination is between each gene pair, let's now determine what the order of the genes is."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose we have a chromosome."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose the chromosome is this chromosome right over here."}, {"title": "Determining Gene Order .txt", "text": "Okay?"}, {"title": "Determining Gene Order .txt", "text": "So the question is if we know what the percent recombination is, how can we use that information to actually determine what the order of the genes is?"}, {"title": "Determining Gene Order .txt", "text": "Well, let's begin with a reference gene."}, {"title": "Determining Gene Order .txt", "text": "So we can begin with any one of these genes."}, {"title": "Determining Gene Order .txt", "text": "Let's suppose we begin with gene A."}, {"title": "Determining Gene Order .txt", "text": "Let's suppose gene A is found right over here."}, {"title": "Determining Gene Order .txt", "text": "So because gene A is given a red, I'm going to designate it with the color red."}, {"title": "Determining Gene Order .txt", "text": "So this is Gene A."}, {"title": "Determining Gene Order .txt", "text": "Now let's move on to gene B."}, {"title": "Determining Gene Order .txt", "text": "Now we know that the percent recombination between gene A and gene B is 5%."}, {"title": "Determining Gene Order .txt", "text": "Now recall in our discussion of gene mapping we said that one map unit or one recombination unit is equal to 1% recombination."}, {"title": "Determining Gene Order .txt", "text": "And what that means is because we have a 5% recombination between A and B, the distance between A and B is equal to five map units or five recombination units."}, {"title": "Determining Gene Order .txt", "text": "Now we can place the gene B either above or below because that doesn't really matter."}, {"title": "Determining Gene Order .txt", "text": "Let's put it below."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose that gene B is found five map units below."}, {"title": "Determining Gene Order .txt", "text": "And so this is gene B right over here given to us in purple."}, {"title": "Determining Gene Order .txt", "text": "So this is Gene B."}, {"title": "Determining Gene Order .txt", "text": "And the distance between this point right over here, let's say the center of gene A and the center of gene B is given to us to be five map units."}, {"title": "Determining Gene Order .txt", "text": "Okay?"}, {"title": "Determining Gene Order .txt", "text": "And the reason we know it's five map units is because 1% recombination."}, {"title": "Determining Gene Order .txt", "text": "So remember, 1% recombination is equal to one map unit."}, {"title": "Determining Gene Order .txt", "text": "And because we have 5% recombination that is equal to five map units."}, {"title": "Determining Gene Order .txt", "text": "Now let's move on to the second pair."}, {"title": "Determining Gene Order .txt", "text": "So B and C. Now the percent recombination between B and C is 3%."}, {"title": "Determining Gene Order .txt", "text": "So that means the distance between B and C is three map units."}, {"title": "Determining Gene Order .txt", "text": "Now we can either place C three units above B or we can place it three units below C. So the question is, should we place it above or should we place it below C?"}, {"title": "Determining Gene Order .txt", "text": "Now to answer that question, we actually have to look at the recombination percent, or the percent recombination between the final pair A and C. So the percent recombination between A and C must be 8%."}, {"title": "Determining Gene Order .txt", "text": "And notice if we place C above B."}, {"title": "Determining Gene Order .txt", "text": "So three units above B, that means it's going to lie somewhere here."}, {"title": "Determining Gene Order .txt", "text": "And so because this total distance is five map units, placing it above B means the distance between A and C would be only two map units because five minus three is two."}, {"title": "Determining Gene Order .txt", "text": "And so what that implies is C. The gene C must be placed below B."}, {"title": "Determining Gene Order .txt", "text": "And that will work out because as we place it right over here, so this is our gene C. We know that the distance is 3%, so three map units."}, {"title": "Determining Gene Order .txt", "text": "And that means this distance right over here is three map units."}, {"title": "Determining Gene Order .txt", "text": "And the final piece of information tells us that A and C between A and C is 8%."}, {"title": "Determining Gene Order .txt", "text": "So that's eight map units."}, {"title": "Determining Gene Order .txt", "text": "And this works out because five map units plus three map units gives us eight map units, which is equivalent to 8% recombination."}, {"title": "Determining Gene Order .txt", "text": "So this is the gene order in this particular case, in case A."}, {"title": "Determining Gene Order .txt", "text": "Now let's move on to case B."}, {"title": "Determining Gene Order .txt", "text": "Now let's suppose that the percent recombination between A and B still 5%, between B and C is 3%."}, {"title": "Determining Gene Order .txt", "text": "And now the percent recombination between A and C is not 8%, but 2%."}, {"title": "Determining Gene Order .txt", "text": "The question is how exactly will the order of the genes actually change?"}, {"title": "Determining Gene Order .txt", "text": "So let's redraw our chromosome."}, {"title": "Determining Gene Order .txt", "text": "So this is our chromosome."}, {"title": "Determining Gene Order .txt", "text": "So now we begin with gene A."}, {"title": "Determining Gene Order .txt", "text": "So let's suppose gene A is up here, just like in this case."}, {"title": "Determining Gene Order .txt", "text": "This is Gene A, gene B."}, {"title": "Determining Gene Order .txt", "text": "So this doesn't change, it's 5%."}, {"title": "Determining Gene Order .txt", "text": "So we're going to place B in the same location as in that particular case."}, {"title": "Determining Gene Order .txt", "text": "So this is our gene B here's, gene B."}, {"title": "Determining Gene Order .txt", "text": "So this is still 5%, so it's still five map units."}, {"title": "Determining Gene Order .txt", "text": "So it's five map units."}, {"title": "Determining Gene Order .txt", "text": "But now we know that the percent recombination between A and C is 2%, not 8%."}, {"title": "Determining Gene Order .txt", "text": "So the question is, where do we place the final gene, gene C?"}, {"title": "Determining Gene Order .txt", "text": "If we place the gene here, three units below B, we're going to get the same arrangement as in this case."}, {"title": "Determining Gene Order .txt", "text": "And that doesn't work because the distance between A and C is eight map units."}, {"title": "Determining Gene Order .txt", "text": "But we want it to be two map units."}, {"title": "Determining Gene Order .txt", "text": "So the only other location we can place C with respect to B is above B."}, {"title": "Determining Gene Order .txt", "text": "So if we place gene C three units above B."}, {"title": "Determining Gene Order .txt", "text": "That's going to be somewhere right over here."}, {"title": "Determining Gene Order .txt", "text": "So this is our gene, C. And that works out mathematically because the distance between B, between B and C is three Map units and that's exactly what we want."}, {"title": "Determining Gene Order .txt", "text": "And the distance between A and C, well, if this is five and this is three, that means the remaining is two Map units, right?"}, {"title": "Determining Gene Order .txt", "text": "Because five minus three is equal to two."}, {"title": "Determining Gene Order .txt", "text": "And that is exactly what we are given."}, {"title": "Determining Gene Order .txt", "text": "We are told that the percent recombination between A and C is 2%, and 2% recombination is equivalent to two Map units."}, {"title": "Determining Gene Order .txt", "text": "So of course, these are very simple cases."}, {"title": "Determining Gene Order .txt", "text": "The more genes we are dealing with, the more complicated this process is."}, {"title": "Determining Gene Order .txt", "text": "If we increase the gene number to four to five to six, it becomes much more complicated."}, {"title": "Determining Gene Order .txt", "text": "And in each particular case, to determine what the order of the genes are, we have to know the percent recovery combination between each pair of genes."}, {"title": "Determining Gene Order .txt", "text": "So this is how you basically calculate the gene order during the process of gene mapping."}, {"title": "Metabolism of Methionine.txt", "text": "Three of the 20 amino acids, namely valine, methionine, and isolucine, can all be transformed into sucalco enzyme A, one of the intermediates of the citric acid cycle."}, {"title": "Metabolism of Methionine.txt", "text": "And this molecule can be transformed into oxalo acetate via the citric acid cycle."}, {"title": "Metabolism of Methionine.txt", "text": "And then inside our liver, that succinco enzyme A is used to generate glucose via glucose gluconeogenesis."}, {"title": "Metabolism of Methionine.txt", "text": "And so that's exactly why valine, methionine, and isolucine are known as glucogenic amino acids."}, {"title": "Metabolism of Methionine.txt", "text": "But notice that before these are transformed into succinct coenzyme A, they all converge."}, {"title": "Metabolism of Methionine.txt", "text": "The pathway of metabolism of these amino acids all converge at ProPanel coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "So we first transform these into proponel coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "Then that becomes methylmolonial coenzyme A, and that ultimately transform into succinct coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "So what I've outlined on the board is the pathway by which we essentially transform methionine into succinct coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "So this will be the focus of this lecture."}, {"title": "Metabolism of Methionine.txt", "text": "We're not really going to look at valine or isolucine, but you should know that these amino acids can also be transformed into suclco enzyme A, just like methionine can."}, {"title": "Metabolism of Methionine.txt", "text": "So there are a total of nine steps that basically take us from methionine to succil coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "And so let's begin with step number one."}, {"title": "Metabolism of Methionine.txt", "text": "And step number one is actually a very important step because it allows us to generate an important molecule that is used by the cells of our body."}, {"title": "Metabolism of Methionine.txt", "text": "And we'll see what that molecule is and why it's important just in a moment."}, {"title": "Metabolism of Methionine.txt", "text": "So let's first see how we actually get there."}, {"title": "Metabolism of Methionine.txt", "text": "So we begin with aromthionine."}, {"title": "Metabolism of Methionine.txt", "text": "Now, within Aromthione, this blue section will ultimately end up being part of the subtle coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "This green section will basically be important in this molecule here, as we'll see in just a moment."}, {"title": "Metabolism of Methionine.txt", "text": "So how do we get from methionine to this molecule?"}, {"title": "Metabolism of Methionine.txt", "text": "Well, basically this step is catalyzed by methionine adenosyl transferase."}, {"title": "Metabolism of Methionine.txt", "text": "And what this enzyme does is it takes an adenosine group from the ATP."}, {"title": "Metabolism of Methionine.txt", "text": "It basically kicks off those phosphate groups and attaches that adenosine onto this sulfur."}, {"title": "Metabolism of Methionine.txt", "text": "And that creates a positive charge on that sulfur as seen in this particular diagram."}, {"title": "Metabolism of Methionine.txt", "text": "So this is the product of step one."}, {"title": "Metabolism of Methionine.txt", "text": "We call it S adenosyl methionine, or simply sam."}, {"title": "Metabolism of Methionine.txt", "text": "Now, what's the importance of this sulfur and the positive charge on the sulfur?"}, {"title": "Metabolism of Methionine.txt", "text": "Well, this is basically a relatively unstable arrangement because we have a positive charge on this relatively electronegative sulfur atom."}, {"title": "Metabolism of Methionine.txt", "text": "And so what that means is this molecule is a very good methyl donor."}, {"title": "Metabolism of Methionine.txt", "text": "And that's precisely what our cells actually use this molecule for."}, {"title": "Metabolism of Methionine.txt", "text": "This sand molecule is one of the more important donors of methyl groups inside our body."}, {"title": "Metabolism of Methionine.txt", "text": "And whenever we want to methylate proteins, enzymes, neurotransmitter, hormones, and so forth, we can use this sam molecule."}, {"title": "Metabolism of Methionine.txt", "text": "We can basically remove this methyl and attach it onto a target molecule."}, {"title": "Metabolism of Methionine.txt", "text": "And that's exactly what happens in step two."}, {"title": "Metabolism of Methionine.txt", "text": "So let's suppose we have some target molecule that we want to methylate and so we take the Sam."}, {"title": "Metabolism of Methionine.txt", "text": "We use it to actually methylate that product molecule that removes this methyl group, and it forms this molecule we call S adenosyl homocysteine."}, {"title": "Metabolism of Methionine.txt", "text": "So once you remove this methyl group, there is no longer positive charge on this sulfur."}, {"title": "Metabolism of Methionine.txt", "text": "And so it's slightly more stable than before."}, {"title": "Metabolism of Methionine.txt", "text": "The enzyme that catalyzes this process is methyl transferase."}, {"title": "Metabolism of Methionine.txt", "text": "That makes sense because this enzyme catalyzes the transfer of this methyl group from Sam on to some target molecule."}, {"title": "Metabolism of Methionine.txt", "text": "All right, so once we form this, what happens next?"}, {"title": "Metabolism of Methionine.txt", "text": "Well, in the next step, we basically want to remove that adenosine group."}, {"title": "Metabolism of Methionine.txt", "text": "And so what happens is this entire group is actually removed, and the enzyme that catalyzes this is adenosyl homocysteinease."}, {"title": "Metabolism of Methionine.txt", "text": "And so the product molecule that we form is the homocysteine."}, {"title": "Metabolism of Methionine.txt", "text": "And notice we still have that blue section that ultimately came from here that will become part of the succinal coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "Now, let's stop here for just a moment."}, {"title": "Metabolism of Methionine.txt", "text": "So before we take the homocysteine and continue on the pathway to actually generate the succinctoenzyme A, what also could actually happen and what we should talk about is the fact that homocysteine can be used to actually regenerate that methionine."}, {"title": "Metabolism of Methionine.txt", "text": "And this is an important step."}, {"title": "Metabolism of Methionine.txt", "text": "And essentially, this is what we call a cycle because we begin with methionine, we move along and we generate that methionine back in the process."}, {"title": "Metabolism of Methionine.txt", "text": "We also generate that sand molecule that can be used to methylate some particular target molecule."}, {"title": "Metabolism of Methionine.txt", "text": "So that's why this step is so important."}, {"title": "Metabolism of Methionine.txt", "text": "But it's also important for the following reason."}, {"title": "Metabolism of Methionine.txt", "text": "What this step allows us to do when we go from homocysteine to methionine is it allows us to regenerate another important molecule known as tetrahydrophobate."}, {"title": "Metabolism of Methionine.txt", "text": "So we can take a methylated tetrahydropholate at the fifth nitrogen."}, {"title": "Metabolism of Methionine.txt", "text": "So five methyl THF."}, {"title": "Metabolism of Methionine.txt", "text": "We essentially remove that methyl group and we regenerate that THF."}, {"title": "Metabolism of Methionine.txt", "text": "And now we can use the THF in some process within our cells."}, {"title": "Metabolism of Methionine.txt", "text": "And so what this step allows us to do is, number one, we regenerate that methionine in the process, we form the sand molecule, and we also regenerate a THF by taking a five methyl THF, removing that methyl and reforming that THF."}, {"title": "Metabolism of Methionine.txt", "text": "And we'll talk about the importance of THF in a future lecture."}, {"title": "Metabolism of Methionine.txt", "text": "So this basically comes from folic acid, our tetrahydrophobate."}, {"title": "Metabolism of Methionine.txt", "text": "Now, the enzyme that catalyzed this step is methionine synthase, and it uses vitamin B twelve."}, {"title": "Metabolism of Methionine.txt", "text": "And vitamin B twelve is also known as Kobalamine."}, {"title": "Metabolism of Methionine.txt", "text": "So this is one of the few enzymes inside our body that actually utilizes vitamin B twelve."}, {"title": "Metabolism of Methionine.txt", "text": "The other enzyme we're going to talk about at the end."}, {"title": "Metabolism of Methionine.txt", "text": "So this is our cycle that allows us to basically, number one, regenerate the methionine while forming that stem, and also regenerating the THF that can be used in various processes within our body."}, {"title": "Metabolism of Methionine.txt", "text": "And we'll talk about these processes in future."}, {"title": "Metabolism of Methionine.txt", "text": "Lectras now, what we want to focus on in this lecture, however, is how we can use methionine and basically create homocysteine and then use that to ultimately generate the substance coenzyme A that can be used by our liver cells to actually generate glucose molecules."}, {"title": "Metabolism of Methionine.txt", "text": "So in that particular case, the homocysteine basically undergoes a reaction that is catalyzed by cystionine beta synthase."}, {"title": "Metabolism of Methionine.txt", "text": "And this enzyme uses vitamin B six, PLP."}, {"title": "Metabolism of Methionine.txt", "text": "So paradoxyl phosphate."}, {"title": "Metabolism of Methionine.txt", "text": "So we take a Serene, we basically remove water and we attach that Serene onto this sulfur here, and we form this intermediate cystionine."}, {"title": "Metabolism of Methionine.txt", "text": "Now, cystionine, by the activity of the enzyme cystionine Gamalayase will essentially be cleaved."}, {"title": "Metabolism of Methionine.txt", "text": "So a water molecule will be used to basically remove that cysteine that is formed."}, {"title": "Metabolism of Methionine.txt", "text": "So we essentially remove this entire molecule here, including this sulfur atom."}, {"title": "Metabolism of Methionine.txt", "text": "And that gives us cysteine."}, {"title": "Metabolism of Methionine.txt", "text": "And we also remove this ammonium group."}, {"title": "Metabolism of Methionine.txt", "text": "And so ultimately, we generate an alpha ketobutyrate, an alpha ketoacid."}, {"title": "Metabolism of Methionine.txt", "text": "Now, notice that this also allows us to actually generate a cysteine amino acid by metabolizing methionine."}, {"title": "Metabolism of Methionine.txt", "text": "So that's also important because this gives us a way to generate one amino acid by beginning with a different amino acid."}, {"title": "Metabolism of Methionine.txt", "text": "And this all happens in this single pathway."}, {"title": "Metabolism of Methionine.txt", "text": "So we can see that this pathway is very rich in important molecules."}, {"title": "Metabolism of Methionine.txt", "text": "So we produce the sand molecule, the methyl donor."}, {"title": "Metabolism of Methionine.txt", "text": "We produce this THF from the five methyl THF."}, {"title": "Metabolism of Methionine.txt", "text": "And that will become important when we'll talk about the synthesis of nucleotide bases."}, {"title": "Metabolism of Methionine.txt", "text": "And we also produce this cysteine shown here."}, {"title": "Metabolism of Methionine.txt", "text": "So this enzyme uses vitamin B six."}, {"title": "Metabolism of Methionine.txt", "text": "Again, vitamin B six is the paradoxyl phosphate that we talked about here."}, {"title": "Metabolism of Methionine.txt", "text": "And this is our alpha keto acid."}, {"title": "Metabolism of Methionine.txt", "text": "Now, the alpha ketobutyrate then undergoes a decarboxylation step where we essentially remove this carbon dioxide."}, {"title": "Metabolism of Methionine.txt", "text": "And the enzyme complex that catalyzed this is alpha keto acid dehydrogenase complex."}, {"title": "Metabolism of Methionine.txt", "text": "So we essentially remove this carbon dioxide and we attach a coenzyme A molecule."}, {"title": "Metabolism of Methionine.txt", "text": "So we form this ProPanel coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "Now, recall that proponel coenzyme A is essentially obtained is obtained when we metabolize odd chain fatty acids."}, {"title": "Metabolism of Methionine.txt", "text": "So the final product of the metabolism of odd chain fatty acids is, in fact, a ProPanel coenzyme A in the same way that we have this proponel coenzyme A when we metabolize our methionine."}, {"title": "Metabolism of Methionine.txt", "text": "So every step from this step onward is exactly the same as we discussed for the metabolism of odd chain fatty acids."}, {"title": "Metabolism of Methionine.txt", "text": "So we take the proponel coenzyme A, the enzyme proponel coenzyme A carboxylase."}, {"title": "Metabolism of Methionine.txt", "text": "So carboxylase means it has to have a carbon source."}, {"title": "Metabolism of Methionine.txt", "text": "It uses biotin and it has to have an energy source."}, {"title": "Metabolism of Methionine.txt", "text": "The carbon source is this bicarbonate."}, {"title": "Metabolism of Methionine.txt", "text": "The energy source is ATP."}, {"title": "Metabolism of Methionine.txt", "text": "And the biotin is a coenzyme prosthetic group that exists within the ProPanel coenzyme acreboxylate."}, {"title": "Metabolism of Methionine.txt", "text": "So what it does is it just basically attaches this CO2 group onto this carbon here."}, {"title": "Metabolism of Methionine.txt", "text": "And so that's exactly what we form here."}, {"title": "Metabolism of Methionine.txt", "text": "So we attach it right over here."}, {"title": "Metabolism of Methionine.txt", "text": "And so we form the Dmethylnal coenzyme A."}, {"title": "Metabolism of Methionine.txt", "text": "Now, in step eight, we basically change the isomer from the deisomer to the L isomer."}, {"title": "Metabolism of Methionine.txt", "text": "And in the final step, this is the other enzyme that utilizes cobalamine."}, {"title": "Metabolism of Methionine.txt", "text": "So vitamin B. Twelve."}, {"title": "Metabolism of Methionine.txt", "text": "So we have methyl Melonal coenzyme A, mutase."}, {"title": "Metabolism of Methionine.txt", "text": "And what this enzyme does is it basically extends, it uses this carbon and inserts it into here."}, {"title": "Metabolism of Methionine.txt", "text": "So it extends this chain by one carbon."}, {"title": "Metabolism of Methionine.txt", "text": "So here we had one, two, three."}, {"title": "Metabolism of Methionine.txt", "text": "Now we have 1234 because this carbon was used to extend this carbon chain."}, {"title": "Metabolism of Methionine.txt", "text": "And so we formed the succil coenzyme A as our final molecule."}, {"title": "Metabolism of Methionine.txt", "text": "So we can see that the metabolism, the breakdown of the methionine to our succinal coenzyme A is actually pretty complicated."}, {"title": "Metabolism of Methionine.txt", "text": "And we see that many important intermediate molecules are formed as a result."}, {"title": "Metabolism of Methionine.txt", "text": "So, namely, we formed the S adenosyl methionine, which is one of the most important methyl donor molecules used by the cells."}, {"title": "Metabolism of Methionine.txt", "text": "We reform that, THF that will become important."}, {"title": "Metabolism of Methionine.txt", "text": "We'll talk about perimedine appearing synthesis."}, {"title": "Metabolism of Methionine.txt", "text": "And we also form the cystine as a byproduct."}, {"title": "Metabolism of Methionine.txt", "text": "And cysteine is one of the amino acids that our body uses to generate protein molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So now we know what the structure of ATP synthase is complex five with electron transport chain."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Let's actually discuss the mechanism of how ATP synthase carries out its function."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So remember, the function of ATP synthase complex five is to actually use that proton motive force, the proton electrochemical gradient established by complexes one, three and four four to actually generate the high energy ATP molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so what I'd like to focus on in this lecture and the next lecture is how the ATP synthase actually carries out its function, the mechanism of its function."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now in this lecture I'd like to focus on the catalytic subunit, the catalytic structure of ATP synthase."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So remember in our previous discussion of the structure of ATP synthase we said that ATP synthase can actually be broken down into two regions."}, {"title": "Mechanism of ATP Synthase .txt", "text": "One of the regions is down in the actual inner membrane of the mitochondria in this region here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And this is known as the f kno region."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And the f knot region actually contains that proton channel that rotates."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And we'll talk about that much more detail in the next lecture."}, {"title": "Mechanism of ATP Synthase .txt", "text": "In this lecture I'd like to focus on the other region, the f one region because it's the f one region that contains the catalytic structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "The catalytic structure is known as the alpha three beta three hexamurine."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So the f one region of ATP synthase contains that hexamurine, the alpha three beta three structure that actually catalyzes the formation of ATP molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And it does this in three different steps."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So in step one it basically binds the reactants, the ATP molecules and the inorganic orthophosphate molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "In step two it actually catalyzed their combination to form the product molecule, the ATP."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And in step number three, the ATP is actually released into the matrix of the mitochondria."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, I have to emphasize the following important point."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So this Heximer structure, this hexamer structure here can actually carry out each one of these steps."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But step one and two can take place in the absence or in the presence of the proton motive four."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So what that means is step one and two can be carried out in the absence or presence of that proton electrochemical gradient."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So step one and two can take place regardless of whether or not we actually have this f zero region present within ATP synthase."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So regardless of whether or not we have that proton electrochemical gradient, dehexemur can bind the ATP and orthophosphates and can actually convert them into ATP."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But for the ATP synthase to actually be able to release the synthesized ATP molecule there has to be a proton electrochemical gradient that must exist between the two sides of the inner membrane of the mitochondria."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Because only when the F Naught structure actually rotates when the C ring rotates will the gamma structure rotate and only then will that structure be able to actually release the ATP molecule."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And we'll talk about that in much more detail in the next lecture."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So let's take a look at the following structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So this is our alpha three, beta three hexamarin."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And let's take a cross section of that structure and examine it from top to bottom."}, {"title": "Mechanism of ATP Synthase .txt", "text": "This is basically what we're going to see."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we have our three alpha units."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we have alpha unit here, alpha unit here and alpha unit here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And we have our beta units, the beta unit here, beta unit here and beta unit here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So let's begin by focusing on these alpha subunits."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, the alpha subunits, even though they're part of the hexama ring, they don't actually play a catalytic role."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And even though these alpha units can in fact bind ATP molecules and they will have ATP molecules bound to them, they will not actually release the ATP molecules nor will they carry out any useful process."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So although the alpha subunits of the hexamarine do contain ATP molecules bound to them, they do not release these ATP molecules nor will they actually carry out or participate in some reaction some useful reaction."}, {"title": "Mechanism of ATP Synthase .txt", "text": "On the other hand, the beta subbunits actually are the ones that will play that catalytic role."}, {"title": "Mechanism of ATP Synthase .txt", "text": "They have the ability to actually undergo these three reactions."}, {"title": "Mechanism of ATP Synthase .txt", "text": "They're the ones that bind the ATP and orthophosphere reactants."}, {"title": "Mechanism of ATP Synthase .txt", "text": "They're the ones that catalyze the synthesis of the ATP and they're the ones that release that ATP molecules once a rotation actually takes place as we'll see in more detail in just a moment."}, {"title": "Mechanism of ATP Synthase .txt", "text": "In fact, notice that we have three different confirmations."}, {"title": "Mechanism of ATP Synthase .txt", "text": "That is, the beta subunits can actually exist in one of three different states and that's because we have three different reactions that have to be carried out by this alpha three, beta three hexamer."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we have the ten state or simply the T state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "We have the Lose state or simply the L state and we have the open state or simply the O state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, in the open state in the open state once the ATP molecule is formed only when that beta submit is in the open state can the ATP molecule be released from that beta submune."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And likewise, only in the open state can the submune actually bind the ADP and orthophosphate reactants."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, in the loose state it actually has the ADP and the orthophosphate bound to it."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But because in the loose state the reactants are not brought close enough, they will not be able to react to form the ATP molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But in the ten state the structure is constrained and the ATP and the orthophosphate are brought close enough to actually synthesize that ATP molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And I have to emphasize the following important points."}, {"title": "Mechanism of ATP Synthase .txt", "text": "In the ten state or in the loose state these two states will not release the ATP molecules or the ADP and orthophosphate molecules they're only released in the open confirmation."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we see that the beta subunit, however, unlike the alpha subunit, can actually buy the ADP and orthophosphate reactants, synthesize the ATP and release the ATP into the matrix."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And at any given moment in time, the beta subunits can exist in one of three distinct states."}, {"title": "Mechanism of ATP Synthase .txt", "text": "We have the ten state in which the ATP and orthophosphate are brought closed so that they can be combined to form that ATP molecule."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And once the ATP is formed, only once the subunit is in the open state can the ATP actually be released from that structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, in the loose state, the bound ATP and Orthophosphate become trapped, but they're not close enough to actually react and form the ATP."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So these are the three states."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, the next question is what determines the actual state of that particular subunit?"}, {"title": "Mechanism of ATP Synthase .txt", "text": "So let's take a look at the following diagram."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So what we see happening in the following diagram is as we go, for instance, from this particular structure to this particular structure, the actual alpha three, beta three hexama ring does not rotate."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But this middle portion, the gamma structure shown red, actually rotate."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So remember, as we discussed previously, it's this gamma structure that actually rotates as a result of the rotation of the C ring."}, {"title": "Mechanism of ATP Synthase .txt", "text": "As we'll see the next lecture that causes a change in confirmation of the beta subunit."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So this is what we see in this diagram."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So to see what we mean, let's begin with this diagram, which is basically this diagram here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And notice I've omitted the ATP molecules in the alpha subunits because the alpha subunits don't participate in this catalysis reaction, only the beta units do."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so in this particular conformation, this particular beta subunit exists in the 10th state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "This exists in the lose state and this exists in the open state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, only in the 10th state are the ATP and orthophosphate molecules brought close enough for them to actually react and form the ATP."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so we see that there is an equilibrium that exists between the reactants and the products."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But once this C structure actually rotates, will this structure actually rotate."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So this, remember, is that gamma structure that creates that central stalk that basically moves through the central cavity of that Hexima ring."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so this is what we see here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so if that central stalk, that gamma unit, actually rotates, let's say 120 degrees in the counterclockwise direction so that this pointer, instead of pointing here, basically moves 120 degrees in this direction."}, {"title": "Mechanism of ATP Synthase .txt", "text": "It will now point the arrow."}, {"title": "Mechanism of ATP Synthase .txt", "text": "The points are here, will point here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And what that means is this will no longer exist in the 10th state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "This will exist in the 10th state, but this will no longer exist in the open state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "This will exist in the loose state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So all of these beta subunits basically switch their confirmations, their states."}, {"title": "Mechanism of ATP Synthase .txt", "text": "This will now exist in the open, this will now exist in the tents and this one will exist in the loose."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so once we synthesize the ATP, once this rotation takes place, only then will the ATP will actually be able to leave this structure here."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So once this rotation takes place this is in an open state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And in the next process, step two, this ATP molecule will be released from this structure and it will travel into the matrix of the mitochondria."}, {"title": "Mechanism of ATP Synthase .txt", "text": "While when this goes from the loose state to the 10th state these two reactants are brought close enough for them to begin producing the ATP molecules and this structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "In the open state these reactants can easily leave and enter this structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But once this conformational change takes place and we enter the loose state these two reactants are now trapped in this conformation."}, {"title": "Mechanism of ATP Synthase .txt", "text": "But even though they're trapped, they're not close enough to actually carry out that catalysis reaction and transform them into ATP molecules."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So once we go from this drug to this structure, the ATP molecule actually leaves and now we have this empty spot."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so in the final step, what happens is once the ATP leaves the ADP and the orthophosphate can actually enter this location and the cycle can basically repeat itself again."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we see that the rotation of the gamma subunit that basically lies within the inner cavity of the hexamer ring basically allows the interconversion of the beta subunits from one state to another state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And notice that at any given moment in time all the beta subunits exist in a particular distinct state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And that applies that any given two subunits, two beta subunits will never exist in the same identical state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we have three of these different subunits and they exist in different states."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And that's a result of the orientation of this central gamma structure that exists in the central cavity of that Hexima ring."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So once again and let's summarize the following diagram and this entire mechanism by which this takes place is known as the binding change mechanism."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So in reaction one, a rotation of the gamma subunit of 120 degrees in a counter clockwise direction."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So when this arrow basically moves here 120 degrees, what happens is this structure here in the 10th state changes into the open confirmation the open state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we see the rotation basically converts the beta subunit in the 10th state into the open state and the other units are also transformed."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So this one becomes the 10th and this one, which was open, becomes Lewis."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now this relaxes the beta subunit and now that ATP that was synthesized in the 10th state can be released in process two."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So in process two, the ATP is actually released."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And in process three, once the ATP is released a new set of ADP Orthophiletate will enter that open beta subunit."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And once they enter, if we have another rotation so if this structure rotates 120 degrees again this way then this open will become a loose state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And once in a loose state these two reactants will become trapped within this beta subunit."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So another rotation of 120 degrees in the counterclockwise direction, which is not shown in this diagram, will lock the reactants, the ADP and the pi in this state and they will not be able to leave this structure."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And so this mechanism is what we call the binding change mechanism."}, {"title": "Mechanism of ATP Synthase .txt", "text": "Now, what we're going to focus on in the next lecture is how the third step actually takes place."}, {"title": "Mechanism of ATP Synthase .txt", "text": "So we actually didn't discuss why the ATP molecule is actually able to leave because what ultimately allows that ATP molecule to actually leave is the fact that this structure is in the open state."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And what creates that open state is the rotation of that gamma unit."}, {"title": "Mechanism of ATP Synthase .txt", "text": "And the next lecture we're going to focus on what causes that gamma unit to actually rotate."}, {"title": "Mechanism of ATP Synthase .txt", "text": "We're going to discuss the rotation of the searing in the F zero region of the ATP synthase molecule."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "The lipid bilare membrane is an extremely important structure that exists extensively inside our body."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So we typically find these lipid bilayer membranes actually surrounding the cells and also enclosing the organelles down within those cells."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, lipid bilayer membranes consist of two major biological molecules lipids and proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, the lipids have two functions."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Function number one is to actually create a semipermeable barrier, a barrier that separates the inner aqueous environment from the outer aqueous environment."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And function number two of lipids is to actually create a medium, an environment in which the proteins can actually dissolve in, because ultimately, it's the proteins that carry out nearly all the other functions of that particular membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So, remember, the proteins greatly diversify the functionality of cell membranes."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "They basically carry out processes such as signal transduction pathway, communication pathways."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "They actually move the molecules and particles across the cell membrane, and they also create an energy storage system, for instance, when they create proton gradients, that creates a separation of charge between the two sides of the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And within that separation of charge, we store energy, electric potential energy."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, depending on the type of membrane that we're examining, and depending on the functionality of that membrane, the mass ratio of lipids to proteins can basically differ."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So it varies anywhere from four to one to one to four."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And to see what we mean by that, let's compare the plasma membrane found on myelinated nerve cells to the membrane that encloses mitochondria."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So what's the function of a neuron?"}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Well, the function of a neuron is to basically carry an action potential to initiate an electrical signal and carry that signal the action potential along the axon."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so, in many of our neurons, on many of our neurons, the plasma membrane is actually myelinated by using these special lipids because it's the lipids that create this insulation layer that basically increases the rate at which that propagation actually takes place, because that signal can basically jump from one node to the next node."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so, because the function of the neuron and the plasma membrane on the neuron is to actually propagate, that signal will find a much higher amount of lipids compared to proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, only about 18% of the plasma membrane of myelin neurons contains proteins by mass."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "On the other hand, if we study the membrane of mitochondria, we'll see that the function of this membrane is to actually produce high energy ATP molecules."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And that involves moving many different types of molecules across the membrane, as well as creating proton gradients."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so what that means is this membrane is very, very active and it contains a high proportion of proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, about 75% of proteins by mass is found within the membrane of mitochondria."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But on average, if we examine the plasma membranes of the cells inside our body, we'll find about 50% of protein by mass."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But it can basically vary anywhere from, let's say, 18% to 75% of protein by mass."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "It really depends on the actual function of that cell and the function of that membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, there are two categories of proteins that we can find in the membranes of our body."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "We have integral proteins and peripheral proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So what exactly is the difference between these two?"}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Well, integral proteins are basically the proteins that remain permanently attached onto that membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And that's because these contain areas of hydrophobic regions that can actually interact with the core hydrophobic region of that membrane, as we'll see in our discussion in just a moment."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "On the other hand, peripheral proteins cannot interact as well with that hydrophobic core of the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so these peripheral proteins can actually dissociate under certain processes."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "For instance, gap junctions that will typically find, let's say, between cardiac cells are examples of integral proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And these gap junctions do not actually dissociate from the cell membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Under normal conditions, we actually have to mix these integral proteins with some type of nonpolar solution, for example, a detergent to actually remove those integral proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But the peripheral proteins can easily be removed by, for example, changing the PH or adding some type of salt solution, because what that does is it disrupts those ionic or hydrogen bonds that exist between the peripheral proteins and that cell membrane, as we'll see in just a moment."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So we see that integral proteins bond to the membrane extensively via extensive hydrophobic regions."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And we even have integral proteins that span the entire width of that bilayer membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And what that means is it basically transverses the entire width of that membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So this is an example of an integral protein."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So is this one, and so is this one."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In this particular case."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In this case, it is a transmembrane protein because it spans the entire width."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But in this case, it's not a transmembrane, but it's still an itchy protein because it interacts extensively via hydrophobic interactions with a hydrophobic core of that membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So the portion of the protein within the core interacts via Vanderbilt forces we call London dispersion forces with the hydrocarbon tails of the phospholipids, these red structures shown in that diagram."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, peripheral proteins, on the other hand, interact with the membrane less extensively."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "They don't have as much of that hydrophobic section to basically be able to interact in the same stabilizing way."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so what they do is they instead use the polar sections to basically interact either with the polar heads of the phospholipids or the polar regions found on the surface of these integral proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And because the cell membrane, or generally the membrane, basically predominantly exists of the hydrophobic core, we see that the peripheral proteins cannot interact very well with the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so, due to these weaker interactions, peripheral proteins can readily dissociate from the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, when we'll discuss the signal transduction pathways and we'll look at G proteins, we'll see that G proteins are examples of these peripheral proteins, they can actually dissociate from that membrane and then go on and carry out some important type of process inside our body."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So once again, integral proteins come in two types."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "We have transmembrane proteins that span the entire membrane, and we also have these integral proteins that only partially interact with that particular hydrophobic region."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "That means they don't actually span the entire membrane, as shown here."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In either case, these integral proteins are attached permanently via these strong hydrophobic nonpolar interactions."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And so what that means is, by changing the PH or adding some type of salt, for instance, sodium chloride, these integral proteins cannot actually dissociate from the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But in the case of peripheral proteins, which only interact via these polar regions, by changing the PH or by adding some type of salt solution, we actually disrupt those bonds and that can cause a dissociation of that particular protein."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So, two major types of proteins."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, we'll focus on this in much more detail in a future lecture."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "But let's discuss integral proteins, and let's take a look at three specific examples that we have studied extensively."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So let's discuss bacteria, porin and prostaglandin h two, synthase one."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And let's begin with bacteria."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, bacteria, doptopsin is a transmembrane into a protein, and that means it spans the entire membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And these transmembrane proteins are found in special types of archaeal bacterial cells."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, the function of this protein is to basically use the energy that is stored in light to basically create a proton gradient."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So it moves protons from the inside to the outside of that cell."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And by creating this proton gradient, what it does is it synthesizes, it is able to synthesize high energy ATP molecules."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, if we examine the structure of this transmembrane protein, we'll see it consists of membrane spanning alpha helices."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, we have 123-4567 of these membrane spanning alpha helices."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, the predominant structure of transmembrane proteins inside our body actually consists of these membranespanic helices."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, the thing about these membranespanic, alpha helices, is they consist predominantly of hydrophobic nonpolar amino acids."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Why?"}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Well, because these alpha helices that basically create this cylindrical structure that allows the movement of these h plus ions, they contain the hydrophobic nonpolar regions or amino acids because they want to be able to interact and stabilize, interact in a stabilizing way with the hydrophobic core, the red portion of that cell membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So we see that the structure of bacteria, or adoption consists largely of membrane spanning alpha helices that contain mostly nonpolar amino acids that can interact via nonpolar vanderviled interactions, lung dispersion forces with the hydrocarbon tails of these phospholipids."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, let's move on to a different type of transmembrane protein that, instead of containing alpha helices, contains beta plepleted sheets."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So even though we typically find membrane spanning alpha helices within these transmembrane into a protein, we also actually sometimes contain these beta pleated sheets."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So let's discuss a specific example called porin."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, porin is basically a transmembrane protein that exists in certain bacterial cells, for instance, E. Coli cells, and it exists on the outer membrane of those on the outer layer of the membrane of those bacterial cells."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Remember, some cells have actually two membranes and this porn exists on the outer membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, porin is actually a channel."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So it's a pore, it's a hole inside the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And what this consists of are these beta pleated sheets that run in an antiparallel direction and they basically curl and create this channel."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, they create the channel because this, because the function of this is to basically move polar molecules across the cell membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "In fact, the entire inner portion of the channel basically is filled with an aqueous solution, with water molecules."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And what that implies is even though the outer portion of this poring structure basically consists of non polar hydrophobic amino acids so that they can interact well with the hydrophobic tails, the intersection of this porin actually must consist of these hydrophilic polar amino acids because the entire inner portion of the poor and is filled with a water solution."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "An aqueous solution."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So porin is an integral protein, more specifically, a transmembrane integral protein, because it spans the entire membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "It's found in bacterial cells, for instance, equalized cells."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "It acts as a channel, a pore, a whole, allowing certain molecules, polar molecules, to actually pass across."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, it consists predominantly of beta pleated sheets that run in an antiparallel direction, as shown here."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So one error goes here, the other error goes here."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And it consists of alternating hydrophobic and hydrophilic amino acids."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "The hydrophobic amino acids interact with the non polar hydrocarbon tails of that membrane, while the polar, the hydrophilic amino acids actually point inward into that porn and that interacts with the aqueous solution and the polar molecules passing through that particular pouring channel."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, in fact, we have many examples of these channels inside our bodies."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So the example I mentioned earlier, the gap junctions that exist, for instance, in cardiac, in cardiac muscle cells, basically are these channels that allow the propagation, the movement of the ions, and that creates the movement of that action potential from one cardiac cell to the adjacent cardiac cell."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And that creates a forceful and a strong contraction of the heart."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And we have many other examples of these types of porns inside our body."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "For instance, we have aquaphorns, which basically allow the movement of water molecules across the membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, the final example we're going to look at is the prostaglantin h, two synthase, one."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And this is actually an example of an integral protein that is not a transmembrane protein."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And what that means is it doesn't actually span the entire width of the membrane, but it does contain a good portion that actually does interact with that core."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "And that's why we call it an integral protein."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So if we basically change our PH or add a salt solution this will not dissociate because a good portion of it actually is permanently bound to that cell membrane."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, where do we find these molecules?"}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Well, typically, we find them in the membrane of the endoplasmic reticulum, and this portion basically points into the aqueous environment of the lumen of the endoplasm reticulum."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "So this is a cytoplasm and this is the endoplasm reticulum."}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Now, what's the function of this protein?"}, {"title": "Integral and Peripheral Membrane Proteins .txt", "text": "Well, actually, unlike in this particular case, this is an enzyme, so it actually catalyzes a specific reaction."}, {"title": "Analysis of Protein Purification .txt", "text": "Thus far in our discussion on purifying proteins we discussed eight different types of techniques or methods that we can use to basically purify a mixture of proteins and isolate a protein that we actually want to study."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, the next question is how do we actually know that the purification method that we carry out is actually working?"}, {"title": "Analysis of Protein Purification .txt", "text": "So how do we know that we are purifying our protein mixture following some type of technique?"}, {"title": "Analysis of Protein Purification .txt", "text": "So in biochemistry, we actually developed five different types of quantities and these five different types of quantities can be measured following that purification procedure."}, {"title": "Analysis of Protein Purification .txt", "text": "And we can compare those quantities to before and basically they can tell us whether or not our procedure is actually working in purifying that protein mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's discuss what these five quantities are."}, {"title": "Analysis of Protein Purification .txt", "text": "We have the total protein."}, {"title": "Analysis of Protein Purification .txt", "text": "We have the enzyme activity, also known as the total activity."}, {"title": "Analysis of Protein Purification .txt", "text": "We have the specific activity."}, {"title": "Analysis of Protein Purification .txt", "text": "We also have yield and purification level."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's begin by discussing what these quantities actually mean and then let's take a look at an example at how we can purify proteins and use these quantities to basically determine whether or not our technique is working."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's begin with the total protein."}, {"title": "Analysis of Protein Purification .txt", "text": "The total protein is simply the total amount of protein that we begin with in our sample before we carry out that particular purification technique."}, {"title": "Analysis of Protein Purification .txt", "text": "And this is usually given in milligrams."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about enzyme activity?"}, {"title": "Analysis of Protein Purification .txt", "text": "Well, the enzyme activity we spoke about before and we said that the enzyme activity tells us the ability of that enzyme to basically promote a specific type of reaction within that sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And the units are micromoles per minute."}, {"title": "Analysis of Protein Purification .txt", "text": "So the classically units are micromoles per minute which is equal to a unit."}, {"title": "Analysis of Protein Purification .txt", "text": "But nowadays we also use moles per second."}, {"title": "Analysis of Protein Purification .txt", "text": "So what the enzyme activity tells us is how many milli or how many micromoles of that product that is produced by the enzyme per minute or how many micro moles of the substrate is transformed by that enzyme every single minute."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about the specific activity?"}, {"title": "Analysis of Protein Purification .txt", "text": "Well, the specific activity is simply the ratio of the enzyme activity to the total protein."}, {"title": "Analysis of Protein Purification .txt", "text": "So the units are unit per milligram are the units of the specific activity or micromol per minute per milligram, are the units of specific activity?"}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what does the specific activity actually tell us?"}, {"title": "Analysis of Protein Purification .txt", "text": "Well, it tells us how pure or by how much more pure our sample is following that purification technique."}, {"title": "Analysis of Protein Purification .txt", "text": "And usually if the technique actually works this specific activity value has to increase as we'll see in just a moment."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, let's move on to our yield."}, {"title": "Analysis of Protein Purification .txt", "text": "So the yield or the percent yield basically tells us how much of that protein that we essentially want to isolate we have left over compared to how much we begin with."}, {"title": "Analysis of Protein Purification .txt", "text": "So this describes the enzyme activity that is retained following each purification step and it is given as a percentage."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, the equation for yield is the following."}, {"title": "Analysis of Protein Purification .txt", "text": "So it's the ratio of the enzyme activity of that specific procedure to the original enzyme activity found in that original sample that we begin with and we multiply the ratio by 100%."}, {"title": "Analysis of Protein Purification .txt", "text": "So because this is a ratio, the units cancel out and our units are simply percent."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, by definition we give our original sample that hasn't yet been purified a yield of 100%."}, {"title": "Analysis of Protein Purification .txt", "text": "And then as we purify our sample more and more the yield should technically decrease."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about the purification level?"}, {"title": "Analysis of Protein Purification .txt", "text": "Well, the purification level is calculated by using the specific activity."}, {"title": "Analysis of Protein Purification .txt", "text": "So these two quantities tell us the same exact thing."}, {"title": "Analysis of Protein Purification .txt", "text": "So this is a measure of how effective each step is in purifying that protein that we want to isolate and study."}, {"title": "Analysis of Protein Purification .txt", "text": "So the purification level is equal to the ratio of the specific activity of that particular procedure to the specific activity of that original sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And notice that it's also ratios the units cancel out and we don't have any units."}, {"title": "Analysis of Protein Purification .txt", "text": "And just like the original mixture is given a percent yield of 100 that original mixture is given a percent yield of one."}, {"title": "Analysis of Protein Purification .txt", "text": "And following our procedure, if that procedure actually worked and we purified our sample this quantity has to increase."}, {"title": "Analysis of Protein Purification .txt", "text": "So specific activity increases and purification level also increases if our procedure is actually working and the yield decreases because as we go from one process to another we usually lose a certain amount of product, a certain amount of protein in that procedure."}, {"title": "Analysis of Protein Purification .txt", "text": "So now, to see actually how these quantities can be used to basically determine if the purification procedure is working let's take a look at a hypothetical example."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's suppose we have a beaker."}, {"title": "Analysis of Protein Purification .txt", "text": "In that beaker we have a sample a mixture of different types of proteins as shown in the following diagram."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what we want to do is we want to use several of the different types of procedures that we spoke of earlier and basically purify our sample, purify and isolate some specific type of protein found inside that mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "And the way that this is usually done is we choose some specific type of procedure."}, {"title": "Analysis of Protein Purification .txt", "text": "We carry that procedure out and then we extract that sample and we place that sample into an SDS page setup."}, {"title": "Analysis of Protein Purification .txt", "text": "So we expose our sample to SDS polyacrylamide gel electrophoresis to basically separate our proteins based on size."}, {"title": "Analysis of Protein Purification .txt", "text": "And as we go from one step to another step, if the procedure is working we have to get less bands and less bands and less bands until we get a single band as we'll see in just the moment."}, {"title": "Analysis of Protein Purification .txt", "text": "And that basically means we're purifying our sample because we're removing some of those proteins with specific mass values as we'll see in just a moment."}, {"title": "Analysis of Protein Purification .txt", "text": "And every time we conduct a procedure we also calculate these five quantities."}, {"title": "Analysis of Protein Purification .txt", "text": "And these five quantities basically tell us if our technique is actually working."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's actually see by what we mean."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's actually see what we mean by taking a look at the following diagrams."}, {"title": "Analysis of Protein Purification .txt", "text": "So this is our initial beaker."}, {"title": "Analysis of Protein Purification .txt", "text": "In that initial beaker, we have that sample."}, {"title": "Analysis of Protein Purification .txt", "text": "So we take a pipette, we extract a small amount from that beaker, and we essentially drop that into this well."}, {"title": "Analysis of Protein Purification .txt", "text": "And this is essentially step A."}, {"title": "Analysis of Protein Purification .txt", "text": "So in Step A, we expose the original homogeneous mixture to the SDS Page setup and we get the following distribution of bands."}, {"title": "Analysis of Protein Purification .txt", "text": "So this is step A, and for step A, these are the different types of bands."}, {"title": "Analysis of Protein Purification .txt", "text": "And each band basically represents a type of protein with a specific type of size, with a specific type of mass."}, {"title": "Analysis of Protein Purification .txt", "text": "So remember, in SDS polyacryla my gel electrophoresis, the proteins that have a higher mass are higher up, but the proteins that are smaller have a lower mass, lower size, are lower along our gel."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, in Step A, we basically find that the total protein in milligrams that we're dealing with is 20,000 milligrams."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, the enzyme activity is 200,000 micromoles per minute, or units."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, the specific activity will calculate in just a moment."}, {"title": "Analysis of Protein Purification .txt", "text": "And because this is our original mixture, the yield is 100% and the purification level is one."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about the specific activity?"}, {"title": "Analysis of Protein Purification .txt", "text": "So we have to calculate the specific activity to be able to determine whether these steps are actually purification steps and whether they are actually working."}, {"title": "Analysis of Protein Purification .txt", "text": "So what is our specific activity?"}, {"title": "Analysis of Protein Purification .txt", "text": "So the specific activity is the ratio of the enzyme activity to the protein, the total protein in our sample."}, {"title": "Analysis of Protein Purification .txt", "text": "So 200,000 divided by 20,000, and that gives us a value of ten."}, {"title": "Analysis of Protein Purification .txt", "text": "So the four zeros cancel, we get 20 divided by two, and that gives us a value of ten."}, {"title": "Analysis of Protein Purification .txt", "text": "So now that we have all these five values, now we can extract another portion of this same sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And now we expose it to the process of salting out."}, {"title": "Analysis of Protein Purification .txt", "text": "And in salting out, we basically separate our protein mixture based on their ability to dissolve in a salt concentration."}, {"title": "Analysis of Protein Purification .txt", "text": "And following salting out, we extract that protein mixture and we essentially apply the process of dialysis to remove those salts that we don't actually want inside our mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "And once we have that extraction, we place it into the second well in the SDS Page apparatus."}, {"title": "Analysis of Protein Purification .txt", "text": "And this is procedure B."}, {"title": "Analysis of Protein Purification .txt", "text": "So notice that this distribution of bands consists of less bands than before."}, {"title": "Analysis of Protein Purification .txt", "text": "And what that basically tells us is, as we go from A to B, we decrease the number of proteins inside that mixture that we actually don't want."}, {"title": "Analysis of Protein Purification .txt", "text": "And so that means it's a good thing, because what that means is we're purifying our protein mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "And if we go to the following table, these values should tell us exactly that."}, {"title": "Analysis of Protein Purification .txt", "text": "So remember, as we are purifying, the specific activity should increase, and that should increase the purification level."}, {"title": "Analysis of Protein Purification .txt", "text": "So these two quantities compared to these should actually increase."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's see if that's true."}, {"title": "Analysis of Protein Purification .txt", "text": "So to calculate the specific activity we take the enzyme activity of that particular sample divided by the total protein once again of that particular sample."}, {"title": "Analysis of Protein Purification .txt", "text": "So we get 175 divided by five because these three zeros cancel out and we get a value of 35."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's express that once again with red."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about the purification level?"}, {"title": "Analysis of Protein Purification .txt", "text": "Let's actually write that down in purple."}, {"title": "Analysis of Protein Purification .txt", "text": "And to find the purification level, we use this equation."}, {"title": "Analysis of Protein Purification .txt", "text": "So the specific activity of that particular sample to the specific activity of the original sample that we began with."}, {"title": "Analysis of Protein Purification .txt", "text": "And so 35 divided by ten and that gives us 3.5."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what that means is that extracted sample that we extracted after salting out is 3.5 times as pure as our original sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And so what that means is our procedure did in fact work because it purified our sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And that is precisely what is shown when we go from this band distribution to this band distribution going here to here, we decrease the number of bands and that means we remove those unwanted proteins from our mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "Now let's oh, and by the way, what is our yield?"}, {"title": "Analysis of Protein Purification .txt", "text": "Well, the yield should decrease because every time we carry out a procedure we lose a certain amount of protein from our mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "And so what is our yield?"}, {"title": "Analysis of Protein Purification .txt", "text": "Now, to find the yield, we have to take the enzyme activity."}, {"title": "Analysis of Protein Purification .txt", "text": "We divide it by the original enzyme activity."}, {"title": "Analysis of Protein Purification .txt", "text": "So the enzyme activity of that sample we extracted divided by the original enzyme activity and we multiply that by 100."}, {"title": "Analysis of Protein Purification .txt", "text": "So this divided by this, the three zeros cancel out."}, {"title": "Analysis of Protein Purification .txt", "text": "We get seven divided by eight multiplied by 100."}, {"title": "Analysis of Protein Purification .txt", "text": "And that gives us 87.5."}, {"title": "Analysis of Protein Purification .txt", "text": "And let's use blue to basically designate that."}, {"title": "Analysis of Protein Purification .txt", "text": "So notice, even though the yield decreased, it didn't decrease by as much."}, {"title": "Analysis of Protein Purification .txt", "text": "And so that's a good thing because that means we're not losing the majority of the protein."}, {"title": "Analysis of Protein Purification .txt", "text": "Now let's move on to C. In C, we take that extracted mixture following salting out and we expose that to ion exchange chromatography."}, {"title": "Analysis of Protein Purification .txt", "text": "And an ion exchange chromatography."}, {"title": "Analysis of Protein Purification .txt", "text": "We basically separate our protein mixture based on the net charge."}, {"title": "Analysis of Protein Purification .txt", "text": "And so based on our electrophoresis setup we see that following ion exchange chromatography, when we extract that mixture and place it into this, well, we produce this distribution of bands."}, {"title": "Analysis of Protein Purification .txt", "text": "And because we decrease the number of bands we see, that means we remove some of those proteins."}, {"title": "Analysis of Protein Purification .txt", "text": "And so we are purifying our mixture."}, {"title": "Analysis of Protein Purification .txt", "text": "And so that should basically correspond to higher values in these two boxes."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's calculate what the specific value is for step C. So we basically take the enzyme activity of that specific sample, right, and we divide it by the total protein because as always, specific activity is this divided by this."}, {"title": "Analysis of Protein Purification .txt", "text": "So this divided by this basically give us gives us."}, {"title": "Analysis of Protein Purification .txt", "text": "So we cross out the three zeros and we get 125 divided by one."}, {"title": "Analysis of Protein Purification .txt", "text": "And that leaves us with 125."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, what about the purification level?"}, {"title": "Analysis of Protein Purification .txt", "text": "The purification level is 125 divided by ten and that gives us 12.5."}, {"title": "Analysis of Protein Purification .txt", "text": "And so we see that this extracted sample following this salting out procedure and on exchange chromatography, this extracted sample of proteins is 12.5 times more pure than our original sample."}, {"title": "Analysis of Protein Purification .txt", "text": "And that is a good thing."}, {"title": "Analysis of Protein Purification .txt", "text": "That means our procedure is working."}, {"title": "Analysis of Protein Purification .txt", "text": "Now, for it to work properly, this yield value shouldn't decrease by too much."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's see what that yield value is."}, {"title": "Analysis of Protein Purification .txt", "text": "To calculate the yield value, we take the empty activity 125,000 divided by 200,000, multiply that by 100."}, {"title": "Analysis of Protein Purification .txt", "text": "So 125 divided by 200 gives us five divided by eight, and we multiply that by 100%."}, {"title": "Analysis of Protein Purification .txt", "text": "And that basically gives us 62.5."}, {"title": "Analysis of Protein Purification .txt", "text": "So 62.5 and that is not that much of a difference."}, {"title": "Analysis of Protein Purification .txt", "text": "And so the point is, if by the end we get about 30% yield, that is a good enough yield to basically be able to work with and study that protein."}, {"title": "Analysis of Protein Purification .txt", "text": "So let's move on to d and d. We take that extracted mixture following in exchange chromatography and we expose it to."}, {"title": "Test Cross.txt", "text": "So let's suppose that you are given a plant, and the only piece of information you have about the plant is the phenotype of that plant."}, {"title": "Test Cross.txt", "text": "So you know that the plant is tall."}, {"title": "Test Cross.txt", "text": "Now, we don't actually know what the genotype of that plant is."}, {"title": "Test Cross.txt", "text": "And the question we want to ask ourselves is what experiment can we conduct with this plant that we are given that will help us determine exactly what the genotype of that plant is with the tall phenotype?"}, {"title": "Test Cross.txt", "text": "Now, the first question we want to ask ourselves what are all the possibilities for a genotype that will produce a tall phenotype?"}, {"title": "Test Cross.txt", "text": "So we know there are two possibilities."}, {"title": "Test Cross.txt", "text": "It's either heterozygous tall or it's homozygous dominant tall."}, {"title": "Test Cross.txt", "text": "So what that means is the phenotype is either uppercase T, lowercase T, in which case this is the heterozygous toll plan, or it can also be homozygous dominant uppercase T, uppercase T both of these genotypes will produce a tall phenotype."}, {"title": "Test Cross.txt", "text": "Now, lower case T lowercase T will not produce a tall phenotype."}, {"title": "Test Cross.txt", "text": "It will produce a short phenotype."}, {"title": "Test Cross.txt", "text": "And that is precisely why we can basically cross this one out."}, {"title": "Test Cross.txt", "text": "So now we can narrow it down to one of these two cases."}, {"title": "Test Cross.txt", "text": "Now, we still don't know exactly which one it is."}, {"title": "Test Cross.txt", "text": "It can be either this or it can be this."}, {"title": "Test Cross.txt", "text": "The question is, now what experiment can we actually conduct with this plant to determine if this if the genotype is this or this?"}, {"title": "Test Cross.txt", "text": "Well, if we take this plant with the unknown genotype and we cross it with a plant whose genotype we actually know, then we can figure this problem out."}, {"title": "Test Cross.txt", "text": "And the only type of plant whose genotype we know for certain is a homozygous recessive."}, {"title": "Test Cross.txt", "text": "So a short plant, because the only time a plant will be short is if its genotype is actually lowercase T. Lowercase T. And this is what we call a test cross."}, {"title": "Test Cross.txt", "text": "A test cross is this experiment that basically allows us determine which one of these genotypes it actually is."}, {"title": "Test Cross.txt", "text": "So by crossing our unknown genotype with a known genotype, we can determine what that initial genotype is."}, {"title": "Test Cross.txt", "text": "So let's actually see how that works."}, {"title": "Test Cross.txt", "text": "Now, let's begin by assuming that the genotype of my unknown plant is this."}, {"title": "Test Cross.txt", "text": "Okay, so we begin by assuming the genotype is this."}, {"title": "Test Cross.txt", "text": "And now we want to basically carry out the pundits square experiment."}, {"title": "Test Cross.txt", "text": "We want to cross our alleles between this genotype and this genotype here."}, {"title": "Test Cross.txt", "text": "So let's suppose this column are the alleles that came from this parent."}, {"title": "Test Cross.txt", "text": "So we have upper case T, lower case T. Remember, the law of segregation tells us that during the process of meiosis, when we actually form the sex cell dirtyamides, we have the separation of these homologous chromosomes."}, {"title": "Test Cross.txt", "text": "And so the separation of these two genes, these two alleles."}, {"title": "Test Cross.txt", "text": "So we have uppercase T goes into this gamete, and we have the lowercase T goes into this gamete."}, {"title": "Test Cross.txt", "text": "And the same thing is true for our genotype T lowercase T, lowercase T. Now we actually cross them."}, {"title": "Test Cross.txt", "text": "So if this Xcel combines with this sex cell, they form a Zygo that will be uppercase T, lowercase T. So we have uppercase T, and we have lowercase T. Now, what about if this crosses with this?"}, {"title": "Test Cross.txt", "text": "So, once again we have the same exact situation."}, {"title": "Test Cross.txt", "text": "We have an uppercase T combines with the lowercase T, and this will be the genotype of our Zygote."}, {"title": "Test Cross.txt", "text": "Or we can have this and this."}, {"title": "Test Cross.txt", "text": "So in this case, it's T mixing with T. So now we have lowercase T lowercase T, and lowercase T lowercase T. So these are the potential genotypes, the possibilities of the genotype for the offspring."}, {"title": "Test Cross.txt", "text": "If the genotype of this plan is uppercase T, lowercase T. So each one of these squares, and we have four squares."}, {"title": "Test Cross.txt", "text": "So four squares is 100, and each one of these four squares is 25%."}, {"title": "Test Cross.txt", "text": "So the likelihood of it happening is 25%."}, {"title": "Test Cross.txt", "text": "So that means 25 plus 25."}, {"title": "Test Cross.txt", "text": "So 50% of the offspring will be heterozygous tall."}, {"title": "Test Cross.txt", "text": "So heterozygous."}, {"title": "Test Cross.txt", "text": "And the phenotype will be tall, the other 50%."}, {"title": "Test Cross.txt", "text": "So 25 plus 25 will be lowercase T, lowercase T, which is homozygous recessive, and in this case it will produce short."}, {"title": "Test Cross.txt", "text": "Now, let's leave this for now and let's go to this case."}, {"title": "Test Cross.txt", "text": "Let's now suppose that the genotype of that plant is actually homozygous dominant."}, {"title": "Test Cross.txt", "text": "So uppercase T, uppercase T. If this is the case, then we have to conduct the same experiment here."}, {"title": "Test Cross.txt", "text": "Because remember, in the beginning, we don't know which one it is."}, {"title": "Test Cross.txt", "text": "So that's why we want to carry out two of these pun and square experiments."}, {"title": "Test Cross.txt", "text": "So we have uppercase T, uppercase T, and then we have once again, lowercase lowercase T because we know the genotype of this short plant is in our test cross and we do the same exact experiment."}, {"title": "Test Cross.txt", "text": "So uppercase t lowercase t produces an uppercase t lowercase t zygote Here we have the same case, uppercase T mixing with that lowercase T, we produce the same exact Zygote as here."}, {"title": "Test Cross.txt", "text": "And if we carry out these experiments here, we basically get the same exact case."}, {"title": "Test Cross.txt", "text": "So uppercase, uppercase T, lowercase T and uppercase T lowercase T. So, unlike in this case, we have 100% of the offspring."}, {"title": "Test Cross.txt", "text": "So the offspring will always be heterozygous."}, {"title": "Test Cross.txt", "text": "And so what that means is we have 100% heterozygous and heterozygous, and the phenotype will always be tall."}, {"title": "Test Cross.txt", "text": "So these are the two possibilities."}, {"title": "Test Cross.txt", "text": "If it's this, then we'll get these offspring."}, {"title": "Test Cross.txt", "text": "But if it's this, we'll get this distribution of our offspring."}, {"title": "Test Cross.txt", "text": "So let's suppose I take the test."}, {"title": "Test Cross.txt", "text": "I conduct this experiment, let's say 1000 times."}, {"title": "Test Cross.txt", "text": "Now, if I conducted 1000 times and about 500 of the offspring are tall and 500 of the offspring are short, then I know that the genotype of my initial plant was in fact heterozygous, because only a heterozygous genotype will produce the short offspring will never see short offspring in this distribution."}, {"title": "Test Cross.txt", "text": "Here."}, {"title": "Test Cross.txt", "text": "So if the short offspring actually appear, we know for sure that the genotype is uppercase t lowercase t. But if we conduct the experiment 1000 times and all the thousand times the offspring is always tall, then what that?"}, {"title": "Test Cross.txt", "text": "Means is most likely the genotype of that offspring is actually uppercase T. Uppercase T. The reason I say most likely and not definitely because what can happen is, and this is very unlikely but it can still happen if I conduct the experiment 1000 times, it will appear tall."}, {"title": "Test Cross.txt", "text": "But on that 1001st time, if the offspring comes out to be short, then what that means is it must be upper case t lowercase T. So if we do get a short offspring, we know definitely it's upper case."}, {"title": "Test Cross.txt", "text": "T lowercase T. But if we never actually get our short offspring, we can say that most likely our genotype of that initial plant following our test cross is T uppercase T uppercase T. So this is what we call a test cross."}, {"title": "Test Cross.txt", "text": "So a test cross is basically this experiment that we can conduct to basically help us determine what the genotype of that initial plant is, assuming we know what the phenotype is."}, {"title": "Test Cross.txt", "text": "So in this case, we have a phenotype that is tall."}, {"title": "Test Cross.txt", "text": "And so we have two possibilities."}, {"title": "Test Cross.txt", "text": "We conduct a test cross by testing, by crossing this tall phenotype with a plant whose phenotype and genotype we actually know."}, {"title": "Test Cross.txt", "text": "And the only such case is when the phenotype is short, we know the genotype must be lowercase T lowercase."}, {"title": "Gastrulation.txt", "text": "Following the implantation of the blastocyst into the endometrium of the uterus, another process known as gastrolation begins."}, {"title": "Gastrulation.txt", "text": "And gastrolation is an early embryological process in which the three distinct germ layers are formed."}, {"title": "Gastrulation.txt", "text": "And these germ layers include the ectoderm, the endoderm and the mesoderm."}, {"title": "Gastrulation.txt", "text": "Now, as we'll see in just a moment, the cells of each one of these these germ layers eventually give rise to specific organs and structures and systems found within the adult human individual."}, {"title": "Gastrulation.txt", "text": "So let's begin by briefly discussing which structures in which organs and systems are formed by each one of these three germ layers."}, {"title": "Gastrulation.txt", "text": "And let's begin with the ectoderm."}, {"title": "Gastrulation.txt", "text": "Now, the ectoderm is the outer layer."}, {"title": "Gastrulation.txt", "text": "It's the external layer of that developing embryo, as we'll see in just a moment."}, {"title": "Gastrulation.txt", "text": "And that ectoderm gives rise to the integumentary system of the human body and that includes the outer portion of the skin, the ears, the nails and the hair."}, {"title": "Gastrulation.txt", "text": "Now because of an invagination process."}, {"title": "Gastrulation.txt", "text": "As we'll see in just a moment, a portion of that ectoder makes its way into that developing embryo."}, {"title": "Gastrulation.txt", "text": "And this forms the nervous system of the human body."}, {"title": "Gastrulation.txt", "text": "And that includes the brain and the spinal cord and it also includes all the nerve cells that are part of the peripheral nervous system."}, {"title": "Gastrulation.txt", "text": "We also form the pituitary gland that is found beneath that hypothalamus in the brain."}, {"title": "Gastrulation.txt", "text": "Now let's move on to the middle layer."}, {"title": "Gastrulation.txt", "text": "Actually not the middle layer."}, {"title": "Gastrulation.txt", "text": "Let's discuss the internal layer."}, {"title": "Gastrulation.txt", "text": "So this is the innermost layer found in that developing organism, in that developing embryo."}, {"title": "Gastrulation.txt", "text": "And this is called the endoderm."}, {"title": "Gastrulation.txt", "text": "Now, the endoderm layer gives rise to the epithelial layer of the lungs, our digestive system, the pancreas, the bladder, the liver, and it also forms the thyroid and the parathyroid gland as well as the thymus."}, {"title": "Gastrulation.txt", "text": "And finally, what about the mesoderm?"}, {"title": "Gastrulation.txt", "text": "Well, the mesoderm is the middle layer of the developing embryo."}, {"title": "Gastrulation.txt", "text": "It's found between these two layers."}, {"title": "Gastrulation.txt", "text": "And so it makes sense that the mesoderm basically creates everything between the skin as well as our digestive epithelium."}, {"title": "Gastrulation.txt", "text": "So we have things like the musculoskeletal system."}, {"title": "Gastrulation.txt", "text": "So that includes the bone and the cartilage, as well as the three types of muscles."}, {"title": "Gastrulation.txt", "text": "We have the cardiac muscle, we have the smooth muscle and we have the skeletal muscle."}, {"title": "Gastrulation.txt", "text": "Now, because we form the cardiac muscle, that means we also form the cardiovascular system of the body and that includes the heart as well as the blood vessels."}, {"title": "Gastrulation.txt", "text": "We also form the excretory system as well as the reproductive system."}, {"title": "Gastrulation.txt", "text": "So that includes the gonads of the female, the ovaries, as well as the gonads of the male, the testes."}, {"title": "Gastrulation.txt", "text": "So these are the three different layers that are formed during the process of gastrelation."}, {"title": "Gastrulation.txt", "text": "The question is, how does gastrolation actually take place?"}, {"title": "Gastrulation.txt", "text": "So let's take a look at the following six diagrams that ultimately describe the process of gastrelation."}, {"title": "Gastrulation.txt", "text": "The formation of the three distinct germ layers."}, {"title": "Gastrulation.txt", "text": "So let's begin with diagram one which describes the process of implantation."}, {"title": "Gastrulation.txt", "text": "When that blastocyst, the embryo actually develop, actually implants itself onto the endometrium, the lining of the uterus."}, {"title": "Gastrulation.txt", "text": "So this is the endometrium, and this is the blastocyst."}, {"title": "Gastrulation.txt", "text": "So recall that the blastocyst consists of a region known as the Trophy Blast."}, {"title": "Gastrulation.txt", "text": "And these are the purple cells, the dark purple cells found as shown."}, {"title": "Gastrulation.txt", "text": "We have the light purple cells that form the inner cell mass."}, {"title": "Gastrulation.txt", "text": "And this entire inner cavity that contains a fluid that provides nutrition to these developing cells is known as the blastocean."}, {"title": "Gastrulation.txt", "text": "Now, the inner cell mass, the cells shown in light purple, eventually form these three distinct germ layers, while the cells of the Trophy Blast eventually give rise to the corian as well as to the placenta."}, {"title": "Gastrulation.txt", "text": "And remember, the placenta is a structure that provides a source of nutrition and oxygen from the mother and to that developing organism that developing fetus."}, {"title": "Gastrulation.txt", "text": "Now, let's suppose we move from diagram one to diagram two."}, {"title": "Gastrulation.txt", "text": "What happens in between these two diagrams?"}, {"title": "Gastrulation.txt", "text": "Well, basically, the cells of the Trophy Blast begins secreting and releasing digestive enzymes."}, {"title": "Gastrulation.txt", "text": "And these digestive enzymes degenerate this section of the endometrium, and that allows the entire blastocyst to make its way entirely into the endometrium."}, {"title": "Gastrulation.txt", "text": "And that hole is eventually sealed off by blood clots, as well as by developing epithelial cells."}, {"title": "Gastrulation.txt", "text": "So, in diagram two, the entire embryo is found inside that endometrium."}, {"title": "Gastrulation.txt", "text": "And also notice that the cells of the inner cell mass differentiate into two different types of cells."}, {"title": "Gastrulation.txt", "text": "We have the green cells that make up the hypoblast, and we have these blue cells that make up the epiblast."}, {"title": "Gastrulation.txt", "text": "Now, the hypoblast cells eventually give rise to the endoderm, while the epiblast eventually gives rise to the ectoderm."}, {"title": "Gastrulation.txt", "text": "And as we'll see in just a moment, the mesoderm develops in between as a result of a process called invagination, when we form that primitive treat, as we'll see in just a moment."}, {"title": "Gastrulation.txt", "text": "Now, when we go from diagram two to diagram three, what happens is the upper portion of the hypoblast and the upper portion of the epiplast eventually migrates upward towards this pole, and we basically form the following diagram."}, {"title": "Gastrulation.txt", "text": "So notice this entire green portion eventually develops into the umbilical vessel."}, {"title": "Gastrulation.txt", "text": "Now, in nonhumans, it's called the yolksac."}, {"title": "Gastrulation.txt", "text": "And the umbilical vesicle eventually becomes part of the umbilical cord system."}, {"title": "Gastrulation.txt", "text": "And we also form this cavity that is created by the epiblast cells."}, {"title": "Gastrulation.txt", "text": "And this is known as the amniotic cavity."}, {"title": "Gastrulation.txt", "text": "And this is where that organism of the fetus will actually be found, as we'll see in just a moment."}, {"title": "Gastrulation.txt", "text": "Now, we also have this extension of the Trophy Blast, this purple section that will develop into the coriane and ultimately into the placenta."}, {"title": "Gastrulation.txt", "text": "Now, when we go from diagram three to diagram four, something important takes place."}, {"title": "Gastrulation.txt", "text": "We form something called the mesoderm."}, {"title": "Gastrulation.txt", "text": "So that's the middle layer of that developing embryo."}, {"title": "Gastrulation.txt", "text": "And these are the retails, as shown in this diagram."}, {"title": "Gastrulation.txt", "text": "Now, what happens is if we zoom in on this section, we get the following diagram."}, {"title": "Gastrulation.txt", "text": "And what happens is we have this invagination process where the blue layer basically invaginates and informs the primitive streak."}, {"title": "Gastrulation.txt", "text": "And along the primitive streak, which is basically this access where invagination takes place, these blue cells essentially invaginate and move inwards."}, {"title": "Gastrulation.txt", "text": "And as they move inwards, these blue cells develop into the red cells that make up the Messider."}, {"title": "Gastrulation.txt", "text": "And as this pushing process takes place, all these red cells eventually are pushed around this entire structure."}, {"title": "Gastrulation.txt", "text": "So if we look at this diagram, what happens when we go from diagram four to diagram five is there is an inward push that goes into this direction and that pushes all these red cells around the following diagram."}, {"title": "Gastrulation.txt", "text": "And so all these red cells eventually make their way around the green structure, around the blue structure and ultimately around the entire trophy blast, the purple section of this diagram."}, {"title": "Gastrulation.txt", "text": "And so when we go from diagram four to diagram five, this is what we produce."}, {"title": "Gastrulation.txt", "text": "So this imagination process along the primitive streak, the movement of the ectoderm cells into the red section, the formation of these red cells eventually pushes all these red cells and the mesodermal layer around the green structure, the blue structure and around this entire purple structure to form the following diagram."}, {"title": "Gastrulation.txt", "text": "So this is basically our umbilical vesicle and this is basically the amniotic cavity where that fetus will be found."}, {"title": "Gastrulation.txt", "text": "Now, what happens when we go from five to six is this section basically moves inwards."}, {"title": "Gastrulation.txt", "text": "So it pushes this way and eventually we form an embryo that looks something like this."}, {"title": "Gastrulation.txt", "text": "And notice that this entire structure here is that developing embryo."}, {"title": "Gastrulation.txt", "text": "It's that developing fetus."}, {"title": "Gastrulation.txt", "text": "So the red portion is the actual embryo along with this green portion and the blue portion, the red portion is basically that middle layer, it's that Messider."}, {"title": "Gastrulation.txt", "text": "And the Messider will basically form the musculoskeletal system, the cardiovascular system, the excretory system, the reproductive system, everything's found in between the green layer and that blue layer."}, {"title": "Gastrulation.txt", "text": "Now the blue layer is found on the outside."}, {"title": "Gastrulation.txt", "text": "It's the external layer."}, {"title": "Gastrulation.txt", "text": "And it will develop that skin layer as well as the ears, the nails and the hair."}, {"title": "Gastrulation.txt", "text": "And not only that, because this blue layer, notice it will eventually move inside."}, {"title": "Gastrulation.txt", "text": "It also forms the nervous system, the brain, as well as our spinal cord."}, {"title": "Gastrulation.txt", "text": "And this green layer which is found on the inside will form our digestive system."}, {"title": "Gastrulation.txt", "text": "It will form the epithelial layer of our digestive system as well as the lungs, the liver, the pancreas and the bladder."}, {"title": "Gastrulation.txt", "text": "Now this structure develops into the umbilical vesicle."}, {"title": "Gastrulation.txt", "text": "This entire structure is the corianic cavity and this outside portion is the coriane."}, {"title": "Gastrulation.txt", "text": "This extension is what becomes our placenta."}, {"title": "Gastrulation.txt", "text": "This structure here that connects the placenta, the corian, to the growing embryo is the embryonic stock."}, {"title": "Gastrulation.txt", "text": "And this will eventually develop into the embryonic tube, that embryonic section, the embryonic cord that connects that placenta to that developing fetus."}, {"title": "Gastrulation.txt", "text": "And this is the amniotic cavity that contains that houses that growing fetus."}, {"title": "Gastrulation.txt", "text": "So this is the process that we call gastrilation."}, {"title": "Gastrulation.txt", "text": "It is based particularly an early phase of embryological development in which following implantation, the three germ layers, the ectoderm, the endoderm and the mesoderm begin to form and ultimately form the different types of structures, organs and systems that are found inside the human body."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So far in our discussion on glycogen metabolism, we only discussed how the liver cells and skeleton muscle cells actually take the glycogen and break it down into the glucose monomer."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So in the case of liver cells, they release the glucose into the blood plasma to help control the blood glucose levels."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "While in the case of skeleton muscle cells, once they break down the glycogen into glucose, they take that glucose and build TP molecules to carry out voluntary motion."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, the question is, how do we go in reverse?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "How do we take the glucose monomers, glucose precursors and build glycogen?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And why would our body actually want to carry out that process in the first place?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Well, let's suppose we ingest the meal that is rich in carbohydrates."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so what that means is inside our blood plasma, we're going to have a rise in blood glucose levels."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And once the blood glucose levels actually rise, the liver cells will want to maintain the proper blood glucose levels."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so they will uptake some of that glucose into the liver cells."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And these liver cells will take the glucose precursor molecules and begin building the glycogen."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And they will store the glycogen in tiny granules found in the cytoplasm of liver cells."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, what exactly is the process by which we synthesize glycogen in liver cells and skeleton muscle cells?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Well, that's what we're going to focus briefly in this lecture and the next lecture."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, in the same analogous way that gluconeogenesis, the building of glucose molecules and glycolysis the breaking down of glucose molecules, in the same analogous way that these two processes are not simply the reverse of one another, we see that glycogen synthesis is not simply the reverse of the breakdown of glycogen."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "In fact, as we'll see in this lecture, glycogen synthesis actually follows a completely different reaction pathway when it uses the glucose precursors to actually build the glycogen polysaccharide."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, there are two important processes that we have to consider when actually building the glycogen."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Before we can actually take the glucose and attach the glucose onto that growing glycogen polymer, we have to make that glucose a reactive molecule, because glucose by itself, and more specifically, glucose one phosphate, is not reactive enough, it's not high in energy to basically attach itself onto that glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "What we have to do before anything is actually activate that glucose molecule."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And by activating, I mean we have to make it more reactive, we have to increase its energy."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So glucose by itself is not active enough to attach on to that growing glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Therefore, the first step in this process is to actually transform glucose into a more reactive and high energy form."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And that's exactly what happens in this step and this step here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So let's begin with this step here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So we begin with the glucose one phosphate."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So this is a glucose molecule shown here, that we ultimately want to attach onto that growing glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "But the problem is this bond here isn't very reactive."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And we want to make it more reactive."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "We want to make it higher in energy."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so what happens inside our cells is we react to glucose one phosphate with urine triphosphate."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So we have the urine and three phosphate groups, UTP."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And the enzyme that catalyzes this step is UDP glucose pyrophosphorase."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so what UDP glucose Pyrophosphorase does is it takes this red structure here and attaches it onto this region here, and we form a urine diphosphate glucose molecule, and we also form a pyrophosphate."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So this pyrophosphate is basically this section here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, the thing about the UDP glucose is it's a much more reactive molecule."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Why?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Well, because we have this additional group that contains a high negative charge."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so that makes this entire molecule, and more specifically, this Esther bond here, becomes much more reactive."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so as we'll see in the next step shown here, we're able to actually cleave that bond and attach this glucose molecule onto that growing glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, this reaction is actually reversible."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And notice the equilibrium doesn't lie on this side."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "It's actually somewhere in between."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so what that means is our body has to couple this reaction with the reaction that is product favored."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And that's exactly where the second reaction comes into play."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "The pyrophosphate here in the presence of water will actually be hydrolyzed into two orthophosphate molecules."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And this reaction is very much product favorite."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so because this reaction takes place towards the product side, we continually use up the pyrophosphate."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And that drives this entire reaction towards this side."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And that's exactly what allows this reaction to actually take place in the first place."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And if we sum up these two reactions, this will be the net reaction for activating the glucose."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So on the reactant side, we have glucose one phosphate, this molecule here, we have the urine triphosphate, this molecule here, we have the water."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And on the product side, we have the UDP glucose that is formed here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And we also have the two orthophosphates that are formed here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Notice the pyrophosphates disappear because they're actually intermediates in these two reactions."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So they cross out from both sides."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And this is what our net reaction actually is."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, once we form that activated glucose molecule, we're now ready to actually attach that activated glucose molecule onto that growing glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And this is what takes place in this step here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So we take that UDP glucose shown here, and this is our growing glycogen chain."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, in the presence of an enzyme known as glycogen synthase, what happens is we essentially take the glucose molecule, this structure here, and we attach it onto this region here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "More specifically, if we examine the terminal glucose residue that contains a free hydroxyl group on the fourth carbon, this essentially acts as a nucleophile."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "It attacks this carbon here of the glucose, and it establishes it creates an alpha one four glycositic bond and it displaces, it kicks off this entire molecule here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So this is what we form after this step."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So the hydroxyl group on the fourth carbon."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So if we actually label our carbons, so let's say this is carbon one, carbon two, carbon three, carbon four, carbon five, and carbon six."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So this hydroxyl group on the fourth carbon of the terminal glucose residue of the growing poly of the growing polysaccharide chain, basically attacks this carbon here."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Carbon one displacing this entire group and that creates that alpha one four glycocitic bond."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Now, notice that glycogen synthase only creates alpha one four glycocitic bonds, but we know glycogen also contains alpha one six glycocytic bonds, about every ten glucose residues."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So how exactly do we create alpha one six glycocitic bonds?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Well, this is what we're going to focus on in the next lecture."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And the final thing that I'd like to mention about glycogen synthase is glycogen synthase can only attach glucose molecules onto a polymer, a growing polysaccharide chain that consists of more than four glucose molecules."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so what that basically means is, before this reaction can actually take place, we have to begin with a primer molecule."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So how do we actually establish the primer molecule?"}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Well, once again, we'll talk about that in the next lecture."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So in this lecture, we have to understand two important things."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "Number one is glycogen synthesis is simply not the reverse process of glycogen breakdown."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "They follow completely different pathways in the same way that gluconeogenesis is not simply the reverse of glycolysis."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And the second thing we have to understand is glucose one phosphate."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "So the glucose molecule that we ultimately want to actually add onto that growing glycogen chain is not reactive enough to actually attach onto it."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "What we have to do is we have to first activate it."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And the way that we activate that glucose one phosphate is by reacting it with the urine triphosphate UTP molecule."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "What that does is it adds an additional charge onto it and it makes this Esther bond much more reactive."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "And so when this process takes place, this can act as a strong nucleophile to this good electrophile."}, {"title": "UDP-Glucose and Glycogen Elongation .txt", "text": "This bond is created and that breaks the bond and kicks off this entire department parting group."}, {"title": "Neuron Structure and Function.txt", "text": "The nervous system is a collection of different tissues whose main function is to allow the cells in our body to communicate with one another in a quick and direct fashion over a very short distance."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the basic unit of a nervous system is a cell known as a neuron or a nerve cell."}, {"title": "Neuron Structure and Function.txt", "text": "And a neuron is a specialized type of cell that can generate electric signals, carry those electric signals and send or pass down those electric signals to other cells either via electrical or chemical means."}, {"title": "Neuron Structure and Function.txt", "text": "Now, a neuron is so specialized that it lost its ability to divide."}, {"title": "Neuron Structure and Function.txt", "text": "So a neuron cannot divide via mitosis and that implies that a neuron is always in the genot phase of interface."}, {"title": "Neuron Structure and Function.txt", "text": "Now, although the size and shape of neurons in the body can actually vary from one location to another they all consist of several important features."}, {"title": "Neuron Structure and Function.txt", "text": "So we have dendrites the cell body also known as the soma."}, {"title": "Neuron Structure and Function.txt", "text": "We have the axon hillock."}, {"title": "Neuron Structure and Function.txt", "text": "We have the axon as well as the axon terminal."}, {"title": "Neuron Structure and Function.txt", "text": "So let's go through each one of these structures and discuss what the function of these structures are."}, {"title": "Neuron Structure and Function.txt", "text": "So let's begin with our dendrites."}, {"title": "Neuron Structure and Function.txt", "text": "So the dendrites are basically projections that come off of our cell body and the purpose of these dentrides is to basically receive the electrical signal that comes from other cells and to send that electrical signals to other parts of our neuron."}, {"title": "Neuron Structure and Function.txt", "text": "So these are the dendrite regions."}, {"title": "Neuron Structure and Function.txt", "text": "Now, this is known as the cell body or the soma."}, {"title": "Neuron Structure and Function.txt", "text": "And the soma is the region of the cell that stores the nucleus and other organelles."}, {"title": "Neuron Structure and Function.txt", "text": "For example, the endoplasmic reticulum, the Golgi apparatus armitochondria and so forth."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the region between this long extension known as the axon and the cell body is something called the exxon hill lock."}, {"title": "Neuron Structure and Function.txt", "text": "So the exxon hillock basically connects the exxon to the cell body and the exxon hill lock is really a specialized section of the cell body that is actually capable of generating an action potential."}, {"title": "Neuron Structure and Function.txt", "text": "And the action potential is basically a voltage difference that allows an electric signal to be sent along the exxon from our cell body."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the exxon is a long extension of our nerve cell that is specialized to actually carry or propagate that electrical signal that is generated in our exxon hillock and it carries that electrical signal away from the sole or from the cell body and to the end of the axon known as the exxon terminal."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the exxon terminal is also known as the synaptic terminal or the synaptic bouton."}, {"title": "Neuron Structure and Function.txt", "text": "And the axon terminal consists of projections at the end of our exxon that basically are specialized to transmit our electrical signals to other cells either by electrical or chemical means."}, {"title": "Neuron Structure and Function.txt", "text": "Now, if we actually zoom in on any one of these projections we get the following bulb like structure."}, {"title": "Neuron Structure and Function.txt", "text": "So at the end of each projection is a bulb shaped structure that can basically release neurotransmitters."}, {"title": "Neuron Structure and Function.txt", "text": "So we can release these chemicals known as neurotransmitters, that can go on and bond to receptors on the post synaptic cell as shown in the diagram."}, {"title": "Neuron Structure and Function.txt", "text": "And that can basically generate an electrical signal in the post synaptic cell."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the post synaptic cell is basically the cell that is adjacent to our synapse, to our axon terminal that receives that signal in the first place."}, {"title": "Neuron Structure and Function.txt", "text": "And the space, the region between this bulb like structure and our postsynaptic cell is known as our synaptic cleft."}, {"title": "Neuron Structure and Function.txt", "text": "Now, this entire region is also sometimes known as the synapse and we're going to discuss the details of the synapse and how it actually works in a future lecture."}, {"title": "Neuron Structure and Function.txt", "text": "So we have these important structures, the dendrites, the cell body or the soma the axon hill at the axon and the axon terminal, also known as our synapse or synaptic terminal."}, {"title": "Neuron Structure and Function.txt", "text": "And all of these neurons contain these types of structures."}, {"title": "Neuron Structure and Function.txt", "text": "Now let's actually briefly discuss the propagation of the electrical signal from the beginning to the end of our neuron."}, {"title": "Neuron Structure and Function.txt", "text": "So the electrical signal is received or accepted by the dendrites of our cells by these projections shown in the following diagram."}, {"title": "Neuron Structure and Function.txt", "text": "Now, once our dendrites actually receive this electrical signal, they can send that electrical signal through the cytosol and the membrane of the cell body."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the cell body is not actually itself capable of producing an action potential, but the cell body can pass down that electrical signal to the axon hillock."}, {"title": "Neuron Structure and Function.txt", "text": "Now, once at the axon hillock, if the stimulation is high enough, if it reaches or exceeds the threshold value, then the axon will generate an action potential."}, {"title": "Neuron Structure and Function.txt", "text": "Now an action potential is basically a difference in the voltage between the outside and the inside of our cell."}, {"title": "Neuron Structure and Function.txt", "text": "And this creates an electric current that is passed down along the axon."}, {"title": "Neuron Structure and Function.txt", "text": "So this electric current is the electric signal."}, {"title": "Neuron Structure and Function.txt", "text": "So eventually the electric signal reaches the synaptic bouton or our axon terminal."}, {"title": "Neuron Structure and Function.txt", "text": "So the electric signal passes along the axon."}, {"title": "Neuron Structure and Function.txt", "text": "Eventually it reaches these bulb like structures that we discussed earlier."}, {"title": "Neuron Structure and Function.txt", "text": "Now this will usually stimulate our bulb like structure to release vesicles that carry neurotransmitters into this region."}, {"title": "Neuron Structure and Function.txt", "text": "And then these neurotransmitters will bind to postsynaptic cell receptors, also known as effective cell receptors, on the cell membrane of this postsynaptic cell."}, {"title": "Neuron Structure and Function.txt", "text": "Now this in turn will usually cause changes to the membrane permeability of the postsynaptic cell and that in turn will generate some type of signal that will be passed down to the postsynaptic cell."}, {"title": "Neuron Structure and Function.txt", "text": "And this is usually how the propagation of the electrical signal actually works along our nerve cell."}, {"title": "Neuron Structure and Function.txt", "text": "And we'll discuss this in much more detail in the next several lectures."}, {"title": "Neuron Structure and Function.txt", "text": "Now, the final important aspect of a neuron that I want to mention is the energy source that it actually uses."}, {"title": "Neuron Structure and Function.txt", "text": "So neurons depend almost entirely on glucose for energy generation."}, {"title": "Neuron Structure and Function.txt", "text": "However, the neuron cannot actually store much of the glucose in the form of glycogen inside the cell and the neuron cannot actually store much oxygen inside the cell either."}, {"title": "Neuron Structure and Function.txt", "text": "So that basically implies that the neuron depends on glucose and oxygen that is found in the blood for a steady supply."}, {"title": "Neuron Structure and Function.txt", "text": "Now, glucose is brought into the neuron via special type of protein molecules found in the membrane of our cell body known as our facilitative transporter proteins."}, {"title": "Neuron Structure and Function.txt", "text": "And unlike most other proteins that transport glucose found in other cells of the body, the proteins in the membrane of the nerve cells do not usually depend on insulin to transport our glucose inside our cell."}, {"title": "Neuron Structure and Function.txt", "text": "Now, that's not to say that insulin doesn't actually play an important role in the transportation of glucose into the inside of the cell."}, {"title": "Neuron Structure and Function.txt", "text": "What this basically means is our glucose can still be brought into the cell in the absence of insulin."}, {"title": "Neuron Structure and Function.txt", "text": "So basically, this is the introduction to our neuron."}, {"title": "Neuron Structure and Function.txt", "text": "So a neuron is the basic functional unit of the nervous system and a neuron consists of these important structures, these important regions that each serve their own primary function."}, {"title": "Neuron Structure and Function.txt", "text": "So the main function of a neuron is to basically generate an electric signal, receive electric signals and carry those electric signals to other way to other cells."}, {"title": "Neuron Structure and Function.txt", "text": "And this is how our cells communicate with one another in a rapid and direct fashion over very short distances."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "In genetics."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "In order to be able to correctly determine and calculate the probability values of different events and different outcomes taking place, we have to be familiar with two important rules."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And these rules come from mathematics and probability."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now rule number one we call the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And rule number two we call the sum rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's begin by defining what, what the product rule is."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So the product rule states that the probability of two or more independent events taking place or occurring is equal to the product of their individual probabilities."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And that's exactly why we call the product rule the product rule because it involves the word product."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So to calculate or to use the product rule, we actually have to multiply the individual probabilities as we'll see in just a moment."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now in order to actually fully understand what the product rule tells us, we have to define what it means for two or more events to be independent of one another."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So to demonstrate the independence of events, let's actually use the following coin."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we're going to flip a coin twice."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So our two events is coin flip number one and coin flip number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now before I actually make the flip, what exactly is the outcome of event number one?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, there are two possible outcomes."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "We either have heads or we have tails."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now we don't actually know what the outcome will be before we actually carry that event out."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's carry the event out."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we flip."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Oh, that was horrible."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Let's try it again a little bit better."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay, so event number one was the coin flip number one."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And our outcome of event number one was tails."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Sorry, heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now before we carry out event number two, we don't know what the outcome is."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So it can be tails or it can be heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Moreover, the outcome of event number one has absolutely no influence."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "It does not actually affect the outcome of event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And that's exactly what we mean by two events being independent of one another."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So two events are said to be independent of one another if the currents of one of the events does not actually influence or affect the occurrence of the second event."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So if I make my second flip flip number two, right, it could be heads or it could be tails."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And the event number one has no bearing, no effect on event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So in event number one we obtained heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "In event number two we also obtained heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "But we could have obtained heads and tails or tails and heads or tails and tails and so forth."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now another example is having children."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And this is more, I guess, important when we're talking about genetics."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So what exactly do we mean by having two children?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So having child number one is event number one."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Having child number two is event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now the outcome of event number one could be either a girl or a boy."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And the outcome of event number two could also be a girl or a boy."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Because event number one is independent of event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "What that means is the gender of the first child has no effect, no bearing, no influence on the gender of that second child."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we can get a boy and a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "We can get a boy and a boy or a girl, a girl and a girl or a boy."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we can have four different possibilities as we'll see in just a moment."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And these different events, two events are independent of one another in the same way that these two coin flips were independent of one another."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So to demonstrate this a bit more, let's actually take a look at example number one and example number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So in example number one we want to use the product rule, this rule here to basically determine the probability of obtaining two consecutive heads on two coin flips."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So basically what that means is we have to apply the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's use the color black."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So essentially so we use the probability of the product rule to basically determine what the probability is in flipping two consecutive heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now if we flip the first time, what's the probability of that?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "This actually landing tails or landing heads in this case?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, it's either this side or this side."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So it's 50 50 and that means there's a one half chance that this will land up and a one half chance that this will land up."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we see that the probability of it landing head the first time around is basically one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So the probability of event number one taking place is one half and likewise the probability of independent event number two taking place, the second coil flip, coin flip is also one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And because they're independent, to find the actual probability of these two events taking place we have to apply the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "We multiply them by one another and we basically get one fourth which is equivalent to zero point 25."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And if we multiply by 100 we get 25%."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So remember this is zero point 25 out of one or equivalently 25%."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now we can also use a Punnett square to basically calculate what the result is."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So in trial number one in the first event we can either get heads or we can get tails."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's use I guess red for heads or actually let's use red for event number one and let's use blue for event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay, so this is event number one first trial, event number two second trial."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now what's the probability of it being hence?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well it's basically one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's write one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "What's the probability of being tails?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "It's also one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Likewise it's one half here and it's one half here."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now this is event number one and this is event number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now when we combine these two H's we basically get an H and an H that comes from here."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And when we combine these HS we have to multiply these two fractions."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Why?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, because these two events are independent so we're basically using the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So one half multiplied by one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So one half, let's use one half multiplied by one half gives us one four."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So one fourth here and the same thing goes for each and every one of these."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So this event is basically both times we have heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "This event is the first time around we get heads, the second time around we get tail."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have an H and we have a T. This is a T and an H and finally we have a T and a T. Okay, now what about the probabilities?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, one two times one two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have one half times one two gives us one four and we have one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So once again we have one fourth and we have one four."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And this makes sense because if we sum up these four values it has to add up to one or 100%."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So 00:25 plus zero point 25 plus zero point 25 plus zero point 25 gives us a total of one."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So notice that these probabilities are the probabilities of these events taking place."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So either we get heads and heads or we get heads and tails or tails and heads and tails and tails."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So these are the four different probabilities."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now example number one tells us use the product rule, which we basically just did by multiplying it to calculate the probability that is obtained when two of those coin slips result in two heads."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So this is basically this first square."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So heads and heads gives us a probability of one four which is exactly what we obtained by simply multiplying these two values."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we can either do it this way or we can actually use the punished square."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now let's move on to example number two which involves slightly more with genetics because we're using not coin flips but we're producing children."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So find the probability of two parents, a female and a male, producing two children who are both female."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now essentially example number two is exactly like example number one, except instead of using tails and coin flips we're using children."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So event number one is having the first child and the two outcomes are either a boy or a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's suppose the color red is the first event so we have boy or we have a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Event number two is blue."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have also the same type of outcome, boy or a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now the probability of this taking place is one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "The probability of this taking place is also one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And here we have one half the same exact probability and one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's actually carry out these events."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have a blue here and a red here."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So what this event tells us is so if they have two children and the two children are a boy and a boy, then the probability is the product of these two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So one half multiplied by one half, which is one four."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay, now what about this one?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, we have a boy and we have a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have a boy, we have a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And the probability of that is once again one half times one half or one four."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And we continue this and in each one of these squares we have a value of one fourth."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have a girl and a boy here and we have a girl and we have a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay, so this is basically our opponent square, for example number two."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we want to find the probability of two parents producing two children who are both female."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And if we look at the pun and square, the only time we have both females, both girls is in this final square."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And this gives us by the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So this multiplied by this a value of one fourth."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So essentially we take one half multiplied by one half because the probability of getting a girl the first time around is one half and the probability of getting a girl the second time around is also one half."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And so we get a value of 00:25 or one four or equivalent to 25%, whichever way you want to actually look at it."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Okay, so now that we have the product rule, let's actually move on to the sum rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's take a look at what the sum rule tells us."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So the probability of two or more mutually exclusive events occurring is equal to the sum of their individual probability."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So unlike here, here we're not going to multiply, we're going to add those probabilities up."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And unlike in this event that deals with independent events, unlike in this rule that deals with independent events, in this rule we deal with something called mutually exclusive rules or mutually exclusive events."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So what exactly do we mean by mutually exclusive events?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, two events are set to be mutually exclusive if one event taking place will prevent the second event from actually taking place."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So two events are set to be mutually exclusive if the occurrence of one of those events prevents the other event from actually taking place."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So what do we mean by that?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So once again let's take a look at the following coin."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now before I actually flip the coin, what can happen?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Well, two events can actually take place within this one event."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So two outcomes, we either get a tails or we get a head."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And in a way we can see those two outcomes as two mutually exclusive events because once this actually takes place and I get tails, then heads cannot actually take place because tails already took place."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And that's what we mean by two mutually exclusive events."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So flipping a coin once we obtain heads and obtaining heads is mutually exclusive to obtaining tails because either one takes place or the other takes place, both of those events in that single coin flip cannot actually take place."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "And in the same analogous way, having one child also creates two mutually exclusive events."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we can either get a boy and a girl, but not both, because that is a single process."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we either get one or we get the other."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So every time we have a child, usually we only produce one child, either a boy or a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So that's what we mean by mutually exclusive events."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's look at example number three to demonstrate the sum rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So if a couple has children, what is the probability that one of them is a girl and the other one is a boy?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So in example number two, both of them should have been female."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now we want one girl and one boy."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "The question is what exactly is the probability?"}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's take a look at the following diagram."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "The following pun and square to basically calculate what the probabilities are, first we actually have to apply the product rule."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So let's say this is event number one and let's suppose that we have so this is our boy and girl and then we have boy and a girl."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So once again we have a probability of one half here, a probability of one, one half here."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Sorry if it's sloppy."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "So we have one half here, one half here."}, {"title": "Sum and Product Rule in Genetics .txt", "text": "Now if we combine this, we get a boy and a boy."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Side of the enzyme."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So summing these two values gives us the total amount of S found inside our beaker."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "But because initially when we add a substrate, this quantity is so much smaller than this quantity because very little of that substrate is actually bound onto the substrate, if this is very small compared to this, then this by itself is approximately equal to this."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "For example, if this is, let's say, 1 million and this is, let's say 999,999, then this is very small and this is approximately equal to this."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so that's where we get this result."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so what that means is in equation five, we can leave as it is what's up with this marker?"}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "One moment."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Okay, so based on six, what that means is we can leave this S as it is because initially at the beginning, the total concentration of S as total is equal to the concentration of S that is not bound to the enzyme because this quantity is very, very small."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now, let's move on to equation seven."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So by the same analogy, we see that the total enzyme inside our mixture is equal to the enzyme that is not bound to the substrate plus the enzyme that is bound to the substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now, the same thing essentially what we assumed just a moment ago, we cannot assume for the enzyme case."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And that's because the concentration of the enzyme is usually much, much smaller than the concentration of the substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "For instance, we can have a million of the substrate molecules, but only 100 of the enzyme molecules."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so what that means is we can no longer make the assumption that this is much smaller than this."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so in this particular case, we actually have to leave the equation as it is."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now we want to use equation seven to basically replace this quantity in terms of the total amount of enzyme and the enzyme substrate concentration."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so what we want to do is we want to use equation seven and solve for this quantity here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Remember, in this case, because of what we did in equation six, this is simply this here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "This does not change, but we want to change e and replace it with something that contains Es."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so we take equation seven, we rearrange equation seven and solve for this."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "We get that the concentration of the enzyme that is not bound to anything is equal to the total enzyme concentration minus the enzyme concentration that is bound to our substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And now we take equation five and replace this quantity with this here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so we get the following result."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now we take this equation, we multiply this out and we solve for the enzyme substrate complex concentration because now we have this term appearing on the left side and this term appearing on the right side."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So we want to solve for this enzyme substrate concentration and we get the following result."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So the enzyme substrate concentration is equal to the total enzyme found inside the midstrip multiplied by the substrate concentration divided by Km."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "This constant we defined here plus the concentration of the substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So now we take this equation."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So remember, let's go back to this equation one."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So this equation here is the equation that describes the V knot that we actually want to solve for."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So we want to have an equation in which the Y value is the V naught, but the X value is the substrate concentration."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And that's precisely why we want to replace this quantity."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So now in this equation we can take this and replace the Es with the right side of this equation."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And that's exactly what we get here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And we call this equation eight."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So we take this, we plug that into here and we get the following result."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now, the final thing that we want to ask ourselves is the following."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So what exactly is the VMAX?"}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So the VMAX is the maximum velocity of that enzyme."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "It's the maximum rate at which the enzyme can operate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And to obtain the maximum rate, all the active sides on all the enzymes have to be occupied with the substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And what that means is the V max."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So this Y value here is equal to so if we use this equation, K two multiplied by well, what has to be the concentration of this for this to be the VMAX?"}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Well, when the enzyme substrate complex."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So when all the active sites are occupied, that means this quantity, the concentration of this will equal to the total concentration of the enzyme."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And that can be seen from this particular equation seven."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So in this equation we see that when this value is equal to zero, that means all the enzymes active sites are filled with a substrate, because when this is equal to zero, this will equal to this."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so what that means is the V max is equal to K two multiplied by the maximum value of the enzyme substrate complex concentration."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And this maximum value can be a maximum of E total."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So we replace this with this quantity here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And so we see that the maximum rate at which the velocity operates is equal to K two multiplied by the concentration of enzyme where all the enzymes active sites are filled with the substrate."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And if we take this equation and solve for if we solve for E total, we basically get E total is equal to D max divided by K two."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And now we take equation eight and we replace E total with V max divided by K. If we plug this into here, the K two s will cancel and we're left with this equation here."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So V Naught, which is the Y value on the following curve, is equal to V max, which is basically this maximum Y coordinate multiplied by the concentration of the substrate S divided by Km plus the concentration of substrate S and this is the equation that describes this blue curve."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And notice in this equation, v max is a constant."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "It's simply this quantity that depends on the height of this red line."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Km is also constant."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "It depends on these three rate constants of the three equations that we described a moment ago."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And this S is simply the x value on the following coordinate plane."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "So the x is simply the concentration of the S. And this is exactly what we basically want to derive in the first place."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "This equation is known as the Michael's mental equation."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "And the Mcales Mental equation is basically used in enzyme kinetics to study the rates at which enzymes actually operate and act on different types of biological reactions."}, {"title": "Derivation of Michaelis Menten-Equation Part II .txt", "text": "Now, in the next lecture, we're actually going to study the meaning behind this equation, what this equation actually tells us about how enzymes behave and how enzymes act and operate on chemical reactions."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "The human skeletal system consists of different types of bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "In fact, the adult human skeletal system consists typically of 206 different bones and all these different types of bones can be categorized into five groups."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And that means the human skeletal system only contains five different types of bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So let's discuss what these five different groups are, are what these five different types of bones are."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Let's discuss their function and then let's take a look at the following diagram and let's place some of these bones into their correct group."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So let's begin with the long bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "The long bone is called the long bone because they're much longer than they are wide."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And the long bone consists of three different sections."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "We have our epiphysis, the metaphysis and we have our diaphysis."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now the epithesis contains our spongy bone, also known as the cancellus bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And this contains our red bone marrow that synthesize red blood cells."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now the metaphysis consists of an important section known as our epiphysical plate and this epiphysical plate is responsible for lengthening and elongating the long bone as the organism as the human actually grows."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now our diaphysis is the long shaft, the long curved shaft that contains our compact bone that basically is responsible for giving our bone its strongness."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So basically our long bones are capable of resisting very high tensile and compressive forces and that's exactly why these bones are responsible for supporting our body."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "In fact, the long bones support the majority of the body's weights."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So we have many different types of long bones in our bodies."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So let's take a look at the following diagram."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So we have the clavicle, also known as the collar bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So this bone here and this bone here, this is our example of a long bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now in the arm we have the humerus, the bone here and we have the two bones here, our radius and the ona, these are examples of long bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now if we examine our legs, the legs also contain long bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So we have the femur, which is the bone that is much stronger than concrete."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "We also have the tibia and our fibula and these are also examples of long bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, if we examine our fingers, the fingers specifically the metacarpals are also examples of long bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "But these are much smaller than these long bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So basically long bones can actually be very long or they can be very small."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So basically what the defining, what the definition of a long bone is?"}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "They are much longer than they are wider."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now let's take a look at the second type of bone known as our short bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So by definition, a short bone has the shape of a cube and that basically means they are as long as they are wide."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now they basically function by providing support as well as stability to other bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And these short bones do not actually move themselves."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now what are some examples of short bones?"}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Well, if we examine our wrist, the wrist contains bones known as the carpals, and these are examples of short bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, if we examine the ankles of our body, these contain the tarsils, which are also examples of short bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, let's move on to our flat bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So flat bones are those bones that are relatively thin and which contain a relatively high surface area."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, these bones can serve two important functions."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "They can either protect our internal organs and our tissues and they can also serve as attachment points for muscles because of their high surface area."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So they contain compact bone on the surface and in the middle, at the center, they contain spongy bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So what are some examples of flat bones?"}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So the skull, the cranium, is an example of flat bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So we have many of these flat bones that essentially fuse together as the organism becomes an adult, as the organism grows."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And the skull."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "These flat bones basically serve the purpose of protecting our brain, our internal organ."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, other examples of flat bones is the ribcage, as well as our sternum."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And this acts not only as attachment points for muscles, but they also basically act to protect the heart, the lungs, as well as the vascular tissue found in this region here."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, other examples of our flat bones is our scapula."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So this is the shoulder blade bone, this bone and this bone here, as well as the pelvis, which is the bone of the hip."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "These are examples of flat bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "They have a relatively large surface area and they are relatively flat, relatively thin."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now let's move on to our irregular bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So basically, these are the bones that have a certain unique shape that we cannot actually label as long bones, short bones, or flat bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So these bones have unique shapes that help them carry out certain types of unique function."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So typically, our irregular bones consist of bull compact as well as spongy bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So they have spongy bone at the center and compact bone, usually on the surface."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And they function in protection as well as in support."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So one example of our irregular bone is our maxilla, or our maxilla as well as the mandible."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So these two bones have an irregular shape."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "The maxilla is the upper jaw bone, the mandible is our lower jaw bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And these function to basically allow us to eat and ingest our food that we need to actually survive."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, another example of an irregular bone is basically our sacrum."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So this is this bone here."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "A third example are the vertebrae."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So we have the cervical and the lumbar vertebrae."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And these are basically responsible in protecting our spinal cord."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So these vertebrae basically surround and protect our spinal cord."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So the regular bones are bones that have unique shapes that do not fit these categories."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And these shapes help them serve their specific purpose."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So they have compact bone and spongy bone and fungus protection and support."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Some examples include our sacram, the mandible, the maxilla and our vertebrae."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, the final type of bone we're going to examine is a sesamoid bone."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So all humans typically contain one sesame bone, and that's basically our patella."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, the patella, or by definition, our sesamoid bone, is a bone that is in the shape of a sesame seed."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And the sesame bones, or sesame bone, basically grows on our tendon."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "So basically, the patella is found on the tendon found in this region."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "Now, as the organism grows, as the person grows, we can basically, basically grow other types of bones that are sesame bones."}, {"title": "Long Bones, Short Bones, Flat Bones, Irregular Bones .txt", "text": "And these bones develop usually as a result of some type of consistent physical stress or physical frictions."}, {"title": "Centrosome and Centrioles.txt", "text": "In our discussion on the cytoskeleton of Eukaryotic cells we briefly mention a structure known as the centrosome."}, {"title": "Centrosome and Centrioles.txt", "text": "But what exactly is the centrosome and what are its functions?"}, {"title": "Centrosome and Centrioles.txt", "text": "These are the questions that we're going to address in this lecture."}, {"title": "Centrosome and Centrioles.txt", "text": "So the centrosome is our Microcubial Organizing Center of Eukaryotic cells, also known as as MTOC."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, one centrosome is found per Eukaryotic cells and only animal Eukaryotic cells have our centrosomes."}, {"title": "Centrosome and Centrioles.txt", "text": "Plant cells and fungi do not have centrosomes."}, {"title": "Centrosome and Centrioles.txt", "text": "They have other structures that are responsible for building microtubules, building and organizing microtubules."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, every single one of our centrosome in any given Eukaryotic animal cell consists of a pair of two centrioles that are oriented at a 90 degree angle with respect to one another."}, {"title": "Centrosome and Centrioles.txt", "text": "And these two centrioles are basically embedded in hundreds of proteins."}, {"title": "Centrosome and Centrioles.txt", "text": "So let's suppose this is our Eukaryotic animal cell."}, {"title": "Centrosome and Centrioles.txt", "text": "So this is our nucleus."}, {"title": "Centrosome and Centrioles.txt", "text": "And right next to our nucleus, we have the centrosome."}, {"title": "Centrosome and Centrioles.txt", "text": "So we have hundreds of proteins."}, {"title": "Centrosome and Centrioles.txt", "text": "In this space, we have a condensed mass of proteins."}, {"title": "Centrosome and Centrioles.txt", "text": "And inside that proteins we have two centrioles that are oriented at a 90 degree angle with respect to one another."}, {"title": "Centrosome and Centrioles.txt", "text": "And we also have these microtubules that permeate throughout the entire cell."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, what exactly is the function of our centrosome?"}, {"title": "Centrosome and Centrioles.txt", "text": "The centrosome basically functions in our cell cycle."}, {"title": "Centrosome and Centrioles.txt", "text": "It helps the cell divide."}, {"title": "Centrosome and Centrioles.txt", "text": "So during our interface of the cell cycle, we replicate our centrosome."}, {"title": "Centrosome and Centrioles.txt", "text": "And during our ProPhase, the centrosome basically migrates to both ends and then they create or extend those microtubules that grab our chromosomes and separate those chromosomes during cell division."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, the centrosome is also involved in organizing and creating and extending the microtubules that constitute our cytoskeleton."}, {"title": "Centrosome and Centrioles.txt", "text": "Remember, the cytoskeleton is basically the scaffolding of our cell."}, {"title": "Centrosome and Centrioles.txt", "text": "It gives the cell structure and it gives the cell its shape."}, {"title": "Centrosome and Centrioles.txt", "text": "And there are three different types of fibers and one of these fibers are our microtubial fibers."}, {"title": "Centrosome and Centrioles.txt", "text": "So within our centrosome, we have our centrioles."}, {"title": "Centrosome and Centrioles.txt", "text": "What exactly is a centriole?"}, {"title": "Centrosome and Centrioles.txt", "text": "So the centrosome contains a pair of centrioles that are a cylindrical array of nine triplep microtubules that are connected to one another by special protein connecting fibers."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, this pattern is commonly known as the nine to three microtubule pattern."}, {"title": "Centrosome and Centrioles.txt", "text": "And we see that the centrioles are simply specialized structures, specialized microtubial structures."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, what exactly is the structure of our centriole?"}, {"title": "Centrosome and Centrioles.txt", "text": "What exactly does it look like?"}, {"title": "Centrosome and Centrioles.txt", "text": "Well, it looks something like this."}, {"title": "Centrosome and Centrioles.txt", "text": "We have the top to bottom view of our centriole and the side view of the centriole."}, {"title": "Centrosome and Centrioles.txt", "text": "So we have 123-45-6789 triplets."}, {"title": "Centrosome and Centrioles.txt", "text": "Each one of these consists of not of three of these individual microtubules."}, {"title": "Centrosome and Centrioles.txt", "text": "And each one of these triplets is connected by our connective protein fiber."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, if we take this centriole and we flip it this way, we rotate it sideways, we get the following side view."}, {"title": "Centrosome and Centrioles.txt", "text": "So we have the nine triplets that are connected by these purple regions, our fibers."}, {"title": "Centrosome and Centrioles.txt", "text": "So now that we know what the centrosome is and what the centriole is."}, {"title": "Centrosome and Centrioles.txt", "text": "What exactly is the function of our centriole that are found within our centrosome?"}, {"title": "Centrosome and Centrioles.txt", "text": "So we have three very important functions."}, {"title": "Centrosome and Centrioles.txt", "text": "So function number one is basically what we mentioned earlier."}, {"title": "Centrosome and Centrioles.txt", "text": "The centrioles, which are found inside a centrosome are involved in cell division, in separating our chromosomes during our cell cycle."}, {"title": "Centrosome and Centrioles.txt", "text": "So centrioles are involved in the formation of mitotic spindle fibers during cell division."}, {"title": "Centrosome and Centrioles.txt", "text": "However, recent evidence shows that if we actually destroy our Centrios our cell cycle still takes place, mitosis still takes place."}, {"title": "Centrosome and Centrioles.txt", "text": "So basically, we can imagine that Centrios make our separation of chromosomes very efficient."}, {"title": "Centrosome and Centrioles.txt", "text": "However, they are not exactly necessary for mitosis to actually take place."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, what exactly is the second function of the centriole?"}, {"title": "Centrosome and Centrioles.txt", "text": "Well, basically, the centriole is our region that extends and creates those microtubules and microtubules compose our cytoskeleton."}, {"title": "Centrosome and Centrioles.txt", "text": "Now, the cytoskeleton is basically responsible for arranging and organizing the organelles found inside our cell."}, {"title": "Centrosome and Centrioles.txt", "text": "So we see that the placement of the centrils within the cell determines the position and location of the nucleus as well as the other organelles inside our body."}, {"title": "Centrosome and Centrioles.txt", "text": "And that's exactly why the centrosome that contains the centrioles is found right next to our nucleus."}, {"title": "Centrosome and Centrioles.txt", "text": "In fact, inside Neuron cells, the location of our centrosome basically determines into which direction the axon will grow on any given Neuron cell."}, {"title": "Centrosome and Centrioles.txt", "text": "So this makes sense because the microtubules are the largest and the thickest components, the thickest fibers of our cytoskeleton."}, {"title": "Centrosome and Centrioles.txt", "text": "Remember, the cytoskeleton is composed of three different types of fibers."}, {"title": "Centrosome and Centrioles.txt", "text": "We have microfilaments, intermediate filaments and our microtubules."}, {"title": "Centrosome and Centrioles.txt", "text": "And finally, the third function of the centriole."}, {"title": "Centrosome and Centrioles.txt", "text": "So the centrioles are responsible for forming the flagella and the cilia that our cells have."}, {"title": "Centrosome and Centrioles.txt", "text": "So one of the centrioles, remember, we have two centrioles."}, {"title": "Centrosome and Centrioles.txt", "text": "One centriole is called the daughter centriole."}, {"title": "Centrosome and Centrioles.txt", "text": "The other centriole is called the mother centriole."}, {"title": "Centrosome and Centrioles.txt", "text": "So it's the mother centriole that can develop into the basal body."}, {"title": "Centrosome and Centrioles.txt", "text": "And the basal body is basically the structure in the cell that is responsible for forming cilia as well as flagella."}, {"title": "Centrosome and Centrioles.txt", "text": "And cilia and flagella are two types of specialized structures that basically allow the cell to move."}, {"title": "Centrosome and Centrioles.txt", "text": "They mobilize the cell."}, {"title": "Centrosome and Centrioles.txt", "text": "So we see that although centrioles are not exactly necessary for the survivor of the individual cell the centrioles and centrosomes are necessary for the survival of the organism as a whole."}, {"title": "Centrosome and Centrioles.txt", "text": "For example, if we examine a specific type of cell that needs flagella our sperm cells."}, {"title": "Centrosome and Centrioles.txt", "text": "If our sperm cells do not have centrioles or centrosomes, they cannot form our basal body and they cannot form the flagella."}, {"title": "Centrosome and Centrioles.txt", "text": "And a sperm cell without a flagella will not be able to reach the target cell."}, {"title": "Centrosome and Centrioles.txt", "text": "And that means our organism will essentially die off."}, {"title": "Centrosome and Centrioles.txt", "text": "It will not survive, although maybe individually the cells will, in fact survive."}, {"title": "Morphogenesis.txt", "text": "Morphogenesis is the process by which the many individual cells within that developing embryo move around and organize themselves to eventually form the specialized and complex structures, organs and systems that make up that adult individual, that adult organism."}, {"title": "Morphogenesis.txt", "text": "Now, morphogenesis is stimulated by two different types of factors bichemical factors and mechanisms mechanical factors."}, {"title": "Morphogenesis.txt", "text": "Now, a chemical factor is simply a special type of chemical while a mechanical factor is simply a physical force that exists between our cells and these two factors basically play together."}, {"title": "Morphogenesis.txt", "text": "There is an interplay between these two factors that stimulates the process of morphogenesis."}, {"title": "Morphogenesis.txt", "text": "And as we'll see in just a moment these two different types of factors can basically influence the different types of processes that takes place within the cell and they can also influence the behavior of that cell."}, {"title": "Morphogenesis.txt", "text": "So a group of molecules that play a particularly important role in the process of morphogenesis are known as morphogens."}, {"title": "Morphogenesis.txt", "text": "So morphogens are these chemicals are these molecules that act as signal molecules and that can actually affect the behavior of the cell."}, {"title": "Morphogenesis.txt", "text": "For example, they can change the different types of processes that take place within the cell and they can actually cause that cell to migrate to move from one location to another location within that nearby developing tissue."}, {"title": "Morphogenesis.txt", "text": "Now, cells generally respond to morphogens based on the level or the concentration of that morphogen found in that local environment."}, {"title": "Morphogenesis.txt", "text": "And to see what we mean by that let's take a look at the following diagram."}, {"title": "Morphogenesis.txt", "text": "So we have cell number one and cell number two."}, {"title": "Morphogenesis.txt", "text": "Notice these cells on their membranes contain these special protein receptors that can actually bind these Morphins, these special signal molecules."}, {"title": "Morphogenesis.txt", "text": "Notice on the left side we have a much higher concentration of these morphogens than on the right side."}, {"title": "Morphogenesis.txt", "text": "And because we have many more of these mortgagen molecules around this cell these signal molecules will be much more likely to actually bind onto the receptor protein than on this cell."}, {"title": "Morphogenesis.txt", "text": "And so the different types of processes that takes place inside this cell will be different than inside this cell as a result of the binding of that mortgagen onto the protein cell receptor on that membrane."}, {"title": "Morphogenesis.txt", "text": "Now, the question is what usually happens when the mortgagen actually binds onto that protein receptor?"}, {"title": "Morphogenesis.txt", "text": "So when the binding takes place usually a type of molecule known as a transcription factor is activated inside that cell."}, {"title": "Morphogenesis.txt", "text": "And that transcription factor which is usually a protein itself basically goes into the nucleus of that cell and it binds onto a special region on the DNA."}, {"title": "Morphogenesis.txt", "text": "And by binding onto the DNA it can either activate it can either turn on or turn off the expression of some particular type of gene."}, {"title": "Morphogenesis.txt", "text": "So for example, let's suppose this morphin binds onto this protein membrane that activates some type of transcription factor and then that transcription factor moves into the nucleus it binds onto the DNA and it activates some sort of gene."}, {"title": "Morphogenesis.txt", "text": "And by activating that gene, it creates some sort of specific protein."}, {"title": "Morphogenesis.txt", "text": "Now, the subsequent protein that is created can either do one of three different things."}, {"title": "Morphogenesis.txt", "text": "It can actually change the composition of different types of proteins found on the cell membrane of that cell."}, {"title": "Morphogenesis.txt", "text": "And that can essentially affect the process of cell to cell adhesion."}, {"title": "Morphogenesis.txt", "text": "And cell to cell adhesion is the process by which cells bind and attach to other cells."}, {"title": "Morphogenesis.txt", "text": "So let's focus for now on cell adhesion."}, {"title": "Morphogenesis.txt", "text": "So cells can bind to one another by using a special type of molecule found on the membrane known as the cell adhesion molecule or CA M. Now, it turns out that morphogens can influence the way that cells attach to other cells by expressing different types of calm molecules on the membrane of those cells."}, {"title": "Morphogenesis.txt", "text": "In fact, it turns out that the reason one cell binds to another cell is because they have the same type of Cam molecules."}, {"title": "Morphogenesis.txt", "text": "So cells tend to aggregate and form groups because they contain the same exact cell adhesion molecule on the membrane."}, {"title": "Morphogenesis.txt", "text": "So we see that cells tend to bind only to those cells that have the same type of cell adhesion molecule."}, {"title": "Morphogenesis.txt", "text": "And this means that the Cam molecule can actually influence the formation of different types of groups of cells and that can lead to the formation of different types of tissues."}, {"title": "Morphogenesis.txt", "text": "For example, we have these blue cells and we have these purple cells."}, {"title": "Morphogenesis.txt", "text": "These purple cells form a group of their own because they have one type of cell adhesion molecule, while the blue cells form a group of their own and bind together because they have a completely different type of cell adhesion molecule."}, {"title": "Morphogenesis.txt", "text": "Now, this process, for example, plays an important role in the formation of the gastrolo stage."}, {"title": "Morphogenesis.txt", "text": "So during gastrolation, our morphogens influence the type of cell to cell adhesion molecules that are found within our cells."}, {"title": "Morphogenesis.txt", "text": "And to see what we mean, let's take a look at the following diagram."}, {"title": "Morphogenesis.txt", "text": "So this is basically our blastula stage."}, {"title": "Morphogenesis.txt", "text": "So we have the trophy blast cells and we have these inner cell mass that are shown in blue."}, {"title": "Morphogenesis.txt", "text": "Now, when we go from our blastula to our gastula, what begins to happen is these blue cells that are part of the inner cell mass not only undergo cell differentiation, they don't only form two different types of cells, but they also begin to move away from one another."}, {"title": "Morphogenesis.txt", "text": "And to move away from one another, they have to detach from one another."}, {"title": "Morphogenesis.txt", "text": "And to detach from one another, what must happen is these morphogens must bind onto the cell membrane, causing the breakdown of these special types of cell membrane molecules known as cell adhesion molecules."}, {"title": "Morphogenesis.txt", "text": "And by decreasing the amount of cell adhesion molecules between these cells, these cells are able to actually detach from one another and they can move away from one another once they actually detach."}, {"title": "Morphogenesis.txt", "text": "And so, by decreasing the amount of cell adhesion molecules, we can eventually form these two structures."}, {"title": "Morphogenesis.txt", "text": "So remember, this eventually forms the Umbilical vesicle, also known as our yolksack."}, {"title": "Morphogenesis.txt", "text": "And this eventually forms the blue cells eventually form our Ambion in which we have the actual embryo that developing embryo."}, {"title": "Morphogenesis.txt", "text": "So Saladesian is a very important process that takes place within morphogenesis and cell to cell adhesion is affected by these morphogens."}, {"title": "Morphogenesis.txt", "text": "Now, what about the other thing that these proteins can actually do?"}, {"title": "Morphogenesis.txt", "text": "So aside from affecting the way that cells actually adhere to one another, these proteins can also change the composition of the extracellular matrix that is found around the cell."}, {"title": "Morphogenesis.txt", "text": "Now, what has the extracellular matrix have to do with the process of morphogenesis?"}, {"title": "Morphogenesis.txt", "text": "Well, basically the entire purpose and function of the extracellular matrix is basically one of two things."}, {"title": "Morphogenesis.txt", "text": "What it does is it separates the different types of cells."}, {"title": "Morphogenesis.txt", "text": "So by producing this extracellular matrix, which consists of different types of protein proteins such as for example, collagen, this cell is separated from this cell."}, {"title": "Morphogenesis.txt", "text": "Now, the other purpose of the matrix is to basically create a system of roads that ultimately allows a cell to move or migrate from one location to a different location."}, {"title": "Morphogenesis.txt", "text": "So by creating a different types or by changing the composition of the matrix, that ultimately allows the formation of some type of roadway system that allows a cell to move from one location to a different location."}, {"title": "Morphogenesis.txt", "text": "So when the mortgage and binds onto the protein receptor it can stimulate that cell to produce a special type of protein that is found inside the extracellular matrix that can ultimately influence the movement of that cell."}, {"title": "Morphogenesis.txt", "text": "Now, the last important part is the fact that these proteins produced as a result of the binding of the mortgagen can also influence the way that the cell actually contracts."}, {"title": "Morphogenesis.txt", "text": "It can influence the shape and the size of that cell."}, {"title": "Morphogenesis.txt", "text": "For example, special types of cells can produce special types of proteins known as myosin and actin."}, {"title": "Morphogenesis.txt", "text": "And when myosin and actin, which are found in muscle cells, contract, they cause those cells to actually contract."}, {"title": "Morphogenesis.txt", "text": "And by contracting, what those cells do is they create mechanical forces, these physical forces that can act on nearby cells."}, {"title": "Morphogenesis.txt", "text": "And by exerting some type of mechanical force on a nearby cell, what that can do is it can basically stimulate the process of not only morphogenesis, but also cell determination, cell differentiation, as well as cell growth and cell proliferation."}, {"title": "Morphogenesis.txt", "text": "So we see that morphogens can also stimulate the expression of contractile proteins such as actin and myosin."}, {"title": "Morphogenesis.txt", "text": "Now, the contraction of these proteins can change the shape and size of the cell and this can exert a force on nearby cells and that can ultimately influence things like gene expression, cell determination, cell differentiation and morphogenesis."}, {"title": "Morphogenesis.txt", "text": "So we see that morphogenesis is stimulated by not only these chemical factors, but also these mechanical factors."}, {"title": "Morphogenesis.txt", "text": "And more specifically, when these morphogens influence the processes inside the cell."}, {"title": "Morphogenesis.txt", "text": "Normally the process that is stimulated is gene expression."}, {"title": "Morphogenesis.txt", "text": "And by producing these proteins inside the cell, these proteins can either change the cell to cell adhesion properties, the composition of that matrix, or the ability of that cell to contract and as a result, to form those mechanical forces to exert those mechanical forces that also influence the process of morphogenesis."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "In prokaryotic cells such as bacterial cells, once we synthesize the mRNA molecule, that mRNA molecule will consist of a continuous sequence of codons that can be used by the ribosomes of that bacterial cell to synthesize a given polypeptide chain."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "In fact, because of this, because the mRNA molecule in prokaryote cells does not have to be modified in any way following the process of transcription, translation usually begins on that mRNA molecule before it is actually synthesized."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And this is in contrast to how it takes place inside our cells, inside eukaryotic cells, so inside bacterial cells and many other prokaryotic cells translation the process of protein synthesis begins on that mRNA molecule before that mRNA molecule is actually completely synthesized."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And that's because the newly synthesized mRNA molecule in prokaryotic cells consists of a continuous sequence of codons."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So if blue means we have these codons, then the entire mRNA molecule in prokaryotic cells consists of this blue region because these blue regions are the codons that express that particular sequence on the polypeptide chain."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now, for quite some time we thought the same exact thing was true in eukaryotic cells such as human cells."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "But in 1977, Philip Sharp and Richard Roberts basically discovered that this was not true when it came to mRNA in eukaryotic cells."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "In fact, in eukaryotic cells the newly synthesized mRNA molecule consists of these intron sections, these sequences of nucleotides that do not code for any protein and they also contain these exons which were the regions that contained the codons that did code for that particular polypeptide chain."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So instead of looking like this one, instead of having a continuous blue section, the mRNA molecule and eukaryotic cells, such as our own human cells consist of these intervening sections known as introns."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "In fact, the int means intervening sequence of nucleotides."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So we have 1234 green regions, the introns in this particular mRNA and we have 12345 of these exons that contain the codons that will be used by the ribosomes to basically synthesize our polypeptide."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So the major difference between these prokaryotic cells and eukaryotic cells is that our eukaryotic mrnade, once it is synthesized, it contains these introns and therefore it cannot be used directly to synthesize the proteins."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "It has to be modified and these introns have to be removed while the exons have to be glued, split together before that ribosome can actually synthesize the protein."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And this is not true in prokaryotic cells because they don't contain the introns."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And that's exactly why transcription and translation can take place at the same exact time as we'll discuss in more detail in future lectures."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now, on average in humans, a human gene contains about eight intros."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "But for those genes that are very, very large, for example, tens of thousands of nucleotides long, we can have as many as hundreds of these intros in a given gene."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now, the question is once the eukaryotic cell actually synthesizes this premRNA molecule, so this mRNA molecule that is not in its fully functional and modified form is commonly known as the precursor mRNA, the pre mRNA or the primary mRNA."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And so once we form the primary mRNA molecule how exactly do we modify this molecule and at what stage do we actually take out these introns?"}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Well, basically within our cell we have this complex of special proteins and special RNA molecules that aggregate and combine together to form a complex, a structure known as a splicosome."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And the splicosome is responsible for essentially locating these introns, removing the introns while at the same time gluing together splicing together those exons."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And this can be seen in the following diagram."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now on top of essentially removing the introns these mRNA molecules in our cells and other eukaryotic cells are modified in two other ways."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "We basically cap the beginning with a special type of nucleotide sequence and that's called the capping process."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And at the end of that mRNA we add an additional sequence that consists of a polyadenosine nucleotides as shown in the following diagram and we'll discuss what that means and what that is used for in more detail in a future lecture."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "In this lecture we're simply going to introduce the fact that in prokaryotic cells we don't have this process taking place but in eukaryotic cells we do have the process of mrname modification."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So as soon as we synthesize that particular mRNA that mRNA is known as the primary mRNA, the precursor mRNA or the pre mRNA molecule."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And it consists of these introns shown in green and the exons shown in blue."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So let's call this exon number one, exxon number two and exxon number three."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now first we basically create these two modifications."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "We cap our five end and we basically add the polya tail on the other end of that particular mRNA molecule."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And what this basically allows that mRNA molecule to do is it prevents the mRNA molecule from being broken down and it also allows it to basically reach that final destination."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And we'll discuss more about that in a future lecture."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now once we cap this end and once we add that tail the next process is the splicing process."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So essentially this splicosome moves onto our molecule."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "It removes these introns by essentially noticing specific sequences at the beginning of the introns."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And by removing the introns it then basically connects these exons by forming the proper phosphor diastol linkages."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "And so eventually we form the following mature and fully functional mRNA molecule that now consists of only these coating regions that contain the codons that can be read by that particular ribosome and synthesize that polypeptide chain."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "Now notice that a common feature in the splicing process in the splicing mechanism is that the exons are actually ordered in the same sequential manner that the gene have those coding regions on the DNA molecule."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So initially we begin with exxon number one, exa number two, exxon number three and what we see here is exxon number one, followed by exxon number two, followed by exxon number three."}, {"title": "Exons and Introns of Eukaryotic mRNA.txt", "text": "So this is usually what we see in the process of splicing, and we'll discuss how this actually takes place and why these modifications actually exist in much more detail when we get into the process of transcription and translation."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "The final topic on hemorrglobin that I'd like to briefly focus on is how high altitude affects our body's ability to bring oxygen to the cells and tissues of our body."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So let's begin by focusing on the oxygen binding curve of hemorrglobin."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So as always, the x axis is the partial pressure of oxygen given to us in millimeters of mercury."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And the Y axis is the fractional saturation duration of hemoglobin."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And what the red curve describes is how much of that hemoglobin inside our blood is saturated with oxygen at some partial pressure value."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, we know that at sea level, the total atmospheric pressure is 760 mercury."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And because the amount of oxygen in the atmosphere is 21%, to find the partial pressure of oxygen, we simply multiply zero point 21 by the total pressure of 760."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that gives us about 159 mercury is the partial pressure of oxygen at sea level."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, as we begin to increase an altitude, for example, as we climb a mountain, what happens is the air becomes less dense."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So the distance between the gas molecules increases."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And what that means is we'll find less gas molecules in the same volume of space at a higher altitude."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, if the air becomes less dense, then the total pressure in the atmosphere decreases."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And if we multiply zero point 21 by a smaller total pressure, that gives us a smaller partial pressure of oxygen."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So if we increase the altitude, the partial pressure of oxygen in the atmosphere decreases."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, what exactly does that mean physiologically?"}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Well, what that means is the lungs will not be able to pump as much oxygen into the blood."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And if there's less oxygen circulating inside our blood, less oxygen will be delivered to the cells and tissues of our body."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that is a problem because the cells need oxygen to produce ATP molecules in an efficient way."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And these ATP molecules are used as energy molecules to carry out all the different types of processes that take place inside the cells and inside our body."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, what our body does immediately is it increases the rate at which we breathe, so it increases the ventilation rate."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And this is known as hyperventilation."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And it also puts stress on the heart by increasing the rate at which the heart actually pumps."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, although these are useful immediately, they're not very useful in the long term because this puts a lot of stress on the heart."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So these responses, although they're effective immediately, they're not actually very safe and they're not very effective."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And so a much more safer and a much more effective and efficient way, a much more long term response is to actually increase the concentration of a molecule we call 23 BPG."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And we'll see why that is in just a moment."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And ultimately, what our body wants to do at a high altitude is it wants to increase the number of hemoglobin molecules inside our blood and also increase the number of red blood cells found in our cardiovascular system."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, the question that I want to answer in this lecture is why does our body actually want to increase the number of two three BPG molecules?"}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Well, recall that two three BPG, two three biphosphoglycerate are allosteric effectors of hemoglobin."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And what that means is they can bind into the center pocket found in hemoglobin."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Now, by binding to the center pocket of two three of the deoxyhemoglobin, the two three BPG stabilizes the T state of that deoxy hemoglobin molecule and that lowers deoxy hemoglobin's affinity for oxygen."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that means this entire curve is shifted to the right side."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So if we examine this curve, the red curve describes this initial curve and the blue curve describes a few days following the exposure to high altitude."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that's when the concentration of two three BPG increases."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So by increasing two three BPG, we basically shift the entire curve to the right side and that decreases definitive of hemoglobin for oxygen."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And what that means is if hemoglobin is less likely to be bound to oxygen at a partial pressure of 20 mercury, which is the partial pressure inside our exercising tissue, this point on the blue curve will have a lower Y value than the red curve."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And what that means is more of the hemoglobin will basically unload and release that oxygen to the tissue."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So the red curve describes a Y coordinate of, let's say about 00:32."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And this describes the blue curve describes a cordon point of about 0.1."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "There's a difference of 22% according to this graph."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that means 22% of the hemoglobin will unload the oxygen in size."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "This situation when we have a higher percentage of two three BPG, a higher concentration of two three BPG inside our blood."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "So how will increasing the amount of two three BPG affect the oxygen binding curve?"}, {"title": "High Altitude and 2,3 BPG.txt", "text": "Well, it will shift the curve to the right, as seen in the following diagram."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And this will decrease the finity of hemoglobin for oxygen."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And this means that hemoglobin will be able to unload and deliver more oxygen to the tissues."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And that's exactly why at high altitudes, our body wants to increase the concentration of two three BPG over time because we don't want to continually put more stress on the heart and cause it to basically increase the rate at which it pumps."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "We want to keep that rate the same."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And to do that, we have to affect hemoglobin in other ways."}, {"title": "High Altitude and 2,3 BPG.txt", "text": "And the way that we affect them is by increasing the concentration of two three BPG."}, {"title": "Secondary Transporters .txt", "text": "So far in our discussion of membrane pumps, we focus on pumps that utilize ATP molecules directly."}, {"title": "Secondary Transporters .txt", "text": "So we focused on two types of ATPases."}, {"title": "Secondary Transporters .txt", "text": "We discussed ptype Atpas, and we also discussed ABC transporter."}, {"title": "Secondary Transporters .txt", "text": "So these are both Atpas, and what that means is they're membrane pumps that break down ATP molecules directly directly and use the energy that is stored within the chemical bonds of the ATP molecules to move other molecules and ions against their electrochemical gradients."}, {"title": "Secondary Transporters .txt", "text": "Now, not all membrane pumps actually utilize ATP molecules directly."}, {"title": "Secondary Transporters .txt", "text": "And membrane pumps that don't break down ATP directly yet are able to actually move molecules and ions against their electrochemical gradients are known as secondary transporters."}, {"title": "Secondary Transporters .txt", "text": "So another important category of membrane pumps are the secondary transporters."}, {"title": "Secondary Transporters .txt", "text": "And as we'll see in just a moment, there are two types."}, {"title": "Secondary Transporters .txt", "text": "So we see that secondary transporters are these transmembrane pumps that do not actually break down ATP molecules directly."}, {"title": "Secondary Transporters .txt", "text": "Instead, what they do is they use an established electrochemical gradient of one molecule to move a different molecule against its electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "So we see that they couple non spontaneous flow of one molecule or ion with a spontaneous flow of a different molecule or ion."}, {"title": "Secondary Transporters .txt", "text": "So we have two types of secondary transporters."}, {"title": "Secondary Transporters .txt", "text": "We have antiporters, also known as exchangers, and we have Simporters, also known as co transporters."}, {"title": "Secondary Transporters .txt", "text": "So let's begin by focusing on antiporters."}, {"title": "Secondary Transporters .txt", "text": "And let's take a look at this diagram."}, {"title": "Secondary Transporters .txt", "text": "So we have the membrane."}, {"title": "Secondary Transporters .txt", "text": "Let's say this is the outside and this is the inside of the cell."}, {"title": "Secondary Transporters .txt", "text": "So we only have two types of molecules that we're going to consider."}, {"title": "Secondary Transporters .txt", "text": "We have the purple molecules and we have these orange molecules."}, {"title": "Secondary Transporters .txt", "text": "Now, let's say on the outside of the membrane, we have a high concentration of these purple molecules and a high concentration of these orange molecules."}, {"title": "Secondary Transporters .txt", "text": "On the inside, we have a low concentration of the purple and a low concentration of these orange molecules."}, {"title": "Secondary Transporters .txt", "text": "Now, what this antiporter basically does is it allows these purple molecules to naturally move down its electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "So from the high concentration to the low concentration."}, {"title": "Secondary Transporters .txt", "text": "And this doesn't actually require energy."}, {"title": "Secondary Transporters .txt", "text": "In fact, it gives off energy and that free energy that is given off when the purple molecules move down, their electrochemical gradient is captured and is used to basically move these other molecules."}, {"title": "Secondary Transporters .txt", "text": "So we have these orange molecules against their electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "So we move them from the inside to the outside."}, {"title": "Secondary Transporters .txt", "text": "So we see that an antiporter or antiporters use the electrochemical gradient of one molecule to move a second type of molecule in the opposite direction against its electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "And we call them anti Porters because they move in opposite direction."}, {"title": "Secondary Transporters .txt", "text": "So this one, the purple one, moves in this direction, the orange one moves in the opposite direction."}, {"title": "Secondary Transporters .txt", "text": "Now let's look at Simporters."}, {"title": "Secondary Transporters .txt", "text": "So SIM Porters, also known as co transporters, are basically the same exact type of transmembrane protein, except they move in the same direction."}, {"title": "Secondary Transporters .txt", "text": "So simporters use the spontaneous flow of one molecular ion to move a different molecular ion in the same direction against its electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "And so to visualize that, let's take a look at this diagram."}, {"title": "Secondary Transporters .txt", "text": "So let's say we have our membrane, this is our Simporter, the outside, the inside of the cell."}, {"title": "Secondary Transporters .txt", "text": "So now what we have is a reverse of these orange concentrations."}, {"title": "Secondary Transporters .txt", "text": "So we have the high concentration of purple outside, a low concentration of purple on the inside, as in this particular case."}, {"title": "Secondary Transporters .txt", "text": "But now we have a high concentration of these orange ones on the inside and a low concentration of the orange ones on the outside."}, {"title": "Secondary Transporters .txt", "text": "And because of this reversal, we see that the orange arrow will point in the opposite direction, as with respect to this case."}, {"title": "Secondary Transporters .txt", "text": "And that happens to be in the same direction as the purple arrow."}, {"title": "Secondary Transporters .txt", "text": "So basically what it does is it allows."}, {"title": "Secondary Transporters .txt", "text": "So this Simporter, also known as a co transporter, allows the spontaneous movement of these purple molecules down the electrochemical gradient that releases free energy."}, {"title": "Secondary Transporters .txt", "text": "That free energy is captured by this importer and it is used to move these orange molecules against electrochemical gradient from a low to a high concentration, from the outside to the inside in the same direction."}, {"title": "Secondary Transporters .txt", "text": "And so that's why we call them co transporters, simporters."}, {"title": "Secondary Transporters .txt", "text": "In this case, they're called anti porters or exchangers, because they move in opposite directions."}, {"title": "Secondary Transporters .txt", "text": "Now, to demonstrate a specific example, let's take a look at a very common type of Simporter."}, {"title": "Secondary Transporters .txt", "text": "So, co transporter that we find in the membranes of E. Coli cells."}, {"title": "Secondary Transporters .txt", "text": "And by the way, prokaryotic organisms as well as eukaryotic organisms have these secondary transporters."}, {"title": "Secondary Transporters .txt", "text": "But to demonstrate, we're going to look at a type of secondary transporter that we find in prokaryotic cells, equalize cells."}, {"title": "Secondary Transporters .txt", "text": "So this is called lactose permeates."}, {"title": "Secondary Transporters .txt", "text": "So this example we're going to look at is known as lactose permease."}, {"title": "Secondary Transporters .txt", "text": "So lactose permeates is an example of a symporter, a cotransporter found in E. Coli cell membranes."}, {"title": "Secondary Transporters .txt", "text": "A structure consists of two six membranespanic, alpha helices, and these are combined to form this simpler."}, {"title": "Secondary Transporters .txt", "text": "So let's take a look at the following diagram to basically see the general idea of what it actually does."}, {"title": "Secondary Transporters .txt", "text": "So we have the equalized cell membrane."}, {"title": "Secondary Transporters .txt", "text": "Let's say this is the outside and this is the inside of the cell."}, {"title": "Secondary Transporters .txt", "text": "So what these ecoly cells basically do is they break down fuel molecules."}, {"title": "Secondary Transporters .txt", "text": "So they oxidize fuel molecules at the same exact time."}, {"title": "Secondary Transporters .txt", "text": "When they use energy to break down these fuel molecules, they establish an electrochemical gradient of protons, hydrogen ions, and what they establish is a gradient in which we have a high outside concentration and a low inside concentration."}, {"title": "Secondary Transporters .txt", "text": "And so what happens is we have this Simporter shown here in green, and it allows the spontaneous movement of these protons from the outside to the inside."}, {"title": "Secondary Transporters .txt", "text": "Free energy is released."}, {"title": "Secondary Transporters .txt", "text": "That free energy is taken in and is used to basically transfer sugar molecules, in this case lactose molecules."}, {"title": "Secondary Transporters .txt", "text": "And we have a higher concentration of lactose on the inside than on the outside."}, {"title": "Secondary Transporters .txt", "text": "And so we move them against electrochemical gradient."}, {"title": "Secondary Transporters .txt", "text": "We use that free energy to move it against from the outside to the inside."}, {"title": "Secondary Transporters .txt", "text": "And so this is what the general idea of what lactose permeates actually does."}, {"title": "Secondary Transporters .txt", "text": "But what exactly are the specifics, what is the action mechanism?"}, {"title": "Secondary Transporters .txt", "text": "Well, let's take a look at the following six diagrams, beginning with diagram one."}, {"title": "Secondary Transporters .txt", "text": "So again we have our equalized cell membrane."}, {"title": "Secondary Transporters .txt", "text": "This is our lactose permeates."}, {"title": "Secondary Transporters .txt", "text": "It consists of these two halves where each half consists of six membranespanic, alpha helices to form a total of twelve membrane spanning alpha helices."}, {"title": "Secondary Transporters .txt", "text": "So we have one half and the other half."}, {"title": "Secondary Transporters .txt", "text": "Now, this is the outside, the inside of our cell."}, {"title": "Secondary Transporters .txt", "text": "So basically what happens is in this particular diagram we see that we have this space, a cavity in the inside portion of that particular transmembrane pump."}, {"title": "Secondary Transporters .txt", "text": "And notice in this particular state it is open to the outside of the cell."}, {"title": "Secondary Transporters .txt", "text": "So what happens is, because it's open to the outside, we have these hydrogen ions, protons which can enter this cavity."}, {"title": "Secondary Transporters .txt", "text": "And when one of these enters the cavity, the positive charge basically interacts with a negative charge found on some type of side chain group of an amino acid."}, {"title": "Secondary Transporters .txt", "text": "So for instance, it can interact with the CEO O negatively charged side chain group and it forms a bond."}, {"title": "Secondary Transporters .txt", "text": "And so now we move on to this particular state."}, {"title": "Secondary Transporters .txt", "text": "So this is bound and by binding it basically creates some type of change that increases the affinity of this pocket for lactose or some other type of sugar."}, {"title": "Secondary Transporters .txt", "text": "So the lactose, which is a disaccharide by the way, moves into the pocket."}, {"title": "Secondary Transporters .txt", "text": "And once it moves into the pocket, as shown here, it basically creates overall conformational change that inverts the entire structure of that particular membrane protein."}, {"title": "Secondary Transporters .txt", "text": "And so now, instead of pointing this way, it inverts."}, {"title": "Secondary Transporters .txt", "text": "And this inversion, by the way, is also known as an eversion."}, {"title": "Secondary Transporters .txt", "text": "We basically, instead of opening to this side, we now are open to the other side."}, {"title": "Secondary Transporters .txt", "text": "So this is the inside or this is the outside, this is the inside of the cell."}, {"title": "Secondary Transporters .txt", "text": "And so in this state we see that now the membrane protein is open to the outside."}, {"title": "Secondary Transporters .txt", "text": "And so, in the next step, the lactose basically detaches, moves into the cell and by the same exact type of mechanism, then the h basically detaches and moves into the cell."}, {"title": "Secondary Transporters .txt", "text": "And once both of these two substances leave the internal cavity of that particular protein, it once again undergoes an aversion in which it inverts and forms back this particular structure."}, {"title": "Secondary Transporters .txt", "text": "And so, once we form back this particular structure, the cycle can basically repeat itself."}, {"title": "Secondary Transporters .txt", "text": "So we see what happens is in this secondary transporter, basically the free energy that is released when a molecule moves down its electrochemical gradient, in this case, the proton is actually used to drive the movement, the uphill movement of the lactose, in this case, against its electrochemical gradients."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the infamous equation that is continually used over and over in enzyme kinetics is the Michaelis Methane equation."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And this is that equation."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And what this equation does is it builds a relationship between the rate at which the enzyme operates on a certain substrate and the concentration of that substrate in that surrounding environment."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we plot the following equation on the x y axis, we get the following red curve and notice an important point about the red curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The red curve initially increases very rapidly, so essentially linearly."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And then the slope begins to decrease over time."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the slope begins to level off and it approaches a maximum value known as the v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "It approaches that value asymptotically."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's a very important mathematical term."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So what do we mean by a curve approaching a number asymptotically?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "What that means is every single time we increase the substrate concentration, the red curve gets closer and closer and closer to that VMAX value."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "But what it means to approach asymptotically is it never quite reaches it."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the red curve is never going to actually reach that VMAX quantity."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now that's problematic because we want to be able to calculate what v max actually is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And in fact, if we can't calculate what v max is, then we cannot calculate what the Km value is, the Macalus constant."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So remember, the Mikalus constant basically describes the affinity of that substrate for the active side."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And the Km value is the concentration of that substrate at which that enzyme operates at a velocity that is exactly half of that v max value."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we know what this y coordinate is, v max divided by two, then we can calculate exactly what the Km value is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "We simply draw a horizontal line until it hits the curve and then we draw a vertical line and that gives us the x coordinate, the Km value."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we can't calculate what v max is, because the slope never actually touches the v max value, then we can't calculate what v max divided by two is and therefore we cannot calculate what Km is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So back in the day before computers, we really had no way of using this graph to actually calculate what v max and Km is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So back in the day, instead of using this Mikhailis Methane equation in this form, we changed the equation into a slightly different form."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And what we did was we took the reciprocal of the left side and the right side of that equation."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now remember, in mathematics, if we have an algebraic equation and we change the right side and the left side in the same exact way, that does not actually change the information that the equation provides us with."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "It doesn't change the information."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "But what it does is it changes the way that that information is actually displayed."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the information from this particular equation basically gives us an asymptotic curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "But if we take the Reciprocal of both sides, we get a linear equation, we get a straight line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And now the same pieces of information, the Km value, the v max and so forth, is given to us in the form of a straight line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And a straight line is much more useful than this asymptotic curve, because a straight line can be used to actually calculate what Km is and what v max is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So instead of using the above Michaela's mental equation that gives us an asymptotic red curve, we can take the Reciprocal of the left and the right side to obtain a double Reciprocal curve, also known as the line weaver Bur curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we take this equation, we take the Reciprocal of v knot, we get one over v knot, we take the Reciprocal of this."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the top is v max multiplied by this, and the bottom is simply kara m plus the concentration of S. So if we reciprocate, this simply goes to the bottom."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the bottom becomes v max multiplied by the substrate concentration, and the top becomes Km plus the concentration of S. And now we essentially rearrange the equation, we distribute our denominator to this quantity and this quantity, and we get the following result."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And notice the concentration of the S cancels out on this second term on the right side of the equation."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And this equation has the same exact form as a straight line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So this left side one over v naught is the y axis."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So here's the y axis, the x axis, this is the x value of that line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the x coordinate is one divided by the concentration of S. The slope of the straight line is Km divided by v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the slope of the red line is km divided by v max, and the y intercept is one divided by v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So what this really tells us is the point where the curve intersects the y axis is the quantity one divided by v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we carry out our experiment, we collect the data points and then we plot the double Reciprocal curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "If we find what this y value is, so let's say it's 20, then we know that is equal to one divided by v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And if we solve for v max, we get that v max is equal to 0.5."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So that allows us to calculate exactly what the v max quantity is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Unlike in this case, where we had no way of actually determining what that v max is, because the curve never actually touches that v max quantity."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "What about the Km?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, notice that the red curve also touches intersects the x axis."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And if we basically let the left side of the equation equal to zero, we can solve for what the x axis is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The x axis is equal to negative of one divided by Km."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so if we find exactly what the x value is, again, let's suppose, I don't know, it's negative two."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Then we set negative two equal to negative one over Km, and we find that Km is equal to zero five."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And in this manner, we can calculate exactly what the v max value is and what the Km value is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "In addition, if we know any two points on the curve, we can calculate what the slope is."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The slope is simply Km divided by v max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So this double reciprocal plot is a very useful way to basically determine exactly what these quantities is, what these quantities are."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And these quantities can be used to basically study the way that enzymes increase the rates of different types of chemical reactions."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, in addition to this usefulness, there is one other important application of the double reciprocal plot."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "We can also actually use a double reciprocal plot to basically differentiate between the three different types of reversible inhibitors."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Remember, we have competitive inhibitors, we have uncompetitive and we have non competitive."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And we can use the double reciprocal plot, as we'll see in just a moment, to basically differentiate between which type of inhibitor is actually present in our mixture."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So let's begin by discussing how a competitive inhibitor will actually affect this double reciprocal curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the red curve describes the curve in the absence of that competitive inhibitor, and the purple curve describes that curve in the presence of that inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So notice what happens in the presence of the inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The slope is greater, the Y intercept is the same, and the X intercept is less negative."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "It's closer to that origin."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The question is why?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, let's recall how this type of competitive inhibitor actually affects the kinetics of enzyme."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So remember, a competitive inhibitor binds exactly into the same location, the same active side, as the substrate does."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And because it binds reversibly, we can simply increase the concentration of the substrate to basically replace and kick out that inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so, ultimately, the v max value is not changed."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And if the v max isn't changed, because one divided by v max is that Y coordinate value, it's that location where the curve intersects the Y axis."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Both of these curves will intersect the same exact coordinate value because this VMAX does not change."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so one or a VMAX also will not change."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, what is affected by a competitive inhibitor?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, the Km value is affected."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Remember, in the presence of a competitive inhibitor, the affinity of that substrate for the active side decreases."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so we have to increase the concentration of S to basically get all those active sites occupied with that substrate."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so Km will actually increase."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, if Km increases, then because the slope of the line is Km divided by VMAX, VMAX will not change, km increases."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so the ratio Km divided by VMAX also increases."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's precisely why the slope of the purple one purple line is greater than the slope of that red line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And finally, because the Km increases, this one divided by K ratio will essentially decrease."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so this X coordinate, the X intercept, will be closer to that origin."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so that's exactly what we see in this particular case."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we basically have some type of unknown inhibitor, we take out the inhibitor, then we plot the red curve, and then we place that inhibitor into our solution and we plot the purple curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "If this is how the curve changes, we know that it must be a competitive inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, what about uncompetitive?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, let's recall what well, actually, let's first look at the following plot."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So, again, the red describes the absence and the purple describes the presence of that uncompetitive inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And notice what happens."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Essentially, we take the curve and we shift it upward."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And notice the slope doesn't change because these lines are parallel."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "What changes is the X coordinate value, where the line intersects the X axis and the Y coordinate value, the Y intercept."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, why does that actually take place?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, recall what an uncompetitive inhibitor does."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "An uncompetitive inhibitor binds onto that side of the enzyme that is only created when the substrate actually binds onto that particular enzyme."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So what that does is it decreases the total number of enzymes that are functional in the mixture."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so it brings down the V max value, decreases the V max value."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, if the V max value is decreased, then the ratio one divided by smaller V max value means we have a Y intercept that is higher up."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's exactly why the Y intercept is higher for the purple curve than that red curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, what happens to the Km?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, the Km is also affected."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The km also decreases."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's because when the inhibitor actually binds onto that enzyme substrate complex to create the enzyme substrate inhibitor complex, it essentially increases the affinity of that substrate for that enzyme."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Because once the inhibitor binds onto that enzyme substrate complex, that substrate cannot actually leave the active side because its affinity is higher."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And if the affinity is higher, the Km value is lower."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So Km will also decrease."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, if Km decreases, the ratio one divided by a smaller Km value will become more negative."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "It will become larger in the negative direction."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so that means the new Km value, the new one divided by Km, will be farther to the left, along the x axis."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's exactly what we see happening here."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, what about the slope?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Why does the slope actually not change?"}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Well, the slope is given to us by the ratio Km divided by D max."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And in this particular case, both Km and v max decrease, and in fact, they decrease by the same exact amount."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "For example, if Km decreases by a half, this also will be half."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so what that means is the ratio does not actually change because the proportion will remain the same."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so the slope Km divided by VMAX will not change, and these two lines will be parallel with respect to one another."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so if we take the case when we have the inhibitor and then we don't have the inhibitor, and we find that the two lines are parallel, they have different X and different Y intercepts, that must mean the inhibitor is, in fact, an uncompetitive inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And finally, let's see how a non competitive inhibitor actually affects that line."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Weaver burke curve."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So if we look at the following graph, we see that the red curve again, the absence of that inhibitor, the purple curve, the presence of that non competitive inhibitor."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And notice that the slopes are different."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The slope of the purple I is greater."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "We see that the Y intercept is different."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "This is greater."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "But we see that the X coordinate is actually the same."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "The X intercept is the same."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And that's because, as we discussed in the non competitive inhibition case, that inhibitor non competitive inhibitor binds onto the enzyme regardless of whether or not the substrate is actually bound onto that enzyme."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "So the inhibitor can bind onto the individual enzyme or onto the enzyme substrate mixture."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And what that basically means is the VMAX will be smaller."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "And so if the VMAX is smaller, the Y coordinate, the Y intercept will be greater, as we see in this particular case."}, {"title": "Lineweaver Burke Plot and Reversible Inhibition.txt", "text": "Now, even though a non competitive inhibitor binds onto the enzyme and changes the shape of the active side of the enzyme, that substrate."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "At this point, we know that eukaryotic cells basically diversify their DNA by using a process known as crossing over that takes place in meiosis."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, prokaryotic cells such as bacterial cells do not actually undergo the process of meiosis and instead divide via a process known as binary fission."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, the problem with binary fission is we produce two genetically identical cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And that's a problem because if we want to diversify our DNA, binary fission is not the way to go."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, instead of undergoing meiosis, the methods by which our bacterial cells and other prokaryotic cells diversify their DNA is by using one of three different processes."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So bacterial cells and other prokaryotes undergo three different types of genetic recombination processes, including conjugation, transformation, and transduction."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So let's go over each one of our processes and see how the bacterial cell is able to actually diversify its DNA."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So let's begin with the process of conjugation."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, conjugation, in a way, is a mating process because it involves two individual bacterial cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, before we actually discuss what conjugation is, let's discuss what types of DNA molecules are found inside our prokaryotic cells, inside bacterial cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, aside from having the main circular DNA molecule inside the bacterial cells, most bacterial cells also contain small circular DNA molecules known as plasmids."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And some of these plasmids basically contain the genes that code for proteins which give the cell resistance to drugs and other antibiotics."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So basically, conjugation is a type of mating process because it involves two individual bacterial cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And aside from the circular DNA that codes for most of the bacterial proteins, these bacterial cells contain additional DNA called plasmids."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So plasmids, as we mentioned, are small circular DNA that replicate independently of the main DNA molecule and which carry genes that code for proteins that give resistance to drugs."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, although most plasmids do exist independently of the main DNA molecules, some plasmids can actually incorporate into the main DNA molecule."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And such plasmids, such plasmids are known as episodes."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So if we take a look at the following prokaryotic cell arabacterial cell, this is the main DNA molecule of our cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And this smaller one is Aroplasmid."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, what's the big deal with plasmids and conjugation?"}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Well, basically, certain types of cells contain special plasmids known as the fertility factor or the F factor."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And these are plasmids that code for special types of proteins that build something called the sex Pillus."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, the sex Pillus is basically the cytoplasmic bridge that connects one cell to another cell and allows one cell to transfer genetic information to a different cell, as we'll see in just a moment."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So a cell that contains this fertility factor, the F factor, is called our F plus, or the donor cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "While the cell that does not contain the F factor, our fertility factor, is known as our recipient or F minus."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So, to initiate the process of conjugation, the donor cell must actually use its F plasmid or f factor to actually replicate or to actually produce the proteins that build our sex Pillus."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, once again, the sex Pillus is basically a hollow protein that connects one cell to the other cell, and it allows the transfer of our genetic information."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So the donor cell, after it builds the cytoplasmic bridge, our sex pillars, then replicates its plasmid and transfers replicated plasmid to the other cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, if the plasmid is in fact an f plasmid, then the recipient cell gains the ability to build the sex pilli and becomes a donor cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So, we have the donor cell or the positive cell, the f positive, that contains this small circular f plasma shown in green."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So when our two cells come in close proximity, this f plasmid is used to build the protein that is involved in the cytoplasmic bridge in the sex Pillus."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And so that connects our two cells at the same time."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "The f plasmid is also replicated."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And once it's replicated, we transfer it onto this cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So this is the recipient."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "It doesn't actually contain our f plasmid initially, but after the f plasmid is transferred, now this recipient becomes a donor, and it can basically go on and transfer the f plasma to other recipient cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, the f plasmid, our fertility factor, is not the only plasma that exists."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "There are other plasmids that exist, such as, for example, the rplasmid."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "The rplasmid is basically a plasmid that not only contains the proteins that code for the sex pillars, it also contains proteins that give our cell resistance to drugs and antibiotics."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So basically, this process is known as mating because we have two individual cells that basically interact via this cytoplasmic bridge known as the sex pillars, and we transfer genetic information from the donor to our recipient in this process of genetic recombination in bacterial cells is known as conjugation."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So let's move on to transformation."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So, transformation is basically a type of genetic recombination process in which our cell takes up DNA fragments from the outside of that cell's environment and brings it into the cell and then integrates that fragment of DNA into its own DNA."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And this transforms our cell into a genetically different cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, one common example of transformation is the following."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Basically, we take a cell or we take a bacterial cell that contains the genes that are harmful to eukaryotic cells."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So we kill off those harmful bacterial cells, and then we bring those harmful bacterial cells that are dead next to living bacterial cells that are living but which are harmful."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Over time, those harmless bacterial cells will eventually become harmful because of transformation."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So basically what happens is our harmless bacterial cell takes up genetic information, our fragments of DNA that came from the harmful bacterial cell, and takes them and brings them into the cell and then incorporates that into its own DNA."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And then when that DNA is transcribed, when we transcribe this section, we build proteins that basically end up harming some type of eukaryotic cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So this is an example of the process of transformation."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So basically, ultimately, the end result is a slightly more genetically diverse DNA molecule, slightly more diverse bacterial cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now let's discuss the final type of genetic recombination process known as transduction."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "But before we get into transduction, let's recall what a bacteriophage is."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "A bacteriophage is a type of virus that only infects bacterial cells and it hijacks the machinery of the bacterial cells and it uses the cells to build its own viral genetic information."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, sometimes these bacteriophages accidentally take up a fragment of DNA of that bacterial cell instead of using its own viral genetic information."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, when these harmless bacteriophages infect other cells, other bacterial cells, they inject the cells, they inject into the cells the DNA fragment from the other cell which can then be integrated with that cell's DNA."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And this increases the genetic information of that bacterial cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So basically, in a way, transduction takes place accidentally."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So this is shown in the following diagram."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So we have our bacterial cell that is hijacked by our bacteriophage."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, instead of the bacteriophage taking up the viral DNA or RNA molecule, it takes up this fragment of DNA that came from our actual DNA of that bacterial cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And so then it carries that DNA fragment that is harmless to another bacterial cell as shown and it injects that DNA fragment into this bacterial cell and then that fragment is incorporated with the DNA molecule of that particular cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And now this new cell is genetically different than this initial cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So this is the final method by which our bacterial cell undergoes the process of genetic recombination."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "So once again, because bacterial cells and other prokaryotic cells do not actually reproduce via the process of meiosis, they reproduce via the process of binary fission."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And because binary fission does not incorporate genetic recombination, they have to undergo other methods of genetic recombination."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And these three methods are conjugation, transformation and transduction."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Conjugation involves the formation of a cytoplasmic bridge, a sex Pillus between a donor cell and a recipient cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And the donor cell transfers the plasma to the recipient cell."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And so that gives our recipient cell a certain amount of genetic diversity."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "Now, transformation is the process by which our bacterial cell takes up DNA fragments from the immediate surroundings of that cell and incorporates the DNA fragments into its own DNA."}, {"title": "Conjugation, Transformation and Transduction .txt", "text": "And finally, transduction is the accidental takeup of DNA fragments by bacterial cells from bacteria phages which brought the DNA fragments from other cells, from other prokaryotic cells."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "Of nucleotides following the primer."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So we have TGC, and then we have ta."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So, tae, then we have GCT, GCT and the rest of it."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So this is basically the five end."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "And this is the three end of this complementary DNA sequence that is complementary to this DNA that we essentially began with."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So if we begin with this DNA primer, so the DNA primer contains the five prime end, then we have TGC."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "And then we continue with these."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "We have tat, then we have GCT, then we have A-T-G and C, and that's the three end."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So you raise this 1% over here, and that's the three end."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "And so now that we know what this sequence is, we can determine what the complementary sequence to this original DNA strand is simply by base parents."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So this is the three N. So this is A, this is CGA, this is T, this is AC Gat, and that's the five N. And so we see that this is exactly what the sequence of this molecule was."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So we have a G, we have a C, we have an A, we have T, we have a T, we have a GC, we have an Ata, then we have a CNA."}, {"title": "Sanger Sequencing of DNA (Part II) .txt", "text": "So we were able to determine exactly what that sequence of that DNA molecule was by using this very effective and very efficient Sanger Died deoxy method."}, {"title": "Cardiac Muscle .txt", "text": "The next type of muscle that we're going to discuss is the cardiac muscle."}, {"title": "Cardiac Muscle .txt", "text": "Now the cardiac muscle is the muscle that makes up the heart and just like skeletal muscle is stretched because it consists of these individual units we call sarcomeres."}, {"title": "Cardiac Muscle .txt", "text": "Our cardiac muscle is also stretched because it consists of sarcomire."}, {"title": "Cardiac Muscle .txt", "text": "So if we take a look at the heart, the heart appears to be striped, it contains these triations shown in red and that's because if we zoom in onto an individual cardiac muscle cell, we contain these myofibrils that consist of sarcomeres."}, {"title": "Cardiac Muscle .txt", "text": "So basically if we take individual sarcomeres and we connect them end to end, we basically form something called a myofibril and we have many of these cylindrically shaped myofibrils in any given cardiac muscle cell."}, {"title": "Cardiac Muscle .txt", "text": "In this case, we have 123-4567 myofibrils in this particular cardiac muscle cell."}, {"title": "Cardiac Muscle .txt", "text": "So the red portion of the cell is the plasma membrane of the cardiac muscle cell and that is known as the sarcolema."}, {"title": "Cardiac Muscle .txt", "text": "And just like we have a sarcolema with T tubules in the skeletal muscle, we also have the sarcolema with the T tubules inside our cardiac muscle cell."}, {"title": "Cardiac Muscle .txt", "text": "So the T tubules are basically the deep in vaginations, these deep tunnels that begin on the plasma membrane and extend throughout the cell and they are basically responsible for allowing the action potential to propagate quickly and uniformly throughout the entire cardiac muscle cell."}, {"title": "Cardiac Muscle .txt", "text": "Now we also have our green section and that is the sarcoplasm reticulum, that is a specialized type of endoplasm reticulum inside the cardiac muscle cell that contains a high concentration of calcium that is needed for the proper muscle contraction."}, {"title": "Cardiac Muscle .txt", "text": "Now we also have a nucleus and that is shown in blue."}, {"title": "Cardiac Muscle .txt", "text": "But unlike in skeletal muscle that contains many nuclei per given cell, the cardiac muscle cell only contains a single nucleus."}, {"title": "Cardiac Muscle .txt", "text": "So this is the first important difference between cardiac muscle cells and skeletal muscle cells."}, {"title": "Cardiac Muscle .txt", "text": "Now the cytoplasm of our cardiac muscle cell is known as the sarcoplasm."}, {"title": "Cardiac Muscle .txt", "text": "So what about some other differences between cardiac muscle cells and skeletal muscle cells?"}, {"title": "Cardiac Muscle .txt", "text": "So, so far we see many of the different structures that are found in skeletal muscles are also found in cardiac muscle cells."}, {"title": "Cardiac Muscle .txt", "text": "Now the next important difference between our cardiac muscle cell and the skeletal muscle cell is the fact that cardiac muscle cells are actually connected to one another."}, {"title": "Cardiac Muscle .txt", "text": "So if we have one cardiac muscle cell, a second cardiac muscle cell will be found right next to it and these two will be connected by regions called intercollated discs."}, {"title": "Cardiac Muscle .txt", "text": "Now intercollated discs are basically these connecting regions that contain two important types of junctions."}, {"title": "Cardiac Muscle .txt", "text": "One of these junctions is known as a gap junction."}, {"title": "Cardiac Muscle .txt", "text": "And what the gap junction is, it's basically this channel that connects one cell to the JSON cell and this channel allows for a quick and uniform propagation of the action potential from one cell to the next cell because it allows the movement of ions between adjacent muscle cells."}, {"title": "Cardiac Muscle .txt", "text": "And this type of arrangement of cardiac muscle cells in the heart basically allows for a uniform and synchronized contraction of our heart."}, {"title": "Cardiac Muscle .txt", "text": "So if we take a look at the following diagram, this is cardiac muscle cell number one, cardiac muscle cell number two."}, {"title": "Cardiac Muscle .txt", "text": "This separating region that connects them is the intercollated discs and it contains one type of junction known as a gap junction, that allows for a rapid communication between cells."}, {"title": "Cardiac Muscle .txt", "text": "And it also contains a second type of intracellular junction known as the desmosome."}, {"title": "Cardiac Muscle .txt", "text": "And the desmosome is basically the intracellular junction that actually glues the two cells together, that holds the two cells together and allows them to stick together when we have that contraction actually taking place."}, {"title": "Cardiac Muscle .txt", "text": "So this is the second important difference between cardiac muscle cells and skeletal muscle cells."}, {"title": "Cardiac Muscle .txt", "text": "So basically, we have our cardiac muscle cells that only contain a single nucleus, they also contain these special connecting regions known as intercalated discs."}, {"title": "Cardiac Muscle .txt", "text": "Now, cardiac muscle cells also contain relatively large mitochondria and that makes sense because the cardiac muscle cells are constantly working, they're constantly pumping that blood throughout the body and so they need to continually make that ATP and that's why they contain large mitochondria."}, {"title": "Cardiac Muscle .txt", "text": "Now, unlike skeletal muscle tissue, which is voluntary because it is controlled by the somatic nervous system, cardiac muscle cell is involuntary because it is controlled by the autonomic nervous system."}, {"title": "Cardiac Muscle .txt", "text": "Now, although it is controlled by the autonomic nervous system, certain cardiac muscle cells actually exhibit something called myogenic activity."}, {"title": "Cardiac Muscle .txt", "text": "And myogenic activity simply means that certain cardiac muscle cells inside the heart can actually initiate a contraction without a stimulus from the nervous system."}, {"title": "Cardiac Muscle .txt", "text": "And we'll talk more about that when we're going to discuss the cardiovascular system."}, {"title": "Cardiac Muscle .txt", "text": "Now, the final concept that I'd like to briefly discuss in regards to our cardiac muscle cell is the action potential and what the action potentially actually looks like compared to the action potential of our neuron."}, {"title": "Cardiac Muscle .txt", "text": "So basically, this is what the graph of the cardiac muscles action potential looks like."}, {"title": "Cardiac Muscle .txt", "text": "And notice that we have this long region known as the plateau phase that we actually don't find in the action potential of a neuron."}, {"title": "Cardiac Muscle .txt", "text": "So during the generation of an action potential inside a cardiac muscle cell, we have this extended period of depolarization that is caused by the presence of voltage gated calcium channels inside the membrane of the cell."}, {"title": "Cardiac Muscle .txt", "text": "So the membrane of the cell doesn't only contain sodium and potassium voltage gated channels, it also contains calcium voltage gated channels."}, {"title": "Cardiac Muscle .txt", "text": "So let's see what happens."}, {"title": "Cardiac Muscle .txt", "text": "So our resting potential is about negative 90 millivolts."}, {"title": "Cardiac Muscle .txt", "text": "And let's suppose we have some type of stimulus that reaches the threshold voltage of about negative 70 millivolts."}, {"title": "Cardiac Muscle .txt", "text": "So what happens next?"}, {"title": "Cardiac Muscle .txt", "text": "Our sodium voltage gated channels on the membrane are very quick to open and basically they allow for the rapid movement of the sodium ions inside the cell and that causes the inside of the cell to become positive."}, {"title": "Cardiac Muscle .txt", "text": "And that leads to our depolarization period."}, {"title": "Cardiac Muscle .txt", "text": "Now, when we reach about positive 30 millivolts, the sodium voltage gated channels close, while the potassium voltage gated channels begin to open."}, {"title": "Cardiac Muscle .txt", "text": "But they open very slowly at first."}, {"title": "Cardiac Muscle .txt", "text": "At the same time, we also open the calcium voltage gated channels and calcium voltage gated channels are very slow to actually close."}, {"title": "Cardiac Muscle .txt", "text": "So basically what happens is because we have this additional voltage gated channel, and because the calcium ions go into the cell while the potassium goes out of the cell, and because the potassium has a larger charge, we see that the inner portion of the membrane stays positive for a longer period."}, {"title": "Cardiac Muscle .txt", "text": "And that means we have a longer depolarization period than normal than what we would see on a neuron."}, {"title": "Cardiac Muscle .txt", "text": "And this longer depolarization period is known as our plateau phase or plateau stage."}, {"title": "Cardiac Muscle .txt", "text": "So eventually the sodium channels or the calcium channels begin to close and our potassium channels begin to open quicker."}, {"title": "Cardiac Muscle .txt", "text": "And eventually we have this repolarization period and then we return to our normal resting membrane potential of negative 90 millivolts."}, {"title": "Cardiac Muscle .txt", "text": "Now, what is the function of this plateau phase?"}, {"title": "Cardiac Muscle .txt", "text": "Why would we want a longer depolarization period?"}, {"title": "Cardiac Muscle .txt", "text": "So basically what the longer depolarization period does is it increases the time of contraction and that allows all the adjacent cardiac muscle cells to basically depolarize uniformly and quickly so that our heart basically contracts in a single and forceful steady contraction."}, {"title": "Cardiac Muscle .txt", "text": "And that ultimately allows the movement of the blood that carries the nutrients and the oxygen through the different parts of our body."}, {"title": "Cardiac Muscle .txt", "text": "So the reason we want the voltage gated calcium channels to basically exist is to create this longer contraction to allow all the adjacent cardiac cells to depolarize uniformly, to create this long and steady, uniform, forceful contraction of our heart."}, {"title": "Cardiac Muscle .txt", "text": "So if this did not exist, our cardiac muscle cells would basically contract very sporadically and that would not create a single forceful contraction."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So, as alluded to the previous lecture here, we're going to focus on something called ketoacidosis."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Ketoacidosis simply means we have high levels of ketone bodies inside our blood."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, what causes ketone acidosis?"}, {"title": "Diabetic Ketoacidosis .txt", "text": "Well, it can be a result of prolonged alcohol consumption."}, {"title": "Diabetic Ketoacidosis .txt", "text": "It can be due to malnutrition or starvation."}, {"title": "Diabetic Ketoacidosis .txt", "text": "But what we're going to focus on in this lecture is diabetes."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So type one insulin dependent diabetes can cause keto acidosis if that diabetes is not regulated."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So how does this actually take place?"}, {"title": "Diabetic Ketoacidosis .txt", "text": "Well, let's suppose we have a diabetic individual and a diabetic individual forgets to take their insulin."}, {"title": "Diabetic Ketoacidosis .txt", "text": "What happens?"}, {"title": "Diabetic Ketoacidosis .txt", "text": "Well, basically, after a meal, we're going to have high levels of glucose inside our blood, a condition known as hyperglycemia."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, if we don't have any insulin, then that means the liver cannot actually absorb that glucose, because remember, the insulin is used to upregulate the absorption of glucose into the liver."}, {"title": "Diabetic Ketoacidosis .txt", "text": "If we have no insulin, we cannot absorb the glucose."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So if we can't absorb the glucose into the liver cells, the pedicides, what that means is we're going to decrease the level of oxalo acetate inside our liver cells."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, why is that important?"}, {"title": "Diabetic Ketoacidosis .txt", "text": "Well, remember, we need high levels of oxyloacetate to actually use the CECL coenzyme A that we get from beta oxidation and fatty acids to help us generate citrate, the intermediate of the citric acid cycle."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And that helps us generate ATP molecules, convert the CTL coenzyme A ultimately into ATP molecules."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, at the same time, in our adipose tissue, in our fat cells, the inability of the glucose to be absorbed by these fat cells will stimulate the breakdown of triglycerides into fatty acids."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so these adipose cells will continue dumping these fatty acids into the bloodstream and these fatty acids will ultimately be absorbed by that liver."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So when we increase the levels of fatty acids inside our liver, we're going to essentially increase the levels of acetyl coenzyme A, which comes from the beta degradation of fatty acids."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So we have low levels of oxylo acetate in the liver cells and high levels of acetyl coenzyme A."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so this process by which we essentially feed the acetylcoenzyme a into the citric acid cycle will be blocked as a result of the low levels of oxalo acetate."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So the only pathway that is left for these acetal co enzyme A molecules is ketogenesis, the production of ketone bodies."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So we're going to increase levels of ketone bodies in the liver and they're going to be dumped into the bloodstream."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we're going to cause something called ketonemia, which is simply elevation of ketone bodies inside our blood as well as ketonuria."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So this is the process by which we're going to excrete those ketone bodies via our urine."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So remember, we have three types of ketone bodies."}, {"title": "Diabetic Ketoacidosis .txt", "text": "We have acetone, we have acetoacetate, and we have D three hydroxybutyrate."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, acetone is simply a ketone body that cannot be metabolized by our cells."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we're simply going to release it via our breath."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we're going to get a fruity odor on breath."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so physicians can test the breadth of individuals to see if they actually have Ketoacidosis."}, {"title": "Diabetic Ketoacidosis .txt", "text": "Now, what about the acetoacetate and D three hydroxybutyrate?"}, {"title": "Diabetic Ketoacidosis .txt", "text": "Well, these are actually acids, and the PKA value of these two acids is around four."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And what that means is once these two molecules into the bloodstream, they're going to dissociate, releasing those H plus ions, and that will increase the acidity of the blood."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So we see that these two Ketone bodies will increase the levels of H plus ions in the blood, and that will, in turn, increase the H plus ion concentration in the tissue."}, {"title": "Diabetic Ketoacidosis .txt", "text": "In addition, what will also happen is as a result of ketonuria, the release of these Ketone bodies in the kidneys, what will happen is osmosis will take place inside the kidneys."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we're going to release much more water than usual."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So on top of increasing the levels of H plus ions in the blood and tissues, we're going to increase the amount of water that we release by the kidneys."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So we essentially decrease the volume because we decrease the water concept in the blood, we increase the concentration of H plus ions in the blood."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And what that does is it causes severe Ketoacidosis."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so this can basically damage tissues and cells of our body."}, {"title": "Diabetic Ketoacidosis .txt", "text": "For example, it can damage the central nervous tissue, the central nervous cells."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we see that it's very important for type one diabetics to actually regulate their insulin, because if they don't regulate their insulin, they're going to basically get Ketoacidosis, which can be very damaging to the tissues."}, {"title": "Diabetic Ketoacidosis .txt", "text": "It can even lead to death."}, {"title": "Diabetic Ketoacidosis .txt", "text": "So we see that the takeaway lesson here is in diabetics, type one diabetics."}, {"title": "Diabetic Ketoacidosis .txt", "text": "If they don't take the insulin, they cannot regulate the absorption of the glucose by these liver cells and by these adipose cells."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so together, this process will lead to an increased levels of Ketone bodies inside the blood, because the cells of our body will not be able to use the Ketone bodies quickly enough."}, {"title": "Diabetic Ketoacidosis .txt", "text": "And so we're going to get a build up of these Ketone bodies in the blood leading to Ketoacidosis."}, {"title": "Blood Clotting Cascade.txt", "text": "So let's begin by imagining what would happen if our blood vessel in our cardiovascular system ruptures."}, {"title": "Blood Clotting Cascade.txt", "text": "So when a blood vessel ruptures, blood will begin to move from a high pressure to low pressure from the inside of the blood vessel to the outside surrounding tissue, surrounding extracellular matrix."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, if that rupture is not sealed off, if it is not not repaired in any way then the leaking of that blood would continue."}, {"title": "Blood Clotting Cascade.txt", "text": "And what that means is our capillaries in our body would expand."}, {"title": "Blood Clotting Cascade.txt", "text": "They would open up and more blood would collect in those capillaries."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is known as the pooling of blood."}, {"title": "Blood Clotting Cascade.txt", "text": "And as a result of the pooling of blood in our capillaries, the blood pressure would drop and this would lead to a medical condition known as shock."}, {"title": "Blood Clotting Cascade.txt", "text": "And shock can be lethal."}, {"title": "Blood Clotting Cascade.txt", "text": "It can actually cause death."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, because our blood vessels rupture constantly in our body, our body has a way to actually repair these ruptures in our blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "And the process by which our body repairs these ruptures is known as the blood clotting cascade."}, {"title": "Blood Clotting Cascade.txt", "text": "So an important property of our blood is its ability to coagulate."}, {"title": "Blood Clotting Cascade.txt", "text": "And what that means is to form these clumps we call blood clots."}, {"title": "Blood Clotting Cascade.txt", "text": "And these blood clots can bind to these ruptures aggregate along the ruptures and they can see law of that rupture in the blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "And this prevents the leakage of our blood out of that blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "So this process of coagulation, the process of forming these blood clots that seal off that rupture is known as the blood clot and cascade."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, what exactly is the blood clot and cascade?"}, {"title": "Blood Clotting Cascade.txt", "text": "Well, it's nothing more than a series of protein interactions and enzyme interactions that ultimately lead to the formation of these clumps of molecules we call blood clots."}, {"title": "Blood Clotting Cascade.txt", "text": "And these blood clots attached to an aggregate along that rupture on the blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "And that creates a watertight seal that prevents the movement of blood out of that blood vessel and that ultimately prevents the medical condition we call shock."}, {"title": "Blood Clotting Cascade.txt", "text": "It prevents the person from going into shock."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, let's begin by taking a look at the following illustration."}, {"title": "Blood Clotting Cascade.txt", "text": "So in this lecture, we're actually going to discuss what the blood clotting cascade is and what the proteins are that are involved in this cascade."}, {"title": "Blood Clotting Cascade.txt", "text": "So let's begin by imagining that we're inside a blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "So this is the endothelial endothelium of one side and this is the endothelium of the other side."}, {"title": "Blood Clotting Cascade.txt", "text": "We're essentially taking a cross section of our blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, this is the outside portion of the blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "It's the surrounding tissue."}, {"title": "Blood Clotting Cascade.txt", "text": "It's the extracellular matrix outside the blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is the inside portion, the lumen of our blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, the first thing we should notice about our blood clotting cascade is all these proteins involved within this cascade are found inside the blood plasma."}, {"title": "Blood Clotting Cascade.txt", "text": "So they are circulating inside that blood plasma."}, {"title": "Blood Clotting Cascade.txt", "text": "And anytime we have a rupture that takes place."}, {"title": "Blood Clotting Cascade.txt", "text": "Because these are found inside the blood plasma, they are ready to be activated and they are ready to basically form those blood clots."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, the second thing we should notice is it looks rather complicated and that's because we have over a dozen different types of enzymes and proteins involved in the process of the blood clot and cascade."}, {"title": "Blood Clotting Cascade.txt", "text": "So the rather difficult aspect about this cascade is remembering the different types of enzymes and how they interact with one another to form these blood clots."}, {"title": "Blood Clotting Cascade.txt", "text": "So, to make things easier, let's actually divide our process into three different processes."}, {"title": "Blood Clotting Cascade.txt", "text": "So generally speaking, we can divide the blood clot and cascade into three processes."}, {"title": "Blood Clotting Cascade.txt", "text": "The first two processes, or the two, the first two pathways are known as the extrinsic pathway and the intrinsic pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, the extrinsic pathway is shown in black with these black arrows and the intrinsic pathway is shown with the blue arrows."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, notice that the black arrows ultimately converge with the blue arrows at this particular location where we designated with the star."}, {"title": "Blood Clotting Cascade.txt", "text": "And so actually, the intrinsic and the extrinsic pathway do converge at a single point and then they go on to form the final pathway, known as the final common pathway or simply the final pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "So this is shown with the red arrow."}, {"title": "Blood Clotting Cascade.txt", "text": "So let's begin by describing the quick acting pathway, the extrinsic pathway, and this is shown by these black arrows."}, {"title": "Blood Clotting Cascade.txt", "text": "So question number one is how exactly do we initiate what begins the extrinsic pathway?"}, {"title": "Blood Clotting Cascade.txt", "text": "Well, let's suppose somehow this endothelial cell ruptures."}, {"title": "Blood Clotting Cascade.txt", "text": "So we have a hole that forms in the membrane and that allows the blood to move from the lumen side and into the outside the tissue area, down its pressure gradient from a high pressure to a low pressure."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, as soon as this endothelial cell is damaged, it will expose a special glycoprotein membrane known as TF, which stands for Tissue factor."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, this glycoprotein wasn't there before."}, {"title": "Blood Clotting Cascade.txt", "text": "It's exposed only when we have this damaging taking place, when the endothelial cell is ruptured."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, remember, we have all these other proteins floating around in close proximity."}, {"title": "Blood Clotting Cascade.txt", "text": "And as soon as the tissue factor is exposed on the membrane, what happens is another active form of another enzyme known as factor Seven, goes on and binds onto the tissue factor to form a dimer protein complex that now consists of two subunits known as tissue factor complex seven."}, {"title": "Blood Clotting Cascade.txt", "text": "So TF seven is basically this dimer protein complex that we form as soon as the rupturing process takes place."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, once we form the TF seven complex, this dimer protein, this becomes acerine protease."}, {"title": "Blood Clotting Cascade.txt", "text": "And what that means is it goes on to activate other enzymes by cleaving them at specific amino acids on their amino acid sequence."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, the TF seven complex has two different proteins that it readily activates."}, {"title": "Blood Clotting Cascade.txt", "text": "We have protein factor nine and protein factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "And notice that protein factor nine when it's activated, it goes on to activate some more of ten."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is an amplification process."}, {"title": "Blood Clotting Cascade.txt", "text": "It's a process by which we amplify the amount of ten that is formed because ultimately it's this ten that will go on to form blood clots as we'll see in just a moment."}, {"title": "Blood Clotting Cascade.txt", "text": "So once again the extrinsic pathway consists of these steps and it's a quick acting pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "It reacts quickly to this rupturing within our blood, within our endothelial cell."}, {"title": "Blood Clotting Cascade.txt", "text": "So when the blood vessel ruptures it exposes a membrane glycoprotein on the damaged cell called the tissue factor TF which is actually attached to the membrane of that cell."}, {"title": "Blood Clotting Cascade.txt", "text": "Now TF binds to the active form of protein factor seven found in close proximity forming a dimer protein complex TF seven."}, {"title": "Blood Clotting Cascade.txt", "text": "This protein is a complex that is a serene protease."}, {"title": "Blood Clotting Cascade.txt", "text": "And now an inactive form of ten can come close to this complex and the complex basically lysis this or activates this inactive form into its active form."}, {"title": "Blood Clotting Cascade.txt", "text": "And the same thing is done with number nine, protein factor nine."}, {"title": "Blood Clotting Cascade.txt", "text": "And protein factor nine goes on and activates some more of factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "So this is extrinsic pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "What about the intrinsic pathway?"}, {"title": "Blood Clotting Cascade.txt", "text": "Well, the intrinsic pathway is a bit more slow acting than the extrinsic pathway and that's why we differentiate them."}, {"title": "Blood Clotting Cascade.txt", "text": "So now let's begin by basically describing how the intrinsic pathway is initiated."}, {"title": "Blood Clotting Cascade.txt", "text": "Well, once again as soon as the rupturing process takes place we expose the blood vessel to the outside tissue."}, {"title": "Blood Clotting Cascade.txt", "text": "And this outside tissue is composed of collagen fibers, collagen protein fibers."}, {"title": "Blood Clotting Cascade.txt", "text": "Now as soon as the inactive version of protein factor twelve is exposed to the collagen in that extracellular matrix it is activated into the active version of factor twelve."}, {"title": "Blood Clotting Cascade.txt", "text": "And protein factor twelve then goes on and activates another protein, protein factor eleven."}, {"title": "Blood Clotting Cascade.txt", "text": "And the protein factor eleven, when it's activated it goes on to activate that same protein factor nine that we dealt with in the extrinsic pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "Now once nine is activated, once again it goes on and activates ten."}, {"title": "Blood Clotting Cascade.txt", "text": "So we see the underlying reason why we have these two different processes is so that we have more pathways by which we can form more of number ten."}, {"title": "Blood Clotting Cascade.txt", "text": "Because once again, it's the number ten that will combine with the factor five to form a dimer complex that will go on and ultimately lead to the formation of our blood clot."}, {"title": "Blood Clotting Cascade.txt", "text": "So we have these two pathways, the extrinsic and the intrinsic that eventually create many of these separate pathways that amplify the number of these complexes that we form."}, {"title": "Blood Clotting Cascade.txt", "text": "And once they converge this complex goes on and forms our blood clots as we'll see in just a moment."}, {"title": "Blood Clotting Cascade.txt", "text": "So once again, let's review the intrinsic pathway."}, {"title": "Blood Clotting Cascade.txt", "text": "So when blood vessel ruptures inactive protein factor twelve is exposed to the collagen in the tissue surrounding our blood vessel and this activates factor twelve."}, {"title": "Blood Clotting Cascade.txt", "text": "Now activated."}, {"title": "Blood Clotting Cascade.txt", "text": "Factor twelve is also a sea of protease and it goes on and cleaves our factor eleven and activates factor eleven, which then goes on to activate factor nine."}, {"title": "Blood Clotting Cascade.txt", "text": "So this one right here, which goes on to activate factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, let's move on to our converging final common pathway which begins in this area."}, {"title": "Blood Clotting Cascade.txt", "text": "So basically, as soon as the extrinsic and the intrinsic pathway activates as much ten as possible, that factor ten will go on and combine with factor five protein and that will form a dimer complex we call prothrombinase."}, {"title": "Blood Clotting Cascade.txt", "text": "And we'll see why."}, {"title": "Blood Clotting Cascade.txt", "text": "We call it Protombinase in just a moment."}, {"title": "Blood Clotting Cascade.txt", "text": "We call it this because it goes on to activate prothrombin into its active form known as Thrombin."}, {"title": "Blood Clotting Cascade.txt", "text": "And once again, it's important to keep in mind that all these enzymes are circulating in close proximity, they're found floating around inside our blood."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, as soon as we form Thrombin, thrombin goes three different ways."}, {"title": "Blood Clotting Cascade.txt", "text": "It does three important things."}, {"title": "Blood Clotting Cascade.txt", "text": "It basically calls upon platelets."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, platelets are these pieces of megacaryocytes that are also used to form that meshlike network of blood clots that creates that seal and prevents that movement of liquid of blood out of that blood vessel."}, {"title": "Blood Clotting Cascade.txt", "text": "So Thrombin calls upon our platelets."}, {"title": "Blood Clotting Cascade.txt", "text": "And by the way, prothrombin is formed in the liver, it's released by the liver cells into our blood."}, {"title": "Blood Clotting Cascade.txt", "text": "So it circulates within our blood and it's activated by this complex prothrombinase."}, {"title": "Blood Clotting Cascade.txt", "text": "So once we form Thrombone, it calls upon platelets, it also activates another fiber protein known as Fibrinogen."}, {"title": "Blood Clotting Cascade.txt", "text": "And fibrinogen basically is activated into fibrin."}, {"title": "Blood Clotting Cascade.txt", "text": "So Fibrin is the active form of Fibrinogen, which is activated by Thrombin."}, {"title": "Blood Clotting Cascade.txt", "text": "And it's Fibrin that actually binds together to form that mesh like network within a rupture and that seals off that rupture."}, {"title": "Blood Clotting Cascade.txt", "text": "So basically the Fibrin, with the help of this protein, factor 13, which is also activated by Thrombin, the Fibrin can form these covalent bonds between other adjacent fibrin proteins."}, {"title": "Blood Clotting Cascade.txt", "text": "And so we eventually form these blood clots."}, {"title": "Blood Clotting Cascade.txt", "text": "So Thrombin not only activates platelets and calls upon platelets, it also forms Fibrin and it activates factor 13 that is needed to form the covalent bonds between many of these adjacent Fibrin that lie along that rupture."}, {"title": "Blood Clotting Cascade.txt", "text": "So we see that the final pathway consists of the following."}, {"title": "Blood Clotting Cascade.txt", "text": "When factor ten is activated by either the extrinsic or the intrinsic pathway, it combines with factor five to form a dimer complex we call prothrombinase."}, {"title": "Blood Clotting Cascade.txt", "text": "And it's prothrombinase, which is also a protease enzyme that activates prothrombin in our blood and turns it into the active With factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates factor eight to combine with factor nine, as well as this VWF, which stands for Von Willebrand Factor, which is another protein that is needed to basically stabilize factor eight."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates the complex that goes on to activate more of ten to form this complex."}, {"title": "Blood Clotting Cascade.txt", "text": "And Thorambin also activates via positive feedback mechanism, more of eleven and eleven is needed to activate nine."}, {"title": "Blood Clotting Cascade.txt", "text": "So we see that we have a really extensive network of positive feedback mechanisms that ultimately greatly amplify."}, {"title": "Blood Clotting Cascade.txt", "text": "They magnify the number of blood clots that can be formed in this process."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is important because, as we know, shock is a very dangerous medical condition and we don't want that individual to go into shock."}, {"title": "Blood Clotting Cascade.txt", "text": "And so this has to be an extremely effective and efficient process."}, {"title": "Blood Clotting Cascade.txt", "text": "And that's why we have many of these amplification positive feedback mechanisms."}, {"title": "Blood Clotting Cascade.txt", "text": "factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates factor eight to combine with factor nine, as well as this VWF, which stands for Von Willebrand Factor, which is another protein that is needed to basically stabilize factor eight."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates the complex that goes on to activate more of ten to form this complex."}, {"title": "Blood Clotting Cascade.txt", "text": "And Thorambin also activates via positive feedback mechanism, more of eleven and eleven is needed to activate nine."}, {"title": "Blood Clotting Cascade.txt", "text": "So we see that we have a really extensive network of positive feedback mechanisms that ultimately greatly amplify."}, {"title": "Blood Clotting Cascade.txt", "text": "They magnify the number of blood clots that can be formed in this process."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is important because, as we know, shock is a very dangerous medical condition and we don't want that individual to go into shock."}, {"title": "Blood Clotting Cascade.txt", "text": "And so this has to be an extremely effective and efficient process."}, {"title": "Blood Clotting Cascade.txt", "text": "And that's why we have many of these amplification positive feedback mechanisms."}, {"title": "Blood Clotting Cascade.txt", "text": "With factor ten."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates factor eight to combine with factor nine, as well as this VWF, which stands for Von Willebrand Factor, which is another protein that is needed to basically stabilize factor eight."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates the complex that goes on to activate more of ten to form this complex."}, {"title": "Blood Clotting Cascade.txt", "text": "And Thorambin also activates via positive feedback mechanism, more of eleven and eleven is needed to activate nine."}, {"title": "Blood Clotting Cascade.txt", "text": "So we see that we have a really extensive network of positive feedback mechanisms that ultimately greatly amplify."}, {"title": "Blood Clotting Cascade.txt", "text": "They magnify the number of blood clots that can be formed in this process."}, {"title": "Blood Clotting Cascade.txt", "text": "And this is important because, as we know, shock is a very dangerous medical condition and we don't want that individual to go into shock."}, {"title": "Blood Clotting Cascade.txt", "text": "And so this has to be an extremely effective and efficient process."}, {"title": "Blood Clotting Cascade.txt", "text": "And that's why we have many of these amplification positive feedback mechanisms."}, {"title": "Blood Clotting Cascade.txt", "text": "form called Thrombin."}, {"title": "Blood Clotting Cascade.txt", "text": "And thrombin does three things."}, {"title": "Blood Clotting Cascade.txt", "text": "It activates our platelets, it calls upon these platelets, it activates Fibrinogen into Fibrin, and it activates facts of 13 that is needed to basically covalently bond these fibrin along that rupture to form that meshlike network of proteins."}, {"title": "Blood Clotting Cascade.txt", "text": "That seals off that rupture and prevents the movement of blood out of that blood vessel and ultimately prevents the person from going into shock."}, {"title": "Blood Clotting Cascade.txt", "text": "Now, the final part that I'd like to briefly talk about and maybe focus more on in the next lecture, are these green arrows?"}, {"title": "Blood Clotting Cascade.txt", "text": "So what the green arrows represent are amplification mechanisms."}, {"title": "Blood Clotting Cascade.txt", "text": "So, positive feedback mechanisms."}, {"title": "Blood Clotting Cascade.txt", "text": "The thrombin not only calls upon platelets, activates the fiber and activates factor 13, but it also positively, via a positive feedback mechanism, activates more of this complex."}, {"title": "Blood Clotting Cascade.txt", "text": "Activates factor five to combine."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "The fluid mosaic model of the membrane describes the structure and the organization of the biological cell membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "What it tells us is the structure is not rigid or static in nature."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "On the contrary, it's very fluidlike."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's because the individual constituents, the molecules that make up the membrane, are in a constant state of motion."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So we have two types of motion."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Obviously, we discussed lateral motion or lateral diffusion."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And what that means is if we take a look at the membrane so we have two sides of the membrane, two leaflets, one leaflet and the posing leaflet."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So the individual fossil lipid molecules, these lipid molecules along any leaflet can move relatively quickly and easily along that leaflet and they move at a rate of about one micro meter per second."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, proteins within the membrane can also move along that membrane in a lateral direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, some proteins move relatively quickly while other proteins are essentially immobile."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Why?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Well, because some proteins, like this one here isn't actually physically attached onto any other molecule or any other structure."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "But other transmembrane proteins or integral proteins are basically attached onto physical structures."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "For instance, in this case, it's attached not only onto the collagen fibers of the extracellular matrix found outside the cell but they're also attached onto the filaments in the cytoskeleton found in the cytoplasm inside of that cell."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So this one will be relatively mobile while this protein will be able to move along that lateral direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, what allows these fossilipids to actually move along that direction?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Well, basically, as the fossilipid moves along the lateral direction those bonds between the water molecules and the polar heads remain."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And likewise, the bonds between the jason hydrocarbon non polar tails also remain."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And so there's really not too much energy that must be overcome as these phospholipids actually move along any given leaflet."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "But let's suppose, instead of moving along the lateral direction one of these phospholipids, let's say this one here wants to actually rotate and move from one side of the membrane from one leaflet to the other side of the membrane, that opposing leaflet."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Will this actually take place."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So this process is known as transverse diffusion, or simply flip flopping."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So do fossil lipids actually flip flop?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And the answer is yes."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "But flip flopping doesn't take place at the same rate that lateral diffusion takes place."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "In fact, lateral diffusion takes place much more quickly than transverse diffusion does."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "The question is why?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Well, to see why, let's compare these two diagrams."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Remember, when we have lateral diffusion the movement of these phospholipids doesn't actually break the net bonds between the water molecules and the polar heads."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And likewise, the hydrophobic interactions within the tail region actually remains the same when they move along that horizontal direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "But what happens if a phospholipid like this one here actually wants to rotate?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So in this diagram, we see that there is a stabilized interaction that takes place between the water molecules in the aqueous environment and the polar head."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And likewise, we should always note, we should also note that there are also stabilizing interactions that take place between these adjacent sections here."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So the hydrocarbon portion of the adjacent hydrocarbon tails of these adjacent phospholipids."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, when the fossil lipid tries to rotate, it actually has to physically rotate and move through that hydrocarbon core of the membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Hydrocarbon core of that membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And when this happens is we actually lose these stabilizing interactions here and these stabilizing interactions here, as shown in this particular case."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So basically, the polar head does not actually want to interact and cannot interact in a stabilizing way with that hydrophobic core of the membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And likewise, the non polar tail portion of the fossil lipid also cannot and does not want to interact with the water molecules of the aqueous environment."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So we see that whenever a flip flop takes place, there is a certain amount of energy, a relatively large amount of energy that actually must be overcome."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So there's a large energy barrier to this process."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's because this process is energetically unfavorable."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "The interactions in this case aren't stabilizing like the interactions are in this particular case."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So we conclude that these fossil lipids can move relatively quickly and easily along a leaflet in the lateral direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "But even though phospholipids can actually flip flop, they can move transversely."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "This process takes place relatively slowly as a result of the high energy barrier that must be overcome."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, what about proteins?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Can proteins actually flip flop?"}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Well, proteins have a much higher hydrophilic region, so polar region, than these fossil lipids do."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's exactly why, if a protein is actually to flip flop, it has to overcome a very large energy barrier much higher than the energy barrier in the phospholipid rotation."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's exactly why these proteins do not actually flip flop."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "They do not actually transverse that membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "They only move along that lateral direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So proteins, which have much more extensive hydrophilic polar regions, must overcome an even higher energy barrier."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's exactly why they do not actually flip flop."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So we conclude three important points."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Point number one, phospholipids move relatively freely and quickly along the lateral direction."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And although proteins can also move relatively quickly along the lateral direction, some proteins are actually immobilized because of attachments to other structures."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, although these phospholipids can actually move transversely, they can flip flop."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "The rate at which they flip flop actually takes place at a much lower rate than lateral diffusion."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And proteins cannot diffuse altogether because of that high energy barrier that must be overcome."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "The polar region, the extensive polar region of the protein cannot interact in a favorable way with the hydrophobic core of that lipid bilayer membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Now, in fact, inside our membranes, we have these special proteins known as flipases that actually allow the movement of these phospholipids across that membrane."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "So lipases are proteins that can assist in the transverse diffusion of lipids."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And we'll discuss these in much more detail in future lectures."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And so number three proteins do not actually flip flop."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And this leads us directly to an important point that we're going to expand on in a future lecture."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "Basically, the fact that these proteins do not actually move transversely and the fact that phospholipids move transversely but do so at a very low rate, that basically implies that the asymmetry of the two leaflets can basically be preserved."}, {"title": "Flip-Flopping and Fluid Mosaic Model .txt", "text": "And that's a very important thing because if the asymmetry of the two sides of the membrane was not preserved, that membrane would basically lose its function functionality, as we'll see in more detail in a future lecture."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Glycolysis consists of three different stages."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And previously we focus on stage one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So we said that in stage one, that glucose molecule is initially transformed into glucose six phosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And what that does is it traps that glucose in a cell and begins to destabilize that glucose."}, {"title": "Stage 2 of Glycolysis .txt", "text": "It makes it more reactive."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, the second step in stage one, one is to basically transform the glucose isomer into the fructose isomer and we form fructose six phosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, the reason we have to form the fructose we'll talk about in just a moment."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But the final step in stage one is to take that fructose, fructose six phosphate and transform it into fructose one six bisphosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And once we form the fructose one six bisphosphate, that molecule is reactive enough to go on to stage two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And this is what I'd like to focus on in this lecture."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So let's begin by describing what the general goal is of stage two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So in stage two, the entire point is to take that highly reactive fructose one six bits phosphate molecule that was formed in stage one and to break it down and form two identical three carbon molecules we call glyceroaldehyde three phosphates or gap gap molecules."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, in this stage, there are actually two different processes and so we use two different enzymes."}, {"title": "Stage 2 of Glycolysis .txt", "text": "One enzyme is known as aldelase and the other enzyme is known as trio's phosphate IsomerA."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So let's begin by focusing on aldos and discuss the reaction that not aldos aldelase, and the reaction that aldolase actually catalyzes."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So aldelase is the enzyme that catalyzes the breakdown of that fructose one six bisphosphate into two different three carbon molecules."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And let's see exactly what these molecules are and what they look like."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So let's begin with that fructose one six bisphosphate in its cyclic form that is formed in stage one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So once we form this, then that aldelase moves into this area."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, before the aldelase can actually catalyze this reaction, this cyclic fructose must be transformed into its open chain counterpart."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And that's because this is the form that will allow the aldeways to actually get to this bond and cleave that bond."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So notice this molecule is color coded."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So the purple region is what eventually becomes this product here, the glyceroaldehyde three phosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But the blue section here is what eventually becomes the other different three carbon molecule known as dihydroxy acetone phosphate or simply DHAP."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So an enzyme called aldelase catalyzes the breakdown of fructose one six bisphosphate that is produced in stage one into two different three carbon molecules, glycero, aldehyde, three phosphate and dihydroxy acetone phosphate, DHAP."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, let's go back to a moment to stage one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So in stage one, the second step of stage one was to transform the glucose into the fructose isomer."}, {"title": "Stage 2 of Glycolysis .txt", "text": "The question is, why was that necessary?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "Well, the reason we transform the glucose into the fructose is so that once this step takes place in stage two, we form two molecules that each have three carbons."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Because if that glucose was not transformed into fructose, and it's the fructose one, six bits phosphate, that moved on to stage two, then once this reaction took place, in that case, we would have formed one molecule with two carbons and the other molecule with four carbons."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so to have this symmetry in which the two products have the same number of carbons, that's why in stage one, we have to transform that glucose into its isomer fructose."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, let's take a look at these two products."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Notice that one of these products is that product that we want to form in stage two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "It's the glyceroaldehyde three phosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, glyceroaldehyde three phosphate actually lies directly on the pathway of glycolysis."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And what that means is, once we form the gap molecule, it can go on directly into stage three without actually being modified in any way."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But what about the other product?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "What about dihydroxyapisode phosphate?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "So this molecule, unlike this molecule, this one, doesn't actually lie directly on the pathway of glycolysis."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so if this molecule is not actually modified in any way, if we leave this molecule as it is, it will not be able to move on to stage three."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so what will happen is we will essentially lose the potential to form ATP molecules in stage three, because if this one is not modified, it cannot go on to stage three."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so in the next step, what happens is, as we'll see in just a moment, this one is actually transformed into this one via an isomerization reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So actually, these two molecules are, in fact isomer."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So, once again, the glyceroaldehyde phosphate lies directly on the glycolytic pathway, which means it could go on directly into stage three to form the ATP molecules, the Pyruvate and the nadhs, as we'll see in the next lecture."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But the dihydroxyantone phosphate does not lie on that pathway directly."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And this means that if the DHAP is not changed in any way, is not transformed into this gap molecule, then what will happen is we will not be able to continue that glycosis process and therefore it will not be used to form those high energy ATP molecule that the cell needs so much to actually carry out processes."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so to prevent the loss of this potential energy that is stored in this three carbon molecule, the DHAP has to transform that molecule into the gap."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And this is where that second enzyme comes into play."}, {"title": "Stage 2 of Glycolysis .txt", "text": "The second enzyme that catalyzes the conversion of the DHAP into the gap, it's known as trios phosphate isomerase, or simply TPI."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Sometimes we also call it T imtim."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So an enzyme called trio sposphetosomerase TPI catalyzes the rapid and the reversible conversion of the DHAP to the gap."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So rapid simply means it takes place very quickly."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And reversible means once we go this way, the enzyme also catalyzes that reverse reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "In fact, once equilibrium is actually formed, this exists as the predominant molecule."}, {"title": "Stage 2 of Glycolysis .txt", "text": "In fact, 96% of the molecule is the DHAP and only 4% is the Gat."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, why is that not a problem?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "Well, it's not a problem because biliciously as principle, once the gap is fed into stage three, it will be used up."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And as soon as we use up this product molecule by lacitley as principal, the equilibrium will basically shift to the product side and this will be continually transformed into the product as we basically pull this away and feed it into stage three."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, let's see exactly what trio's phosphate actually does."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So we have carbon one, carbon two, carbon three, carbon one, carbon two, carbon three."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, notice this is the same molecule as we have in this particular case."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, I've labeled this hydrogen as the blue hydrogen."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And the reason is because in this reaction, the net changes, the movement, the transfer of the age from carbon one onto the carbon two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so this is nothing more than an oxidation reduction reaction in which this trio spausia isomerase basically transforms this ketos into an aldos by transferring the eight from carbon one onto this carbon number two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So we see that trio's phosphate, isomerase TPI catalyzes, the conversion of the keto, the DHAP, into the aldos, the gap, via an intramolecular oxidation reduction reaction in which a hydrogen is transferred from carbon one onto carbon two."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So this is a keto is because we have the carbon attached onto two carbons here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "This is an aldos because we have an H and a carbon atom attached to the carbon of the carbonyl."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, that's the general idea of what happens, but what exactly happens within the active side of this enzyme?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "So let's take a look at the following four picture diagrams."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So let's begin with diagram one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, if we go into the active side of this enzyme, we'll basically see a bunch of these alpha beta barrels."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So we'll see these structures, and in the active side, there are basically two catalytic residues that catalyze this reaction and they catalyze via an acid base reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So we'll see exactly what that means in just a moment."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So what are these two catalytic residues?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "Well, we have the glue 165 and the his 95."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, the glue 165 in the first step acts as a base, and the his 195 in the first step acts as an acid."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So essentially, this histidine 95 donates an H to this carbon."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So essentially, this pi bond here goes on to take the H away."}, {"title": "Stage 2 of Glycolysis .txt", "text": "At the same time this acts as a base and takes away that H. And so what happens is, once this bond is broken, when the H is taken away, this reforms a pi bond between this carbon one and this carbon two to form this intermediate that contains two alcohol groups."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And that's why we call it an anodial intermediate dial simply means we have two hydroxyl, two alcohol groups, one here and one here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, by the way, if we take this molecule and we flip it upside down, this is basically the orientation of this molecule here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So this is carbon one, carbon one, carbon two, carbon two, and carbon three, carbon three."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now let's move on to this second step."}, {"title": "Stage 2 of Glycolysis .txt", "text": "In the second step, this basically so this molecule, this nitrogen that's lost an H shown here, basically acts as a base, takes away the H from this oxygen."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so once we take away that H, we form this intermediate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, this intermediate is not very stable because it contains a negative charge on the oxygen."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so that negative charge wants to go away."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so what happens is this lone pair of electrons and this oxygen forms a pi bond."}, {"title": "Stage 2 of Glycolysis .txt", "text": "At the same time, this pipeline here between carbon one and two actually breaks."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And those two electrons in the pi bond go and grab that H atom shown in blue."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And this is the same H atom that was initially attached onto carbon number one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so we see that's how the carbon moves from carbon one to carbon number two as a result of this process."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So in this process, the H is temporarily transferred onto the oxygen from carbon one."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And then carbon two grabs that same HOA from that oxygen of this catalytic residue."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so, in the final step, we basically form this molecule, the aldos, our gap."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And we also reform these two catalytic residues of the enzyme because, remember, enzymes are never actually used up at the end."}, {"title": "Stage 2 of Glycolysis .txt", "text": "They have to be regenerated."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so, ultimately, this is the process by which this catalysis reaction actually takes place."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, there are two important things that this enzyme, trio phosphate isomerase, actually does."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Number one is it greatly increases the rate of the reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And that's not surprising because that's exactly what catalysts actually do."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But the rate at which it increases is by a value of 10 billion."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And that's a very, very high rate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "That's why we say this reaction is very, very rapid."}, {"title": "Stage 2 of Glycolysis .txt", "text": "It takes place very quickly."}, {"title": "Stage 2 of Glycolysis .txt", "text": "Now, the second thing, important thing that the enzyme actually does is it creates this pocket of space that places this molecule in close proximity with these two catalytic residues."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So that speeds up the reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But what it also does is it prevents other reactions, competing reactions, from actually taking place."}, {"title": "Stage 2 of Glycolysis .txt", "text": "For instance, let's suppose this enzyme was not here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "If the enzyme was not here, what exactly would be the pathway of this molecule right over here?"}, {"title": "Stage 2 of Glycolysis .txt", "text": "Well, instead of following this pathway, another reaction that would be 100 times more likely to actually take place in the absence of this enzyme is this reaction here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so instead of forming this final product, this molecule will be 100 times more likely to go on and form this molecule here."}, {"title": "Stage 2 of Glycolysis .txt", "text": "That's why it's so important that this enzyme is actually here, because in the absence of this enzyme, this DHAP, would go on to form the nodiol intermediate, but then the nodiol intermediate would be 100 times more likely to go on and form this product, which we actually don't want to form."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And so what this enzyme does is it basically stops these competing reactions from actually taking place."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And the way that it stops them is it places this molecule into this active side, into this perfect environment in which these catalytic residues can actually interact and promote this specific type of reaction."}, {"title": "Stage 2 of Glycolysis .txt", "text": "And that's why we need this trio's phosphate isomerase in the cell, because it's the molecule that can very quickly and rapidly transform this molecule, die hydroxy acid phosphate, into the molecule that we want."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So the glycero aldehyde three phosphate."}, {"title": "Stage 2 of Glycolysis .txt", "text": "So to conclude, we see it's that the point of stage two is to take this fructose one six bisphosphate that was formed in stage one and to transform it into two identical glycerol dehyd three phosphate molecules."}, {"title": "Stage 2 of Glycolysis .txt", "text": "But the way that actually takes place."}, {"title": "Glucose Transporters .txt", "text": "Inside our body, we have all these different types of cells, trillions of cells."}, {"title": "Glucose Transporters .txt", "text": "And these cells carry out these biochemical processes."}, {"title": "Glucose Transporters .txt", "text": "And many of these biochemical processes exist in every single cell of our body."}, {"title": "Glucose Transporters .txt", "text": "For instance, glycolysis takes place in every single cell of our body."}, {"title": "Glucose Transporters .txt", "text": "Now, we know that we have many different types of cells and many different types of tissues."}, {"title": "Glucose Transporters .txt", "text": "And what that means means is these different types of cells, even though they carry out the same type of process for instant glycolysis, the requirements for those biochemical processes in the different types of cells actually might be different."}, {"title": "Glucose Transporters .txt", "text": "And so what that means is our cells must also be able to closely regulate these biochemical processes and fine tune those regulatory pathways to actually meet the needs and demands of those specific types of cells."}, {"title": "Glucose Transporters .txt", "text": "And one way by which our body is able to actually regulate and fine tune these specific biochemical processes in the different types of cells in our body is by using molecules known as isozymes or Isa enzymes."}, {"title": "Glucose Transporters .txt", "text": "And we actually discussed many examples of isozymes previously."}, {"title": "Glucose Transporters .txt", "text": "For instance, when we discussed the regulatory pathway of glycolysis in skeletal muscle cells and liver cells, we said that pyruvate kinase, the enzyme that catalyzes the final step in glycolysis that we find in skeleton muscle cells and in liver cells, actually come in different forms."}, {"title": "Glucose Transporters .txt", "text": "In muscle cells, we have predominantly the misosign, but in liver cells we have predominantly that l isosine of pyruvate kinase."}, {"title": "Glucose Transporters .txt", "text": "And although they carry out the same type of catalytic and regulatory process, they do have slightly different properties."}, {"title": "Glucose Transporters .txt", "text": "And that's because they have slightly different amino acid sequences and slightly different structures."}, {"title": "Glucose Transporters .txt", "text": "So we see that isozymes are proteins that carry out the same type of biochemical process, but have slightly different amino acid sequences and slightly different structures."}, {"title": "Glucose Transporters .txt", "text": "And so because of that, they display slightly different properties."}, {"title": "Glucose Transporters .txt", "text": "For instance, they might have different mechanics, constant values, they might have different turnover numbers and so forth."}, {"title": "Glucose Transporters .txt", "text": "Now these is allow our body to actually fine tune these regulatory pathways to actually meet the needs and demands of all different types of cells that exist inside our body."}, {"title": "Glucose Transporters .txt", "text": "Now, what I'd like to focus on in this lecture is the biochemical process by which we actually bring the glucose molecules into the cells of our body."}, {"title": "Glucose Transporters .txt", "text": "So remember, glucose molecules have many polar groups, they have many hydroxyl groups, and that makes glucose a polar molecule."}, {"title": "Glucose Transporters .txt", "text": "And so what that means is, even if we have a concentration gradient that exists across the cell membrane, because the membrane is predominantly nonpolar hydrophobic, these polar glucose molecules and sugar molecules cannot make their way across the cell membrane."}, {"title": "Glucose Transporters .txt", "text": "And so the cells create these transmembrane proteins that contain twelve transmembrane alpha helices that we call glucose transporters."}, {"title": "Glucose Transporters .txt", "text": "And these allow the movement, allow the shuttling of these glucose molecules across the cell membrane."}, {"title": "Glucose Transporters .txt", "text": "So essentially, upon the binding of the glucose molecule or other monosaccharide onto the glucose transporter, a conformational change takes place that allows the movement of that glucose or other monosaccharide into the cytoplasm of that cell."}, {"title": "Glucose Transporters .txt", "text": "So let's suppose we have a high concentration of glucose in the blood plasma, a low amount in the inside the cell."}, {"title": "Glucose Transporters .txt", "text": "And so the glucose will move down into concentration gradient from the outside to the inside."}, {"title": "Glucose Transporters .txt", "text": "So inside our body, to be able to fine tune the regulation of this biochemical process, we basically depend on different types of isozymes of glucose transporters."}, {"title": "Glucose Transporters .txt", "text": "And in fact, we have over ten different isozymes of glucose transporters."}, {"title": "Glucose Transporters .txt", "text": "And in this lecture, we're going to focus on the first five, perhaps the most important of these glucose transporter molecules."}, {"title": "Glucose Transporters .txt", "text": "So we have glute one, glute two, glute three, glute four and glute five, where glute basically stands for glucose transporter."}, {"title": "Glucose Transporters .txt", "text": "Let's begin with glute one and glute three."}, {"title": "Glucose Transporters .txt", "text": "Now, glute one as well as glute three are actually responsible for establishing something called the basal rate of glucose uptake."}, {"title": "Glucose Transporters .txt", "text": "So what exactly is the basal rate of glucose uptake?"}, {"title": "Glucose Transporters .txt", "text": "Well, it's basically the rate at which these glucose molecules are continually being taken up by the cell, even when our body is at rest."}, {"title": "Glucose Transporters .txt", "text": "Because our cells essentially always require these glucose molecules to create ATP molecules to carry out all the different types of processes."}, {"title": "Glucose Transporters .txt", "text": "Because just because we're at rest, that doesn't mean our cells aren't actually carrying out these processes."}, {"title": "Glucose Transporters .txt", "text": "So we find these glute one molecules essentially in all the cells of our body."}, {"title": "Glucose Transporters .txt", "text": "But these glute one membrane proteins predominate in the membranes of red blood cells, while the glute three predominate in the membranes of neurons found in the brain."}, {"title": "Glucose Transporters .txt", "text": "So we find them on dendrites as well as on exons of neurons found in the brain."}, {"title": "Glucose Transporters .txt", "text": "Now, both of these glucose transporters, glute one and glute three, basically have a relatively low Km value."}, {"title": "Glucose Transporters .txt", "text": "Now, before we talk about that, let's define what the concentration of glucose is normally in our blood."}, {"title": "Glucose Transporters .txt", "text": "So the blood glucose levels are maintained at around a value of 5 million molar."}, {"title": "Glucose Transporters .txt", "text": "That's the concentration."}, {"title": "Glucose Transporters .txt", "text": "And the Km value of these two transporters is around 1 million molar."}, {"title": "Glucose Transporters .txt", "text": "Now notice that first of all, it's lower than the five than the normal amount in our blood."}, {"title": "Glucose Transporters .txt", "text": "And before we discuss what that actually means, let's remember what a Km value actually tells us."}, {"title": "Glucose Transporters .txt", "text": "So the Km is simply the Mikhailus constant and the Km value basically tells us the concentration at which exactly half of the active size of that particular enzyme are actually filled."}, {"title": "Glucose Transporters .txt", "text": "And that gives us the velocity value that is exactly half of the maximum velocity value."}, {"title": "Glucose Transporters .txt", "text": "And because the Km value is much lower than the five millimolar value, what that means is these are very effective at binding those glucose molecules and transporting those glucose molecules across the cell."}, {"title": "Glucose Transporters .txt", "text": "So because of the low Km values of these two glucose transporters, we see that when we have a five millimolar concentration of blood glucose, which is the normal one."}, {"title": "Glucose Transporters .txt", "text": "These molecules are continually shuttling and moving these glucose molecules down their concentration gradient."}, {"title": "Glucose Transporters .txt", "text": "So, once again, glute one is the glucose transported that we find all over our body in all different types of cells."}, {"title": "Glucose Transporters .txt", "text": "And we find them predominantly in the membranes of red blood cells."}, {"title": "Glucose Transporters .txt", "text": "And these are responsible, along with the help of glute three, for generating the basal rate of glucose uptake."}, {"title": "Glucose Transporters .txt", "text": "So we see that blood glucose levels are maintained at a value of around five millimolar concentrations."}, {"title": "Glucose Transporters .txt", "text": "But the Km value of glute one, as well as glute three is around 1 million molar."}, {"title": "Glucose Transporters .txt", "text": "And what that means is they have a very high affinity for the substrate molecule of the glucose."}, {"title": "Glucose Transporters .txt", "text": "And under these normal blood concentrations of glucose, these two transporters are continually on and they're continually moving these glucose molecules down their concentration gradient."}, {"title": "Glucose Transporters .txt", "text": "Now, let's talk a bit more about the glute three."}, {"title": "Glucose Transporters .txt", "text": "So the glute three are these molecules that also generate the basal uptake rate, but we also find them predominantly in the nerve cells found inside our brain, in the neurons."}, {"title": "Glucose Transporters .txt", "text": "We find them in the membrane of the dendrites, as well as the axons of the nerve cells of the brain."}, {"title": "Glucose Transporters .txt", "text": "Now, why is it important that we have a high concentration of these glute three in the brain?"}, {"title": "Glucose Transporters .txt", "text": "Well, because the brain cells depend on glucose molecules."}, {"title": "Glucose Transporters .txt", "text": "And the brain cells are arguably some of the most important cells in our body."}, {"title": "Glucose Transporters .txt", "text": "And they need to get that glucose first before any other cell actually gets the glucose."}, {"title": "Glucose Transporters .txt", "text": "And so that's why they have a high concentration of the glute three, because this has a Km value around one."}, {"title": "Glucose Transporters .txt", "text": "That makes it very, very effective in binding that glucose and bringing that glucose into the cytoplasm of the nerve cells."}, {"title": "Glucose Transporters .txt", "text": "Now let's move on to glute three, glute four and glute five."}, {"title": "Glucose Transporters .txt", "text": "And let's imagine that we just ingested a meal that is high in carbohydrates."}, {"title": "Glucose Transporters .txt", "text": "And what that basically means is the blood level of glucose will essentially rise."}, {"title": "Glucose Transporters .txt", "text": "And what will begin to happen is the beta cells of our pancreas of the eyelids of Langerhons will begin to produce insulin."}, {"title": "Glucose Transporters .txt", "text": "And what allows those cells, the beta cells of the pancreas, to actually sense this increase in the glucose levels in the blood are these glute two protein membranes."}, {"title": "Glucose Transporters .txt", "text": "So these transporters are typically found in the pancreas."}, {"title": "Glucose Transporters .txt", "text": "So the beta cells of the pancreas that release the insulin, as well as the liver, and we also find them in the vasilateral membrane of things like the kidneys, as well as our intestines."}, {"title": "Glucose Transporters .txt", "text": "And so these membrane proteins, unlike these two, actually have a relatively large Km value of 15 nm."}, {"title": "Glucose Transporters .txt", "text": "Now, why is that physiologically significant?"}, {"title": "Glucose Transporters .txt", "text": "Well, what that basically means is the liver cells and the pancreas cells will only begin to uptake the glucose molecules and will only begin to sense the presence of these glucose molecules if the blood levels rise."}, {"title": "Glucose Transporters .txt", "text": "And this only happens after we actually eat a meal rich in carbohydrate, so after we eat that carbohydrate rich meal, the blood glucose levels will rise."}, {"title": "Glucose Transporters .txt", "text": "And that will allow these glue too to actually sense that increase in glucose levels, because they have a km value that is high, so they're not as effective in binding the glucose as these two other molecules."}, {"title": "Glucose Transporters .txt", "text": "And that's important, because they don't need to be effective, because it's the brain cells and muscle cells of our body that need that glucose more than the liver cells."}, {"title": "Glucose Transporters .txt", "text": "And so once we eat, it's these liver cells that begin to secrete the insulin."}, {"title": "Glucose Transporters .txt", "text": "And the insulin, as we'll see in just a moment, actually goes on and affects glute four."}, {"title": "Glucose Transporters .txt", "text": "So let's finish with glute two."}, {"title": "Glucose Transporters .txt", "text": "So this implies that because they have a high km value, they have a low affinity for the glucose substrate molecules and will only uptake the glucose at high blood glucose levels."}, {"title": "Glucose Transporters .txt", "text": "So, after we eat a carbohydrate rich meal, now let's move on to glute four."}, {"title": "Glucose Transporters .txt", "text": "So, glute four we actually find in our muscle cells and adipose tissue, so fat cells of our body, and the km value of these transporters is around five millimolar."}, {"title": "Glucose Transporters .txt", "text": "So it's not as low as these two and it's not as high as this."}, {"title": "Glucose Transporters .txt", "text": "And actually, these glute four membrane proteins are sensitive to the insulin."}, {"title": "Glucose Transporters .txt", "text": "So the insulin is able to actually stimulate these muscle cells and adipose tissue cells, so fat cells to express more of these glute four on the membrane of these cells."}, {"title": "Glucose Transporters .txt", "text": "And once they express more of these glute four, they're able to actually uptake all those glucose molecules from the blood plasma following the ingestion of that carbohydrate rich meal."}, {"title": "Glucose Transporters .txt", "text": "So glute four are found in the cells of muscle and adipose tissue, they have a km value, the maclus constant of about five millimolar and respond to insulin."}, {"title": "Glucose Transporters .txt", "text": "And following food ingestion, muscle and fat cells express many more glute four membrane proteins to assist with glucose uptake."}, {"title": "Glucose Transporters .txt", "text": "So we essentially ingest that food, our glucose levels basically rise, and the rise in glucose levels allow the liver cells and our kidney cells and other cells to basically uptake that glucose as a result of the action of this glue too."}, {"title": "Glucose Transporters .txt", "text": "And the pancreas cells also uptake the glucose, sensing that glucose increase."}, {"title": "Glucose Transporters .txt", "text": "And so the pancreas releases the insulin, which goes on to stimulate the muscle cells and fat cells to begin basically expressing more of these glute four, to uptake more of those glucose molecules to essentially bring that glucose level in the blood back to normal, back to a value of about five millimolar."}, {"title": "Glucose Transporters .txt", "text": "And finally, I'd also like to mention glute five, because glute five is actually responsible for uptaking the fructose monosaccharides that we find in the small intestine following a carbohydrate rich meal."}, {"title": "Glucose Transporters .txt", "text": "So glute five is found predominantly on the apical side of the small intestine cells, and these are responsible for actually uptaking those fructose monosaccharide molecules from the lumen of the small intestine."}, {"title": "Glucose Transporters .txt", "text": "So we see that this individual process of taking up the glucose molecules into the cell is very important and must take place in every single cell of our body."}, {"title": "Glucose Transporters .txt", "text": "But because different cells basically have different requirements requirements, we must be able to fine tune this process to meet the to meet the needs of those specific cells."}, {"title": "Glucose Transporters .txt", "text": "And that's where these different ISMES actually come into play."}, {"title": "Life Cycle of HIV .txt", "text": "To gain a better understanding of how viruses actually infect cells and specifically how viruses infect human cells, let's take a look at the way that our HIV actually gets inside the human cell, the cells found in the immune system of the human body and how the HIV essentially replicates and creates more HIV cells systems."}, {"title": "Life Cycle of HIV .txt", "text": "So HIV is a human virus, is a virus that infects human cells and it stands for human immunodeficiency virus and it can basically lead to AIDS."}, {"title": "Life Cycle of HIV .txt", "text": "Now, basically the way that the HIV system looks like is as following."}, {"title": "Life Cycle of HIV .txt", "text": "We have our single stranded RNA molecules shown in red, found inside the protein capsid shown in green."}, {"title": "Life Cycle of HIV .txt", "text": "And inside that capsid we also have different types of proteins."}, {"title": "Life Cycle of HIV .txt", "text": "We have a specific type of protein known as reverse transcriptase, which is basically a protein enzyme that acts to transcribe RNA into DNA as we'll see in just a moment."}, {"title": "Life Cycle of HIV .txt", "text": "Now, the HIV also contains the purple lipidrich layer and this purple lipid rich layer contains protrusions which are basically receptors which will bind to the protein receptors found on the cell membrane of the human cell."}, {"title": "Life Cycle of HIV .txt", "text": "So in step number one, we basically have the HIV, the virus that approaches the cell membrane of our human cell."}, {"title": "Life Cycle of HIV .txt", "text": "And in step two we have the binding process taking place."}, {"title": "Life Cycle of HIV .txt", "text": "These purple protrusions basically bind to the receptors, the protein receptors found on the cell membrane and specifically they bind to the protein receptors called CD four and CCR four."}, {"title": "Life Cycle of HIV .txt", "text": "Now, once that binding takes place and the HIV recognizes this specific type of human cell, we have the fusion taking place, the fusion between this lipid rich layer found on the virus and the cell membrane of that human host cell."}, {"title": "Life Cycle of HIV .txt", "text": "So in three, once bound, the lipid rich envelope of the virus fuses with the plasma membrane of the host human cell injecting the contents, including the proteins as well as the single RNA molecules into the cytoplasm of that cell."}, {"title": "Life Cycle of HIV .txt", "text": "And next we move on to step number four."}, {"title": "Life Cycle of HIV .txt", "text": "In step number four, right within the cytoplasm of that human cell, these reverse transcriptase enzymes basically transcribe the RNA into DNA and we form the viral double stranded DNA as shown in blue."}, {"title": "Life Cycle of HIV .txt", "text": "So we form one and two strands and then they basically fuse to form our double stranded DNA, the viral double stranded DNA."}, {"title": "Life Cycle of HIV .txt", "text": "Now, in step five we have the viral double stranded DNA, then basically travels into the nucleus of that cell and in the nucleus of that cell, another special type of enzyme known as retroviral integrates or simply integrates, acts to basically integrate or incorporate that viral double stranded DNA shown in blue into the DNA genome of that human cell."}, {"title": "Life Cycle of HIV .txt", "text": "Now, once that actually takes place, we move on to step six."}, {"title": "Life Cycle of HIV .txt", "text": "So in step six, the cell then transcribes the viral DNA back into the viral RNA as well as viral mRNA that can be used to synthesize viral proteins."}, {"title": "Life Cycle of HIV .txt", "text": "So in step six, we see that the ribosomes of our human cell basically use the mRNA, the viral mRNA, to produce special types of proteins that need to be used by the new HIV system, by the new virus, the HIV system."}, {"title": "Life Cycle of HIV .txt", "text": "Now we move on to step seven."}, {"title": "Life Cycle of HIV .txt", "text": "Once we synthesize all the proteins as well as the protein capsid within the cytoplasm of the cell, all these important contents then basically move towards the cell membrane of the human cell and they begin to push on that cell membrane to form this lipid layer, as shown in purple."}, {"title": "Life Cycle of HIV .txt", "text": "So the single strand viral RNA, as well as the viral proteins move towards the membrane of the cell and begin to push outward on that cell membrane."}, {"title": "Life Cycle of HIV .txt", "text": "And finally, in step seven, once our system is outside, the virus matures into our HIV system, the human immunodeficiency virus that can go on to infect other cells within the human body."}, {"title": "Life Cycle of HIV .txt", "text": "So this is basically the lifecycle of HIV."}, {"title": "Life Cycle of HIV .txt", "text": "It's the method by which the HIV system infects the human cells and uses them machinery, the organelles of the human cell, to basically replicate our HIV system, to produce more HIV systems that can go on to, in fact even more HIV, even more cells."}, {"title": "Life Cycle of HIV .txt", "text": "And this can basically lead to a syndrome known as AIDS."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So far we discussed DNA molecules and we said that DNA molecules inside our cells exist predominantly as a double helix structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, this double helix structure consists of two individual strands of nucleic acids."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So we have these two strands of DNA molecules running in an antiparallel fashion and bonding via hydrogen bonds and Vanderbilt forces."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, what about the other type of nucleic acid?"}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So we also have ribonucleic acids, RNA molecules."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "The question is what exactly is the structure of these RNA molecules?"}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Well, unlike DNA molecules which exist in a double stranded form, RNA molecules inside our cells exist mostly as single strands of nucleotides."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "But these single trans of nucleotides under the conditions found in our cells usually twist and fold into a well defined threedimensional structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, the most common type of form that these RNA molecules fold into is known as a stem loop form."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And this stem loop form is formed when the ribonucleic acid folds into this double helical structure just like in DNA in which we contain these complementary sequences, these complementary nucleotides that can form base pairs."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "But in these stem loop structures we also commonly contain these mismatched nucleotides and that destabilizes our structure in that localized region and causes the bulging out of that structure as we'll see in just a moment."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So let's suppose we have the following sequence of nucleotides in a given RNA molecule."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So this is the beginning, the five end and this is the end, the three end of the ribonucleic acid."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, if we take this RNA molecule and place it into an aqueous environment found in our cell, it can fold into some type of three dimensional structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And to demonstrate what a stem loop structure actually looks like, let's suppose it folds into the following structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So this is the five and here and this is the three and here."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, notice that this sequence C-U-G-A GGU, is complementary to the sequence gacucca."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, what that means is these will essentially fold onto themselves to basically interact because these two sequences of RNA are complementary."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And that means when they interact, they form these hydrogen bonds which is a stabilizing effect."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And we form the following stem of this structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, this is the loop and that's because when these two interact we have this section here that is not complementary to itself."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And so it will form this loop structure in which we don't have any hydrogen bonds formed between these bases."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And that means this will destabilize this localized region of the structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And that can play an important role in further determining what that RNA molecule actually folds into."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And we'll discuss that in much more detail in future lectures."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So this is what we call a stem loop diagram."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "We have this stem section here in which the DNA molecules essentially intertwine along a common axis."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And this is the same type of structure that we see in the DNA molecules."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So we have these two complementary strands."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "The problem here is these strands actually consist of a single strand and in DNA molecules we have two different strands."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So in RNA molecules because they exist predominantly as a single strand these complementary sequences here and here."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So the blue and the red come from that same polynucleotide chain."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "But in DNA the complementary sequences in the double helix structure come from two opposite polynucleotide chains."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So that's the difference between the double helix in DNA and the double helix in RNA molecules."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So we have these complementary sections that interact to form hydrogen bonds and that's a stabilizing effect."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "While this is the loop, they contain the mismatched nucleotides and that means they cannot interact and so they will destabilize this localized region of space in our RNA molecule."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, just like in proteins we have this tertiary structure and secondary structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "RNA molecules can also form secondary and tertiary structures."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So when nucleotides found in close proximity along that particular polynucleotide chain interact via these hydrogen bonds between the nucleotide bases that can form a secondary structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "In fact when we have these nucleotides down far away interacting via these base pairings then that can form tertiary structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So just like proteins contain this secondary and tertiary structure because these bases along the polynucleotide chain of the RNA molecule can interact with one another RNA molecules can also form secondary and tertiary structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And this complexity, this ability of the RNA molecule to form this complex structure gives it the ability to function in many different ways."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And this means just like proteins can function biological catalysts RNA molecules can also act as biological catalysts as we'll see, for example when we discuss the process of protein synthesis."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So in protein synthesis we have these cellular machinery structures known as ribosomes and ribosomes contain RNA molecules and these RNA molecules act as biological catalysts to basically synthesize that protein chain."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And we'll discuss that in much more detail in a future lecture."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "Now, the final thing that I like to mention is the tRNA molecule or the transfer RNA molecule as we'll see in a future lecture there are many types of RNA molecules that exist inside our cells and these RNA molecules can basically act in certain specific ways."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "One of these RNA molecules is the tRNA molecule and this is the shape that the tRNA molecule actually takes."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So we have one, two, three of these loops and these loops are a result of these mismatched nucleotides and so they destabilize the structure ever so slightly."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "But we also have these stabilizing regions, the stem regions where we have these complementary sequence of nucleotides."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "For example, here we have Ugcg and this is ACGC which is complementary to that blue sequence."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And so these stabilize the structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "They intertwine in the way that we show here."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "While these sections essentially destabilize the molecule and because of this specific structure of our RNA molecule what it is able to do is it is able to actually find and carry the specific amino acid to the ribosome and that allows the elongation and the synthesis of protein molecules."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "So just like proteins can form secondary intertwined structure, our RNA molecule molecules can also exist as these molecules that contain secondary and terrace share structure."}, {"title": "Stem-Loop Structure of RNA .txt", "text": "And the most common type of structure is the stem loop structure of RNA molecules."}, {"title": "The Menstrual Cycle .txt", "text": "As a woman begins to approach puberty, her hypothalamus, found in the brain, begins to release a special hormone known as the gonadotropinreleasing hormone or GnRH."}, {"title": "The Menstrual Cycle .txt", "text": "And what this hormone does is it goes down to the anterior pituitary gland found right below the hypothalamus in the brain and it stimulates it to release two important hormones."}, {"title": "The Menstrual Cycle .txt", "text": "One called the luteinizing hormone LH and another one called the follicle stimulating hormone or FSH."}, {"title": "The Menstrual Cycle .txt", "text": "And what these two hormones do is they go down to the ovaries and they activate the ovaries."}, {"title": "The Menstrual Cycle .txt", "text": "Now, by activating the ovaries, they initiate a monthly process known as the menstrual cycle."}, {"title": "The Menstrual Cycle .txt", "text": "Now what the menstrual cycle is it's a series of events that lasts about 28 days."}, {"title": "The Menstrual Cycle .txt", "text": "Now of course, this number can differ from one individual to another."}, {"title": "The Menstrual Cycle .txt", "text": "In some women it's slightly longer, in others it's slightly shorter."}, {"title": "The Menstrual Cycle .txt", "text": "But the entire point of this menstrual cycle is to ultimately prepare that woman for a possible pregnancy."}, {"title": "The Menstrual Cycle .txt", "text": "And more specifically, it's to prepare the lining of the uterus for a possible implantation by a zygote."}, {"title": "The Menstrual Cycle .txt", "text": "Now we know a zygote is only formed if the woman is sexually active, if fertilization actually takes place."}, {"title": "The Menstrual Cycle .txt", "text": "But most of the time fertilization does not take place."}, {"title": "The Menstrual Cycle .txt", "text": "So what happens during the menstrual cycle?"}, {"title": "The Menstrual Cycle .txt", "text": "Well, what happens if fertilization does not occur is the inner lining that is developed during the cycle known as the endometrium begins to break down and it is discharged along with that secondary oicide in a process known as menstruation."}, {"title": "The Menstrual Cycle .txt", "text": "And this is categorized by bleeding and by cramping."}, {"title": "The Menstrual Cycle .txt", "text": "So this is what women experience on a monthly basis as a result of the fact that no fertilization of their excel actually takes place."}, {"title": "The Menstrual Cycle .txt", "text": "So generally speaking, the menstrual cycle can be broken down into three phases."}, {"title": "The Menstrual Cycle .txt", "text": "We have the follicular phase, we have ovulation and we have the luteal phase."}, {"title": "The Menstrual Cycle .txt", "text": "Now the follicular phase is categorized by the development of the immature XL into the mature Xcel."}, {"title": "The Menstrual Cycle .txt", "text": "So we go from a primary OSI to a secondary OSI."}, {"title": "The Menstrual Cycle .txt", "text": "Now, once that follicle has matured, the follicle ruptures in a process known as ovulation."}, {"title": "The Menstrual Cycle .txt", "text": "The second phase and ovulation releases that secondary OCIL into the peritoneal cavity and then into the fallopian tube."}, {"title": "The Menstrual Cycle .txt", "text": "And the final phase is called the luteal phase."}, {"title": "The Menstrual Cycle .txt", "text": "This is the process by which inside the ovary we form that corpus luteum that acts as a gland during the menstrual cycle, as we'll see in just a moment."}, {"title": "The Menstrual Cycle .txt", "text": "Now, menstruation actually takes place at the beginning of the follicular phase and at the end of our luteal phase."}, {"title": "The Menstrual Cycle .txt", "text": "So let's take a look at the following diagrams that describe the menstrual cycle."}, {"title": "The Menstrual Cycle .txt", "text": "And then let's describe the different steps of the menstrual cycle."}, {"title": "The Menstrual Cycle .txt", "text": "So if we examine the diagram, notice the X axis describes our progression of days."}, {"title": "The Menstrual Cycle .txt", "text": "So we begin at day zero and we end at day 28."}, {"title": "The Menstrual Cycle .txt", "text": "And then the cycle repeats all over again."}, {"title": "The Menstrual Cycle .txt", "text": "Now, what this describes is the increase in thickness of the endometrium found on the walls of the uterus."}, {"title": "The Menstrual Cycle .txt", "text": "So we have an increase in the endometrium."}, {"title": "The Menstrual Cycle .txt", "text": "Eventually we reach a point where the zygote does not implant because no fertilization took place."}, {"title": "The Menstrual Cycle .txt", "text": "And then we have the process of menstruation, which basically decreases the thickness of that endometrium back to its basal of value."}, {"title": "The Menstrual Cycle .txt", "text": "Now, what this describes is the fluctuation, the change in concentration of the levels of the hormone."}, {"title": "The Menstrual Cycle .txt", "text": "So we have four hormones we have to consider."}, {"title": "The Menstrual Cycle .txt", "text": "We have estrogen shown in green."}, {"title": "The Menstrual Cycle .txt", "text": "We have progesterone, shown in blue."}, {"title": "The Menstrual Cycle .txt", "text": "We have the luteinizing hormone in red."}, {"title": "The Menstrual Cycle .txt", "text": "And we have the follicle stimulating hormone in purple."}, {"title": "The Menstrual Cycle .txt", "text": "And finally, this describes the development of that follicle, the rupture of the follicle, the release of the secondary oxide and the formation of the corpus luteum and the eventual deterioration of the corpus luteum into the corpus albicans assuming no fertilization actually took place."}, {"title": "The Menstrual Cycle .txt", "text": "So in this lecture we're going to assume that no fertilization actually takes place."}, {"title": "The Menstrual Cycle .txt", "text": "So let's begin at the beginning what happens during the follicular phase."}, {"title": "The Menstrual Cycle .txt", "text": "So during the follicular phase, at the beginning we have menstruation."}, {"title": "The Menstrual Cycle .txt", "text": "And so part of the endometrium is actually discharged along with that secondary oicide."}, {"title": "The Menstrual Cycle .txt", "text": "And so what begins to happen is the hypothalamus of that woman begins to release the gonadotropin releasing hormone GnRH."}, {"title": "The Menstrual Cycle .txt", "text": "And what GnRH does is it stimulates the release of the follicle stimulating hormone and the luteinizing hormone from the interior pituitary gland."}, {"title": "The Menstrual Cycle .txt", "text": "Now these two hormones then go down to the ovary and affect the immature follicle the follicle stimulating hormone as well as LH causes that follicle to begin to develop into the secondary follicle."}, {"title": "The Menstrual Cycle .txt", "text": "So what happens first is the primary follicle or the primary oocide in the primary follicle undergoes meiosis one and produces a secondary follicle."}, {"title": "The Menstrual Cycle .txt", "text": "And inside that secondary follicle we have that secondary oicide."}, {"title": "The Menstrual Cycle .txt", "text": "So to see what we mean, let's take a look at the following diagram so initially the GnRH causes, let's say, the follicle stimulating hormone to increase in concentration as shown in the following diagram."}, {"title": "The Menstrual Cycle .txt", "text": "And as FSH increases, that stimulates the primary follicle to become the secondary follicle."}, {"title": "The Menstrual Cycle .txt", "text": "Now inside the secondary follicle."}, {"title": "The Menstrual Cycle .txt", "text": "So this is the mature secondary follicle."}, {"title": "The Menstrual Cycle .txt", "text": "We have this fluid shown in green and we have the actual x cell, the secondary oocyte shown in red."}, {"title": "The Menstrual Cycle .txt", "text": "And all these cells around the follicle are the FECA cells and the granulosa cells."}, {"title": "The Menstrual Cycle .txt", "text": "And we'll discuss their function in just a moment."}, {"title": "The Menstrual Cycle .txt", "text": "So as our LH de luthanizing hormone and FSH, follicle stimulating hormone, increases in concentration, they affect the, theca cells and the granulosa cells found in the follicle."}, {"title": "The Menstrual Cycle .txt", "text": "So our LH stimulates the Thicka cells to produce androgens and the androgens are taken up by the other cells called the granulosis cells, also found the follicle and the granulosis cells, they use the androgens to produce estrogen."}, {"title": "The Menstrual Cycle .txt", "text": "And that's exactly why, if we look at the diagram, when the follicle begins to develop, the estrogen concentration shown in green begins to increase in concentration."}, {"title": "The Menstrual Cycle .txt", "text": "So we have an increase as shown here."}, {"title": "The Menstrual Cycle .txt", "text": "Now, as estrogen increases, that causes the initiation of the thickening of the endometrium."}, {"title": "The Menstrual Cycle .txt", "text": "And so as estrogen increases, the endometrium begins to thicken as a result."}, {"title": "The Menstrual Cycle .txt", "text": "So the developing follicle begins to release estrogen, which stimulates the thickening and formation of the endometrium in preparation for the implantation."}, {"title": "The Menstrual Cycle .txt", "text": "And this is what is described by the cycle."}, {"title": "The Menstrual Cycle .txt", "text": "So GnRH released by the Hypothalamus stimulates FSH and LH to also release and that causes estrogen to increase in concentration as a result."}, {"title": "The Menstrual Cycle .txt", "text": "Now eventually what happens is Ovulation."}, {"title": "The Menstrual Cycle .txt", "text": "So notice as we have an increase in our estrogen, the increase in estrogen basically creates a positive feedback loop."}, {"title": "The Menstrual Cycle .txt", "text": "It positively affects the amount of LH produced."}, {"title": "The Menstrual Cycle .txt", "text": "So it causes more GnRH to release and that causes more LH to actually release and eventually causes something called the luteinizing surge or the luteinizing hormone surge or the LH surge."}, {"title": "The Menstrual Cycle .txt", "text": "So as soon as we have the sharp increase in LH, as soon as he experienced the LH surge, ovulation takes place."}, {"title": "The Menstrual Cycle .txt", "text": "So the mature secondary follicle ruptures, releasing this red secondary Oicide into the Peric neal cavity and then into Araphylopian two, while the remaining portion of that becomes into the corpus luteum."}, {"title": "The Menstrual Cycle .txt", "text": "So the remaining portion of that secondary falcon that remains inside the Ovary develops into the corpus luteum, also as a result of the increase in LH during our LH surge."}, {"title": "The Menstrual Cycle .txt", "text": "So the continued release of LH stimulates the remaining portion of the secondary follicle to become the corpus luteum."}, {"title": "The Menstrual Cycle .txt", "text": "So there should be a U here."}, {"title": "The Menstrual Cycle .txt", "text": "And that's exactly why the LH is called the luteinizing hormone because it causes the formation of the corpus lutein."}, {"title": "The Menstrual Cycle .txt", "text": "Now what the corpus lutein begins to do is it begins to release estrogen and it begins to release another hormone known as progesterone."}, {"title": "The Menstrual Cycle .txt", "text": "So if we look at the following diagram, when the corpus luteum is formed, it begins to release estrogen."}, {"title": "The Menstrual Cycle .txt", "text": "So we have an increase in estrogen and it also begins to release progesterone, shown here."}, {"title": "The Menstrual Cycle .txt", "text": "And that's why we have an increasing level of these two hormones."}, {"title": "The Menstrual Cycle .txt", "text": "And what progesterone does is it maintains the thickening of that endometrium."}, {"title": "The Menstrual Cycle .txt", "text": "So it's estrogen that initiates the thickening process, but it's progesterone that maintains the thickening of that endometrium as shown in the following diagram."}, {"title": "The Menstrual Cycle .txt", "text": "Now, in this particular case, estrogen created a positive feedback loop, but in this case, it will create a negative feedback loop as shown in this diagram."}, {"title": "The Menstrual Cycle .txt", "text": "So at this particular point and by the way, notice that Ovulation and the LH surge took place on the 14th day mark."}, {"title": "The Menstrual Cycle .txt", "text": "So that means after about two weeks, ovulation will take place as a result of that LH surge."}, {"title": "The Menstrual Cycle .txt", "text": "So let's go back to this section here."}, {"title": "The Menstrual Cycle .txt", "text": "So what happens as progesterone increases?"}, {"title": "The Menstrual Cycle .txt", "text": "Well, as progesterone increases, it causes a negative feedback loop on GnRH."}, {"title": "The Menstrual Cycle .txt", "text": "And at this particular point, our estrogen will now create also a negative feedback loop."}, {"title": "The Menstrual Cycle .txt", "text": "So estrogen is interesting because it not only creates a positive feedback loop in this area, but it also creates a negative feedback loop in this section here."}, {"title": "The Menstrual Cycle .txt", "text": "So at this point we see that estrogen and progesterone create a negative feedback loop and decrease the amount of GnRH that is released."}, {"title": "The Menstrual Cycle .txt", "text": "And because we have less GnRH released, that means we'll have less of SSH and LH being produced."}, {"title": "The Menstrual Cycle .txt", "text": "Now, it's the LH that is needed to maintain the corpus luteum."}, {"title": "The Menstrual Cycle .txt", "text": "And if we have less LH being produced as a result of the negative feedback process, then that means the corpus luteum will begin to slowly deteriorate and eventually it will break down into the corpus albicans."}, {"title": "The Menstrual Cycle .txt", "text": "Now, if the corpus luteum decreases its function, that means progesterone concentration will decrease and so will estrogen."}, {"title": "The Menstrual Cycle .txt", "text": "And that's because it's the corpus luteum that releases those two hormones."}, {"title": "The Menstrual Cycle .txt", "text": "And as we decrease the amount of progesterone and estrogen that means our endometrium will begin to break down, the blood vessels will begin to rupture, releasing blood."}, {"title": "The Menstrual Cycle .txt", "text": "And so we'll have the process of menstruation that will initiate and this will discharge the endometrium along with that secondary oxide."}, {"title": "The Menstrual Cycle .txt", "text": "And so the thickness of the endometrium will begin to decrease."}, {"title": "The Menstrual Cycle .txt", "text": "And at the end of the 28th period, when the estrogen and progesterone concentration drops that entire process, the menstrual cycle will essentially repeat itself once again."}, {"title": "The Menstrual Cycle .txt", "text": "So this is the process we call the menstrual cycle."}, {"title": "The Menstrual Cycle .txt", "text": "It's the process by which the female individual prepares the uterus for a possible pregnancy, for a possible implantation."}, {"title": "The Menstrual Cycle .txt", "text": "But as the case is usually if no if the woman is not sexually active and no fertilization actually takes place, then that leads to the process of menstruation which is categorized by the discharge of the endometrium and the secondary oicide to the outside environment."}, {"title": "The Menstrual Cycle .txt", "text": "And this includes the bleeding and the cramping."}, {"title": "The Menstrual Cycle .txt", "text": "Now, the final question I want to address is why does the woman feel these pains, the cramping?"}, {"title": "The Menstrual Cycle .txt", "text": "Well, that's because progesterone doesn't only increase the thickening of that endometrium but it also blocks it inhibits the uterus from contracting."}, {"title": "The Menstrual Cycle .txt", "text": "But when the progesterone level drops, that doesn't only cause the deterioration of the corpus lutein and the eventual discharge of the endometrium."}, {"title": "The Menstrual Cycle .txt", "text": "It also lifts that inhibition from the uterus."}, {"title": "The Menstrual Cycle .txt", "text": "And what that means is the uterus can now contract."}, {"title": "The Menstrual Cycle .txt", "text": "And so that contraction is what the woman feels when they experience the crapping effect."}, {"title": "The Menstrual Cycle .txt", "text": "So this is the process we call the menstrual cycle."}, {"title": "Ionizable Amino Acids .txt", "text": "Seven of the 20 amino acids that exist inside our body have side chain groups that are readily ionizable."}, {"title": "Ionizable Amino Acids .txt", "text": "And what that means is, at certain PH values, these ionizable sidechain groups will be able to exchange hydrogen atoms."}, {"title": "Ionizable Amino Acids .txt", "text": "They can donate and accept hydrogen atoms."}, {"title": "Ionizable Amino Acids .txt", "text": "And that gives them the ability not only to participate in acidbased reaction actions, but to also form ionic bonds."}, {"title": "Ionizable Amino Acids .txt", "text": "Because if the side chain groups can form ions, the ions have full charges, and those charges can participate in forming ionic bonds with other macromolecules."}, {"title": "Ionizable Amino Acids .txt", "text": "So that's exactly what makes these seven amino acids reactive."}, {"title": "Ionizable Amino Acids .txt", "text": "And that's what gives them the ability to participate in a variety of different types of biological reactions that take place inside our bodies."}, {"title": "Ionizable Amino Acids .txt", "text": "So what are these seven amino acids?"}, {"title": "Ionizable Amino Acids .txt", "text": "So we have aspartic acid and glutamic acid, Aratu, acidic amino acids, and the rest are histidine, cysteine, lysine, tyrosine, and arginine."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, on top of these ionizable side chain groups found on these seven amino acids, every one of our amino acids also contains ionizable alphacroboxyl groups and ionizable alpha amino group."}, {"title": "Ionizable Amino Acids .txt", "text": "So remember, every single alpha amino acid contains a central carbon that is bound onto a carboxyl group and onto an amino group."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, let's take a look at the following table and discuss what it actually tells us."}, {"title": "Ionizable Amino Acids .txt", "text": "So, the first column basically describes that particular ionizable group or that particular ionizable amino acid."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, the middle column describes that acid based reaction that takes place."}, {"title": "Ionizable Amino Acids .txt", "text": "On the left side, we have the acid."}, {"title": "Ionizable Amino Acids .txt", "text": "On the right side, we have the conjugate base that is formed when an H plus ion is actually lost."}, {"title": "Ionizable Amino Acids .txt", "text": "And the final column describes the PKA value."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, what is the PKA value?"}, {"title": "Ionizable Amino Acids .txt", "text": "Well, if the PH of our solution, in which that molecule is in, is equal to the PKA value, then what that means is exactly 50% of the molecules will exist in the acid form, and the other 50% will exist in the conjugate base form."}, {"title": "Ionizable Amino Acids .txt", "text": "So if we're below a PH of the PKA, so let's say in this particular case, if we're below a PH of 3.1, then the acid form of the molecule will predominate."}, {"title": "Ionizable Amino Acids .txt", "text": "But if we're above a PH of 3.1, then what that means is this conjugate base form will predominate."}, {"title": "Ionizable Amino Acids .txt", "text": "And that's exactly why at a normal physiological PH of around seven, every single one of our amino acid contains an alpha called a carboxyl group that exists in the carboxylate ion form, because the PH of seven is above a PH of three is above the PH of 3.1."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, what about the alpha amino group?"}, {"title": "Ionizable Amino Acids .txt", "text": "Well, the Alpha amino group contains a PKA of 8.0."}, {"title": "Ionizable Amino Acids .txt", "text": "And what that means is, because our normal physiological PH is seven, and because a PH of seven is below a PH of eight, what that means is every single one of our amino acids at the normal physiological PH will contain an alpha amino group that will predominate in this form because it is below a PH of eight."}, {"title": "Ionizable Amino Acids .txt", "text": "So if we put these two together, we see that because at the normal physiological PH, this will be negatively charged, and this will be positively charged, these two charges will essentially cancel out."}, {"title": "Ionizable Amino Acids .txt", "text": "And so the net charge on that amino acid at the normal physiological PH will depend on the charge that is found on that side chain group."}, {"title": "Ionizable Amino Acids .txt", "text": "And remember, a zwitter ion or a dipolar form of the amino acid basically means it will exist with this negative charge and this positive charge."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, let's actually focus on the seven amino acids that have ionized the bulk side chain groups."}, {"title": "Ionizable Amino Acids .txt", "text": "So let's begin with aspartic acid and glutamic acid."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, both of these acids, both of these amino acids contain a side chain group that contains a carboxylic acid."}, {"title": "Ionizable Amino Acids .txt", "text": "And the PKA value of this carboxylic acid is 4.1."}, {"title": "Ionizable Amino Acids .txt", "text": "So what that means is if we're at 4.1, we'll have 50% of the acid and 50% of the conjugate base."}, {"title": "Ionizable Amino Acids .txt", "text": "If we're below a PH of 4.1, this will predominate."}, {"title": "Ionizable Amino Acids .txt", "text": "If we're above a PH of 4.1, this will predominate."}, {"title": "Ionizable Amino Acids .txt", "text": "And what that means is, at the normal physiological PH, because that is higher than 4.1, these ions will predominate over these neutral species."}, {"title": "Ionizable Amino Acids .txt", "text": "And so, because they're going to have a full negative charge, they can actually form many ionic bonds."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, let's move on to Histidine."}, {"title": "Ionizable Amino Acids .txt", "text": "Histidine has PKA of 6.0, which is actually relatively close to the normal physiological PH."}, {"title": "Ionizable Amino Acids .txt", "text": "And that's exactly what makes histidine very special."}, {"title": "Ionizable Amino Acids .txt", "text": "Because this is so close to the normal physiological PH of our cells, this amino acid that contains this side chain group can actually readily exchange our h atoms."}, {"title": "Ionizable Amino Acids .txt", "text": "It can donate h atoms, and it could also accept h atoms on this nitrogen."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, what about cysteine?"}, {"title": "Ionizable Amino Acids .txt", "text": "Well, cysteine is that amino acid that can participate in forming disulfide bridges."}, {"title": "Ionizable Amino Acids .txt", "text": "And not only that, it has a PK of 8.3."}, {"title": "Ionizable Amino Acids .txt", "text": "And what that means is, if we're at 8.3, if our PH is at zero point, 350 percent will exist in this form, and the remaining will exist in this negatively charged form."}, {"title": "Ionizable Amino Acids .txt", "text": "So if we're in a very basic solution, let's say a solution with a PH of ten, all of our cysteine molecules will predominate, will exist in this ion form, and this will be able to form ionic bonds with positively charged species."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, lying, tyrosine and arginine have a very basic PKA value."}, {"title": "Ionizable Amino Acids .txt", "text": "It's above ten."}, {"title": "Ionizable Amino Acids .txt", "text": "For lycine, it's 10.8, for tyrosine, it's 10.9, and for arginine, it's all the way at 12.5."}, {"title": "Ionizable Amino Acids .txt", "text": "And what that means is, at the normal physiological PH, these three amino acids will always exist in this form."}, {"title": "Ionizable Amino Acids .txt", "text": "In the tyrosine case, we have a neutral, non polar sidechain group."}, {"title": "Ionizable Amino Acids .txt", "text": "In this case, we have a very polar, hydrophilic side chain group because we have those full positive charges."}, {"title": "Ionizable Amino Acids .txt", "text": "And so at the normal physiological PH, these two amino acids will be able to form ionic bonds, but this one will act as a very hydrophobic molecule."}, {"title": "Ionizable Amino Acids .txt", "text": "And so it will be found inside that protein structure."}, {"title": "Ionizable Amino Acids .txt", "text": "Because usually on the outside, we have the polar water molecules, and this will observe the hydrophobic effect and will tend to interact with the non polar side chains found inside that protein."}, {"title": "Ionizable Amino Acids .txt", "text": "So these are the seven ionizable amino acids."}, {"title": "Ionizable Amino Acids .txt", "text": "It's ionizable because they have these side chain groups that can lose or gain h atoms at specific PH values."}, {"title": "Ionizable Amino Acids .txt", "text": "Now, all 20 varia amino acids contain an alphacroboxyl group and an alpha amino group."}, {"title": "Ionizable Amino Acids .txt", "text": "And so, technically, at specific PH values, all of our amino acids can actually gain and lose h atoms."}, {"title": "Ionizable Amino Acids .txt", "text": "But because normally our body is at a specific PH value at around seven is is usually negatively charged."}, {"title": "Ionizable Amino Acids .txt", "text": "This is usually positively charged."}, {"title": "Ionizable Amino Acids .txt", "text": "And so these two charges usually cancel one another out."}, {"title": "Ionizable Amino Acids .txt", "text": "And the actual charge on that amino acid depends on what the charge is on our side chain group of that amino acid."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Our immune system consists of two divisions."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "We have the innate immune system which we're going to focus on in this lecture and we have the quiet or adaptive immune system which we're going to focus on in the next lecture."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So, what exactly is the innate immune system?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well, the innate immune system consists of many nonspecific defense mechanisms that begin to act immediately after infection takes place."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what that means is the innate immune system is the primary line of defense against these invading pathogens."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "That is, the innate immune system acts way before the choir immune system which usually takes several days to actually act as we'll see in the next lecture."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So the innate immune system begins to act immediately and it's the primary line of defense against our pathogens."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, another name for the innate immune system is the non specific immune system."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "The question is, what do we mean by nonspecific?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well, nonspecific implies that the innate immune system does not actually depend on the presence of any specific antigen like the acquired immune system does."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what that means is the innate immune system will attack all the different types of pathogens without actually considering what type of antigen is found on those pathogens."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "That is, it attacks all the pathogens with equal likelihood."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now let's discuss some of the different types of physical anatomical barriers that exist inside our body that are part of the innate immune system and which basically function not to only prevent the physical movement of these pathogens into."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Our body, but to also create an inhospitable environment to prevent the growth of different type of pathogens on our body and in our body."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So let's begin with our skin."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So, as we know, our skin consists of several layers and these different types of layers create an impermeable membrane that prevents the physical movement of pathogens into our body."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "On top of that, our skin also contains glands which secrete fatty acids."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And when we create a layer of fatty acid on our skin we essentially create an inhospitable environment on which most bacteria cannot actually grow on and live on."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, let's go into our mouth."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Inside our mouth we essentially produce a special type of proteolytic enzyme known as a lysosome."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And the lysosome is also produced by our eyes."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what the lysosome essentially does is it breaks down the cell walls of bacterial cells killing off those bacteria."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So in our saliva and in our tears we find this proteolytic enzyme called lysozyme which essentially kills off bacterial cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now let's move into our passageways the air passageways of our body."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And this includes the nasal cavity inside our nose the trachea, the windpipe as well as the bronchi and our bronchioles."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So along these air passageways we have specialized types of cells called goblet cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And these goblet cells basically secrete a special type of slimy and mucus like material we call the mucus membrane."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So the air passageways of our body essentially are line with this mucus membrane."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And when we breathe in air and we breathe in these different types of pathogens, these pathogens ultimately are trapped inside that mucus."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, inside the air pathogeways we also have these hair like projections we call cilia."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And the cilia are continually moving in a wavelike fashion."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what the cilia ultimately do is they move these pathogens which are trapped inside the mucus all the way up to our pharynx."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And from the pharynx we can actually spit out the mucus along with the pathogens or we can swallow it and the mucus and the pathogens will ultimately end up in our stomach."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, why would we want to basically take that pathogen and place it in our stomach as a result of swallowing?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well, because inside our stomach we have parietal cells and these parietal cells basically secrete gastric acid, hydrochloric acid, HCL."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And this HCL creates a very acidic environment inside our stomach and most bacterial cells and pathogens will not survive in this acidic environment."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And so that's why we want to swallow that mucus or food that contains the pathogens because we know that pathogens will eventually die as a result of the high acidity of that stomach."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So basically the PH is around to inside our stomach when the stomach is in the process of digestion."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So we see that these barriers don't only prevent the pathogens from actually entering our blood and our tissue, but they also create an inhospitable environment in which pathogens cannot actually grow."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now let's suppose we get a cut in our skin and what that means is the skin essentially fails in preventing the movement of pathogens because now that we have a cut that pathogen will have no problem making its way into the tissues of our body."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So once the anatomical physical barriers are breached and the pathogen makes its way into our tissue or into our blood, what happens is the innate immune system responds in another way."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "It responds by initiating a process known as inflammation and more specific acute inflammation."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, what exactly is inflammation?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well, inflammation is this process by which we have many different types of things take place as we'll see in just a moment."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And these things together basically help us kill off the different types of invading pathogens that insert our tissue."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So let's take a look at what actually happens and let's look at the following flowchart to basically help us guide through the process of inflammation."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So let's suppose the pathogen essentially invades our tissue via some type of cut inside our skin."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So the skin fails at preventing and acting as a physical barrier."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, once a pathogen actually enters the tissue of our body, what happens is nearby cells called mass cells, which are basically cells that are physically situated in our tissue around that area begin to secrete special types of chemicals known as cytokines as well as histamine."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And these chemicals basically help dilate the blood vessels that lead to the infected area and we'll see why that's important in just a moment."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So mast cells are situated within the tissue and release histamine and other chemicals called cytokines that promote inflammation."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And actually, as we'll see in the next lecture what cytokines also do is they actually bridge the innate immune system with adaptive immune system it basically promotes the interaction between the two different divisions of our immune system."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "While the histamine, what that does is it actually dilates our blood vessels and it also makes the capillaries more permeable to water."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, along with the mass cells we have these basicil cells which are granulocytes and which travel within our blood."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what the basic fields also do is they also release that histamine."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So the histamine causes the dilation of blood vessels leading to that infected area and that is why we have this area of redness along our cut because the redness is caused by the flow of blood into that infected area."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now the capillaries are also affected as a result of that histamine and the capillaries in that infected area essentially become more leaky, become more permeable to that water, to that blood plasma and this ultimately causes the process of swelling which we call edema."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, why would we actually want to increase the blood flow to that infected area?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well for one thing we want to bring those special immune cells that are responsible for killing off those bacterial agents, those pathogens."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And another thing we also want to bring the nutrients to that area because those cells in that tissue will be working harder."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "We also want to bring the chemicals that are involved in initiating and promoting the process of inflammation."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So we have the bastards and the mast cells release histamine and other chemicals and that ultimately causes the capillaries to become more permeable and more blood to actually flow to that area as a result of the dilation of the blood vessels."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, what else does that actually do?"}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Well, it basically recruits special types of immune cells, white blood cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So we have macrophages as well as the three different types of granulocytes."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So we have neutrophils, we have Basophils, which we spoke about already and we have these eosinophils."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now these eosinophils are granulocytes that are specialized to fight certain parasites."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So if the pathogen is parasitic then it's these cells that will ultimately end up fighting those parasites."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now neutrophils are basically a type of phagocytic cell."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "These neutrophils are capable of engulfing up to 20 bacterial cells before they actually die off."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, when these phagocytic cells actually die off as a result of engulfing too many bacterial cells that is when we form our pus."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So basically the nutrient fields are granulocytes recruited to the infected area and engulfed bacterial cells and other harmful agents and kills them intracellularly."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And that means inside that cell."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So once they engulfed the pathogen they break down that pathogen and kill it off."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And once they engulfed about 20 bacterial cells these essentially die off and begin to form pus."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, another type of phagocytic cell that is recruited in this process of inflammation are macrophages."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And macrophages come from lymphocytes."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So from a specific type of lymphocyte known as monocide."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, macrophages are the largest type of white blood cell."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "They're much larger than neutrophils and that's exactly why they can actually engulf and break down about 100 bacterial cells before they actually die off and become pus."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, the last type of cell that I'd like to discuss but I should note that is not actually part of the inflammation process directly is a cell known as the natural killer cell."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So although these natural killer cells are not really involved in the inflammation process directly, they do kill off infected cells that have been infected by, let's say, some type of viral agent."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And they do kill off cancer cells in a non specific way."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And that means these cells don't care about any type of specific antigen that might exist on the membrane of those cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "If the natural kill knows it's either an infected cell or a cancer cell, it will kill off those cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So the natural kill cell is a non specific wide blood cell that kills off these pathogens infected cells and cancer cells without worrying about the specific type of antigen that exists on the membrane of those cells."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So this is what we call the innate immune system."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "The innate immune system is nonspecific."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "It attacks everything that is pathogenic, it creates immediate response and it also is the primary line of defense."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, unlike the adaptive immune system, which we'll talk about in next lecture, the innate immune system does not actually learn."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So that means there are no memory immune cells that exist within our innate immune system and we'll talk more about memory cells in the next lecture."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, the last thing I'd like to mention is the following."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So we see that once the pathogen invades our tissue, the basic fields and mass cells secrete the histamine and other chemicals that ultimately make the capillaries more permeable to water more leaky."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And that results in edema."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "It also results in the passageway of antibodies that flow into or out of our blood."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, we also dilate those blood vessels and that gives us the redness along that area of infection and it also brings phagocytes, it also brings antibodies and nutrients to that infected area."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And finally, these basic films and mass cells also recruit macrophages and neutrophils, the two types of phagocytic cells in our immune system."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "Now, these don't only engulf those pathogens and eventually form pus but they also secrete a special type of cytokines."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "So interleukin, one that alter ultimately creates this mechanism known as fever."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what fever is it basically increases the temperature of our body to the higher the normal value."}, {"title": "Innate (Non-specific) Immune System .txt", "text": "And what that does is it creates, once again, an inhospitable environment that can cause those pathogenic cells, for example, bacterial cells, to actually die off."}, {"title": "Signal Transduction Pathways .txt", "text": "Humans are what we call eukaryotic organisms."}, {"title": "Signal Transduction Pathways .txt", "text": "And what that means is we consist of many, many, many individual cells."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, for the human to actually function correctly the individual cells must be able to work together and they must be able to communicate with one another."}, {"title": "Signal Transduction Pathways .txt", "text": "And on top of that, these individual cells must be able to carry out the processes at the correct time."}, {"title": "Signal Transduction Pathways .txt", "text": "And the question is, is how does a given cell actually know to carry out a specific set of processes at a given time?"}, {"title": "Signal Transduction Pathways .txt", "text": "So to demonstrate what I mean by that, let's imagine the following scenario and we're going to use this scenario as we go along this lecture."}, {"title": "Signal Transduction Pathways .txt", "text": "So let's suppose I'm walking in the national park and I come across a bear and that bear happens to be hungry."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, if the bear is that size I'm clearly not going to run away."}, {"title": "Signal Transduction Pathways .txt", "text": "But if the bear is a large bear and if I panic I'm going to run."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, when I run, what happens inside my body?"}, {"title": "Signal Transduction Pathways .txt", "text": "Well, somehow my cells know to generate more ATP molecules because the skeletal muscle and the cardiac muscle will need those ATP molecules to basically increase the rate of contraction."}, {"title": "Signal Transduction Pathways .txt", "text": "So for instance, the heart will be able to pump more blood and the rate at which the heart actually pumps the blood to the tissues will increase as a result of those ATP molecules."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, the question is how do the cells know to basically begin carrying out these processes?"}, {"title": "Signal Transduction Pathways .txt", "text": "Well, the short answer is the cells actually respond to changes in the chemicals in the molecules that exist on the outside of the cell."}, {"title": "Signal Transduction Pathways .txt", "text": "And these chemicals, these molecules can actually influence the processes that the cells carry out."}, {"title": "Signal Transduction Pathways .txt", "text": "And these processes ultimately lead to physiological responses such as running away from that hungry bear."}, {"title": "Signal Transduction Pathways .txt", "text": "So chemical changes in the environment around cells can influence the cells to carry out processes that ultimately lead to specific physiological responses."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, beginning with that signal molecule that increases in concentration around that cell and ending all the way with that physiological response all the events that take place between these two points of time, this is what we call a signal transduction pathway."}, {"title": "Signal Transduction Pathways .txt", "text": "Transduction simply means we're passing that, that we're passing down that signal from one area to another area and we'll see exactly what that means in just a moment."}, {"title": "Signal Transduction Pathways .txt", "text": "So to go back to our bear example, when we see that bear we panic and we begin running."}, {"title": "Signal Transduction Pathways .txt", "text": "What happens is or one of the things that begins happening is the endocrine system and more specifically the adrenal glands that on top of the kidneys begins producing a specific type of signal molecule we call epinephrine."}, {"title": "Signal Transduction Pathways .txt", "text": "Epinephrine diffuses into the bloodstream then goes around the cells and so the concentration of epinephrine around the cells increases and that ultimately influences the cells to carry out specific types of processes that lead to that physiological response of running away."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, epinephrine is not the only example of this signal molecule that initiates the signal transduction pathway."}, {"title": "Signal Transduction Pathways .txt", "text": "We have many, many other examples."}, {"title": "Signal Transduction Pathways .txt", "text": "And two other examples that we're going to study in detail in the lectures to come are insulin and the epidermal growth factor."}, {"title": "Signal Transduction Pathways .txt", "text": "But we have many other examples."}, {"title": "Signal Transduction Pathways .txt", "text": "For instance, other hormones are also these signal molecules."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, what I'd like to do in this lecture is generalize the steps of the signal transduction pathway."}, {"title": "Signal Transduction Pathways .txt", "text": "So how does this pathway actually take place?"}, {"title": "Signal Transduction Pathways .txt", "text": "Let's begin with step number one."}, {"title": "Signal Transduction Pathways .txt", "text": "So I see the bear, I panic and I begin to run."}, {"title": "Signal Transduction Pathways .txt", "text": "And at that moment what happens is the adrenal gland begins releasing that epinephrine."}, {"title": "Signal Transduction Pathways .txt", "text": "So I have some stimulus."}, {"title": "Signal Transduction Pathways .txt", "text": "The stimulus is that hungry bear."}, {"title": "Signal Transduction Pathways .txt", "text": "And so that stimulus induces the release of that particular signal molecule."}, {"title": "Signal Transduction Pathways .txt", "text": "And this signal molecule is known as the primary messenger molecule."}, {"title": "Signal Transduction Pathways .txt", "text": "So step number one is the release of the appropriate primary messenger molecule as a result of some type of external stimulus."}, {"title": "Signal Transduction Pathways .txt", "text": "Step number two is now that the epinephrine is released, it travels through the bloodstream."}, {"title": "Signal Transduction Pathways .txt", "text": "Eventually it diffuses into the extracellular matrix around the cells and then it binds until specific receptor transmembrane proteins found on the membranes of those cells."}, {"title": "Signal Transduction Pathways .txt", "text": "So the primary messenger locates and attaches onto a receptor which are usually transmembrane proteins."}, {"title": "Signal Transduction Pathways .txt", "text": "These receptors have an extracellular component found outside the cell and an intracellular component found inside the cell."}, {"title": "Signal Transduction Pathways .txt", "text": "And that ligand, that primary messenger shoulder red actually binds onto the outside portion of that transmembrane protein, the receptors."}, {"title": "Signal Transduction Pathways .txt", "text": "So this is the membrane, the outside the cell, the inside the cell."}, {"title": "Signal Transduction Pathways .txt", "text": "And notice that this ligand, the primary Messer, binds onto this region on the outside."}, {"title": "Signal Transduction Pathways .txt", "text": "And once it binds, it creates a conformational change that in some cases basically causes a portion of that protein on the intracellular side to basically detach."}, {"title": "Signal Transduction Pathways .txt", "text": "And that can lead to other processes as we'll see in lectures to come."}, {"title": "Signal Transduction Pathways .txt", "text": "So this is basically step number two."}, {"title": "Signal Transduction Pathways .txt", "text": "The formation of that receptor primary messenger or ligand complex is what we call step two."}, {"title": "Signal Transduction Pathways .txt", "text": "And what happens in step two is that message that is stored in that primary messenger is now transduced passed down to that cell."}, {"title": "Signal Transduction Pathways .txt", "text": "Now that the binding took place, the cell nodes to carry out specific types of processes."}, {"title": "Signal Transduction Pathways .txt", "text": "So what happens next is the following step three."}, {"title": "Signal Transduction Pathways .txt", "text": "And in step three, as a result of this process that cell begins to increase the concentration of some type of molecule found inside the cell some type of intracellular molecule we call the secondary messenger."}, {"title": "Signal Transduction Pathways .txt", "text": "So once the information is passed down transduced across the cell membrane to one step two takes place, the cell reacts by increasing the production of some sort of intracellular molecule called a secondary messenger."}, {"title": "Signal Transduction Pathways .txt", "text": "So, for instance, one example of a secondary messenger is cyclic adenosine monophosphate."}, {"title": "Signal Transduction Pathways .txt", "text": "Another example of is a calcium."}, {"title": "Signal Transduction Pathways .txt", "text": "And we have many other examples that we're going to look at."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, the important part about step three is it creates an amplification of that signal."}, {"title": "Signal Transduction Pathways .txt", "text": "Why and what is that?"}, {"title": "Signal Transduction Pathways .txt", "text": "Well, normally we have a low concentration of that primary messenger."}, {"title": "Signal Transduction Pathways .txt", "text": "We can have as low as a single molecule that binds onto that receptor, onto that transmembrane protein."}, {"title": "Signal Transduction Pathways .txt", "text": "And even though we only have this single primary messenger, what happens inside the cell is we produce many of these intracellular secondary messengers and then they can basically go on to carry out their individual processes."}, {"title": "Signal Transduction Pathways .txt", "text": "And this greatly amplifies the overall effect of this information."}, {"title": "Signal Transduction Pathways .txt", "text": "So we see that these secondary messengers, this step basically amplifies that signal."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, once secondary messengers are produced, they can easily diffuse across that cell."}, {"title": "Signal Transduction Pathways .txt", "text": "So they can enter other organ nouns such as the nucleus or the mitochondria or so forth."}, {"title": "Signal Transduction Pathways .txt", "text": "So secondary messengers are free to move or diffuse around the cell."}, {"title": "Signal Transduction Pathways .txt", "text": "This means that they can go on and influence processes within different compartments of that cell."}, {"title": "Signal Transduction Pathways .txt", "text": "So once again, we can have two of the same secondary messengers go on to different places in that cell and basically influence different processes and that could amplify the effects of that signal."}, {"title": "Signal Transduction Pathways .txt", "text": "Let's move on to four activation or in some cases inhibition of effectors."}, {"title": "Signal Transduction Pathways .txt", "text": "So what exactly is an effector?"}, {"title": "Signal Transduction Pathways .txt", "text": "An effector is some type of molecule."}, {"title": "Signal Transduction Pathways .txt", "text": "It could be an enzyme, it could be a protein pump, it could be a membrane channel or it could be some type of transcription inducing molecule."}, {"title": "Signal Transduction Pathways .txt", "text": "So basically, these effectors are actually themselves responsible for carrying out some type of specific process that takes place inside the body."}, {"title": "Signal Transduction Pathways .txt", "text": "And all these processes basically work together to carry out that specific physiological response."}, {"title": "Signal Transduction Pathways .txt", "text": "So effectors are molecules that are responsible for carrying out some type of cellular process that ultimately leads to that physiological response."}, {"title": "Signal Transduction Pathways .txt", "text": "And effectors can be transcription inducing molecules, enzymes."}, {"title": "Signal Transduction Pathways .txt", "text": "We have membrane pumps, we have membrane channels and so forth."}, {"title": "Signal Transduction Pathways .txt", "text": "So for instance, when we'll discuss insulin, we'll see that what insulin does is it increases the rate at which we update glucose molecules into the cell."}, {"title": "Signal Transduction Pathways .txt", "text": "And what that does is that means it influences the cells to produce many more of these protein molecules that can actually uptake the glucose molecules and that might involve the process of gene expression."}, {"title": "Signal Transduction Pathways .txt", "text": "So transcription of those proteins, the pumps that eventually are placed into the membrane of the cell to actually uptake the glucose molecules."}, {"title": "Signal Transduction Pathways .txt", "text": "Now, the final step in this signal transduction pathway is to actually terminate that pathway."}, {"title": "Signal Transduction Pathways .txt", "text": "It's very important that we terminate a pathway at the proper time because if we can't terminate a pathway, that can lead to various very negative detrimental effects as we'll see in electra to come, basically, in some cases certain cancers are actually a result of the inability of our body to effectively terminate signal transduction pathways."}, {"title": "Introduction to Digestive System .txt", "text": "The human digestive system plays two important roles."}, {"title": "Introduction to Digestive System .txt", "text": "It digests our food and also absorbs our food."}, {"title": "Introduction to Digestive System .txt", "text": "Now digestion refers to the process by which we actually break down our macromolecules into their constituents and we have two types of digestion."}, {"title": "Introduction to Digestive System .txt", "text": "We have mechanical digestion and we have chemical digestion and we'll see what the difference is between the two to in just a moment."}, {"title": "Introduction to Digestive System .txt", "text": "Now our digestive system also plays a role in actually absorbing those broken down nutrients into our blood system and lift system and those nutrients eventually travel to the cells that require the nutrients to basically produce ATP molecules that are used as the energy molecules in our cells."}, {"title": "Introduction to Digestive System .txt", "text": "So let's begin by discussing several important types of structures that exist within our digestive system."}, {"title": "Introduction to Digestive System .txt", "text": "So let's follow the pathway of the food as we place it inside our mouth."}, {"title": "Introduction to Digestive System .txt", "text": "Now the mouth portion is basically known as the oral cavity."}, {"title": "Introduction to Digestive System .txt", "text": "This is where we place our food."}, {"title": "Introduction to Digestive System .txt", "text": "Now as we chew our food we're basically mechanically digesting that food."}, {"title": "Introduction to Digestive System .txt", "text": "Mechanical digestion refers to the process by which we break down large food particles into smaller food particles."}, {"title": "Introduction to Digestive System .txt", "text": "And what this does is this increases the surface area on which the enzymes, the proteolytic digestive enzymes can actually act on."}, {"title": "Introduction to Digestive System .txt", "text": "So inside the oral cavity we have mechanical digestion but we also have chemical digestion as well."}, {"title": "Introduction to Digestive System .txt", "text": "Chemical digestion refers to the process by which our digestive proteolytic enzymes actually act on the macromolecule food molecules and break them down into their constituents."}, {"title": "Introduction to Digestive System .txt", "text": "They cleave the bonds via the process of hydrolysis."}, {"title": "Introduction to Digestive System .txt", "text": "So inside or around the oral cavity we have these specialized types of glands that we're going to focus on in a future lecture."}, {"title": "Introduction to Digestive System .txt", "text": "And these glands release secrete, these specialized proteolytic enzymes that help break down our food inside the oral cavity."}, {"title": "Introduction to Digestive System .txt", "text": "Now the carbohydrates are the macromolecules that are broken down inside the oral cavity and we'll discuss that in much more detail in a future lecture."}, {"title": "Introduction to Digestive System .txt", "text": "So we ingest our food."}, {"title": "Introduction to Digestive System .txt", "text": "Mechanical and chemical digestion begins in our mouth."}, {"title": "Introduction to Digestive System .txt", "text": "Next, it travels to the pharynx."}, {"title": "Introduction to Digestive System .txt", "text": "The pharynx is basically the region that connects our oil cavity to the esophagus as well as to our trachea and larynx."}, {"title": "Introduction to Digestive System .txt", "text": "Basically the windpipe that is not shown in this diagram that connects to our lungs."}, {"title": "Introduction to Digestive System .txt", "text": "Now within the pharynx we have this cartilage known as epiglottis."}, {"title": "Introduction to Digestive System .txt", "text": "And what the epiglottis basically does is it prevents the food products from actually going into our windpipe."}, {"title": "Introduction to Digestive System .txt", "text": "If the food products were to go into the windpipe we would basically choke."}, {"title": "Introduction to Digestive System .txt", "text": "So the pharynx connects the oral cavity and the nasal cavity to the esophagus."}, {"title": "Introduction to Digestive System .txt", "text": "And the windpipe, a structure called the epiglottis prevents food from going into the wrong tube into our windpipe."}, {"title": "Introduction to Digestive System .txt", "text": "Now the stophagus basically carries that food bolus from our oral calvary to our stomach and the process that ultimately carries that allows the movement of the food is known as peristalis."}, {"title": "Introduction to Digestive System .txt", "text": "And we'll see what this is in a future lecture."}, {"title": "Introduction to Digestive System .txt", "text": "It's basically the process by which we have an involuntary movement of the muscle that lines the esophagus and this propels, this moves our food down into our stomach."}, {"title": "Introduction to Digestive System .txt", "text": "Now, once the food is inside our stomach, the stomach plays several important roles."}, {"title": "Introduction to Digestive System .txt", "text": "Firstly, it basically acts to store the food."}, {"title": "Introduction to Digestive System .txt", "text": "So it has a certain capacity, about two liters of capacity, to basically store that food."}, {"title": "Introduction to Digestive System .txt", "text": "Now, the stomach also consists of specialized types of cells and these cells basically secrete different types of enzymes and different types of substances."}, {"title": "Introduction to Digestive System .txt", "text": "For example, a cell known as the parietal cell."}, {"title": "Introduction to Digestive System .txt", "text": "And we'll discuss these cells in more detail in a future lecture."}, {"title": "Introduction to Digestive System .txt", "text": "But these parietal cells found inside the stomach secrete gastric acid that contains hydrochloric acid and this lowers the PH and makes our stomach much more acidic."}, {"title": "Introduction to Digestive System .txt", "text": "And this in turn activates the proteolytic enzymes that basically cleave our proteins."}, {"title": "Introduction to Digestive System .txt", "text": "So inside our stomach, not only do we have mechanical digestion taking place, but we also have chemical digestion."}, {"title": "Introduction to Digestive System .txt", "text": "Basically, the enzymes break down our peptide, the polypeptides, into their amino acids as well as into smaller peptides."}, {"title": "Introduction to Digestive System .txt", "text": "Now, inside the stomach, we have ultimately no absorption taking place."}, {"title": "Introduction to Digestive System .txt", "text": "Certain substances such as alcohol and aspirin are absorbed by the stomach."}, {"title": "Introduction to Digestive System .txt", "text": "But the food products are not absorbed in the stomach."}, {"title": "Introduction to Digestive System .txt", "text": "The absorption of the food products, as we'll see in just a moment, takes place in the small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So the stomach serves a purpose in storage as well as in digestion."}, {"title": "Introduction to Digestive System .txt", "text": "It typically has a capacity of two liters and is composed of special types of cells that serve several important functions."}, {"title": "Introduction to Digestive System .txt", "text": "For example, we have parietal cells that secrete the hydrochloric acid and make our stomach acidic."}, {"title": "Introduction to Digestive System .txt", "text": "So the acidity of the stomach is about two."}, {"title": "Introduction to Digestive System .txt", "text": "And this activates special types of proteolytic enzymes that begin the breakdown of proteins into their smaller constituents."}, {"title": "Introduction to Digestive System .txt", "text": "Now, although some substances, such as alcohol can be absorbed by the cells of the stomach, the stomach acts mostly in mechanical and chemical digestion."}, {"title": "Introduction to Digestive System .txt", "text": "Now, let's move on to our small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So basically, the food goes into the oral cavity, travels into the pharynx, the epiglottis blocks it from going into our windpipe that is found here not shown, it goes into our esophagus."}, {"title": "Introduction to Digestive System .txt", "text": "We have special types of sphincter muscles that open up and allow the movement of our food into the stomach, inside the stomach, and then goes into this section, the small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "And this entire convoluted region is our small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So basically this and this section is part of our small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "Now, specialized types of accessory organs such as the liver, the gallbladder and the pancreas basically work together to create and secrete special types of enzymes, proteolytic enzymes that break down our carbohydrates proteins as well as fats."}, {"title": "Introduction to Digestive System .txt", "text": "And they also secrete special types of substances that ultimately are secreted into the small intestine and that increases the PH of our small intestine and that ultimately activates the special types of proteolytic enzymes that are involved in the breakdown of our food products inside the small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So the liver, pancreas and gallbladder all play a role in producing and secreting special enzymes and other substances into our small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "And we'll discuss what these are in the next several lectures when we focus on the small intestine."}, {"title": "Introduction to Digestive System .txt", "text": "Now, these enzymes play a role in digestion of carbohydrates into monosaccharides, in digestion of proteins into amino acids, dipeptides and tripptides, and fats into mostly fatty acids."}, {"title": "Introduction to Digestive System .txt", "text": "Now, the small intestine doesn't only play a role in digestion, it also plays an important role in absorption."}, {"title": "Introduction to Digestive System .txt", "text": "So all these individual constituent molecules are monosaccharides amino acids and fatty acids that are ultimately broken down from the carbohydrates."}, {"title": "Introduction to Digestive System .txt", "text": "The proteins and fats are absorbed by the cells found in the small intestine, known as anterocytes."}, {"title": "Introduction to Digestive System .txt", "text": "So interracytes absorb these nutrients and ultimately dump these nutrients into our blood system as well as into our lymph system."}, {"title": "Introduction to Digestive System .txt", "text": "And these circulate through our body and eventually end up at the tissues and the cells that require those nutrients."}, {"title": "Introduction to Digestive System .txt", "text": "And finally, we have the large intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So everything that was not absorbed by the small intestine ends up in our large intestine."}, {"title": "Introduction to Digestive System .txt", "text": "So we have this large intestine, we have the ascending section, descending section."}, {"title": "Introduction to Digestive System .txt", "text": "We have our section, we have the rectum, we have the anus."}, {"title": "Introduction to Digestive System .txt", "text": "And this is our appendix."}, {"title": "Introduction to Digestive System .txt", "text": "So basically, the most important role of the large intestine is to push those waste products to the outside of the body."}, {"title": "Introduction to Digestive System .txt", "text": "And it also plays as the last location where we have absorption taking place."}, {"title": "Introduction to Digestive System .txt", "text": "So the large intestine acts mostly to basically absorb the water that was not absorbed by other organs of our bodies, such as our kidneys."}, {"title": "Introduction to Digestive System .txt", "text": "So the large intestine absorbs mostly water, and it also plays a role in absorbing some of those useful things that were left behind in our small intestines, such as, for example, minerals such as calcium."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So two important types of cells found in our body are epidermal cells and epithelial cells."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Epidermal cells are found on the largest organ of our body the skin."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And epithelial cells are basically found covering the inside portion of different organs and different structures of our body."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, anytime either one of these two cell types is damaged in some way for instance I may make some type of cut in my skin so that the epidermal cells are damaged."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "What happens is a molecule known as epidermal growth factor is released and this molecule is a peptide molecule."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "It's a protein that acts as a primary messenger in the EGF signal transduction pathway where EGF stands for epidermal growth factors."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this is a signal transduction pathway that we're going to focus on in this lecture."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we see that this pathway stimulates the growth and division."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So processes like cell proliferation, cell division, cell growth, cell differentiation of these epidermal and epithelial cells."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So let's begin by focusing on the actual structure of that protein receptor that binds the EGF molecules."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is basically what it looks like here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we have the cell membrane the outside and the inside of the cell."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now in its unbound state."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Before the EGF molecules bind onto this receptor we see that the EGF receptor actually consists of two identical but separated monomeric units."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this is monomer number one and this is monomer number two."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And these two monomers are not attached by any type of bond so they're actually separated."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And as we'll see in just a moment they actually dimerize."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "They form a dimer only upon the binding of the EGF molecule."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now let's examine each one of these individual monomers."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we have this purple region found on the extracellular side and this is a region that contains a binding side for that EGF molecule."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "This brown section is that section that essentially spans the membrane and it anchors that molecule in that membrane."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is the intracellular domain region found on the inside portion of the cell."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is the region that contains the tyrannine protein kinase domain that will be responsible for initiating the first phosphorylation process as we'll see in just a moment."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, this is the Seatile, the carboxyl terminal end of this polypeptide and we'll see why that's important in just a moment."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we basically have these two identical monomers in their unbound form."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "They're separated because the EGF is not bound to this structure."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "But let's see what happens upon the binding of EGF."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And notice that unlike the insulin case where a single insulin binds to the insulin receptor in this case two EGF molecules actually bind to this EGF receptor."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "One binds on this side and the other binds on this opposing side."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, upon the binding of these two EGF molecules onto these extracellular domains what happens is there is a section on this side and this side of these two domains that we call the dimerization arm."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And upon the binding, each one of these dimerization arms basically stretches out and reaches out into a pocket found on the posing domain."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this arm stretches and binds here and this arm stretches and binds here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Because upon the binding of the EGF, there is a conformational change that takes place that allows these two intersurfaces to basically interact with one another."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is the process we call dimerization."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "It produces a dimer."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Whereas before we had these two individual separated monomers, now these two monomers basically come together to form a dimer structure."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So when a total of two EGF signal molecules, the primary messengers bind onto the extracellular region, they induce the dimerization arm of one monomer to stretch out and reach into the pocket of that second monomer which leads to the formation of that dimer structure."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is what we basically show here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Upon the binding these reach out to interact and form this dimer structure and these also slightly change in confirmation and they also interact with one another."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So let's now focus on what happens here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So the conformational changes here lead to conformational changes here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so what happens here is this C terminal tail that we mentioned just a moment ago basically moves into the active side of that corresponding of that opposing unit."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this he tail basically moves into the active side of this one and this heat tail moves into the active side of this one."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And once they move in, what that active side does is it phosphorylates the tyrosine residues and it phosphorylates up to five residues found on this Sea terminal tail."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "In this case I've only shown four."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So again, when we form the dimer, when this conformational change takes place, the carboxyilic, the Sea terminal end of one tyrosine kinase domain moves into the aesthetic side of the posing tyrosine kinase domain."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this is what we call the cross phosphorylation process."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So in the same way that in the insulin pathway we carry out crossfosphorylation here, we also carry out crossfosphorylation, except in this particular case it's not the activation side, but it's the C terminal tail that moves into the active side of that opposing tyrosine kinase domain."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So basically in this step we conclude the following the binding of the EGF molecules onto these binding sides basically causes this dimerization process to actually take place."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And what that leads to is the cross phosphorylation of these C terminal tails on both of these sides."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And what this cross phosphorylation process actually does is it creates attachment points for further attachment of other proteins as we'll see in just a moment."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So the entire point of these regions is to basically allow the attachment of other important proteins that are part of the EGF signal transduction pathway."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we can see that there are many different types of proteins and enzymes involved in this process."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so I've labeled 123-4567."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So let's basically see what each one of these steps actually involves."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And let's begin with step number one."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So once we phosphorylate this section, what happens is an important protein, basically known as GRB Two, actually binds onto a phosphoryl group."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So a phosphorylated tyrosine residue found on this section here."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this serves as an attachment point for this GRB Two, where by the way, GRB stands for growth Factor Receptor bound Protein Two."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so this one, shown in Brown, binds until this section."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this protein acts as an adaptive protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this molecule itself doesn't actually activate anything, but rather what it does is it acts as an anchoring point."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "It allows the attachment of an important protein shown in two, that is known as the SOS protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So in one we have the phosphorylated region of the EGF receptor."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "This section here acts as an anchor for and adapt the protein we call GRB Two."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Next, what this GRB Two does is it allows the attachment of the SOS protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So GRB Two recruits another protein called SOS, shown in dark purple."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And what the SOS does is it contains an active side that basically binds."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "This green structure we call rats."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And rats is basically a small g protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "It basically allows the binding of GDP molecules and GTP molecules."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And just like the g proteins we spoke of in the previous lectures, this small g protein in its inactive state binds GDP."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And in its active state it binds GTP."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so what happens is once two the SOS binds onto one, the GRB two that activates this protein called SOS, showed in purple, that allows it to bind this Ras."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, Ras is a small g protein and once this binding takes place, it essentially constricts this space and allows this molecule to expel the GDP guanosine diphosphate and instead it buys a peak guanosine triphosphate and that activates this Ras protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So in step three we have the SOS then binds Ras, a small g protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "This activates Ras by expelling a GDP and binding instead a GTP."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, this Ras is actually attached into the membrane and that's because the Rasp protein contains a covalently modified amino acid that contains a lipid attachment and that lipid attachment remains inside the membrane."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, once the Ras is in its inactive form, it goes on to activate another membrane, membrane bound protein known as RAF."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And just like this structure contains the covalently modified lipid, this structure also contains a covalently modified lipid component that is found within the membrane."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So both of these are essentially attached into the membrane."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So in five or here we see activator Ras moves on to activate a protein kinase called a Ras."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this is a protein kinase and once this is activated, it goes on and activates other molecules via the process of asphylation."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And what it activates are molecules known as Mechs or simply Mech."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So activate a wrap then goes on to activate protein kinases called Mech."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So what exactly does Mech actually stand for?"}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Well, it stands for Mitigation activated protein kinases and we have many different types."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So what these activated Mechs do is they go on to activate further protein kinases so they go on to activate further processes, namely they go on to activate kinases we call Hercs or IRC."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now, ERC stands for extracellular signal regulated kinases."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And once we activate the Hercs, these Irks basically move on into the nucleus of our cell."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And in the nucleus these Irks ultimately stimulate transcription factors to basically bind onto specific genes and express proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And the more proteins we're able to express, the quicker our cells can actually grow."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Because remember, for the cell to actually grow and increase in size and ultimately divide, we have to basically grow proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "We have to build proteins because the organelles and all the different components inside our cells are essentially formed from proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "In fact, the entire cytoskeleton is formed from proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So we see in this final step activated ERCs move into the nucleus and stimulate transcription factors to increase gene expression."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "This increases the rate of protein production which enlarges the cytoskeleton and leads to cell growth and ultimately might lead to cell division to basically produce many more of these cells that were damaged as a result of, let's say, that particular cut that we experienced on our skin."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this is what we call the EGF signal transduction pathway."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "It is basically used to allow the growth and division of either epidermal cells or the epithelial cells of our body."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And notice that in this particular case, just like in the Insulin case, this receptor actually contained a tyrosine protein kinase domain."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And this particular pathway, just like the epinephrine pathway also used a specific type of molecule that is stimulated as a result of the binding of GTP."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And these are known as G proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And in this case this is known as a small G protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Now the final question is once this pathway takes place and accomplishes what it actually wanted to accomplish so those cells divide and grow, how exactly does our body basically shut off this pathway?"}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Because if the body isn't able to shut off the pathway, that can lead to many different types of negative effects, for instance, cancer cells."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so there are two ways by which our body actually deactivates this process."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Number one is because this process actually involves many kinases."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So this is a kinase, these are kinases, these are kinases."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "Our body basically can reverse the effects of these kinases by using phosphatases."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so phosphatases are used by the body to basically remove those phosphoryl groups that were attached by these kinases."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And that's the first way by which our body can shut off this process."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "The second way is to actually turn off this green molecule, the Ras protein."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So just like in the case of our insulin not insulin, the Epinephrine signaling pathway where Epinephrine basically used what that pathway used?"}, {"title": "EGF Signal Transduction Pathway.txt", "text": "G proteins."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And the G proteins have the ability to turn off their own activity."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "In this case, this small G protein, the Ras, also contains Gtpa's activity."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "So it basically has a built in clock that allows it to turn off itself after some time has passed."}, {"title": "EGF Signal Transduction Pathway.txt", "text": "And so that's the second method by which this pathway can actually be turned off by the cells of our body."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "And this will be known as a pseudo first order reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "And that's because if we have lots of B by increasing or decreasing B, that basically does nothing to the rate."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "But if we have very little A, then changing A will actually have a drastic effect on the rate of that reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "And so that's exactly why this case is a pseudo first order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "It's actually a second order reaction that behaves as if it was a first order."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "So in the next lecture we're going to begin our discussion on enzyme kinetics."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "And the main important point in this lecture was to basically realize how enzymes actually affect the rate law and the rate constant."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "Enzymes basically change the activation energy and that changes, that increases K and that is what increases the rate and changes the rate law of that particular reaction."}, {"title": "Effect of Enzymes on Rate Law and Rate Constant (Part II) .txt", "text": "Enzymes do not actually affect the concentrations of the reactants or the products."}, {"title": "Cell Membrane Transport .txt", "text": "Cells contain a semipermeable membrane, which basically means certain materials will pass across the membrane while others will be blocked."}, {"title": "Cell Membrane Transport .txt", "text": "The question is what exactly determines the ability of a given molecule or atom to be able to pass across that cell membrane?"}, {"title": "Cell Membrane Transport .txt", "text": "Well, it turns out that two factors influence the ease with which atom our molecule or atom passes across our cell membrane."}, {"title": "Cell Membrane Transport .txt", "text": "And these factors include the size of our molecule as well as the polarity of that molecule."}, {"title": "Cell Membrane Transport .txt", "text": "Now, the size aspect is a bit intuitive, so the larger our molecule, the less likely it will pass through that cell membrane."}, {"title": "Cell Membrane Transport .txt", "text": "Now, what about polarity?"}, {"title": "Cell Membrane Transport .txt", "text": "Why exactly does polarity influence the ability of the molecule to pass across the cell membrane?"}, {"title": "Cell Membrane Transport .txt", "text": "Well, to answer this question, we have to remember the structure of our cell membrane."}, {"title": "Cell Membrane Transport .txt", "text": "The cell membrane is a phospholipid bilayer."}, {"title": "Cell Membrane Transport .txt", "text": "That means there are two layers of phospholipids."}, {"title": "Cell Membrane Transport .txt", "text": "And phospholipids themselves are predominantly fatty acids."}, {"title": "Cell Membrane Transport .txt", "text": "So that means we have a predominant portion of the cell membrane that is non polar inside."}, {"title": "Cell Membrane Transport .txt", "text": "In fact, the entire intermediate space between these heads is basically non polar."}, {"title": "Cell Membrane Transport .txt", "text": "And so that means nonpolar molecules, no matter how large, will be able to move across."}, {"title": "Cell Membrane Transport .txt", "text": "And that's exactly why cholesterol, which is a large molecule, has no problem moving across our cell membrane."}, {"title": "Cell Membrane Transport .txt", "text": "But even a very small atom that has a full positive or full negative charge, such as the sodium atom, will not be able to move across because it is very polar."}, {"title": "Cell Membrane Transport .txt", "text": "It contains a full charge."}, {"title": "Cell Membrane Transport .txt", "text": "So we see that the two things we should consider when determining whether a given molecule can make it across the phospholipid bilayer is the size of it and the polarity."}, {"title": "Cell Membrane Transport .txt", "text": "And we have to weigh the two things together."}, {"title": "Cell Membrane Transport .txt", "text": "So even though cholesterol is so big, because it has no charge and essentially not polar at all, it will not have any problem moving across that cell membrane."}, {"title": "Cell Membrane Transport .txt", "text": "Now, let's discuss a special type of cell transport known as passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "This is basically what we just discussed."}, {"title": "Cell Membrane Transport .txt", "text": "So certain molecules, such as cholesterol and water can travel through the cell membrane down its electrochemical gradient, much like a ball falls down the gravitational potential gradient."}, {"title": "Cell Membrane Transport .txt", "text": "This process does not require any use of energy in the form of ATP, nor does it actually require the use of an integral protein."}, {"title": "Cell Membrane Transport .txt", "text": "And this process is known as passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "Passive means we are not using any type of energy source."}, {"title": "Cell Membrane Transport .txt", "text": "So basically the example I can give is this marker falling down its potential gradient."}, {"title": "Cell Membrane Transport .txt", "text": "So basically, we have a high potential."}, {"title": "Cell Membrane Transport .txt", "text": "We have a low potential."}, {"title": "Cell Membrane Transport .txt", "text": "And as soon as we let go, this marker moves down its gravitational potential gradient."}, {"title": "Cell Membrane Transport .txt", "text": "And we have to expend absolutely no energy in moving this marker in the same exact way cholesterol and water will move down our electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "And we will have to use no source of energy for this type of movement."}, {"title": "Cell Membrane Transport .txt", "text": "This is known as passive diffusion because we are not using energy and we are not using any type of transport protein, integral protein."}, {"title": "Cell Membrane Transport .txt", "text": "Now, water is such a common molecule that undergoes path of diffusion that we give it a special type of name."}, {"title": "Cell Membrane Transport .txt", "text": "So basically, the passive diffusion of water via a semipermeable membrane is known as osmosis."}, {"title": "Cell Membrane Transport .txt", "text": "And in osmosis, water always travels from a high water concentration to a low water concentration or equivalently from a low solved concentration to a high solub concentration."}, {"title": "Cell Membrane Transport .txt", "text": "These two statements are exactly equivalent."}, {"title": "Cell Membrane Transport .txt", "text": "And to see what we mean, let's take a look at the following three conditions."}, {"title": "Cell Membrane Transport .txt", "text": "So, let's discuss the Hypotonic solution, the hypertonic solution and the isotonic solution."}, {"title": "Cell Membrane Transport .txt", "text": "In the Hypotonic solution we have a very high concentration of solutes inside the cell, much higher than the solute concentration outside the cell."}, {"title": "Cell Membrane Transport .txt", "text": "And so there will be a net movement of water into our cell."}, {"title": "Cell Membrane Transport .txt", "text": "And so that means over time the cell will enlarge and it could eventually potentially burst."}, {"title": "Cell Membrane Transport .txt", "text": "Now, this is known as the hypertonic solution."}, {"title": "Cell Membrane Transport .txt", "text": "And osmosis states that water always moves from a low solute concentration to a high solub concentration."}, {"title": "Cell Membrane Transport .txt", "text": "In this case, it moves into our cell."}, {"title": "Cell Membrane Transport .txt", "text": "Now, a hypertonic solution is the opposite inside the cell."}, {"title": "Cell Membrane Transport .txt", "text": "In the cytosol of the cell, we have a low solute concentration."}, {"title": "Cell Membrane Transport .txt", "text": "On the outside, however, we have a high solute concentration."}, {"title": "Cell Membrane Transport .txt", "text": "And this implies that the net movement of water will be from the low solub to the high solub concentration or equivalently from the high water concentration inside to the low water concentration outside."}, {"title": "Cell Membrane Transport .txt", "text": "And so the net movement is towards the outside."}, {"title": "Cell Membrane Transport .txt", "text": "Over time, this cell will in fact get smaller, it will shrink."}, {"title": "Cell Membrane Transport .txt", "text": "And finally, let's discuss the case of the isotonic solution."}, {"title": "Cell Membrane Transport .txt", "text": "In the isotonic solution we have the same exact solute concentration inside as outside of the cell."}, {"title": "Cell Membrane Transport .txt", "text": "And so even though we still have a movement across the cell membrane of water, water still moves into and out of the cell."}, {"title": "Cell Membrane Transport .txt", "text": "There is no neck movement."}, {"title": "Cell Membrane Transport .txt", "text": "The two rates are exactly the same."}, {"title": "Cell Membrane Transport .txt", "text": "And so the shape and size of the cell will remain the same."}, {"title": "Cell Membrane Transport .txt", "text": "And this type of transport, once again, is known as passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "So we are not using energy, we are not using any type of integral protein and our molecules are moving down our electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "Now, let's move on to a different type of cell membrane transport known as facilitated diffusion or passive transport."}, {"title": "Cell Membrane Transport .txt", "text": "So certain molecules, such as sugar molecules, are too large and simply too polar to actually pass across our cell membrane via the process of passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "Yes, these molecules must enter the cell if the cell is to actually survive for a long period of time."}, {"title": "Cell Membrane Transport .txt", "text": "So such molecules can be assisted by integral proteins known also as transfer proteins or carrier proteins."}, {"title": "Cell Membrane Transport .txt", "text": "And such a mode of transport is known as facilitated diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "Basically, diffusion means we still have a movement down the electrochemical gradient but now we actually need a protein to move that molecule across."}, {"title": "Cell Membrane Transport .txt", "text": "So basically, in this case, as in this case, we have the movement of our molecule down the electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "In this case, we don't use any type of protein and we don't use any energy."}, {"title": "Cell Membrane Transport .txt", "text": "In this case, we don't use energy, but we do need our protein because as in this case, we use sugar."}, {"title": "Cell Membrane Transport .txt", "text": "Sugar is a large molecule."}, {"title": "Cell Membrane Transport .txt", "text": "It's also very polar."}, {"title": "Cell Membrane Transport .txt", "text": "And that's exactly why it will not be able to pass across our phospholipid bilayer because it's simply too polar."}, {"title": "Cell Membrane Transport .txt", "text": "Now let's move on to a transport known as active transport."}, {"title": "Cell Membrane Transport .txt", "text": "So we saw that in passive diffusion and facilitate the fusion, in both cases, the molecules moved down the electrochemical gradient and so we needed no energy."}, {"title": "Cell Membrane Transport .txt", "text": "In this case, in active transport, we see that we actually move the molecule against the electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "So in some cases, we need to move ions or molecules against their electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "And one example is the neuron cell that basically uses active transport to create an electrochemical gradient to allow the propagation of our action potential, our electrical signal."}, {"title": "Cell Membrane Transport .txt", "text": "And we'll discuss that in much greater detail when we get to that subject."}, {"title": "Cell Membrane Transport .txt", "text": "So basically, this type of active transport requires not only energy, it also requires a specialized type of integral protein."}, {"title": "Cell Membrane Transport .txt", "text": "And two types of active transport exist."}, {"title": "Cell Membrane Transport .txt", "text": "In one active transport, we use the ATP energy molecule to move that molecule against the electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "In a second type of active transport, known as secondary active transport, we first use an ATP molecule to create an electric potential gradient, an electrochemical gradient, and then we use that electrochemical gradient to move our molecule across our semipermeable membrane."}, {"title": "Cell Membrane Transport .txt", "text": "So, to summarize, let's take a look at the following diagram."}, {"title": "Cell Membrane Transport .txt", "text": "Let's begin with passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "So once again, passive diffusion means the molecule is either nonpolar, as the case is with cholesterol, or it's very small and only slightly polar, as the case is with water."}, {"title": "Cell Membrane Transport .txt", "text": "And these types of molecules can simply move directly through our phospholipid bilayer, as the case is with cholesterol and water, without the use of any type of protein, and down the electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "So we use no energy."}, {"title": "Cell Membrane Transport .txt", "text": "Let's move on to facility diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "This is shown in diagram one."}, {"title": "Cell Membrane Transport .txt", "text": "So this is facility diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "We see that our glucose contains all these hydroxy groups and that means it's polar."}, {"title": "Cell Membrane Transport .txt", "text": "So it cannot simply go through that phospholipid bilayer."}, {"title": "Cell Membrane Transport .txt", "text": "It's too large and it's too polar."}, {"title": "Cell Membrane Transport .txt", "text": "So instead, what our cell membrane does is it uses a special type of protein and integral protein that basically allows the glucose to move from a high electropotential gradient to a low electric potential gradient."}, {"title": "Cell Membrane Transport .txt", "text": "So down the electropotential gradient."}, {"title": "Cell Membrane Transport .txt", "text": "And so in this case, we do not use any type of energy."}, {"title": "Cell Membrane Transport .txt", "text": "But in the case of active transport, as we describe in section three, we basically use we expend an ATP molecule to basically move our sodium as well as the potassium, which normally cannot move through the phospholipid bilier because they have positive charge."}, {"title": "Cell Membrane Transport .txt", "text": "We use this type of integral protein to basically move these molecules against our electrochemical gradient."}, {"title": "Cell Membrane Transport .txt", "text": "So whenever we move things against electrochemical gradient, that requires proteins as well as energy."}, {"title": "Cell Membrane Transport .txt", "text": "But whenever we move things down the electrochemical gradient, that does not require any energy whatsoever."}, {"title": "Cell Membrane Transport .txt", "text": "In some cases, we do not even require our integral protein, as the case is with passive diffusion."}, {"title": "Cell Membrane Transport .txt", "text": "So these are the different modes by which our molecules can move across our cell membrane inside the eukaryotic cell."}, {"title": "Membrane Channels .txt", "text": "Membrane pumps are transmembrane proteins that utilize energy to basically form electrochemical gradients."}, {"title": "Membrane Channels .txt", "text": "And then these electrochemical gradients are used by another category of membrane proteins we call membrane channels."}, {"title": "Membrane Channels .txt", "text": "So channels are these transmembrane proteins that use the same electrochemical gradient that is established by these pumps to actually move ions and molecules across the membrane down that electric chemical gradient."}, {"title": "Membrane Channels .txt", "text": "And what that means is membrane channels, unlike membrane pumps, do not actually use any energy."}, {"title": "Membrane Channels .txt", "text": "So we see that membrane pumps use energy to establish the electric chemical gradients, but then the membrane channels use those same electrochemical gradients to then move these ions and molecules spontaneously across that cell membrane without actually using any energy."}, {"title": "Membrane Channels .txt", "text": "And these membrane channels basically respond to chemical or sometimes physical changes in the environment around that particular channel."}, {"title": "Membrane Channels .txt", "text": "And that's exactly what stimulates the opening or the closing of that channel as we'll discuss in just a moment."}, {"title": "Membrane Channels .txt", "text": "So we're going to focus on three different types of membrane channels."}, {"title": "Membrane Channels .txt", "text": "We're going to look at ligand gated ion channels, we're going to look at voltage gated ion channels and also discuss gap junction."}, {"title": "Membrane Channels .txt", "text": "So in this lecture, I'd like to introduce these three different types of channels."}, {"title": "Membrane Channels .txt", "text": "And in the following lectures, we're actually going to focus on the details of each one of these channels."}, {"title": "Membrane Channels .txt", "text": "And let's begin with the ligand gated ion channel."}, {"title": "Membrane Channels .txt", "text": "Now, this is basically a channel, a transmembrane protein that allows the flow of different types of ions."}, {"title": "Membrane Channels .txt", "text": "So sometimes we have sodium, we can have potassium, we can have chloride calcium."}, {"title": "Membrane Channels .txt", "text": "So basically, these ions flow across the cell membrane from a high concentration to low concentration gradient."}, {"title": "Membrane Channels .txt", "text": "And the opening of these channels is a result of the binding of some type of stimulatory molecule."}, {"title": "Membrane Channels .txt", "text": "And this stimulatory molecule is known as a ligand."}, {"title": "Membrane Channels .txt", "text": "So ligand gated ion channels are these channels that respond to the binding of a special type of molecule."}, {"title": "Membrane Channels .txt", "text": "And once that molecule binds, so let's say this green molecule is the ligand, it binds onto the outer portion of this transmembrane protein we call a ligand gated ion channel."}, {"title": "Membrane Channels .txt", "text": "Once it binds, let's say, on the outside, it causes a conformational change that opens up the internal pocket of that particular transmembrane protein."}, {"title": "Membrane Channels .txt", "text": "And then some type of ion can flow across that membrane from one side to the other side."}, {"title": "Membrane Channels .txt", "text": "In this case, let's say it's from the outside to the inside of the cell."}, {"title": "Membrane Channels .txt", "text": "So this is the sodium ion flowing in this direction."}, {"title": "Membrane Channels .txt", "text": "Now, there are many examples of ligand gated ion channels inside our body."}, {"title": "Membrane Channels .txt", "text": "And the one that we're going to take a look at in a future electri is the acetylcholine receptor that we basically find on the postsynaptic membranes of cells found within the neuron pathway."}, {"title": "Membrane Channels .txt", "text": "So let's suppose this is the presynaptic neuron cell and this is the postsynaptic cell and this is the membrane of the post synaptic cell."}, {"title": "Membrane Channels .txt", "text": "So along the membrane we have many of these Ligand gated on channels we call Acetylcholine receptors."}, {"title": "Membrane Channels .txt", "text": "And they're essentially closed."}, {"title": "Membrane Channels .txt", "text": "Now, because they're closed, the sodium ions, which are found at a higher concentration on the outside of the cell, cannot move into the cell."}, {"title": "Membrane Channels .txt", "text": "But what happens is when an action potential basically reaches this section of the neuron, it stimulates these vesicles to be released to this environment."}, {"title": "Membrane Channels .txt", "text": "And once these vesicles are released via exocytosis, they release these neurotransmitters we call Acetylcholine."}, {"title": "Membrane Channels .txt", "text": "And acetylcholine is the ligand that binds onto these ligand gated ion channels, which open up and then allow the spontaneous movement of these sodium ions from the outside into the inside of that cell."}, {"title": "Membrane Channels .txt", "text": "And that can create another action potential."}, {"title": "Membrane Channels .txt", "text": "Or it can make a muscle contract or do many other things, as we'll discuss in a future lecture."}, {"title": "Membrane Channels .txt", "text": "Now let's move on to voltage gated ion channels."}, {"title": "Membrane Channels .txt", "text": "So we essentially see that these ligand gated ion channels respond to the binding of special types of stimulating molecules."}, {"title": "Membrane Channels .txt", "text": "In this particular case, these transmembrane proteins, which also allow the movement of these ions across the cell, a membrane, respond to a change in the electric potential difference between the two sides of the membrane."}, {"title": "Membrane Channels .txt", "text": "So in a change of the membrane voltage, So let's suppose this is some particular voltage gated ion channel."}, {"title": "Membrane Channels .txt", "text": "For instance, one Voltage gated ion channel that We're Going To focus on in detail is the Sodium Voltage gated ion channel."}, {"title": "Membrane Channels .txt", "text": "And this voltage gate ion channel exists across the axon membrane of neurons, and it plays a very important part in actually generating and propagating action potentials along the exxon of that neuron."}, {"title": "Membrane Channels .txt", "text": "So this is our sodium voltage gated ion channel."}, {"title": "Membrane Channels .txt", "text": "And let's suppose when we're at the resting membrane potential."}, {"title": "Membrane Channels .txt", "text": "So a voltage difference of about negative 60 millivolts."}, {"title": "Membrane Channels .txt", "text": "This channel is closed."}, {"title": "Membrane Channels .txt", "text": "Now, as a result of the action of these ligand gated ion channels, there might be a change in the membrane voltage as we'll discuss in a future election."}, {"title": "Membrane Channels .txt", "text": "So this might become less positive or less negative."}, {"title": "Membrane Channels .txt", "text": "Let's say it decreases or it increases to about negative 40 millivolts."}, {"title": "Membrane Channels .txt", "text": "Now, when this change takes place, as a result of that change in the membrane voltage, the electric potential difference between the two sides of the cell, what happens is this opens up."}, {"title": "Membrane Channels .txt", "text": "And once it opens up, it allows the movement of the sodium ions down their electrochemical gradient."}, {"title": "Membrane Channels .txt", "text": "From this from the outside to this side, to the inside."}, {"title": "Membrane Channels .txt", "text": "And again we'll study the specifics of these types of voltage gate ion channels in electra to come."}, {"title": "Membrane Channels .txt", "text": "Now let's focus on Gap Junction."}, {"title": "Membrane Channels .txt", "text": "So what are Gap junctions?"}, {"title": "Membrane Channels .txt", "text": "Well, in the case of ligand gated ion channels and the voltage gated ion channels, the actual spaces between the two sides of the membrane within the protein."}, {"title": "Membrane Channels .txt", "text": "So this space here and this space here is actually relatively small."}, {"title": "Membrane Channels .txt", "text": "But for gap junctions, these are relatively wide channels."}, {"title": "Membrane Channels .txt", "text": "And these relatively wide channels basically exist between closely packed cells."}, {"title": "Membrane Channels .txt", "text": "So let's say this is a cell membrane of one cell, this is a cell membrane of a closely packed adjacent cell, and this is our gap junction."}, {"title": "Membrane Channels .txt", "text": "So it basically transverses these two cell membranes."}, {"title": "Membrane Channels .txt", "text": "And what it ultimately does is it allows the movement of not only small ions, but also relatively large polar molecules, for instance, sugar molecules."}, {"title": "Membrane Channels .txt", "text": "So monosaccharides things like glucose, it allows the movement of amino acids, it allows the movement of nucleotides and so forth."}, {"title": "Membrane Channels .txt", "text": "And so there are four important functions of gap junction."}, {"title": "Membrane Channels .txt", "text": "So they function in, number one, intercellular communication."}, {"title": "Membrane Channels .txt", "text": "Number two, in cell nourishment."}, {"title": "Membrane Channels .txt", "text": "So for instance, those cells of our body which are not found in close proximity to capillaries cannot receive the food from the capillaries."}, {"title": "Membrane Channels .txt", "text": "And so things like glucose and amino acids are received as a result of these gap junctions."}, {"title": "Membrane Channels .txt", "text": "Number three, movement of the action potential."}, {"title": "Membrane Channels .txt", "text": "So, for instance, in very excitable cells of our body, for instance, cardiac muscle cells, cardiac muscle cells actually use gap junctions to propagate the lecture, the action potential across the entire heart."}, {"title": "Membrane Channels .txt", "text": "And what that does is it creates a continuous and a forceful contraction that allows the movement of the blood through the cardiovascular system of the body."}, {"title": "Membrane Channels .txt", "text": "And finally, these gap junctions, as we'll see, are also involved in development and differentiation."}, {"title": "Membrane Channels .txt", "text": "So we see that we have not only membrane pumps that actually utilize ATP molecules and other energy sources to generate these electrical potentials, electroelectrochemical potentials, but we also have these membrane channels that utilize those established electrochemical gradients to actually move these ions and molecules across the two sides of the membranes found inside our cells."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Skeletal muscle is a type of muscle found in the human body and skeleton muscle is innervated, is controlled by the somatic nervous system."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now that basically means skeleton muscle is responsible for voluntary motion such as walking or running some motion that we are consciously in control of."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now skeletal muscle is positioned next to blood vessels, vessels as well as lymph vessels."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And that means when we contract our skeleton muscle, for example when I'm contracting, when I'm moving my hand the skeleton muscle inside my hand is contracting and that increases the blood flow as well as the lymph flow inside the vessels of our body."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now when our skeletal muscles contract they also release a good deal of energy, of energy that we cannot actually use."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And so the way that our body gets rid of this energy is by releasing it is by dissipating it in the process of sweating."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now if we're outside and it's very cold outside, what our body does, the hypothalamus basically induces our somatic nervous system to essentially contract our skeletal muscle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And what this does is it increases the amount of energy that is released and that increases the temperature of our body."}, {"title": "Structure of Skeletal Muscle .txt", "text": "It basically helps maintain the core temperature of our body at 36.7 degrees Celsius."}, {"title": "Structure of Skeletal Muscle .txt", "text": "In this process is known as shivering."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So the skeletal muscle is responsible for the process of shivering when it's really cold outside or when we're very sick."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now let's move on to our structure of our skeletal muscle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now we know that the smallest functional unit of the skeletal muscle is our sarcomere."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And the sarcomere consists of thick filaments made up of a protein known as myosin and thin filaments made up of a global protein known as actin."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And this is shown in this diagram."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So we have the thick filament shown in purple with the myosin heads that basically attach to our thin filament that is shown in black."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now many of these sarcomeres are connected end to end to form a very long fiber we call the myofibro."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is our myofibril that consists of many adjacent sarcommirs that are connected end to end."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is one z line, this is a second z line and this is our sarcomere."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And many of these sarcomeres are connected to form the myofibro."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now many of these myofibers are placed inside the cytoplasm of the muscle cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So the muscle cell is also known as the muscle fiber or the myocide."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And inside our muscle cell we contain many of these myofibrils as shown in the following diagram."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So if we take a cross section of the muscle cell we get the following diagram."}, {"title": "Structure of Skeletal Muscle .txt", "text": "We have many of these red regions which are aromiofibels."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now notice the cytoplasm has its own name."}, {"title": "Structure of Skeletal Muscle .txt", "text": "The cytoplasm of the muscle fiber is known as arosarco plasma."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now inside the sarcoplasm around each one of the myofibrils we have a specialized type of endoplasmic reticulum known as the sarcoplasmic reticulum."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now what's so special about the sarcoplasmic reticulum is that it contains a high concentration of calcium."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And calcium is involved in the contraction of muscle, as we'll see in the next lecture."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Basically the sarcoplasmic reticulum releases the calcium and that induces the contraction of our muscle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So around the entire muscle cell, we also have a specialized type of cell membrane."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So basically, the surrounding region is our cell membrane that is known as the sarcolema."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is our entire muscle fiber, it's the muscle cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And this portion that is covering our muscle cells, shown in red, is our sarcoplasm, or our sarcolema, the cell membrane."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, if we peel off a bit of this sarcolema, we basically expose our sarcoplasmic reticulum that is shown in green."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this green portion inside the muscle cell is our sarcoplasmic reticulum."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, what exactly is so special about the membrane, the plasma membrane of our muscle cell?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "Well, the sarcolema basically consists of these deep tunnels, these deep in vaginations that tunnel all the way inside our cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And these are known as T tubules or transverse tubules that is shown in orange."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So basically, these T tubules go inside the cell and they are perpendicular to our myofiable."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So if the myofiables'extend this way, our T tubules go inside the cell perpendicular at a 90 degree angle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, what's so special about our T tubules?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "What is the function of these channels known as T tubules?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "Basically, these tubules extend to our sarcoplasmic reticulum and the T tubules allow for a quick and rampant activation of those sarcoplasmic reticulum."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Basically, our T tubules allow for the action potential to actually get inside the cell quickly and efficiently."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So once again, we see that the sarcoplasmic reticulum contains a high concentration of calcium that is released during muscle contraction."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, the plasma membrane that surrounds the muscle cell is called the sarcolema."}, {"title": "Structure of Skeletal Muscle .txt", "text": "This specialized membrane contains in vaginations known as T tubules or transverse tubules that run perpendicular with respect to our myofriles and which run very deep into the cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And they allow the action potential to actually travel through the cell quickly and efficiently."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, how does the action potential actually get to the cell in the first place?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "Well, basically they arrive to the cell via the neurons, the axons of our neurons."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is one particular neuron."}, {"title": "Structure of Skeletal Muscle .txt", "text": "We have the axon that basically deviates and eventually binds onto the membrane of the cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And this is known as the neuromuscular junction, the motor and the motor neuron ends."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So basically, at the neuromuscular junction, we have the synapse between our axon terminal of the neuron and our cell membrane of this muscle cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And the neurotransmitter that is used to pass down that actual potential onto our cell membrane is known as our acetylcholine."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now, along with these axons of the neuron, we also have capillaries that run adjacent along the cell membrane of the muscle cell."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And these capillaries are shown in brown and what these capillaries do is they basically carry blood which supplies our cell with oxygen and other nutrients such as for example glucose."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now many of these muscle fibers, many of these muscle cells are basically stacked together along with the neurons and the capillaries to form a cylindrical bundle that is known as our fascicles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is a fascicle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "It consists of many of these muscle cells and these fascicles are even further bundled together to basically form the actual muscle that we can see on the macroscopic level."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So this is the muscle that we can see without actually using a microscope."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So we see that the muscle actually consists of many divisions so inside the muscle we contain these fascicles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "These fascicles actually contain our muscle cells and these muscle cells contain the myofibrils that are composed of these sarcommer subunits these sarcomere building blocks."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now since our muscle cell is actually so long it contains many nuclei and that means that our skeletal muscles are multinucleated."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now we know that just like our neurons muscle cells skeletal muscle cells do not actually divide by mitosis and the way that our skeletal muscle grows when we for example exercise is by increasing the thickness of our muscle cells so the muscle cell will actually increase in thickness."}, {"title": "Structure of Skeletal Muscle .txt", "text": "It will increase its diameter for example because we're going to grow our myofibos because the sacramentors will grow and this will increase the size of our muscle cells and will ultimately increase the size of the muscle overall."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So that's what happens when we exercise in this concept this type of growing of the skeletal muscle is known as hypertrophy."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now let's move on to the different types of skeletal muscle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So we have type one skeletal muscle we have type two A and we have type two B."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now let's begin by describing what distinguishes each one of these muscles from the other."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So type one muscle basically contains a high concentration of myoglobin the special protein that carries oxygen in our muscles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now myoglobin is similar to hemoglobin and that it carries the oxygen but it contains a different structure and myoglobin can only carry a single oxygen per myoglobin protein per myoglobin molecule."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now because our type one contains a high concentration of myoglobin it appears red under the microscope."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now our type one skeletal muscle also contains a very high concentration of mitochondria and when it breaks down ATP type one skeletal muscle breaks down ATP very slowly and as a result these are known as slow twitch muscles because they break down ATP slowly and that means these have a very low velocity of contraction."}, {"title": "Structure of Skeletal Muscle .txt", "text": "The contraction of type one muscles takes place relatively slowly and because of this they are actually slow to fatigue and contract slowly as mentioned earlier."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now where exactly in our body would we normally find type one skeleton muscle?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "So these are basically our postural skeletal muscles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Our skeletal muscles found in the back that basically give us our posture that allow us to actually stand and walk around without bending over or anything like that."}, {"title": "Structure of Skeletal Muscle .txt", "text": "And that's exactly why they essentially are slow to fatigue."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now let's move on to the type two A and type two B scale to muscle."}, {"title": "Structure of Skeletal Muscle .txt", "text": "These are known as fast twitching skeleton muscles because they actually contract quickly."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now just like type one, type two A also appear red under the microscope because they also have a high concentration of myoglobin."}, {"title": "Structure of Skeletal Muscle .txt", "text": "However, they actually break down ATP at a high rate and that's exactly why they contract quickly and that's exactly why we call them fast twitch fibers, fast twitch muscles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now although they are still slow to fatigue, they have a low resistance to fatigue than our type one."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So type one muscles are capable of resisting fatigue at a very high percentage while type two A basically resist fatigue at a lower rate than type one."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now what about type two B?"}, {"title": "Structure of Skeletal Muscle .txt", "text": "Well, type two B muscles are basically those muscles that appear white and that's because they contain a relatively low concentration of myoglobin."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now they break down ATP quickly but at the same time they actually fatigue very quickly and they contain a very high concentration of glycogen, our glucose stored inside our muscles."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So type one skeleton muscles we usually find inside the postural muscles, they give us aroposture."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Type two A are those muscles that are usually found within our legs and type two B are those muscles that are usually found within our arms and upper arms."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So basically these are the three different types of skeletal muscle that we can find inside our body."}, {"title": "Structure of Skeletal Muscle .txt", "text": "Now of course, these concentrations of these muscles inside an individual will vary from one individual to the next and they depend on not only genetics."}, {"title": "Structure of Skeletal Muscle .txt", "text": "The concentration of these muscle types inside our individual depends not only on genetics but it also depends on how active they are in terms of exercising."}, {"title": "Structure of Skeletal Muscle .txt", "text": "So if they exercise a lot, for example, if they're runners, they're going to have a lot of type two A muscles because these are the muscles found inside the legs."}, {"title": "Stomach.txt", "text": "When our bolus, the small spherical mass of food actually reaches the lower portion of our esophagus there is a muscle known as the cardiac sphincter that opens up, relaxes and allows that food to actually exit the esophagus and enter our stomach."}, {"title": "Stomach.txt", "text": "Now, this is our stomach shown in this diagram and the stomach is a very flexible pouch of very flexible sad that is the size of mechanical as well as chemical digestion especially the digestion the breakdown of proteins into smaller polypeptides."}, {"title": "Stomach.txt", "text": "Now, depending on how much food we actually ingest and how much protein is found in that food the stomach can actually store that food anywhere from several minutes to several hours."}, {"title": "Stomach.txt", "text": "For example, if we ingest ingest a lot of food that contains lots of protein then the stomach will store that food for hours to basically ensure that the food is broken down into smaller components and all the protein is broken down into smaller polypeptides."}, {"title": "Stomach.txt", "text": "Now, after our food is broken down into the smaller components and after protein is broken down into smaller polypeptides that food exits the stomach and enters our small intestine and will focus on the small intestine in the next lecture."}, {"title": "Stomach.txt", "text": "Now, within our stomach we do not have a lot of absorption taking place so none of the nutrients, the protein, the carbohydrates and a lipids are actually absorbed in our stomach."}, {"title": "Stomach.txt", "text": "What is absorbed are molecules such as caffeine, alcohol and aspirin and other molecules."}, {"title": "Stomach.txt", "text": "Now, if we examine the walls of our stomach the walls of the stomach contain a lining that contains millions of exocrine glands and two types of exocrine glands found in the stomach lining are gastric glands as well as pylori glands."}, {"title": "Stomach.txt", "text": "Now, an exocrine gland is a gland that produces a molecule or a substance and releases that directly into a duct that empties out into our cavity into the lumen in this case, the cavity or the lumen of our stomach."}, {"title": "Stomach.txt", "text": "So if we zoom in on a small section of the lining we basically get the following microscopic diagram."}, {"title": "Stomach.txt", "text": "So our exocrine glands consist of four important types of cells."}, {"title": "Stomach.txt", "text": "We have mucous cells, we have chief cells, parietal cells and Gsels down all the way at the bottom of these ducts of our exocrine glands."}, {"title": "Stomach.txt", "text": "Now, adjacent to our ducts we basically have our capillary system that connects to our blood vessels as well as to our lymph vessels and these vessels exchange waste products and bring nutrients and oxygen to the cells found on the lining of our stomach and the lining of these exocrine glands."}, {"title": "Stomach.txt", "text": "Now below the blood vessels we have our muscle."}, {"title": "Stomach.txt", "text": "We have a three layer muscle system that is responsible for contraction of the stomach and that ultimately allows the movement of our food from our stomach along the stomach and into our small intestine."}, {"title": "Stomach.txt", "text": "So now let's focus on each one of these four cells and discuss the functionality of these cells."}, {"title": "Stomach.txt", "text": "And later we're also going to mention a fifth cell found in our stomach lining, also known as the anterochromaphin like cell."}, {"title": "Stomach.txt", "text": "So, let's begin with our mucus cell."}, {"title": "Stomach.txt", "text": "So, mucus cells are easy to remember because what their function is to secrete a special type of substance known as mucus."}, {"title": "Stomach.txt", "text": "Now, mucus is a fluidlike substance that consists of glycoprotein, water, electrolytes, so our ions as well as other molecules."}, {"title": "Stomach.txt", "text": "And what the mucous does is it ultimately lubricates our stomach lining."}, {"title": "Stomach.txt", "text": "And that allows the movement of our fluid along of our food, along that stomach lining."}, {"title": "Stomach.txt", "text": "And what it also does, and perhaps the more important function of the mucus, is to basically provide protection to the epithelial cells, the epithelial lining of our stomach."}, {"title": "Stomach.txt", "text": "So, as we'll see in just a moment, the stomach has a very high acidity, a very low PH, and that can easily destroy the lining of that stomach."}, {"title": "Stomach.txt", "text": "And to prevent our epithelial lining from destroying itself as a result of that high acidity, these mucol cells secrete this mucus that protects our epithelial lining from degradation."}, {"title": "Stomach.txt", "text": "Now, as we see from this diagram, the mucous cells are found on the lining of that stomach and also on the upper portion of our exocrine gland ducts."}, {"title": "Stomach.txt", "text": "So let's move on to our achieve cell."}, {"title": "Stomach.txt", "text": "So, chief cells are also pretty easy to remember and that's because chief cells secrete a principal zymogen of the stomach known as Pipsinogen."}, {"title": "Stomach.txt", "text": "So these cells, the chief cells release the principal or chief zymogen of the stomach, known as Pipsinogen."}, {"title": "Stomach.txt", "text": "And once pepsinogen is actually released into our dust and it enters our aluminum of the stomach, if the PH is low enough, if the PH is around two, so if we have a very highly acidic environment, then our Pipsnogen will transform into the active form, the active enzyme known as pepsin."}, {"title": "Stomach.txt", "text": "And pepsin is that protein, the enzyme, the proteolytic enzyme found in the stomach that is responsible for breaking down the protein into smaller polypeptides."}, {"title": "Stomach.txt", "text": "And unlike these mucous cells, the chief cells are found lower within our duck region."}, {"title": "Stomach.txt", "text": "So these purple cells are the cheap cells."}, {"title": "Stomach.txt", "text": "Now, let's move on to our parietal cells."}, {"title": "Stomach.txt", "text": "So, earlier we mentioned that the stomach has a very low PH."}, {"title": "Stomach.txt", "text": "So when we have a full stomach and we have digestion taking place, the PH is around two."}, {"title": "Stomach.txt", "text": "The question is why?"}, {"title": "Stomach.txt", "text": "What creates that low PH?"}, {"title": "Stomach.txt", "text": "What gives our stomach such a high acidity?"}, {"title": "Stomach.txt", "text": "So the answer is these parietal cells, parietal cells are responsible for generating hydrochloric acid and releasing that hydrochloric acid into our ducks and ultimately into the lumen of the stomach."}, {"title": "Stomach.txt", "text": "So parietal cells produce and secrete hydrochloric acid, which serves several important purposes."}, {"title": "Stomach.txt", "text": "There are four purposes that you have to be familiar with."}, {"title": "Stomach.txt", "text": "So, by releasing hydrochloric acid, we ultimately decrease the PH and increase the acidity of the lumen of the stomach."}, {"title": "Stomach.txt", "text": "And that stimulates our chief cells to release our Pipsinogen into our stomach lumen."}, {"title": "Stomach.txt", "text": "Secondly, it actually activates aropipcinogen, it transforms it into pepsin the active form of the enzyme it also denatures it breaks down the three dimensional shape of the protein into its primary sequence to basic and that basically allows our pepsin to actually cleave those bonds."}, {"title": "Stomach.txt", "text": "And as a result of that low PH that low PH can also kill off our bacterial cells that enter our stomach along with our food."}, {"title": "Stomach.txt", "text": "Now parietal cells don't only secrete hydrochloric acid they are also responsible for producing a glycoprotein known as the gastric intrinsic factor."}, {"title": "Stomach.txt", "text": "And this intrinsic factor is basically responsible for allowing the small intestine as we'll see in the next lecture to basically absorb an important type of vitamin known as B twelve."}, {"title": "Stomach.txt", "text": "And finally let's move on to our g cells."}, {"title": "Stomach.txt", "text": "So the mucous cells are these brown cells the cheap cells are these purple cells the red cells are the parietal cells and these blue cells found all the way at the bottom are the g cells."}, {"title": "Stomach.txt", "text": "Now g cells are also easy to remember because g cells as the name implies release a type of hormone known as gastrin."}, {"title": "Stomach.txt", "text": "So g cells are found deep in the exocrine glands of the stomach and release a peptide hormone known as gastrin and this peptide hormone stimulates our parietal cells to release hydrochloric acid into the stomach lumen."}, {"title": "Stomach.txt", "text": "Now g cells themselves are actually stimulated by our acetylcholine molecule."}, {"title": "Stomach.txt", "text": "So acetylcholine stimulates the g cells to release gastrin and the peptide hormone the gastroent stimulates the parietal cells to basically produce hydrochloric acid."}, {"title": "Stomach.txt", "text": "Now another important type of cell that is found in the lining of the stomach are cells known as anterochhromaphin cells or anterochromathin like cells."}, {"title": "Stomach.txt", "text": "Our anterochromaphinlike cells are responsible for secreting a type of molecule known as histamine and what histamine does is it also stimulates the parietal cells to release hydrochloric acid."}, {"title": "Stomach.txt", "text": "So we see two important components."}, {"title": "Stomach.txt", "text": "Two important molecules stimulate parietal cells, so g cells secrete gastroin which stimulates parietal cells and our interchromethanlike cells also secrete a molecule known as histaminene that also stimulates the parietal cells to release our hydrochloric acid."}, {"title": "Stomach.txt", "text": "And then the parietal cells, by releasing the hydrochloric acid, basically stimulate the chief cells to release our pipsinogen, which is then transformed into pepsin as a result of that hydrochloric acid as a result of that relatively low PH."}, {"title": "Stomach.txt", "text": "So what can we actually conclude about the functionality and the purpose of our stomach?"}, {"title": "Stomach.txt", "text": "So we see that in our stomach we have the process of mechanical digestion taking place as a result of that continuous movement of our fluid and the contraction of our smooth muscle in our stomach that allows mechanical digestion to actually take place."}, {"title": "Stomach.txt", "text": "So we further break down our food into smaller particles."}, {"title": "Stomach.txt", "text": "Now inside our stomach we also break down our macromolecules."}, {"title": "Stomach.txt", "text": "We break down the protein into smaller peptides as a result of those proteolytic enzymes specifically the pepsin the enzyme that cleaves the peptide bonds in our proteins."}, {"title": "Stomach.txt", "text": "Inside the stomach we have a very low PH and that denatures our proteins and allows Pepsin to actually cleave those bonds."}, {"title": "Stomach.txt", "text": "And this hydrochloric acid also basically kills off bacterial cells that enter our stomach with our food."}, {"title": "Stomach.txt", "text": "Now, although our stomach does actually absorb certain types of molecules such as, for example, caffeine as we mentioned earlier aspirin, as well as alcohol it acts mostly in digestion."}, {"title": "Stomach.txt", "text": "It doesn't actually absorb the nutrients in the stomach."}, {"title": "Stomach.txt", "text": "Where the nutrients are absorbed are in the small intestine as we'll see in the next lecture."}, {"title": "Stomach.txt", "text": "Now, the cells of our stomach basically work together to secrete this gastric juice that consists of many different things."}, {"title": "Stomach.txt", "text": "It consists of hydrochloric acid, it consists of these enzymes as well as these other molecules that basically help stimulate the cells to release our gastric juice."}, {"title": "Stomach.txt", "text": "And what the gastric juice does is it breaks down our food into smaller molecules and together the mixing of the gastric acid and the food turns the food into a fluid like substance we call chain."}, {"title": "Stomach.txt", "text": "And chain ultimately exit the stomach and enters our small intestine."}, {"title": "Stomach.txt", "text": "And inside the small intestine we have the further breakdown digestion of our food into its constituent molecules and those are ultimately absorbed by the cells of the small intestine."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So now that we have a general idea of what oxidative phosphorylation is and what the electron transport chain actually does, let's begin by discussing briefly the major types of complexes that we find along the electron transport chain."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So we have four major types of complexes protein complex one, protein complex two, protein complex three, and protein complex four."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "In addition, additionally also have two very important electron carrier molecules used by the electron transport chain."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "One of them is known as Q, which stands for Coenzyme Q, also known as Ubiquinone, and the other known as the other one is known as Cytochrome C. So in this lecture, I'd like to briefly discuss these different types of structures."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And in the next many lectures to come, we're basically going to look at the details of what actually happens within each one of these complexes."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So let's begin with protein Complex to one."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, by the way, this is a diagram of only one of the electron transport chains of the many electron transport chains that exist in a single mitochondrial inner membrane."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So this is the inner mitochondrial membrane, this is the mitochondrial matrix and this is the intermembrane space that exists between the two membranes of the mitochondrion."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So protein complex one is also known as NADH dehydrogenase or NADH oxidoreductase."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And that's because this is the protein complex that actually accepts those high energy electrons from the NADH molecules which were produced in glycolysis as well as the citric acid cycle."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, this complex is actually a very large complex."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "In fact, it consists of about 46 individual polypeptide chains."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And if we examine the shape of protein complex one, we'll notice that it looks like the letter L. So the letter L, which basically looks like this, contains a horizontal component and a vertical component."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, the vertical component is basically exposed to the matrix of the mitochondria."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "But the horizontal component, this component, lies entirely in the membrane, the inner membrane of the mitochondria."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So the entire function of protein complex One is to accept those high energy electrons from NADH molecules and to move those electrons along a special pathway within the complex that we're going to focus on in detail in electra to come."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And those electrons ultimately are transferred onto the electron carrier molecule known as coenzyme Q Ubiquinone that we're going to look at in just a moment."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, this protein complex number one also acts as a proton pump."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So the fact that we have the movement of electrons within this complex that generates a form of energy that allows us to actually move these H plus ions across this membrane to this side and that ultimately allows us to actually generate a proton electrochemical gradient that will ultimately be used by the ATP synthase molecule to form the ATP molecule."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So this is protein complex one."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So once again, complex one, also known as NADH dehydrogenase or NADH oxidore ductase, is a very large complex that consists of about 46 individual polypeptide chains."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "It has an l shape that contains a horizontal component found within the inner membrane and the vertical component that lies within the matrix of the mitochondria."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And the transfer of electrons, as we'll see in the future lecture, actually takes place within this vertical component of this complex."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, the function of the complex is to actually oxidize the NADH back to NAD plus, accept those high energy electrons, and then move those high energy electrons along a specific pathway."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And that generates an electric current that basically allows us to pump those H plus ions across the membrane from the matrix and into the intermembrane space."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, let's move on, or actually, since we're on the subject, let's look at coenzyme Q."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So coenzyme Q, also known as Ubiquinone, is pretty much this small molecule that is dissolved in the membrane of the mitochondria."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "This is shown here."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And because it contains a relatively large hydrophobic region, it can dissolve easily in the membrane."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And so it can move across the membrane."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And what it does is it takes those electrons from protein complex ones that were received by the NADH molecule, and it shuttles, it moves those electrons onto protein complex three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "In addition, this coenzyme Q is also used to actually pick up the electrons received by protein complex one and move those electrons onto protein complex three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So let's move on to protein complex two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, the entire function of protein complex two is to actually accept and extract those hiding electrons from the fadh two molecules which are synthesized in the citric acid cycle."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So if we recall the citric acid cycle, there's a step in the citric acid cycle where we basically transform we oxidize succinate into fumerate."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And in this process, we have an enzyme known as succinate dehydrogenase that essentially reduces the fad into fadh two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So, remember, fad is Flavin adenine dinucleotide, which is capable of actually receiving extracting those high energy electrons."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So these two h plus ions and one electron from each one of these two bonds is extracted and placed onto the fad to form the fadh two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And actually, this sucks in."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "A dehydrogenase that is used by the citric acid cycle is found within complex two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So complex two, found on the inside portion of the inner membrane of the mitochondria, as shown here, contains the succinate dehydrogenase that is used by the citric acid cycle."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And so actually, when we synthesize the fadh two in the citric acid cycle, it remains attached onto the succinate dehydrogenase of this protein complex two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And within that complex, that fadh two is actually oxidized back into fad."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And that allows those two high energy electrons to be extracted by this complex."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And as we'll see in the future lecture, those electrons are then taken by this coenzyme Q carrier, our Ubiquinone."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And so Ubiquinone is able to shuttle to move the electrons not only from protein complex one to three, but also from protein complex two to three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So protein complex two, also known as Succinate reductase, contains the Succinate dehydrogenase enzyme that is used by the citric acid cycle to transform Succinate into fumerate in the process forming Fadh two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, one important distinction between protein complex two and the other protein complexes is protein complex two is not a proton pump."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "It does not actually move the protons from the matrix side to the intermembrane side only protein complex two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And as we'll see in just a moment, protein complex three and four are actually proton pumps and are used to generate electrochemical gradients for protons."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So let's move on to complex three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So complex three is shown here, and this complex is also known as cytochrome C oxidoreductase or Q cytochrome C oxidoreductase and sometimes known as cytochrome Reductase."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And what this proton comp, or what this complex does is it accepts those electrons from the Q carrier molecule, the Ubiquinone."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And then it takes those electrons and transfers them onto another electron carrier known as cytochrome C. Now, this, just like protein complex one, is also proton pump."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And as a result of the movement of those electrons within this complex, that allows this structure to actually pump those protons into the intermembrane space from the matrix of the mitochondria."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And finally, if we examine protein complex four, this is essentially where we take those electrons and we use them to reduce oxygen molecules into water molecules."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So this is where we find the final electron acceptor of the electron transport chain."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And this also uses the movement of those electrons to pump those protons out of the matrix and into the space between the two membranes."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And so together, protein complex one, three and four are basically proton pumps which help establish a proton gradient."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And then, as we'll see in a future lecture, the ATP synthase uses that proton gradient to generate those ATP molecules via oxidative osphorylation."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And it's called oxidative because protein complex four uses oxygen as that final electron acceptor."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So we see that Coenzyme Q, also known as Ubiquinone, shown here, is basically a small hydrophobic molecule that is dissolved in the inner mitochondrial membrane."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And it acts as an electron carrier that shuttles electron from protein complex one or protein complex two, ultimately, to protein complex three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Now, in its oxidized form, we call it Ubiquinone Q."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And this is what the structure actually looks like."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And notice we have a long hydrophobic tail."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "In humans, the end value is usually ten."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And that's why we call it Coenzyme Q ten."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And what happens is the two electrons and two H plus ions are accepted."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So one electron and one H plus ion is accepted by each one of these groups shown here and here to form the fully reduced form we call Ubiquinol or QH two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So this structure accepts electrons from either complex one or two to form the reduced form, QH two."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And then that travels to complex three, where it gives off those electrons to complex three, which ultimately move along the complex and onto cytochrome C. And cytochrome C, unlike Coenzyme Q, is a small water soluble protein."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "So remember, this structure is not a protein."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "Coenzyme Q is not a protein."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "By cytochrome C is a protein, and it's a water soluble protein."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "It is bound onto the intermembrane region of complex three."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And once it accepts those electrons, it moves and attaches onto protein complex four on this side of the complex."}, {"title": "Introduction to Electron Transport Chain .txt", "text": "And then it transfers those electrons, which ultimately used to actually reduce that oxygen and form the watermelon molecules, as we'll see in much more detail in lectures to come."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "The liver cells in our body are responsible for bringing down glycogen into glucose and then using that glucose to actually regulate the glucose levels in our blood."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "But once that process actually takes place and once the glucose levels in our blood return back to normal, the liver cells must be able to actually terminate and shut down glycogen breakdown."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So this is what, what I'd like to briefly focus on in this lecture."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So we're going to examine five different ways by which liver cells of our body are capable of shutting down glycogen breakdown."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Now the first way by which or the first method by which our body is able to actually shut down the Glucagon signal transduction pathway that initiates the Glycogen breakdown is to stop releasing the hormones that initiate this process in the first place."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So in this particular case, it's glucagon."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So Glucagon is no longer released."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And what that means is glucagon can no longer act as a primary messenger and so this pathway will no longer be initiated."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Now, the second method is the G protein."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So the G proteins involved in this particular pathway, namely this G protein shown here, actually contains an intrinsic Gtpa's activity."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And what that basically means is sometime after this process actually turns on the G protein, the G protein itself has the ability to hydrolyze the GTP back into GDP."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And what that does is it turns off the G protein, the G protein returns back to this location here."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And once the G protein dissociates from adenylate cyclist, that turns off the catalytic activity of adenylate cyclase and that stops transforming ATP into camp."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So number One or A hormones are no longer released and B, G proteins have an intrinsic GCPA activity which allows them to basically turn themselves off."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Now, what also happens is in the cytoplasm we basically have these proteins known as phosphodiestases."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And these phosphodiaesterases, what they do is they begin to basically transform the CA and P cyclic adenosine monophosphate molecules into Amp."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Remember, in the Glucagon signal transduction pathway that initiates Glycogen breakdown, the canp acts as a secondary messenger that is used to basically activate the inactive protein kinase Apka into the active version of PKA."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "But now that we are no longer producing cyclic Amp as a result of the inactivation of the adenaline cyclist, and because the CA and P are being transformed into A and P, the PKA is no longer activated."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Now let's move on to D. So in D and E, what we basically want to do is we want to inactivate the phosphoralase kinase that is needed to activate the Glycogen phosphorase and we also want to inactivate the Glycogen phosphorase that is ultimately needed in step one of Glycogen breakdown."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So let's focus on D. So essentially, in order to inactivate the phosphoralase kinase, what happens is the PKA must phosphorylate the alpha subunits of Asphylase kinase."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So the same PKA that is used to activate phosphorylase kinase is also actually used to inactivate phosphorase kinase."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "Remember when PKA phosphorylates the beta subunits, that activates this, but when PKA phosphorlates the alpha subunits, that causes the phosphorylase kinase to become a good substrate for another protein known as PP one, which stands for protein phosphatase one."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "And what happens is once PTA phosphorlates the alpha subunits, the phosphorlase kinase acts as a substrate to protein phosphatase one, and protein phosphatase one basically defosphorylates the beta subunits of phosphorase kinase and that inactivates this molecule."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So PKA phosphorlates the alpha units of phosphorlase kinase, which in turn makes it a good substrate molecule for protein phosphatase one."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "PP one and PP one removes the phosphoryl groups from the beta subunits and this deactivates the other kinase."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "In addition, the same protein phosphatase one also actually acts upon glycogen for sporilase, and it deactivates the glycogen phosphorase by removing those phosphoryl groups."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So once we deactivate the glycogen for sporalase, the glycogen breakdown process can no longer take place."}, {"title": "Termination of Glycogen Breakdown .txt", "text": "So this is basically how our liver cells and generally our body basically shut down and terminate glycogen breakdown in the liver cells of our body."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Carbohydrate molecules aren't only used as energy molecules and they're not only used to actually provide the matrix around the cell structure and integrity, but they can also be used to actually modify the properties and increase the functionality of protein molecules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So the process by which we covalently attach a carbohydrate component onto a protein molecule is known as protein glycosylation, and this type of molecule is known as the glycoprotein."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, previously we also discussed proteoglycans and we said that proteoglycans are also an example of biological molecules that contain a protein component as well as a sugar component."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So what exactly is the difference between a proteoglycan and a glycoprotein?"}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Well, in the case of glycoproteins, the sugar component makes up a much smaller percentage by mass of the biological molecule than compared to the proteoglycan."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And this is the main difference between these two types of biological molecules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So glycoproteins are an important class of biological molecules that play a variety of different roles inside our cells and inside our body, as we'll see in future lectures."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And they can be found along the cell membrane."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "They can also be found in the extracellular matrix."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "For instance, in our blood plasma, which is an example of an extracellular matrix, we'll find many different types of glycoproteins that play a variety of different roles."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, how exactly does the process of protein glycosylation actually take place?"}, {"title": "Glycosylation and Glycoproteins .txt", "text": "This is what we're going to focus on in the remaining of this lecture."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, oligosaccharides are basically very small polysaccharides that can have anywhere from three monosaccharides to, let's say, twelve monosaccharides."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, oligosaccharides can be attached onto proteins and we attach them onto proteins via specific amino acids."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So there are only three different amino acids that we can actually modify by covalently attaching these sugar molecules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And this includes asparagine, amino acids, serine, amino acids, and three an amino acids."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And out of these three types of attachments, we only have two types of bonds that can actually form."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "We can have the N glycocitic bond that can form between the sparring and the sugar, or we can have the O glycocitic bond that can form between the oxygen on the serine or thorianine and that corresponding sugar molecule."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So oligosaccharides may be attached to proteins via the nitrogen atom on the side chain of asparagne."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And this is called the anglecocitic linkage, or via the oxygen atom of the side chain of three aniner serene and that particular corresponding oligosaccharide."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And this is known as the Ogliac acidic linkage."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, to see exactly what we mean by all that, let's take a look at these two diagrams."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So, in this particular case, we have the sparrogene amino acid."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So this is the side chain of asparagine."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And notice we have an Ngycocytic bond between the nitrogen atom on the side chain of asparagine and the anamary carbon carbon number one of this modified glucose molecule, which happens to be the N acetyl glycosamine."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So this green bond is called the N glycocitic bond because it's between the nitrogen of the side chain of the spare gene amino acid, and the anameric carbon, carbon number one of that glucose amino acid."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, in this particular case, we have the Oglycocity bond, and we call it the Oglycocitic bond because it's between the oxygen of the side chain of serena."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Also, we can have three ane and this anomeric carbon number one of this modified galactose sugar molecule, which is known as an acetyl galactose amine."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So these are the two types of linkages that we can have in glycoprotein molecules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So along a protein molecule, we can have many of these asparagine three anine and serene amino acids."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "The question is, how exactly does a cell actually know which one of these amino acids must be glycosylated?"}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Well, the way that it knows is it looks at the sequence next to that particular amino acid."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So the size at which glycosylation takes place depends on the sequence of amino acids adjacent to that particular amino acid."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So in the case of a sparrogene, the cell will only modify the spare gene and attach that particular sugar molecule if the sequence around is a specific sequence."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And these are the two sequences that the cell uses."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So right next to the spargian, ASM asparagine, we have to have an arbitrary x, so an arbitrary amino acid where x cannot be proline."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And right next to this arbitrary x, we have to have either threeline or serene."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So only if the sequence is like these two sequences will that sparrogene actually be modified."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "On top of that, what also determines the amino acids where we modify is the actual structure of that protein and the cell that is actually carrying out that protein glycosylation process."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So we see that it also depends the size of glycosylation also depends on the type of cell that is producing that protein and on the overall structure of that protein itself."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, what exactly is the general process by which protein glycosylation actually takes place inside the organelles of our cell and which organelles are responsible for the process of protein glycosylation?"}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So let's take a look at the following diagram."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "There are two organelles that play a role in the process of glycosylation."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "We have the rough endoplasmic reticulum as well as the Golgi apparatus, the Golgi complex."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, within our endoplasmic reticulum, this is where the N linkages are actually formed."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So N link glycosylation between the sparring and that respective oligosaccharide begins at the endoplasm reticulum and is completed at the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "On the other hand, the old linkages are only formed exclusively and entirely inside the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, to see exactly how the process takes place, let's take a look at this diagram."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And let's begin on the endoplasmic reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So along the outer membrane of this or along the outer section of the membrane of the endoplasm reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So on the cytoplasmic side."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So this is the cytoplasm."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And on the cytoplasmic side of the endoplasm reticulum, we have these ribosomes shown by these dots."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So let's suppose at this ribosome, we begin the process of protein synthesis on the cytoplasmic side of the membrane."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And as we continually synthesize that protein strand, the protein strand moves into the lumen of that endoplasm reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So the lumen is the inside portion of that endoplasmic reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And once inside the endoplasmic reticulum, there are special enzymes, complex of enzymes, which are responsible for actually creating the end linkage between asparagine and the respective oligosaccharide."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So we essentially attach those sugar molecules onto asparagine via the end linkage inside the endoplasm reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Now, once we form the protein, the protein then leaves the endoplasm reticulum."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "It goes into a special transport vesicle that carries it onto this side, which is known as the cyst side of the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So, once on the CIS side of the Golgi apparatus, which is this side here, it basically moves along the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And as it moves, that particular N linked sugar molecule is even further modified."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And on top of that, we also form the old glycosytic linkages between either the serene and threatening and that particular sugar molecule."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And this takes place inside the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So inside the Golgi, we form the old linkages and we also continue modifying those sugars which have been formed via the end linkages."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And once they essentially end up on the trans side of the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So the side where the Golgi receives these molecules is assists."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "The side where it sends these completely and fully modified glycoproteins is at the transide and it sends them to three different locations."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So depending on the sequence of amino acids and the structure of that particular glycoprotein, these glycoproteins, once they're modified in the Golgi apparatus and once they're sorted, they can be sent either to the cell membrane, where they can actually be embedded into the cell membrane, they can be sent and stored inside these special secretory granules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And when some type of action potential or some type of stimulus stimulates the cell to release these granules, they can basically be released via the process of exocytosis."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And these glycoproteins can also be stored in these organelles we call lysosomes."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "Remember, lysosomes are these organelles that have these special digestive enzymes which are responsible for actually breaking down different types of molecules that are found within our cell."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So, once again, to summarize, at position one, we have ribosomes attach the cytoplasmic side of the Er."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "These dots basically synthesize the proteins."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And as the proteins are being synthesized, and as they move into the lumen of our endoplasmaticulum, special protein enzyme complexes basically attach those sugar molecules via the end glycocytic linkages."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And once that forms, they basically move into the Golgi apparatus."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So the proteins move out of the lumen of the Er and into the cytoplasm, where they then travel into the Golgi apparatus via these special transport vesicles."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And inside the Golgi complex, the end link sugars are modified and the oglycosylation actually takes place."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And once the Golgi complex modifies and sorts the glycoproteins, it then directs these glycoproteins to basically move into different locations depending on what their function actually is."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And so they can end up in the lysosomes, they can end up being stored in secretary granules, or they can be stored in the bilayer membrane around that particular cell."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So we see that glycoproteins are a very important class of biological molecules."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "And glycoproteins basically consists of protein component as well as a carbohydrate component."}, {"title": "Glycosylation and Glycoproteins .txt", "text": "So by modifying an adding the sugar component onto the protein, we increase the functionality and change the properties of the protein molecules."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Another method by which our cells can regulate and control the activity of enzymes and change the functionality of proteins is known as covalent modification."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now generally speaking, in covalent modification what happens is we actually transfer a functional group, a functional amid from one molecule onto that target enzyme that target protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So we actually covalently attach a group onto that enzyme and that's precisely what changes the activity of that enzyme or the functionality of that protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It can either turn on or in some cases turn off the activity of that enzyme."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now there are many different types of covalent modifications that can take place inside our cells."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So we can modify the proteins in many different ways."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "For instance, we have processes like methylation acetylation, sulfination and many others that we're going to discuss in future lectures."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "But the one that we're going to focus on is known as phosphorylation."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And phosphorylation is a very common method of covalent modification."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It's a very common method by which we actually control the activity of enzymes and change the functionality of proteins."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "In fact, it's so common that nearly 30% of all the proteins and this includes enzymes in eukaryotic cells are actually phosphorylated."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now why is this method so common?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Well as it turns out phosphorylation is a very effective, very efficient and a very convenient process and we'll see why that is."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So in just a moment."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "First let's actually discuss the family of enzymes that are responsible for catalyzing controlling the rate of this phosphorylation process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So basically, just like any biological process that takes place inside our body is controlled by enzymes, this process of phosphorylation is also regulated by enzymes."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And the family of enzymes that regulates this process, this family is known as the protein kinase family."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "In fact, inside our body we have over 500 homologous protein kinases which are responsible for regulating the rates of this process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So basically these different protein kinases catalyze the phosphorylation of different substrate molecules, different proteins and different enzymes."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now what exactly does the process of phosphorylation actually entail?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Well in this process that functional group that we transfer from some molecule onto that target enzyme of protein is the phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now the question is what is the source of this phosphoryl group?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "What is that molecule that exists inside our cells that we can actually detach the phosphoryl group and attach it onto that protein?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Well, inside our body, inside our cells we have a very high abundance of high energy ATP molecules adenosine triphosphates which are produced by the mitochondria of the cell."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so because we have this abundancy of high energy ATP molecules that contain the phosphoryl groups, these are the molecules that are the source of this phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So basically, in this process, the protein kinase catalyze the transfer of a terminal phosphoryl group, shown in red from that ATP molecule, onto a hydroxyl containing group, hydroxyl containing side chain found on that protein, the target protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And because serine 13 and Tyrosine all contain hydroxyl groups on the side chains of these amino acids, these are the three residues that are capable of actually using the hydroxyl group to accept that transfer, that phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So in this process, on the reactant side, we have an ATP molecule and the target enzyme of protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And then on the product side, we basically have the ADP molecule adenosine diphosphate."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "We have a single H plus ion that comes from this oxygen here."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And we have this modified residue that is part of that target enzyme, the target protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So the red term phosphoryl group has been transferred onto this oxygen."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now because inside our cells, we have this abundancy of ATP molecules."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It's inside the cells that the proteins basically undergo this process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And those proteins found outside the cells do not actually undergo this process of phosphorylation because outside the cells, ATP is not abundant."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So reversible phosphorylation occurs inside the cells where the concentration of ATP is high and abundant."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "But proteins found outside the cells are not regulated in this method of phosphorylation because outside the cells we don't have an abundant supply of ATP like we have inside the cells."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now, the next topic that I'd like to discuss is why is phosphorylation so common?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So why is this one of the more common methods of Covalent modifications?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And as I mentioned earlier, it's because phosphorylation is very effective, very efficient and very convenient."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "The question is why?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "What makes this process so effective and so convenient?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Well, there are seven things that have listed several reasons that I've listed on the board."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So let's quickly go through each one of these reasons and let's begin with reason number one."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So in the process of phosphorylation, what we actually do is we transform a neutral residue to a residue, modified residue that contains a negative charge."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And because of the presence of the negative charge, it can basically break the old interactions and form better interactions, more stabilized interactions."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And what that usually means is if this residue is found inside the active side of the enzyme, the presence of this modified phosphoryl group, what it basically does is it forms new interactions with, let's say, the substrate molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And that can in turn change the activity, the rate at which the enzyme actually catalyzes that particular reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So number one is this process gives a net negative charge and that's precisely what allows these new electric interactions to actually take place between this residue and that target substrate molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And this leads us directly into reason number two."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "As a result of this modified negatively charged groove found on this residue, because of this negative charge, that essentially gives this modified residue a high potential to form hydrogen bonds."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so the negatively charged oxygen atoms of the phosphorylated side chain residue can form hydrogen bonds with other molecules, for instance, the target enzyme or the target substrate molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so this can increase the specificity of the interaction between the active side of the enzyme and that substrate molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now number three is the protein kinases are actually able to easily adjust the rates, the kinetics of this reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So depending on the physiological needs of the cells, this reaction can take place very, very quickly in a matter of seconds or it can take place over a very long period of time."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And the rate at which it actually the rate at which it takes place and the rate at which the protein kinases catalyze the reactions basically depends on the conditions found inside our cells."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "If we have to undergo this process, the protein kinases can basically allow the process to take place very quickly."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "But if we don't want to carry out the process, these protein kinases can easily adjust the kinetics and slow down the speed at which this reaction actually takes place."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now, number four is actually what we spoke about previously."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It's the fact that inside our cells we have these high energy adenosine triphosphate molecules that can act as the source of that phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So we see that phosphorylation requires the transfer of this phosphoryl group from some molecule onto that residue of that enzyme."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And these high energy ATP molecules which are so abundant inside our cells can easily be used and very effectively be used to actually transfer that phosphoryl molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Number five is, and we'll discuss this in much more detail, we have the process of amplification that takes place whenever protein kinases are involved."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And that's because usually a single protein kinase enzyme can actually catalyze many enzymes at once."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so if each one of these enzymes itself carries out some type of reaction, the protein kinase, by activating all these other enzymes, basically amplifies the result."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It amplifies all these different types of reactions and that greatly speeds up the number of substrate molecules which are transformed to the product molecules."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And we'll discuss this in much more detail in a future lecture."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So activated protein kinases can be used to regulate many different enzymes and many different reaction pathways."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And this can lead to an amplification effect in which we essentially amplify the amount of final product that we produce."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now, number six is whenever this reaction takes place because essentially what we're doing is we're defosphorylating this ATP molecule and the breakdown of the ATP molecule is a very exergonic reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It releases energy."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "We see that this process is in fact thermodynamically stable and the energy of the product is lower than the energy of the reactants."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And in fact, about half of the energy, half of the free energy that is released in the defasphorylation of this ATP molecule is stored inside this protein phosphoryl group complex."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So defosphorylation of ATP is a very exergonic reaction and it releases a large amount of free energy and that's precisely why this reaction itself is thermodynamically stable."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "In fact, because the products are so much more stable than the reactants."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "This reaction ultimately takes place in a single direction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So it takes place this way and this reverse reaction doesn't actually take place, at least not at a very high rate."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And that leads us directly into number seven."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So if the process of asphorylation is to actually be a convenient process, we have to actually be able to reverse this process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Because if, asphorylation let's say, turns on a proteins activity, we have to be able to basically turn off the activity of that enzyme by for instance, removing that phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "But as I mentioned just a moment ago, this process as shown here, because this is so much more thermodynamically stable than the reactants, this process is essentially a one way reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So the question is how can we actually reverse this process?"}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Well, instead of using the protein kinase to actually reverse the reaction, we use a different enzyme known as protein phosphatases."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So inside our body it's these protein phosphate phosphatases which are actually used to reverse the effects of the protein kinases."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So protein kinases are responsible for phosphorylating that enzyme or the protein."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "But the protein phosphatases use a completely different reaction mechanism, a completely different reaction pathway to actually reverse the effect of the protein kinase and remove this phosphoryl group."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And that can basically either activate or deactivate the activity of that enzyme."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So if phosphorylation activates that enzyme, then defosphorylation will deactivate the activity of that enzyme."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And protein kinase is basically phosphorylate while protein phosphatases defosphorylate."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And they use the following hydrolysis reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So basically this is that modified residue of that enzyme."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And what protein phosphatases do is they use a water molecule to basically remove this group and produce reform this enzyme that now contains this original residue that we basically had right over there."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So these are the seven reasons for why phosphorylation is a very effective and a very convenient process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "So again, it produces a residue that is modified and contains a net negative charge."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And that's precisely what gives it a potential to form many hydrogen bonds and that allows it to actually interact in a much more stabilizing fashion with that substrate molecule."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Number three is these protein kinases can easily adjust the rate at which the reaction takes place and the rate really depends on the physiological conditions found inside the cell."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Number four is we have an abundance of these high energy ATP molecules that exist inside our cells until we can quickly and effectively use them to actually transfer those phosphoryl groups."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Number six is again with the ATP molecule because the breakdown, the defaults formation of the ATP molecule is in fact an exergonic process."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "It releases an ample amount of free energy."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "That free energy is used to basically drive this reaction."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so the, thermodynamic stability of the products will shift the reaction all the way to the product side."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so these products are much lower in energy than these reactants."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Now let's go back to number five."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "Whenever dealing with protein kinase is typically a single protein kinase, usually catalyzes many individual enzymes."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so instead of catalyzing one reaction, catalyzes many reactions at once."}, {"title": "Covalent Modification and Phosphorylation .txt", "text": "And so."}, {"title": "Genetic Probability Example .txt", "text": "So now that we know what the product and the sum rule is, let's take a look at the following example that applies those two rules."}, {"title": "Genetic Probability Example .txt", "text": "Let's begin by stating the problem."}, {"title": "Genetic Probability Example .txt", "text": "So if a couple decides to have three children total, what is the probability that A all three are girls, b all three children are boys?"}, {"title": "Genetic Probability Example .txt", "text": "C the first one is a boy, the second child is a girl girl, and the third one is a boy?"}, {"title": "Genetic Probability Example .txt", "text": "D two of them are boys and one of them is a girl, and E they produce, at most, two boys."}, {"title": "Genetic Probability Example .txt", "text": "So let's begin by creating the Punnett square."}, {"title": "Genetic Probability Example .txt", "text": "Now the way that we're going to create the Punnett square is in the following manner."}, {"title": "Genetic Probability Example .txt", "text": "So this column basically deals with the first possibility of the child."}, {"title": "Genetic Probability Example .txt", "text": "So we have either a boy or girl."}, {"title": "Genetic Probability Example .txt", "text": "This row basically deals with the second possibility."}, {"title": "Genetic Probability Example .txt", "text": "So child number two can be their boy or girl."}, {"title": "Genetic Probability Example .txt", "text": "And this is the third possibility right over here."}, {"title": "Genetic Probability Example .txt", "text": "So let's suppose that child number one we're going to designate with blue."}, {"title": "Genetic Probability Example .txt", "text": "So the possibilities are we either have a boy or we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "Now what about possibility number two, child number two."}, {"title": "Genetic Probability Example .txt", "text": "So the same exact thing."}, {"title": "Genetic Probability Example .txt", "text": "Let's use red, we have boy or we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "And possibility number three is also a boy or girl."}, {"title": "Genetic Probability Example .txt", "text": "But to make this work out properly, we're going to do it in the following way."}, {"title": "Genetic Probability Example .txt", "text": "So we either have a boy or we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "And we also have either a boy or we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "And actually let's change this up and do it in the same way that we did below."}, {"title": "Genetic Probability Example .txt", "text": "So we have boy and a girl."}, {"title": "Genetic Probability Example .txt", "text": "And the reason we did this is to basically work out the pun and square correctly."}, {"title": "Genetic Probability Example .txt", "text": "So this is child number one, the possibilities for child number one, the possibilities for child number two and the possibilities for child number three."}, {"title": "Genetic Probability Example .txt", "text": "Now let's actually write out the fractional probability of each one of these events actually taking place."}, {"title": "Genetic Probability Example .txt", "text": "So we have a one half probability of this being a boy."}, {"title": "Genetic Probability Example .txt", "text": "So let's write one half."}, {"title": "Genetic Probability Example .txt", "text": "We have a one half probability that this takes place."}, {"title": "Genetic Probability Example .txt", "text": "So one half and one half."}, {"title": "Genetic Probability Example .txt", "text": "We have one half probability that this takes place."}, {"title": "Genetic Probability Example .txt", "text": "One half probability that this takes place."}, {"title": "Genetic Probability Example .txt", "text": "And the same thing is true with each one of these events, right?"}, {"title": "Genetic Probability Example .txt", "text": "Because out of two possibilities we can have either a boy or girl."}, {"title": "Genetic Probability Example .txt", "text": "And so each one of those possibilities is equally likely and so they are given 50%."}, {"title": "Genetic Probability Example .txt", "text": "So we have a half and a half which are equivalent to 50%."}, {"title": "Genetic Probability Example .txt", "text": "So now let's actually create the Punnett square."}, {"title": "Genetic Probability Example .txt", "text": "So we combine B, red B, we have the second event or a blue B, a red B and a purple B."}, {"title": "Genetic Probability Example .txt", "text": "So we have a B, then we have the red B boy and we have the third one."}, {"title": "Genetic Probability Example .txt", "text": "And so what this basically means is this square here describes the event in which the first child is a boy, the second child is a boy, and the third child is also a boy."}, {"title": "Genetic Probability Example .txt", "text": "And because these events are basically independent of one another, we multiply their individual probability by the product rule to find the total probability of these independent events."}, {"title": "Genetic Probability Example .txt", "text": "So we have one half multiplied by one half multiplied by one half."}, {"title": "Genetic Probability Example .txt", "text": "And that gives us one eight."}, {"title": "Genetic Probability Example .txt", "text": "Now let's look at this block right here, this square."}, {"title": "Genetic Probability Example .txt", "text": "So this basically describes the probability."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy in the first time, the boy in a second time, and a girl on the third time on the third try."}, {"title": "Genetic Probability Example .txt", "text": "So we have a blue boy, then we have the second child, we have the red boy, and then we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "And once again, to calculate what the probability of this event taking place is, we take the product of the individual probabilities of these three events."}, {"title": "Genetic Probability Example .txt", "text": "And so we have one half multiplied by one half multiplied by one half."}, {"title": "Genetic Probability Example .txt", "text": "And that gives us one 8th."}, {"title": "Genetic Probability Example .txt", "text": "And we continue the process."}, {"title": "Genetic Probability Example .txt", "text": "Now we move on to this square."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy the first time around."}, {"title": "Genetic Probability Example .txt", "text": "Then we have a girl the second time around, and the third time around, we have a boy."}, {"title": "Genetic Probability Example .txt", "text": "And the probability of this is the product of the three individual probabilities."}, {"title": "Genetic Probability Example .txt", "text": "And so that is, as of these two cases, one eight."}, {"title": "Genetic Probability Example .txt", "text": "In this case, we have a boy."}, {"title": "Genetic Probability Example .txt", "text": "We have a girl, and we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy."}, {"title": "Genetic Probability Example .txt", "text": "We have a girl, and we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "And so if we multiply these out, once again, we get one 8th and we can and we can basically conceive the process out with these three."}, {"title": "Genetic Probability Example .txt", "text": "With these four cases, we multiply them out and we always get one 8th in each one of these boxes."}, {"title": "Genetic Probability Example .txt", "text": "So let's continue with this one."}, {"title": "Genetic Probability Example .txt", "text": "So we have now we have the first time around, a girl."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy, and then we have a boy."}, {"title": "Genetic Probability Example .txt", "text": "So we have girl, boy, boy."}, {"title": "Genetic Probability Example .txt", "text": "So we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy, and then we have a boy again."}, {"title": "Genetic Probability Example .txt", "text": "And if we take the product, we get one half multiplied by one half multiplied by one half."}, {"title": "Genetic Probability Example .txt", "text": "And that gives us too many markers."}, {"title": "Genetic Probability Example .txt", "text": "We have 1818."}, {"title": "Genetic Probability Example .txt", "text": "Okay, here we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "A girl and a boy."}, {"title": "Genetic Probability Example .txt", "text": "So we have a boy here."}, {"title": "Genetic Probability Example .txt", "text": "We have a girl here, and we have a girl here."}, {"title": "Genetic Probability Example .txt", "text": "Okay, here we have a girl, a boy and a girl."}, {"title": "Genetic Probability Example .txt", "text": "And here we have a girl, a girl and a girl."}, {"title": "Genetic Probability Example .txt", "text": "And we have a girl."}, {"title": "Genetic Probability Example .txt", "text": "Okay?"}, {"title": "Genetic Probability Example .txt", "text": "And the probabilities are, as usual, one eight for each one of these."}, {"title": "Genetic Probability Example .txt", "text": "Now notice, we have eight of these squareds and each one of the square has a probability of one eight."}, {"title": "Genetic Probability Example .txt", "text": "And that makes sense because if we add up all these probabilities, we should get a probability of one, which represents 100."}, {"title": "Genetic Probability Example .txt", "text": "So 100%."}, {"title": "Genetic Probability Example .txt", "text": "So what that means is one of these will actually take place."}, {"title": "Genetic Probability Example .txt", "text": "So let's move on to A."}, {"title": "Genetic Probability Example .txt", "text": "If a couple decides to have three children, what is the probability that A all three are girls?"}, {"title": "Genetic Probability Example .txt", "text": "Now which one of these boxes describes this situation?"}, {"title": "Genetic Probability Example .txt", "text": "Well, the only box that describes the situation is the final box where we have a girl the first time around, a girl the second time around and a girl the third time around."}, {"title": "Genetic Probability Example .txt", "text": "And so the probability of that event is simply one 8th."}, {"title": "Genetic Probability Example .txt", "text": "So in part A we simply have one 8th."}, {"title": "Genetic Probability Example .txt", "text": "Let's move on to B, all three are boys."}, {"title": "Genetic Probability Example .txt", "text": "Well, once again we look at the pundit square that we created and we look for BBB when all three children are boys."}, {"title": "Genetic Probability Example .txt", "text": "And this is this box here."}, {"title": "Genetic Probability Example .txt", "text": "And the probability is once again one 8th."}, {"title": "Genetic Probability Example .txt", "text": "Now?"}, {"title": "Genetic Probability Example .txt", "text": "What about C?"}, {"title": "Genetic Probability Example .txt", "text": "The first one is a boy, the second one is a girl."}, {"title": "Genetic Probability Example .txt", "text": "And the third one is also boy."}, {"title": "Genetic Probability Example .txt", "text": "Now, how many possibilities do we have like that?"}, {"title": "Genetic Probability Example .txt", "text": "Well, one as well."}, {"title": "Genetic Probability Example .txt", "text": "We want the boy, then we want the girl, and then we want the boy."}, {"title": "Genetic Probability Example .txt", "text": "And the only time we have that is right over here."}, {"title": "Genetic Probability Example .txt", "text": "So boy, girl, boy."}, {"title": "Genetic Probability Example .txt", "text": "And so that means the probability is one 8th."}, {"title": "Genetic Probability Example .txt", "text": "Now D, two are boys and one is a girl."}, {"title": "Genetic Probability Example .txt", "text": "Now notice we are not given the order of these children."}, {"title": "Genetic Probability Example .txt", "text": "So it doesn't matter which two are boys and which one is a girl."}, {"title": "Genetic Probability Example .txt", "text": "All we want is a total of two boys and one girl."}, {"title": "Genetic Probability Example .txt", "text": "So the order doesn't matter."}, {"title": "Genetic Probability Example .txt", "text": "Now let's see which one of these eight cases satisfy this situation here."}, {"title": "Genetic Probability Example .txt", "text": "Two boys and one girl."}, {"title": "Genetic Probability Example .txt", "text": "So in case number one, we have three boys."}, {"title": "Genetic Probability Example .txt", "text": "So that doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "In case number two here we have two boys."}, {"title": "Genetic Probability Example .txt", "text": "So the first one is a boy, the last one is a boy and the middle one is a girl."}, {"title": "Genetic Probability Example .txt", "text": "And this satisfies this case."}, {"title": "Genetic Probability Example .txt", "text": "So the probability here is one 8th."}, {"title": "Genetic Probability Example .txt", "text": "Now let's move on to this case."}, {"title": "Genetic Probability Example .txt", "text": "We have a boy, a boy and a girl."}, {"title": "Genetic Probability Example .txt", "text": "And once again that satisfies D. Because we have two boys and one girl."}, {"title": "Genetic Probability Example .txt", "text": "And because these two events are mutually exclusive."}, {"title": "Genetic Probability Example .txt", "text": "Meaning if one takes place, the other one cannot possibly take place."}, {"title": "Genetic Probability Example .txt", "text": "To find the total probability, we simply add up the probabilities and this is the sum rule."}, {"title": "Genetic Probability Example .txt", "text": "Now what about case four?"}, {"title": "Genetic Probability Example .txt", "text": "So we have case one, case two, case three and case four."}, {"title": "Genetic Probability Example .txt", "text": "Here we have a boy and two girls."}, {"title": "Genetic Probability Example .txt", "text": "So that doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "If we move on to case five, we have a girl, boy and a boy."}, {"title": "Genetic Probability Example .txt", "text": "So that works."}, {"title": "Genetic Probability Example .txt", "text": "And once again they are mutually exclusive."}, {"title": "Genetic Probability Example .txt", "text": "So by the sum rule we add them up."}, {"title": "Genetic Probability Example .txt", "text": "Case number six is girl, girl, boy."}, {"title": "Genetic Probability Example .txt", "text": "That doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "Case number seven is girl, boy, girl."}, {"title": "Genetic Probability Example .txt", "text": "Once again that doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "And case number eight also doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "So this is what we do."}, {"title": "Genetic Probability Example .txt", "text": "We sum up these three values and we get three eight."}, {"title": "Genetic Probability Example .txt", "text": "So this is the probability for these."}, {"title": "Genetic Probability Example .txt", "text": "So let's box these in and let's look at e. So they produce at most two boys."}, {"title": "Genetic Probability Example .txt", "text": "And this is basically the key word."}, {"title": "Genetic Probability Example .txt", "text": "So what exactly do we mean by at most two boys?"}, {"title": "Genetic Probability Example .txt", "text": "Well, what this means is we actually have to look at three different cases."}, {"title": "Genetic Probability Example .txt", "text": "So at most means we can have no boys or we can have one boy or we can have two boys, but we cannot have three boys because we want at most two boys."}, {"title": "Genetic Probability Example .txt", "text": "So basically we have to look at three individual cases when we have zero boys, when we have one boy, and when we have two boys, okay?"}, {"title": "Genetic Probability Example .txt", "text": "And then we find the probabilities of these events and we sum them up because they are mutually exclusive."}, {"title": "Genetic Probability Example .txt", "text": "So let's begin with zero boys."}, {"title": "Genetic Probability Example .txt", "text": "So zero boys is the same thing as saying all three are girls."}, {"title": "Genetic Probability Example .txt", "text": "And so we know from part A the probability of that is one 8th."}, {"title": "Genetic Probability Example .txt", "text": "Now, the second case is one boy."}, {"title": "Genetic Probability Example .txt", "text": "And we don't care if the, if this one boy is the first child, the second child or the third child."}, {"title": "Genetic Probability Example .txt", "text": "So either case will actually work."}, {"title": "Genetic Probability Example .txt", "text": "So we're looking for scenario a case in which one of them is a boy and the other two are girls."}, {"title": "Genetic Probability Example .txt", "text": "So all three are boys."}, {"title": "Genetic Probability Example .txt", "text": "That doesn't work here."}, {"title": "Genetic Probability Example .txt", "text": "Here we have two boys."}, {"title": "Genetic Probability Example .txt", "text": "Does not work."}, {"title": "Genetic Probability Example .txt", "text": "Here we have two boys, also does not work."}, {"title": "Genetic Probability Example .txt", "text": "Here we have one boy, so we have one 8th."}, {"title": "Genetic Probability Example .txt", "text": "This case has two boys."}, {"title": "Genetic Probability Example .txt", "text": "Doesn't work."}, {"title": "Genetic Probability Example .txt", "text": "This case does work."}, {"title": "Genetic Probability Example .txt", "text": "We have one boy, so plus one 8th."}, {"title": "Genetic Probability Example .txt", "text": "And here we have also one boy."}, {"title": "Genetic Probability Example .txt", "text": "So that also works."}, {"title": "Genetic Probability Example .txt", "text": "So we see that for this particular event, the probability is three eight."}, {"title": "Genetic Probability Example .txt", "text": "Now, what about two boys?"}, {"title": "Genetic Probability Example .txt", "text": "Well, this is the same thing as saying two are boys and one is a girl."}, {"title": "Genetic Probability Example .txt", "text": "And we know from part D that this is equal to also one eight plus one 8th plus one eight or three eighths."}, {"title": "Genetic Probability Example .txt", "text": "So to find the final probability, we simply add up these individual probabilities of these three mutually exclusive events."}, {"title": "Genetic Probability Example .txt", "text": "So we have one eight plus three eight plus three eighths."}, {"title": "Genetic Probability Example .txt", "text": "And that gives us seven eights."}, {"title": "Genetic Probability Example .txt", "text": "So this is the probability of these two individuals, the couple producing at most two boys."}, {"title": "Genetic Probability Example .txt", "text": "So we have one eight in this case for zero boys, three eights for one boy, and three eighths for two boys."}, {"title": "Genetic Probability Example .txt", "text": "And this is how, how you apply the product or the product and the sum rule in genetics and probability."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "In medicine, it's very important to be able to study and analyze the function of the kidney."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And one important quantity, one important measurement that doctors use to actually study the function of our kidney is known as the renal clearance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So this will be the topic of this lecture."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, what exactly is renal clearance?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, renal clearance of a given and substance basically tells us how much volume of blood plasma is completely cleared of that substance over some time period by our kidneys."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And the units of renal clearance are milliliters the volume per minute, our time."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So let's begin by taking a look at the simplified diagram of our nephron, the basic functional unit of our kidney."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So we have the apharyine arterial that brings our blood vessels, that brings the blood plasma into the network of capillaries found inside the bow, its capsule known as the glomerylus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, within this network of capillaries, we have filtration taking place."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Some portion of the blood plasma that enters the glomerylus is filtered through a filtration membrane and into the Bowman's capital or the Bowman space of the Bowman's capsule and then enters our tubular section of the nephron, which includes the proximal convolute tubule, the lupus henley, the distal convolute, as well as the collecting duct."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, within the tubular section, we also have reabsorption and secretion taking place."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, the rest of that blood plasma that is not filter travels into the Ethernet arterial that then enters our peritubular capillaries."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And these are the capillaries where we have reabsorption and secretion taking place between the blood capillaries and our tubules of the nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, let's begin by discussing the rate at which blood actually flows into the nephron for normal kidneys."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, the normal kidneys pass about 625 blood plasma through the Aaron arterial and into the glomerulus every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And this is known as the renal plasma flow, where flow is simply the movement of our fluid."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "The plasma is the blood plasma that moves across our blood vessels and renal refers to our kidneys."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So 625 blood plasma passes through the aphrin arterio every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, in our discussion on the renal corpus of the glomerulus and our Bowman's capsule, we said that about 20% of that blood plasma that enters our glomerulus is actually filtered into the Bowman space of the Bowman's capsule and then enters the tubules of our nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And because 20% of 625 is 125, that means 125 milliliters of blood plasma filters through the glomerulus every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, because we have 625 going in and 125 comes out of this side, then that means this minus this or 500 blood volume actually travels through the efair and arterial and into the peritubial capillaries every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, the filtration rate of 125 ML/minute is also known as the glomerul filtration rate."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So this is the normal filtration rate of the glomerulus and this is the normal value for the renal plasma flow."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now recall, as we mentioned earlier, within our tubular section of the nephron, we have reabsorption and secretion taking place between our peritubular capillaries."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So certain substances that are actually filtered across and into the Bowman's capsule are reabsorbed back by that body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And this includes things like amino acids and glucose, sodium chloride, as well as many other things."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now we can also have secretion taking place."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Certain substances that end up traveling into the Eve farin arterial and then into the peritubular capillaries can actually be secreted back into our filtrate and eventually ends up in our urine that is released by our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So we see that there are actually only two ways by which a given substance can actually end up being in the filter."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "It and eventually ends up in our urine and is released by our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And these two methods are as follows."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Number one, that substance can be filtered through our glomerulus and then not reabsorbed by our tubules."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And what that means is that substance, because it is filtered and not reabsorbed, it will end up being in the urine that is released by the body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now the second method is the following."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "It is not filtered through our glomerilus, but as it travels through the Ethernet arterial and eventually ends up in the periobular capillaries, it can be secreted by those capillaries into the tubules and then it ends up in our urine."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So these are the only two ways by which some given substance can end up in the filtrate and ultimately released in our urine."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, as I mentioned earlier, different substances have different values for the renal clearance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So let's begin by supposing we have some hypothetical substance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Let's call this substance X and let's discuss how it can actually move within our nephron and what can happen to it within our nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And let's study what the renal clearance value is of this substance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So I've outlined four different cases, but you should note that there are more cases than this."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "These are probably the four most common cases that you should be familiar with."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Case number one."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So we basically have freely filtered through the glomerulus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And what this basically means is whatever this substance is, when it enters this blood plasma, when it enters the glomerulus, it can easily pass across our glomerulus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that means the concentration of this substance in the Bowman's capsule will be exactly the same as the concentration of the substance inside our blood plasma found in our glomerulus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now not absorbed means when that substance is within our tubule of the nephron, it is not reabsorbed back into our peritubular capillaries."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And not secrete means if any of this substance is found in the Ethernet arterial, it is not actually secreted by the peritubular capillaries back into our filter."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So case number one freely filtered, not absorbed, not secret."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So for a substance X that is freely filtered visaglomerilus, but it is neither reabsorbed nor secreted, what exactly will be our renal clearance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, let's take a look at the following diagram."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So, we basically have 625 milliliters of blood volume enters this glomerulus every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And every single minute 125 ML/minute is actually cleared."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, because this substance is assumed to be freely filtered, that means 125 ML/minute is actually filtered."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So that means as it passes across the tubular section of the nephron, because none of it is actually reabsorbed and none of it is secreted by these peritubular capillaries back into our tubule, the filtrate that means the renal clearance is simply equal to our globe Maryal filtration rate of 125."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So this quantity of blood plasma that enters this tubular section of the capillary is completely cleared of that substance."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, what's an example of such a substance?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, one example that is not naturally found in our body, but our doctors use to study the global filtration rate is known as insulin."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So inulin or inulin is this polysaccharide that we can basically ingest into our body and which is basically follows this pathway as described."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So it is completely filtered by our global illus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "It can basically travel across freely, but it is not reabsorbed, nor is it actually secreted."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So the global filtration rate, or GFR is equal to the filtration rate of this substance, our inulin."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So our doctors basically can study the globeal filtration rate of our kidneys by giving the patient this substance and then study what our renal clearance is of our inulin."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, let's move on to case number two."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "In case number two, we also have the substance freely filtered, but now it is fully reabsorbed and it is not secreted."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So let's take a look at what that actually looks like."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So we have 625 milliliters per minute coming in into our capillaries, the glomerulus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And because it is freely filtered, it passes freely across."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So that means 125 ML/minute flows into the Bowman's capsule and into the tubular section of our nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, because it is fully reabsorbed, that means all that substance found within the 125 ML/minute is completely reabsorbed back into the peritubular capillaries that are found in close proximity to the tubular section of the nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that means 125 ML/minute will basically be filtered back into our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, what does that tell us about the renal clearance of such a substance?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, if we take this and subtract this, we simply get zero."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that means the renal clearance of this substance is 0 ML/minute or none of that substance is actually removed from the blood plasma."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, in what cases does this actually take place?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "What are some examples?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, some examples include glucose and amino acids."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So remember, glucose and amino acids are tiny enough to actually be filtered across our glomerlus."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "But these are important nutrients that are needed by the body and that means we don't actually want to lose these nutrients."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that's exactly why these nutrients are reabsorbed back by our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, let's move on to case number three."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So, in case number three, we have freely filtered."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "We have not absorbed, but we have fully secreted."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So let's take a look at what happens."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "We have freely filtered."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So that means out of the 625 ML/minute that comes in, 125 ML/minute is basically filtered through our membrane into the tubular section of the nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, when the filtered is traveling through our nephron, it is fully secreted."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "That substance that ends up in the peritubular capillaries is fully secreted into our filtrate found traveling along our tubular section of that nephron."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So what does that tell us about our renal clearance?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Well, because none of it is actually reabsorbed, we have 125 plus 500 and that gives us 625 blood volume."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Every single minute is cleared."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that means none of that substance will actually remain in our blood plasma."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And one example of such a substance is Peh PAH, which stands for the para aminohipric acid."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So this is a substance that is essentially completely cleared by our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Actually, a small percentage of it is left over in the blood plasma, but for all approximation purposes, we can assume that all of it is actually cleared."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, what about case number four?"}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So here we have freely filtered, only slightly reabsorbed, and none of it is actually secreted."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So let's take a look at the following example."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So, we have 625 milliliters per minute is the renal plasma flow that enters our glomerulus every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And because it's freely filtered, 125 milliliters is cleared every single minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "But when the filtering is traveling within our tubular section of our nephron, a small amount, some amount is actually reabsorbed back into our body."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, in this case, it was fully reabsorbed."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So we have a renal clearance of zero, but in this case, only a slide and mouth was reabsorbed."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "And that means whatever the renal clearance is, it will be slightly less than 125 ML/minute, but it will be greater than 0 ML/minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, one example of such a substance is urea."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Urea is small enough to actually filter easily through our glomerulus, but a small percentage of it is actually reabsorbed."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "In fact, 60 ML/minute is reabsorbed, and that means 125 gives us about 65 ML/minute."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "So this is the renal clearance of urea."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "This is how much volume of blood plasma is cleared of urea every single minute by the nephron of our kidney."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "Now, there are other cases that exist."}, {"title": "Renal Clearance, Renal Plasma Flow and Glomerular Filtration Rate .txt", "text": "For example, we can have a case where we have freely filtered, not absorb, but slightly secreted, and in this case will have a renal clearance value somewhere between 125 milliliter per minute and 625 milliliters per minute."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Prokaryotic and eukaryotic cells contain a structure known as Flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And flagella serves in locomotion."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "It gives the cell the ability to move inside the fluid environment in which that cell is found in."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, although both eukaryotic and prokaryotic cells contain Flagella, and they serve the same exact purpose, the actual structure, the composition, and the mechanism by which our Flagella functions in the two types of cells differs."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And this is what we're going to examine in this lecture."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We're going to discuss the structure, the composition, and the mechanism by which prokaryotic Flagella works."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And then we're going to compare that to eukaryotic Flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So let's begin with the prokaryotic case."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So prokaryotic Flagellum consists of a single global protein known as Flagellin and Flagellin."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "This protein basically wraps around in a helical fashion to create a rigid hollow cylinder."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So let's suppose we have one type of prokaryotic organism, let's say a gram negative bacteria."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And a gram negative bacteria contains our cytoplasm, which is this section."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have an inner membrane."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have a cell wall that consists of peptidoglycan."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have our outer membrane, and this entire structure is our prokaryotic Flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So we essentially inside the inner membrane, we have two proton rings."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Attached to that, we have a shaft or rod."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Then we have this sleeve structure."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have the hook, and finally, this entire portion, which basically extends this way, our Flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, the Flagellum, this portion is the rigid hollow cylinder that is composed of the protein Flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So this section is the hook that is attached to our sleeve, to the rod, and these proton rings."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, the proton rings basically serve as proton pumps."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "They essentially pump our protons, the hydrogen ions, across our cell membrane."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And by pumping our protons, our hydrogen ions, down our electrochemical gradient, we rotate the proton rings, which in turn rotates the rod and the sleeve, which in turn rotates the rest of our Flagellum structure."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And this rotation creates the motion of our Flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, whenever our Flagellum in prokaryotic cells rotates counterclockwise, that creates a unidirectional emotion, meaning our cell moves along one axis, along one direction."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "But if our prokaryotic cell wants to actually change direction, it can rotate clockwise in the opposite direction, and that changes the entire direction of motion of that prokaryotic organism."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So once again, the protein rings found in the inner membrane of our cell of our bacterial, the gram negative bacteria, the proton rings, act as proton pumps that allow the movement of hydrogen ions across the cell membrane down their electrochemical gradient."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "This movement of ion rotates our entire Flagella in our counterclockwise direction, and that allows the movement of our cell in one direction."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, if it rotates clockwise, it will basically change direction."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, let's move on to eukaryotic Flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So what exactly is the difference?"}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So we see that the type of protein that essentially composes our prokaryotic Flagella is Flagellant."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "However, in the eukaryotic case, the protein filaments that compose flagella for eukaryotic cells are microtubules."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So basically, the centrosome of our animal cell of our eukaryotic organism contains two centrioles."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And one of the centrioles, the dota centriole, basically creates the basal body."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So let's suppose we have this is our cell, this is the cytoplasm."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "One of the centrioles of the central stone creates the basal body."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And what the basal body does is it basically creates more of these microtubules that extend outward and that essentially creates our flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, the flagella is enclosed inside our plasma membrane that is continuous with our plasma membrane of the rest of the cell."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So we see for eukaryotic flagella, it actually contains that plasma membrane as shown in this diagram."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, if we take a small cross sectional area, a cross sectional picture of this flagella, and we zoom in and we look at the two dimensional slides, we basically get the following arrangement of microtubules."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So it consists of nine doubled pairs of microtubules that create this circular like diagram, circular like arrangement around a section of two central microtubules."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And this arrangement of nine to two, known as nine, is known as nine plus two."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So this is a very common arrangement inside eukaryotic flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "It's the nine to two microtubule arrangement."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have nine of these doublets 123-45-6789 that forms a circular arrangement around this central microtubial doublet."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, we also have other proteins."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We have these blue proteins, as shown known as the radial spokes."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "These are essentially polypeptides."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We also have a protein known as a Dinan."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So Dinan is basically shown by these purple regions here."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And Dinan is basically a motor protein."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "It uses ATP to essentially create a motion of these microtubules."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So it's the Dynam that uses ATP to basically slide across our nine doublet microtubules and that creates a bending like motion for this particular eukaryotic flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So the dynamic motor proteins utilize ATP adenosine triphosphate molecules to force the double microtubules to slide against one another, creating a bending like motion and propelling that cell forward."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So we see that there are several important differences between eukaryotic and prokaryotic flagellum."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So there are differences in not only structure and composition, but also the source of energy as well as the type of motion that is made by our flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So let's look at the following table that basically summarizes the most important differences between prokaryotic and eukaryotic flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So there is a difference in motion."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "For eukaryotic, we have our dynamic proteins that basically use our ATP energy source to slide along our microtubules, creating a bendinglike motion."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So for eukaryotic case, we have a bendinglike motion, for our prokaryotic case, we have our rotating motion."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So remember, these proton rings rotate as a result of the movement of protons down the electrochemical gradient, and that rotates this entire flagella in the counterclockwise fashion if we're moving forward and clockwise, if we want to change direction."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, the energy source for our eukaryotic flagella is basically ATP."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "However, for the case of prokaryotes, we don't use ATP directly."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "We instead use our proton pumps, so we allow the flow of hydrogen ions down the electrochemical gradient."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, the structure of eukaryotic flagella is much more complicated than our prokaryotic flagella."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "For the eukaryotic case, we have a nine plus two arrangement of microtubules."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "In this case, we simply have our single protein, the Flagellum, that wraps around in a helical fashion, creating a rigid hollow cylinder, as shown in this section here."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "Now, what about the actual protein involved in the structure?"}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "So, if we actually examine the tail like flagella section, it's composed of a single protein flagellin."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "But in this case, it's composed of proton filaments, our microtubules, which are essentially synthesized by the centrioles, found in the centrosome of our eukaryotic cells."}, {"title": "Prokaryotic vs. Eukaryotic Flagella .txt", "text": "And these are the major differences between the two types of flagella that are found in two types of organisms prokaryotic cells and eukaryotic cells."}, {"title": "Islets of Langerhans .txt", "text": "The next organ that we're going to focus on that has endocrine capabilities is our pancreas."}, {"title": "Islets of Langerhans .txt", "text": "Now, the pancreas is found in our abdominal cavity, it's found below the liver and in the back of our stomach."}, {"title": "Islets of Langerhans .txt", "text": "So if this is the stomach and this is the liver, then this is our pancreas shown in purple."}, {"title": "Islets of Langerhans .txt", "text": "Now, the pancreas doesn't only have endocrine capabilities."}, {"title": "Islets of Langerhans .txt", "text": "In fact, when we'll discuss the digestive system of the human body, we'll see that the pancreas can also act as an exocrine gland."}, {"title": "Islets of Langerhans .txt", "text": "Bud."}, {"title": "Islets of Langerhans .txt", "text": "Since we're on the topic of the endocrine system in this lecture, we're only going to focus on the endocrine capability of Aropankreas."}, {"title": "Islets of Langerhans .txt", "text": "Now, the collection of millions of cells inside the pancreas that have this endocrine capability, the ability to produce hormones and release these hormones into our bloodstream are known as the eyelids of Langerhons."}, {"title": "Islets of Langerhans .txt", "text": "And there are four major types of cells that make up that constitute the eyelids of Langerhans."}, {"title": "Islets of Langerhans .txt", "text": "These cells are alpha cells, beta cells, delta cells, and gamma cells."}, {"title": "Islets of Langerhans .txt", "text": "So let's discuss each one of these cells."}, {"title": "Islets of Langerhans .txt", "text": "Let's discuss the hormone that each one of these cells releases and what the function of that specific hormone is."}, {"title": "Islets of Langerhans .txt", "text": "So basically, each one of these four types of cells that make up the eyelids of Langrehons are capable of producing and secreting its own hormone."}, {"title": "Islets of Langerhans .txt", "text": "So let's begin with alpha cells."}, {"title": "Islets of Langerhans .txt", "text": "So alpha cells are basically those cells that produce and secrete a peptide hormone known as glucagon."}, {"title": "Islets of Langerhans .txt", "text": "And glucagon is stimulated and released when we have low glucose concentration inside our blood, for example, when we are fasting."}, {"title": "Islets of Langerhans .txt", "text": "Now, certain people experience a condition known as hypoglycemia."}, {"title": "Islets of Langerhans .txt", "text": "And hypoglycemia simply means we have an abnormally low concentration of glucose inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "And what happens is these alpha cells release glucagon."}, {"title": "Islets of Langerhans .txt", "text": "And what glucagon does, as we'll see in just a moment, is ultimately increase the concentration of glucose inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "And that means the cells can use that glucose to basically create ATP and use it as an energy source."}, {"title": "Islets of Langerhans .txt", "text": "So we mentioned that glucagon is a peptide hormone and that means it's water soluble and so it can easily dissolve inside our blood and it doesn't need any protein carrier to transport it inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "Now, the fact that our glucagon is a peptide hormone also means it is not lipid soluble."}, {"title": "Islets of Langerhans .txt", "text": "And that means it cannot actually pass across the cell membrane."}, {"title": "Islets of Langerhans .txt", "text": "So what glucagon does is it finds the target cell, which is usually the cell inside the liver, known as the liver cells."}, {"title": "Islets of Langerhans .txt", "text": "It binds onto the membrane of that liver cell and it initiates a secondary message system."}, {"title": "Islets of Langerhans .txt", "text": "And what it basically does is it causes our liver cells to break down glycogen."}, {"title": "Islets of Langerhans .txt", "text": "Glycogen is the polymer that consists of glucose molecules."}, {"title": "Islets of Langerhans .txt", "text": "And what these liver cells do is they break down glycogen into glucose and release that glucose into our blood."}, {"title": "Islets of Langerhans .txt", "text": "And this increases the concentration of glucose inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "So the process by which our liver cells and other cells break down."}, {"title": "Islets of Langerhans .txt", "text": "Glycogen into glucose is known as glycogenolysis."}, {"title": "Islets of Langerhans .txt", "text": "So our glucagon basically stimulates the process of glycogenolysis."}, {"title": "Islets of Langerhans .txt", "text": "Now, when we have high concentrations of glucose of a glucagon, glucagon can also basically make or stimulate our adipose tissue, the fat cells inside the adipose tissue, to break down triglycerides into fatty acids and glycerol."}, {"title": "Islets of Langerhans .txt", "text": "And this can basically empty out into our bloodstream."}, {"title": "Islets of Langerhans .txt", "text": "And the cells can use can then pick up the fatty acids and our glycerol and form new glucose molecules and then release those glucose molecules into our blood plasma."}, {"title": "Islets of Langerhans .txt", "text": "And this increases the concentration of glucose inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "So the method by which cells use non carbohydrate materials such as glycerol to basically form glucose is known as gluconeogenesis."}, {"title": "Islets of Langerhans .txt", "text": "So glucagon stimulates the process of glycogenolysis as well as gluconeogenesis."}, {"title": "Islets of Langerhans .txt", "text": "Now, the overall result of a glucagon released by alpha cells is to basically raise glucose levels."}, {"title": "Islets of Langerhans .txt", "text": "And when the concentration of glucose increases to a certain amount, that can basically inhibit the release of glucagon into our blood."}, {"title": "Islets of Langerhans .txt", "text": "Now, glucagon is also inhibited by other proteins, by other enzymes, for example, insulin, as well as somatostatin."}, {"title": "Islets of Langerhans .txt", "text": "And we'll discuss these in just a moment."}, {"title": "Islets of Langerhans .txt", "text": "Now, we said that glucagon is stimulated by low concentrations of glucose."}, {"title": "Islets of Langerhans .txt", "text": "It can also be stimulated by other protein, by other hormones."}, {"title": "Islets of Langerhans .txt", "text": "For example, it's stimulated by CCK, which is a hormone that stands for Cola Cystic Iin."}, {"title": "Islets of Langerhans .txt", "text": "So colocystociain is the hormone that can also stimulate the release of glucagon into our blood."}, {"title": "Islets of Langerhans .txt", "text": "Now, let's move on to beta cells."}, {"title": "Islets of Langerhans .txt", "text": "So beta cells in our eyelids of langorgons can also basically release a peptide hormone."}, {"title": "Islets of Langerhans .txt", "text": "But this peptide hormone is known as insulin."}, {"title": "Islets of Langerhans .txt", "text": "And insulin acts antagonistically with respect to our glucagon."}, {"title": "Islets of Langerhans .txt", "text": "And we'll see what that actually means in just a moment."}, {"title": "Islets of Langerhans .txt", "text": "So basically, our glucagon is released when we have low concentrations of glucose, but insulin is released when we have high concentrations of glucose."}, {"title": "Islets of Langerhans .txt", "text": "For example, right after we ate."}, {"title": "Islets of Langerhans .txt", "text": "So let's suppose we just ate a meal and our body broke down our glucose."}, {"title": "Islets of Langerhans .txt", "text": "And now we have plenty of glucose circulating inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "So what happens is glucagon is inhibited, but insulin is stimulated."}, {"title": "Islets of Langerhans .txt", "text": "And these baby cells basically release insulin, which is a peptide hormone, it's a water soluble hormone."}, {"title": "Islets of Langerhans .txt", "text": "So we can easily dissolve inside our blood, just like glucagon can."}, {"title": "Islets of Langerhans .txt", "text": "And insulin also binds onto the cell membrane of our target cells, the liver cells or the muscle cells."}, {"title": "Islets of Langerhans .txt", "text": "And it basically stimulates the opposite process that we discussed earlier."}, {"title": "Islets of Langerhans .txt", "text": "Now, what happens is, because we have plenty of glucose and amino acids floating around inside our bloodstream, what insulin does is it causes the cell membrane to become more permeable to amino acids and to glucose."}, {"title": "Islets of Langerhans .txt", "text": "And now glucose and amino acids go into our cells, into liver cells and muscle cells."}, {"title": "Islets of Langerhans .txt", "text": "And those cells basically use the amino acids to form protein and they use the glucose to form our glycogen."}, {"title": "Islets of Langerhans .txt", "text": "Now, what insulin also does is it causes our fat cells to take up glycerol and fatty acids and to form our triglyceride."}, {"title": "Islets of Langerhans .txt", "text": "So what our insulin ultimately aims to do is to basically decrease the concentration of our glucose found inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "So these two hormones are essential in controlling the concentration of glucose and amino acids and fatty acids found inside our blood."}, {"title": "Islets of Langerhans .txt", "text": "So insulin is inhibited by low glucose concentrations, which is the opposite of glucagon."}, {"title": "Islets of Langerhans .txt", "text": "So we see when glucagon is inhibited, our insulin is activated."}, {"title": "Islets of Langerhans .txt", "text": "And when our glucagon is activated, the insulin is inhibited."}, {"title": "Islets of Langerhans .txt", "text": "Now, insulin can also be inhibited by other hormones, just like glucagon can, for example."}, {"title": "Islets of Langerhans .txt", "text": "Norepinephrine, the hormone that is released by our adrenal gland, can also inhibit our insulin hormone."}, {"title": "Islets of Langerhans .txt", "text": "So let's take a look at the following diagram that basically describes the connection between glucagon and insulin."}, {"title": "Islets of Langerhans .txt", "text": "So let's suppose we are fasting for a long time."}, {"title": "Islets of Langerhans .txt", "text": "And because we are fasting, that means the glucose concentration inside our blood is low."}, {"title": "Islets of Langerhans .txt", "text": "So let's suppose we are experiencing high pole glycemia."}, {"title": "Islets of Langerhans .txt", "text": "So that basically means the concentration of glucose inside our blood plasma is low, and our cells in the body cannot obtain the proper amount of glucose."}, {"title": "Islets of Langerhans .txt", "text": "So what the body does is our pancreas uses the alpha cells to release glucagon."}, {"title": "Islets of Langerhans .txt", "text": "And then glucagon basically goes on and binds onto protein receptors on the membrane target cells in the liver, and it basically causes the process of glycogenolysis, the breakdown of glycogen into glucose."}, {"title": "Islets of Langerhans .txt", "text": "We have the process of gluconeogenesis, the use of our non carbohydrate sources to produce glucose, and then the breakdown of triglycerides into fatty acids and into glycerol, which is ultimately used to form glucose."}, {"title": "Islets of Langerhans .txt", "text": "And all this glucose that is formed is dumped into our blood plasma and this ultimately increases the concentration of glucose inside our blood plasma."}, {"title": "Islets of Langerhans .txt", "text": "Now, when our concentration is high, the glucagon is eventually inhibited."}, {"title": "Islets of Langerhans .txt", "text": "And when it rises high enough, we basically have insulin that is released by our beta cells."}, {"title": "Islets of Langerhans .txt", "text": "And what the insulin does is the opposite of what glucagon does."}, {"title": "Islets of Langerhans .txt", "text": "So insulin acts antagonistically with respect to the glucagon."}, {"title": "Islets of Langerhans .txt", "text": "So because we have a lot of glucose and amino acids and fatty acids inside our blood, let's suppose after we ate, what happens is the insulin causes our cells to become more permeable to glucose and amino acids and that causes the glucose to leave the blood plasma and into our cell."}, {"title": "Islets of Langerhans .txt", "text": "And we use the glucose to form glycogen in our liver cells, in our muscle cells."}, {"title": "Islets of Langerhans .txt", "text": "We uptake our amino acids and we form proteins."}, {"title": "Islets of Langerhans .txt", "text": "And we also have our triglyceride synthesis."}, {"title": "Islets of Langerhans .txt", "text": "So our fat cells inside adipose tissue take up fatty acids and glycerol and form our triglyceride."}, {"title": "Islets of Langerhans .txt", "text": "So eventually, this lowers the amount of glucose and amino acid found inside our blood plasma."}, {"title": "Islets of Langerhans .txt", "text": "So this is the method by which our body basically controls the amount of sugar found inside our blood, as well as the concentration of amino acids and fats."}, {"title": "Islets of Langerhans .txt", "text": "Now, the last two cells are the delta cells and the gamma cells."}, {"title": "Islets of Langerhans .txt", "text": "So the delta cells are the cells that basically release a special type of peptide hormone known as Arsomatostatin, which is the protein that we mentioned earlier that inhibits our glucagon."}, {"title": "Islets of Langerhans .txt", "text": "Now, Somatostatin doesn't only inhibit glucagon, it also actually inhibits our insulin."}, {"title": "Islets of Langerhans .txt", "text": "So Somatostatin has a wide range of functions, and one of its function is to inhibit the release of both glucagon and our insulin."}, {"title": "Islets of Langerhans .txt", "text": "And finally, we also have a type of eyelid of Langerhan, a type of cell in that region known as gamma cells."}, {"title": "Islets of Langerhans .txt", "text": "And these cells are responsible for secreting a type of hormone known as our pancreatic polypeptide."}, {"title": "Islets of Langerhans .txt", "text": "And this hormone is basically believed to regulate various activities of the pancreas, such as our excretion of the pancreatic hormones that we've just discussed."}, {"title": "Islets of Langerhans .txt", "text": "So these are the four different types of cells that make up the eyelids of Langerhons inside Arop pancreas."}, {"title": "Islets of Langerhans .txt", "text": "And the eyelids of Langerhons are those cells that contain endocrine ability."}, {"title": "Islets of Langerhans .txt", "text": "So, the ability to synthesize a hormone and release that hormone into our bloodstream."}, {"title": "Structure of the Heart.txt", "text": "The human heart is a very important component of our cardiovascular system and that's because it creates the hydrostatic pressure that is needed to actually move all that blood through the blood vessels of our body."}, {"title": "Structure of the Heart.txt", "text": "Now let's begin by discussing what the structure of the heart is."}, {"title": "Structure of the Heart.txt", "text": "Now the heart is an organ that is located inside a protective covering, a protective active sac we call the pericardial sac or simply the pericardium."}, {"title": "Structure of the Heart.txt", "text": "Now, as we'll see in just a moment, the pericardium actually consists of two different layers."}, {"title": "Structure of the Heart.txt", "text": "And the function of the pericardium is not only to protect the heart from physical damage, it's to also lubricate the heart and it's to also attach the heart to other parts of our body."}, {"title": "Structure of the Heart.txt", "text": "So to actually examine what the pericardium looks like, let's take a cross section of the heart."}, {"title": "Structure of the Heart.txt", "text": "We get the following diagram."}, {"title": "Structure of the Heart.txt", "text": "So we have the blood vessels around the heart."}, {"title": "Structure of the Heart.txt", "text": "We have the four chambers of the heart shown here."}, {"title": "Structure of the Heart.txt", "text": "We have the actual heart shown in red."}, {"title": "Structure of the Heart.txt", "text": "And we have this protective covering found outside the heart."}, {"title": "Structure of the Heart.txt", "text": "This is the pericardium."}, {"title": "Structure of the Heart.txt", "text": "Now if we zoom in on this segment of this diagram, we get the following blown up image and this consists of the pericardium."}, {"title": "Structure of the Heart.txt", "text": "So this entire layer right here, not including this red layer, is the pericardium."}, {"title": "Structure of the Heart.txt", "text": "The red layer, as we'll see in just a moment, is the actual heart itself."}, {"title": "Structure of the Heart.txt", "text": "So let's begin with the pericardium."}, {"title": "Structure of the Heart.txt", "text": "We can divide the pericardium into two layers."}, {"title": "Structure of the Heart.txt", "text": "We have the outer layer and the inner layer."}, {"title": "Structure of the Heart.txt", "text": "The outer layer is shown in purple in the following diagram."}, {"title": "Structure of the Heart.txt", "text": "And the outer layer consists of strong fibrous proteins that give our pericardium its strength."}, {"title": "Structure of the Heart.txt", "text": "So the outer layer is responsible for not only attaching the heart to different parts of the body, but it also protects the heart from physical damage."}, {"title": "Structure of the Heart.txt", "text": "Now the inner portion of the pericardium is also known as the inner cirrus layer and cirrus comes from the word serum because this section actually contains of a fluid that resembles serum."}, {"title": "Structure of the Heart.txt", "text": "Now our inner cirrus layer can actually be subdivided into two regions."}, {"title": "Structure of the Heart.txt", "text": "We have the parietal and the visceral layer."}, {"title": "Structure of the Heart.txt", "text": "Now the parietal layer of the inner pericardium is this orange layer right here, while the visceral layer of the inner pericardium is this inner layer of our pericardium shown in orange."}, {"title": "Structure of the Heart.txt", "text": "And this space between the visceral and the parietal layer of the inner pericardium is known as the pericardial space or the pericardial cavity."}, {"title": "Structure of the Heart.txt", "text": "And this contains the pericardial fluid and that fluid lubricates our heart, decreasing the friction that the heart feels every time it actually contracts."}, {"title": "Structure of the Heart.txt", "text": "So together these two layers of the pericardium protect the heart."}, {"title": "Structure of the Heart.txt", "text": "They attach the heart to other parts of the body and they lubricate the heart."}, {"title": "Structure of the Heart.txt", "text": "Now let's move on to the actual heart itself."}, {"title": "Structure of the Heart.txt", "text": "So if we examine this red segment of the heart, this segment actually consists of three individual layers."}, {"title": "Structure of the Heart.txt", "text": "So the heart can be divided into three layers."}, {"title": "Structure of the Heart.txt", "text": "We have the epicardium, the outermost layer."}, {"title": "Structure of the Heart.txt", "text": "We have the myocardium, the middle layer, and we have the inner layer of the heart known as the endocardium."}, {"title": "Structure of the Heart.txt", "text": "So this layer, the epicardium, is actually physically attached."}, {"title": "Structure of the Heart.txt", "text": "It's fused with our visceral layer of the inner pericardium."}, {"title": "Structure of the Heart.txt", "text": "So this visceral layer of the inner pericardium is attached to the epicardium, this layer of the heart."}, {"title": "Structure of the Heart.txt", "text": "And together these two layers play a role in lubricating our heart along with the fluid found within the pericardial cavity."}, {"title": "Structure of the Heart.txt", "text": "Now, the thickest segment of the heart is the myocardium and this is the middle portion."}, {"title": "Structure of the Heart.txt", "text": "This consists of specialized heart cells known as myocytes, also known as cardiac muscle cells."}, {"title": "Structure of the Heart.txt", "text": "And these are the cells that are responsible for contracting and creating that hydrostatic pressure that is needed to pump all that blood through all the blood vessels of our body."}, {"title": "Structure of the Heart.txt", "text": "Now, the innermost portion of the heart that is in direct contact with the blood of our chambers, found inside the chambers of the heart, this is known as the endocardium."}, {"title": "Structure of the Heart.txt", "text": "And the endocardium consists of endothelial cells of simple squamous opel cells that are in direct contact with the blood found inside our chambers."}, {"title": "Structure of the Heart.txt", "text": "So once again, the heart can be broken down into three layers."}, {"title": "Structure of the Heart.txt", "text": "So we have our epicardium, we have the myocardium and we have the endocardium."}, {"title": "Structure of the Heart.txt", "text": "And these three layers form four different chambers inside our heart."}, {"title": "Structure of the Heart.txt", "text": "So now let's focus on the four different chambers."}, {"title": "Structure of the Heart.txt", "text": "Now, the entire heart can actually be broken down into two pumps."}, {"title": "Structure of the Heart.txt", "text": "So if we are examining our body from this image, from this direction, we have the right side and we have the left side."}, {"title": "Structure of the Heart.txt", "text": "Now, the heart is found inside this section, right to the left of our sternum bone."}, {"title": "Structure of the Heart.txt", "text": "Now, we have the left side of the heart, this segment, and the right side of the heart, the right side."}, {"title": "Structure of the Heart.txt", "text": "So this section right over here consists of our right pump and the left side."}, {"title": "Structure of the Heart.txt", "text": "This segment over here consists of our left pump."}, {"title": "Structure of the Heart.txt", "text": "And each one of these pumps consists of two chambers."}, {"title": "Structure of the Heart.txt", "text": "We have the atrium and we have the ventricle."}, {"title": "Structure of the Heart.txt", "text": "Now, the atrium is the chamber that receives our blood from the rest of our body and the ventricle receives the blood from the atrium and it pumps the blood to the organs, tissues and cells of our body."}, {"title": "Structure of the Heart.txt", "text": "So the heart consists of two pumps that are connected in serious next to one another."}, {"title": "Structure of the Heart.txt", "text": "We have the right pump and we have the left pump."}, {"title": "Structure of the Heart.txt", "text": "And each pump contains an atrium and arabetrical."}, {"title": "Structure of the Heart.txt", "text": "So let's take a look at the right atrium."}, {"title": "Structure of the Heart.txt", "text": "The right atrium receives deoxnated blood from the systemic circulation of our cardiovascular system from the organs, the tissues and cells of our body."}, {"title": "Structure of the Heart.txt", "text": "Now, once the blood fills the right atrium, it then moves into the right ventricle and it's the right ventricle that is responsible for creating that contraction and moving that deoxynated blood into the pulmonary circulation of the cardiovascular system into these pulmonary arteries that extend into the left lung and into the right lung."}, {"title": "Structure of the Heart.txt", "text": "So we have the left lung here and we have the right lung here."}, {"title": "Structure of the Heart.txt", "text": "Now, once our blood is inside the lung, it is oxygenated and then it moves into our left atrium via the pulmonary vein."}, {"title": "Structure of the Heart.txt", "text": "So this is the left atrium."}, {"title": "Structure of the Heart.txt", "text": "The left atrium, once it fills with blood, it moves into the left ventricle."}, {"title": "Structure of the Heart.txt", "text": "And it's the left ventricle that is the thickest of all these chambers."}, {"title": "Structure of the Heart.txt", "text": "It contains the thickest layer of myocardium and that means it can create the highest hydrostatic pressure."}, {"title": "Structure of the Heart.txt", "text": "And that is important because it's this ventricle that is responsible for moving all that blood into the order and all the different organs and tissues and cells of our body."}, {"title": "Structure of the Heart.txt", "text": "So we have the right atrium, the right ventricle that make up the right pump of the heart."}, {"title": "Structure of the Heart.txt", "text": "And we have the left atrium and the left ventricle that make up the left pump of our heart."}, {"title": "Structure of the Heart.txt", "text": "And these pumps work at the same exact time."}, {"title": "Structure of the Heart.txt", "text": "And that means when the right pump contracts, the left pump contracts at the same time."}, {"title": "Structure of the Heart.txt", "text": "And when the right pump relaxes, our left pump relaxes at the same exact time."}, {"title": "Structure of the Heart.txt", "text": "So when the right ventricle contracts, the left ventricle contracts at the same time."}, {"title": "Structure of the Heart.txt", "text": "Now, we know that inside our cardiovascular system the blood actually flows in only one direction."}, {"title": "Structure of the Heart.txt", "text": "It's very important that the heart actually creates a unidirectional motion of blood."}, {"title": "Structure of the Heart.txt", "text": "And to ensure that the blood doesn't actually flow backwards inside the heart we have a system of four different valves found inside our heart."}, {"title": "Structure of the Heart.txt", "text": "So the heart must be able to pump blood in a unidirectional fashion."}, {"title": "Structure of the Heart.txt", "text": "And in order to prevent our backflow of blood inside our heart the heart uses our four different valves."}, {"title": "Structure of the Heart.txt", "text": "Now, actually, it's two sets of different valves."}, {"title": "Structure of the Heart.txt", "text": "So we have the atrial ventricular valves that connect the atrium and our ventricle."}, {"title": "Structure of the Heart.txt", "text": "And we also have our semi lunar valves which connect the ventricle to our blood vessels."}, {"title": "Structure of the Heart.txt", "text": "So let's discuss these four types of valves."}, {"title": "Structure of the Heart.txt", "text": "So let's take a look at the following diagram."}, {"title": "Structure of the Heart.txt", "text": "So, once again, this is the right atrium."}, {"title": "Structure of the Heart.txt", "text": "This is our right ventricle."}, {"title": "Structure of the Heart.txt", "text": "And the valve that connects the right atrium to our right ventricle is number one."}, {"title": "Structure of the Heart.txt", "text": "This is the right atrio ventricular valve, also known as the tricuspid valve."}, {"title": "Structure of the Heart.txt", "text": "Now, what the function of this valve is the following."}, {"title": "Structure of the Heart.txt", "text": "During relaxation, valve number one is actually open and that's to make sure that the blood flows from the right atrium and into our right ventricle."}, {"title": "Structure of the Heart.txt", "text": "But when this right ventricle is filled with blood, it needs to contract."}, {"title": "Structure of the Heart.txt", "text": "And to prevent the back flow of blood from the right ventricle back to the right atrium, this valve actually closes as a result of pressure and that ventricle contracts and it pumps blood from the right ventricle and into the pulmonary circulation via these pulmonary arteries that move DEOX data blood into the left and the right lung."}, {"title": "Structure of the Heart.txt", "text": "So this is the right atriove ventricular valve, valve number one."}, {"title": "Structure of the Heart.txt", "text": "Now what about valve number two?"}, {"title": "Structure of the Heart.txt", "text": "So valve number two is this valve here."}, {"title": "Structure of the Heart.txt", "text": "It basically connects the right ventricle to these pulmonary arteries."}, {"title": "Structure of the Heart.txt", "text": "So this is known as the pulmonary semi lunar valve or simply the pulmonary valve."}, {"title": "Structure of the Heart.txt", "text": "Now when the ventricle when the right ventricle actually relaxes, blood flows from this location to this right ventricle."}, {"title": "Structure of the Heart.txt", "text": "But at the same time that this valve number one is open, valve number two, the pulmonary valve has to be closed because we don't want a backflow of blood from the pulmonary arteries back into the right ventricle."}, {"title": "Structure of the Heart.txt", "text": "But when the right ventricle actually contracts, it moves deoxygenated blood from the right ventricle into the pulmonary arteries."}, {"title": "Structure of the Heart.txt", "text": "And valve number two pulmonary valve is actually open."}, {"title": "Structure of the Heart.txt", "text": "So when valve number one is open, valve number two is closed."}, {"title": "Structure of the Heart.txt", "text": "But when valve number one is closed, valve number two is open."}, {"title": "Structure of the Heart.txt", "text": "Now what about the left pump of our heart?"}, {"title": "Structure of the Heart.txt", "text": "This consists also of an atrial ventricular valve, but this one is known as the left atrial ventricular valve."}, {"title": "Structure of the Heart.txt", "text": "And this one is also known by the name of the mitral valve or the bicuspid valve."}, {"title": "Structure of the Heart.txt", "text": "Now what exactly is the point of the left atrial ventricular valve?"}, {"title": "Structure of the Heart.txt", "text": "This is valve number three."}, {"title": "Structure of the Heart.txt", "text": "So when our left ventricle is relaxed, blood flows from the left atrium into the left ventricle."}, {"title": "Structure of the Heart.txt", "text": "And to make sure this blood flows, this valve number three must be open."}, {"title": "Structure of the Heart.txt", "text": "But when our left ventricle contracts, valve number three closes to prevent the backflow, the movement of blood back into the left atrium."}, {"title": "Structure of the Heart.txt", "text": "Now what about valve number four?"}, {"title": "Structure of the Heart.txt", "text": "This is known as the aortic valve or the aortic semi lunar valve."}, {"title": "Structure of the Heart.txt", "text": "This is the valve that connects the left ventricle to our aorter and our systemic circulation."}, {"title": "Structure of the Heart.txt", "text": "So when the left ventricle is relaxed, it accepts that blood from this left atrium."}, {"title": "Structure of the Heart.txt", "text": "So valve number three is open, but valve number four, the aortic valve, is closed."}, {"title": "Structure of the Heart.txt", "text": "But when contraction of the left ventricle takes place, number three closes."}, {"title": "Structure of the Heart.txt", "text": "But number four, the aortic valve has to open to allow the movement of our blood into the systemic circulation of the cardiovascular system."}, {"title": "Structure of the Heart.txt", "text": "So what can we conclude about these four valves?"}, {"title": "Structure of the Heart.txt", "text": "So basically, when relaxation takes place, valve number one and valve number three are open."}, {"title": "Structure of the Heart.txt", "text": "These are the atrium ventricular valves."}, {"title": "Structure of the Heart.txt", "text": "And they must be open to actually accept that blood from the atrium and into that ventricle."}, {"title": "Structure of the Heart.txt", "text": "But when contraction takes place, the right and left atrial ventricular valves number one and three are actually closed."}, {"title": "Structure of the Heart.txt", "text": "But number two and four, the semilunar valves we have, the pulmonary and the aortic valve, these open up to basically allow the movement of our blood from our heart into the systemic and into the pulmonary circulatory system of our our body."}, {"title": "Structure of the Heart.txt", "text": "So when one and three are open, two and four are closed."}, {"title": "Structure of the Heart.txt", "text": "But when one and three are closed, two and four are open."}, {"title": "Structure of the Heart.txt", "text": "And these work together to ensure that the heart creates a unidirectional flow of our blood."}, {"title": "Structure of the Heart.txt", "text": "To ensure the blood flows in a single direction from the heart to the organs and then back to our heart."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Thus far in our discussion on glucose metabolism, we focus primarily on anaerobic processes such as glycolysis, gluconeogenesis, and lactic acid fermentation."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, glycolysis, as we discussed, is basically a ten step process that takes place within a silent plasma of our cell, and the glucose is transformed into two Pyruvate molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, to simplify of things, I've only included a single Pyruvate molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "But if you want, you can multiply all these values by two to get the net result."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, in the process of glycolysis, we also produce two ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And these two ATP molecules can be used by other processes of the cells that actually require energy."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, even though glycolysis actually does produce a net amount of ATP molecules, glycolysis only collects a very small portion of that usable energy that is stored in the chemical bonds of the glucose molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So it only harvests a very small amount of potential energy that is stored in the bonds of glucose."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And to actually be able to collect the remaining energy stored in the chemical bonds of glucose, we have to undergo aerobic cell respiration."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And this only takes place in the presence of oxygen and if we have mitochondria in the cells of our body, because remember, certain cells don't actually have mitochondria."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "For instance, red blood cells don't have mitochondria, and so they cannot actually undergo aerobic cell respiration."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the majority of the high energy ATP molecules generated in breaking down glucose are produced via aerobic respiration, which must take place in the presence of oxygen and inside the mitochondria of our cell."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So let's take a look at the following diagram."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So, notice that when glucose is broken down to pyruvates, we produce not only ATP molecules, but we also actually collect electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we abstract four electrons when a single glucose molecule is broken down into two Pyruvate molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, those two electrons aren't actually by themselves."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "They're collected by special Co enzyme NAD plus."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Remember NAD plus."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So nicotine amide adenine dinucleotide forgot the a."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the nicotine amide adenine dinucleotide is a molecule that collects electrons, which are basically abstracted from that glucose."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Because remember, glucose is oxidized into Pyruvate."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "What that means is it loses electrons because it gains positive charge."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so those two electrons don't exist by themselves, and they're actually found on an H plus ion."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So when these electrons combine with that H, we form a hydride."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so what happens is this hydride is picked up, and these electrons are picked up by this molecule here, nicotine amide and nucleotide."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so two of these electrons are found on a single NAD."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so this is the same thing as saying we form two NADH molecules, because when these combine, we form NADH."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Okay?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So that's what we mean by these four electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And we'll come back to these electrons in just a moment."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "We'll see why they're actually so important."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, under aerobic conditions, when we have oxygen inside our cells, what will happen to that pyruvate is it will enter the mitochondrion of that cell."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And once the pyruvate enters the mitochondrion, as we'll see in the next several Electras, that pyruvate undergoes a decorboxylation reaction in which we oxidize the pyruvate to form acetylcoand A and we release CO2 molecule and we collect two electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Again, those two electrons are picked up by an NAD plus to form NADH."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So here we have one NADH."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Here we have two NADH molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And instead of using the NADH, I simply represent them as electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "We'll see why again in just a moment."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, this acetyl coenzyme a is a relatively large molecule and only a small portion of that molecule will actually be used in the next process."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So acetyl coenzyme a looks like this."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we essentially have this component and then the remaining portion, which is a big portion."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "I'm not going to draw it on the board, but this is basically the portion that will go into this next process known as the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So acetylco enzyme A donates a portion of itself to the next process which consists of a series of oxidation reduction reactions that we collectively known as the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, we also sometimes call it the crop cycle or the TCA cycle, where TCA stands for tricarboxylic acid because as we'll see in just a moment, tricarboxylic acid TCA is actually an intermediate of the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, every time one cycle of the citric acid cycle actually takes place, what happens is two carbon dioxide molecules are produced, a GTP molecule is produced and eight electrons are collected via the oxidation reduction reactions."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, six of these electrons are picked up by three of these NAD plus molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we have three NAD plus pick up three of these hydride ions to form three nadhs."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "But two of these electrons are picked up by another important carrier found in our body known as Flavin adenine dinucleotide."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we have Fad that picks up two of these h ions that each contain one electron each."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so we form when this happens, we form Nfadh two because each of these HS contains an electrons and that gives a total of two electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so three of these are nadhs and one of them is fadh too, as we'll see in this discussion here."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, this is what we form when a single pyruvate is broken down."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "But actually we have two of these."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we have to multiply all this by two."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the net result of the citric acid cycle is we form two or four co, twos 16 electrons and two GTP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, what exactly is the function of the citric acid cycle?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Why does it actually take place?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So what is it?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Well, the citric acid cycle is the center of glucose metabolism."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "This is where all these fuel molecules actually meet up to then go on and form the ATP molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So things like amino acids and fatty acids, they ultimately enter the citric acid cycle, or more specifically, aerobic cellular respiration as acetylcoenzy."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Some amino acids can actually enter as intermediates of the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And the citric acid cycle has other important functions as well."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "It also actually gives us those intermediate molecules, the building block molecules such as oxalo acetate molecules that we use to form many building blocks."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So things like nitrogenous, nucleotide bases, amino acids, glucose molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Because we have the oxalo acetate in the citric acid cycle that we can use to form glucose via gluconeogenesis, we also form things like porphyrin molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Remember that porphyrin is the organic carbon based component of heme groups used by things like hemoglobin proteins and my global protein."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the citric acid cycle is a very important cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "It's the center of aerobic cellular respiration, of glucose metabolism."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the citric acid cycle functions to provide a means by which any fuel molecule so what is a fuel molecule?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Well, a fuel molecule is a molecule that contains carbon atoms and can be oxidized to obtain these electrons, which then can be used, as we'll see, in just a moment, to form ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, the citric acid cycle also functions to provide the building blocks needed to form biological molecules such as nucleotide bases, amino acids, glucose molecules, porphyrin molecules and so forth."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And we'll discuss all this in much more detail in lectures to come."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "But let's actually generalize what the steps of the citric acid cycle actually are."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So the Cecil Coenzyme A donates a small component of that molecule, a two carbon component, the Cecil group, into the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And this is what is shown here."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, once this goes into the citric acid cycle, it combines with a four carbon molecule called oxalo acetate."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And this is the same oxyacetate that is formed in the process of gluco neogenesis."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we can see that the oxalo acetate form in a citric acid can be used by gluconyogenesis to actually form glucose molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So in step number one, the two carbon acetal group of acetyl, Coenzyme A, is combined with the four carbon oxylacetate to form this six carbon molecule known as the tricarboxylic acid."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And that's why sometimes we call it the tricarboxylic acid cycle TCA cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, in the next two steps, in step two and three, we undergo a decarboxylation reaction, an oxidation reduction reaction."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So in step two, the six carbon molecule becomes a five carbon molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "In the process, we release a CO2 and we also generate, we release, we abstract two electrons from the carbon six molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And those two electrons are picked up by the NAD plus molecule to form NADH."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "In the next step, we have the five carbon component that again undergoes an oxidation reduction reaction in which we generate a CO2 molecule and an NADH molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So again, two electrons are abstracted and collected by the NAD plus molecule to form these two molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And we form the four carbon intermediate C four."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, in the next year's of steps, we essentially transform this four carbon molecule back into oxyloacetate."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "In the process, we generate a high energy GTP molecule and NADH molecule as well as the fadh two molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So essentially four electrons are released here, two of these electrons are picked up by NAD and the other two electrons are picked up by the fad molecule."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So again, nicotine amide adenine dinucleotide and fad is flavin adenine dinucleotide."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And so because this takes place twice, because we have two Pyruvate molecules entering the mitochondria, we produce two, four, six nadhs, two fadh twos and two GCP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And we also form two and two."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So four CO2 molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Now, notice that we said that the citric acid cycle actually used to generate the high energy electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Notice that the cycle doesn't actually itself generate any ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Although we do generate a total of two GTP molecules, every time two Pyruvate molecules go into the citric acid cycle, we don't actually generate any ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So why is that?"}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Well, because the citric acid cycle is like the gateway for forming ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "Because once the citric acid cycle takes place and once we abstract all these electrons from these molecules, the carbon fuel molecules, these electrons, which are carried by NADH molecules and Fadh two molecules, can now move on to a series of proteins on the inner mitochondrial membrane we call the electron transport chain."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And these series of proteins shown here basically allow the movement of these electrons down their potential gradient."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And as electrons flow along these protein membranes on the membrane of the mitochondria, that generates a proton gradient across the two sides of the membrane."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And as the proton gradient is generated, that is then used to basically create ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So it's not the citric acid cycle that creates the ATP, but it's the oxidative osphorylation processes that take place across electron transport chain proteins that ultimately forms these ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So notice that no high energy ATP molecules are actually formed in the citric acid cycle."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And this is simply because the citric acid cycle is actually the gateway to forming the ATP."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "It doesn't actually form the ATP."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "What it does is it harvests these high energy electrons."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "We call them high energy electrons because they're used to form the high energy ATP molecules across the electron transport chain found on the inner membrane of the mitochondria."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So essentially, these electrons produced here flow across these membranes."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "So we have one, two, three and four."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And then we have this Atpace pump that generates ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And as electrons flow, H plus ions essentially are pulled this way because every time, let's say this molecule, this molecule and this molecule gives off those H ions, they are pulled from the matrix into the inter membrane space that creates a proton gradient, where we have a high concentration of H plus ions in this space."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And then this final ATP ATP based protein can use that gradient to drive the formation of those ATP molecules."}, {"title": "Introduction to Citric Acid Cycle .txt", "text": "And this takes place entirely on this electron transport chain."}, {"title": "Large Intestine.txt", "text": "The large intestine is the organ that follows the small intestine in our digestive system, in our digestive tract."}, {"title": "Large Intestine.txt", "text": "And the large intestine connects directly to the small intestine."}, {"title": "Large Intestine.txt", "text": "Now, just as the name applies, the large intestine has a thicker diameter, it has a larger diameter than our small intestine."}, {"title": "Large Intestine.txt", "text": "However, the large intestine is is actually shorter in length than the small intestine."}, {"title": "Large Intestine.txt", "text": "Now, just like we can divide the small intestine into three sections, we can also divide the large intestine into three regions."}, {"title": "Large Intestine.txt", "text": "We have the seacum, we have the colon, and we have the rectum."}, {"title": "Large Intestine.txt", "text": "And we also have a section known as the anus."}, {"title": "Large Intestine.txt", "text": "And we'll see exactly what that is in just a moment."}, {"title": "Large Intestine.txt", "text": "So let's begin by describing the anatomy and the position of the small intestine inside our body."}, {"title": "Large Intestine.txt", "text": "So basically, within this section that is not shown, we have the small intestine."}, {"title": "Large Intestine.txt", "text": "And the final portion of the small intestine is known as the ilium."}, {"title": "Large Intestine.txt", "text": "So the ilium is basically connected to our secum."}, {"title": "Large Intestine.txt", "text": "So this small pouch, this small section, is known as our secum."}, {"title": "Large Intestine.txt", "text": "And the ilium of the small intestine basically connects directly to our secum."}, {"title": "Large Intestine.txt", "text": "Now, the sequm contains a structure known as the pending, which is shown in the shaded region here."}, {"title": "Large Intestine.txt", "text": "And the sequm basically plays the role of receiving the kind, the digested product, food products, from the ileum of the small intestine to our large intestine, to our sequm."}, {"title": "Large Intestine.txt", "text": "Now, in certain animals, for example, herbivores, the sequm actually contains bacterial cells that are able to digest certain types of materials such as cellulose."}, {"title": "Large Intestine.txt", "text": "So herbivores inside the sea can carry these bacterial cells that give them the ability to basically break down cellulose, which is a carbohydrate, into its individual sugars and use those sugars as an energy form."}, {"title": "Large Intestine.txt", "text": "Humans, on the other hand, do not have the ability to digest cellulose because they do not have these same bacterial cells inside the sequm portion of our large intestine."}, {"title": "Large Intestine.txt", "text": "So basically, our chi moves from the ilium and into our secum."}, {"title": "Large Intestine.txt", "text": "And the sequm connects our ilium of the small intestine to this section of the colon."}, {"title": "Large Intestine.txt", "text": "Now, the colon is the longest portion of our large intestine and that's because the colon's role is to absorb the water, the ions, the minerals, as well as certain vitamins that have not been absorbed by other organs, by other structures inside our body."}, {"title": "Large Intestine.txt", "text": "So we can divide the colon into four segments."}, {"title": "Large Intestine.txt", "text": "This ascending portion along which the kind travels upward is known as our ascending colon."}, {"title": "Large Intestine.txt", "text": "This portion along which the kind travels horizontally is known as the transverse colon."}, {"title": "Large Intestine.txt", "text": "This portion along which our kind travels down is known as the descending colon."}, {"title": "Large Intestine.txt", "text": "And this S shaped colon section is known as the sigmoid colon."}, {"title": "Large Intestine.txt", "text": "So the colon can be divided into our ascending, transverse, descending and sigmoid colon."}, {"title": "Large Intestine.txt", "text": "And the function of this colon of the large intestine is to basically absorb water ions such as calcium and sodium ions and vitamins that have not been absorbed by other parts of the body."}, {"title": "Large Intestine.txt", "text": "And in our colon we also have specialized types of bacterial cells such as E. Coli that are actually capable of producing important types of vitamins and minerals such as vitamin K and vitamin B twelve."}, {"title": "Large Intestine.txt", "text": "Now, the final portion of our large intestine is known as the rectum."}, {"title": "Large Intestine.txt", "text": "And the purpose of the rectum is to basically receive and store the feces that comes from our colon."}, {"title": "Large Intestine.txt", "text": "Now, the feces is basically all the different types of materials and molecules and cells that have not been digested and have not been absorbed by our body by the large intestine and a small intestine and other organs in our body."}, {"title": "Large Intestine.txt", "text": "So the rectum is the location where feces is stored before being excreted out of the body and the walls of the rectum can basically expand to fit more feces as necessary."}, {"title": "Large Intestine.txt", "text": "Now the final section is our anus and the anus is basically this opening that is able to open and close to allow that feces to exit our body."}, {"title": "Large Intestine.txt", "text": "Now the question is what exactly is the composition of feces?"}, {"title": "Large Intestine.txt", "text": "So feces is composed of water."}, {"title": "Large Intestine.txt", "text": "It contains dead bacterial cells that basically have been killed by some type of agent."}, {"title": "Large Intestine.txt", "text": "For example, the high acidity of our stomach kills all bacterial cells and those cells end up in the feces that we excrete to the outside of our body to the outside environment of our body."}, {"title": "Large Intestine.txt", "text": "Now, feces also contains something called roughage."}, {"title": "Large Intestine.txt", "text": "Roughage, for example, consists of some type of indigestible material such as cellulose."}, {"title": "Large Intestine.txt", "text": "Remember we do not have those special types of cells, bacterial cells that give us the ability to break down cellulose."}, {"title": "Large Intestine.txt", "text": "But certain animals, certain herbivores, for example cows, they do have those bacterial cells that produce special types of proteolytic enzymes that can cleave the bonds in cellulose to produce the individual sugars which can then be used to basically produce ATP molecules."}, {"title": "Large Intestine.txt", "text": "Now, feces also contains proteins, for example proteolytic enzymes that have not been absorbed by our body that were used to basically break down the different types of macromolecules into their constituents inside our mouth, inside our stomach and inside the small intestine."}, {"title": "Large Intestine.txt", "text": "Feces also contains things like bile which was produced inside the liver and was used by the small intestine to basically emulsify break down our fat gloves into smaller fat molecules."}, {"title": "Large Intestine.txt", "text": "And the feces also consist of those cells that were basically scraped off of the lining of our small and large intestines and other organs in our body such as our stomach."}, {"title": "Large Intestine.txt", "text": "So at the bottom of the rectum we have the structure that is known as the anus."}, {"title": "Large Intestine.txt", "text": "And the anus consists of two muscles of two sphincter muscles."}, {"title": "Large Intestine.txt", "text": "One of those sphincter muscles known as the internal sphincter muscle is under involuntary control and that means the autonomic nervous system is responsible for opening and closing that internal sphincter muscle."}, {"title": "Large Intestine.txt", "text": "Now the second sphincter muscle known as the external sphincter muscle is actually controlled voluntary."}, {"title": "Large Intestine.txt", "text": "So we are capable of controlling the external sphincter muscle."}, {"title": "Large Intestine.txt", "text": "And that means it is controlled by our or somatic nervous system."}, {"title": "Large Intestine.txt", "text": "So the internal sphincter is controlled by the autonomic, but the external is controlled by the somatic nervous system."}, {"title": "Large Intestine.txt", "text": "So this concludes our discussion of the large intestine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "In the next several lectures, we're going to discuss the concept of a genetic mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, any sort of change or alterations of the composition of a DNA molecule other than genetic recombination is known as a genetic mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, how exactly do genetic mutations actually arise?"}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Well, our genetic mutations can arise as a result out of two things."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "They can either arise spontaneously due to the mistakes that take place in the natural processes inside the cell, or they can also arise."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "They can be induced by outside physical or chemical agents by outside forces, such as UV radiation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So if our mutation arises as a result of the natural processes that take place inside our bodies, such as a mistake that takes place during DNA replication, in which our DNA polymerase does not actually fix the mistake, such a mistake, such a mutation, is known as a spontaneous mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "On the other hand, those mutations that arise in the DNA as a result of some outside factor, some outside physical or chemical agents, such as a mutagen, these types of mutations that are induced inside our DNA are known as induced mutations."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So we have two reasons why our mutations take place."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "They take place spontaneously or are induced as a result of outside factors."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, what types of mutations do we have?"}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So, mutations can be categorized in two ways."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So we have point mutations, which are also known as base pair mutations or base pair substitutions."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And we also have frame shift mutations."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And there are two types of frame shift mutations."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "We have insertions and deletions."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So, frame shift mutations we're going to focus on in the next lecture."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "In this lecture, we're going to focus primarily on the point mutation, also known as a base pair mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, what exactly is a point mutation?"}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Basically, when a mutation takes place on a single nucleotide on the DNA molecule, such a mutation is known as a point mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, our point mutation can either take place on the non coding region of the DNA, the region that does not code for any protein, or it can take place on the gene on the coding region that codes for a protein."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "In either case, if our mutation if the point mutation takes place on either our non coding region or on the coding region, and if the mutation does not actually cause any significant damage, any significant change, such a point mutation is known as a silent mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, it's kind of obvious why a point mutation on a noncoding region will lead to silent mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "That's because our non coding region doesn't actually code for any protein."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "We do not use our noncoding region to synthesize any type of polypeptide chain."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And so when we have a point mutation taking place on our non coding region, that will lead to a silent mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So a mutation in the non coding region will not cause negative effects because the non coding region is not actually used to synthesize our proteins."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "But what about a mutation that takes place on the coating region?"}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So he said that sometimes a mutation can take place, a point mutation can take place on our coating region and still not actually cause any harmful effect."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "It can still produce the same exact protein with the same exact structure and the same exact function."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Well, the answer lies in the genetic code."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Remember, the genetic code contains 64 codons, and we only have 24 amino acids."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And that means we have more than one codon that basically codes for the same exact amino acid."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And this means our genetic code is degenerate."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "It is redundant."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And so that means sometimes if we basically change as a result of our point mutation, if we change one codon for a second codon, and that second codon codes for the same exact amino acid as the first, then such a point, mutation on the gene will be a silent mutation because it will produce the same exact amino acid sequence and therefore the same exact protein."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So, once again, what about a mutation in the coding region?"}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So remember that codons are a sequence of three nucleotides that are used to link amino acids."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So we used our codons to basically create our proteins."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "There are 64 codons and only 20 amino acids, which means that the different codons can code for the same exact amino acid."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And this makes our genetic code degenerate."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Therefore, if a point mutation occurs, if a point mutation occurs and causes a change in the codon, but the new codon still codes for the same exact amino acid, no change in protein structure will take place because our sequence of amino acids will be exactly the same."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, to see what that actually means, let's take a look at the following diagram."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So, let's suppose this is our DNA template that we're going to use to basically synthesize our mRNA molecule."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "This is our antisense strand."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So basically, on the five end, we have the C, then the A, the C, the G, the C, and on the three N, we have the g nucleotide."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, if we actually use this DNA molecule and transcription takes place, then we synthesize the following mRNA molecule where the C becomes a G, the A becomes a U, the C becomes a G, the G becomes a C. The C becomes a g and the g becomes a C. So this is our sequence of nucleotides on the mRNA molecule that will be used to synthesize our protein."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, if we look on our genetic code, we see that CGC stands for the amino acid arginine, while the gug stands for our amino acid, the valine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So let's suppose a point mutation takes place, and we basically replace the fourth nucleotide guanine with this nucleotide cytosine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So basically, this is our point mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So this will be an example of a point mutation that takes place on our coding region that is a silent mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So basically, this C or this G becomes a C. Now, when we take this DNA template and it undergoes the process of transcription, we form the following mRNA molecule."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So the C becomes a g, the A becomes a u, the C becomes a g, and now the C becomes a g. Whereas here, our g became a C. So then the C becomes a g, and this g becomes a C. Now, if we look on our genetic code, we see that this will be an arginine and this will be a valley."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Notice these two amino acids are exactly the same."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And that's because our genetic code is degenerate, it's redundant."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And that means that more than two codons or more than one codon can basically code for the same exact amino acid, our arginine amino acid."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So this is an example of a point mutation that takes place on the coating region on the gene, and that is a silent mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "That is, it does not produce any type of change."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, on the other hand, we can have a point mutation that actually causes a change in the amino acid that is produced during the process of translation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And to see what we mean by this example, let's look at the following diagram."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So, let's suppose we begin with the same exact DNA template."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "This is our antisense strength."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So we have CAC GCG."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So if we transcribe this, we form the following mRNA molecule that contains arginine and valine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So basically when we translate, we form arginine and valine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, if our mutation takes place on the third nucleotide, if the cytosine is changed into an adenine now, when we actually transcribe, the C becomes a g, the A becomes a u, the A becomes a u."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "The g. Becomes A-C-C becomes a G and G becomes a C. So this is the mRNA molecule that is used by the ribosome in translation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And when we translate, this will stay an arginine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "But now this becomes a leucine because the UG codon codes not for a valid but for a leucine."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So basically, anytime we have a point mutation that takes place on the coating region and which does change the amino acid that is produced, this type of point mutation is known as a miscense mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So a point mutation in which one nucleotide is substituted for another, and this causes a change from one amino acid to another."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "This type of mutation is known as a miscense mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So this is shown in the diagram above."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And one very common example of a point mutation known as a Nissan Mutation is sickle cell anemia, in which the hemoglobin that is formed is basically not as active as it should be."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So a Nissan Mutation may or may not lead to problems."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And an example where it does lead to problems is in sickle cell anemia."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So sickle cell anemia is an example of a miscensed mutation that alters the structure of our hemoglobin."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "It basically changes our amino acid glutamic acid into a valium."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And by changing our amino acid, that changes the three dimensional shape of the hemoglobin molecule."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And it basically causes the hemoglobin molecules to aggregate with one another, and that can lead to many problems."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "Now, the last thing that I want to mention is something called a nonsense mutation."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "So a nonsense mutation is a mutation that changes a codon that codes for some type of amino acid to a stop codon that basically terminates our polypeptide chain prematurely."}, {"title": "Point Mutations (Base-Pair Substitutions).txt", "text": "And by terminating our polypeptide chain prematurely, that basically creates a protein that is nonfunctional and point mutations as well as frameship mutations, which we're going to discuss in the next lecture, can lead to nonsense mutations."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Phospholipid molecules are amphipathic."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And what that means is they have this natural ability, they have the propensity to form bilayer membranes, as we discussed in the previous lecture."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And we can actually utilize their propensity to form these cell membranes, these bilayers, to actually create these specialized lipid vesicles we, we call liposomes."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And liposomes can be very important because we can use liposomes to basically study the permeability of cell membranes."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And we can use liposomes to basically deliver drugs and things like DNA molecules to the cells of patients."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So what exactly does a liposome actually look like?"}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Well, a liposome is basically this aqueous compartment that is surrounded by a bilayer, a membrane that consists of two layers of phospholipid molecules."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So this is what it actually looks like."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So it's kind of like a cell, except it's much smaller."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And inside this compartment, we don't have organelles, the cell nucleus or anything like that, but we can put in special molecules, as we'll see in just a moment, like drugs or DNA into this compartment."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And that can be delivered to cells of our body."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So liposomes are relatively small, so about 50 nm in diameter acquisition compartments that are surrounded by phospholipid bilayer membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So essentially the red portion is that non polar hydrophobic region of those phospholipid, the tails."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And these blue sections are basically those polar heads."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So we have one side, one leaflet, and the other side the second leaflet."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And so this is the bilayer membrane, this is the internal compartment and it is separated from the external compartment by this bilayer membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Now the question is, how do we build these liposomes?"}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Well, if we want to build a liposome that is about 50 nm in diameter, this is the method that we have to follow."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "But you should know that we can also build larger liposomes if we use other techniques."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So let's suppose we have an aqueous solution and then we have a second solution that contains the phospholipid that we want to use to actually create that bilayer membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So what we do is we basically mix these two solutions and because the phospholipids won't mix very well in the aqueous solution, we basically form these two separate layers."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So we have the Aqueous layer and we have that phospholipid layer."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Now, to actually allow these phospholipids to spontaneously form these vesicles, these liposomes, what we have to do is we have to disperse these phospholipids within the aqueous solution."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And in order to disperse these phospholipids, what we do is we basically undergo a process known as sonication."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And what sonication does is it uses the energy that is stored in sound waves."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So we essentially bombard our solution with sound waves and the energy stored within those sound waves basically disperses and agitates."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "The solution of phospholipids allows them to basically move around and disperse within the aqueous solution."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And that's exactly what allows us to form those liposomes, these vesicles that consist of this bilayer lipid membrane in which we have this internal aqueous compartment that is separated from the external Aqueous compartment."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So, once again, lipid vesicles can be formed by mixing a lipid solution into an aqueous solution and then sonicating the solution."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And sonication involves bombarding the solution with sound waves."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "The energy carried within the sound waves is used to basically increase the energy of these phospholipids, and that increases the kinetic energy, and so it disperses all these phospholipids."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And that's exactly what allows these phospholipids to actually collectively aggregate and form the bilayer membrane and form these liposomes of interest."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Now, we can also actually place specific types of molecules, molecules of interest, into the internal acreage compartment of our liposome."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And the only thing that we really have to change in this procedure is instead of using a regular plane Aqueous solution, we use a solution that contains that molecule of interest."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So, for instance, let's say we want to input we want to insert amino acids into this particular internal compartment."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And so instead of using the aqueous solution, we would use an Aqueous solution of amino acids."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So we take the aqueous solution of amino acids, we essentially mix them with that phospholipid solution, the phospholipids that we want to use to form that Bilay, and then we solicit our solution."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So this is basically what takes place."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "We have the individual amino acids shown in purple."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "We have these individual phospholipid molecules, which, as a result of this bombarding of sound waves, basically disperses and allows them to actually form this bilayer membrane, as shown in this particular diagram."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And so what happens is some of these amino acids will randomly end up within the internal Aqueous compartments as these liposomes are actually formed, as these fossil whippets spontaneously naturally form this bilayer membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And other amino acids will end up on the outside portion of that cell membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And so now, to separate these amino acids in solution from the liposome of interest, all we have to do is undergo some type of purification process."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So, for instance, we can use dialysis or gel filtration chromatography to basically separate and isolate those liposomes of interest."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And then we can, for example, use those liposomes to basically study the rate at which these amino acids actually leave that cell membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And what that tells us is it gives us the permeability of the cell membrane to that particular amino acid."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And we can conduct many different types of experiments that basically provide us with information about different aspects, different properties of that membrane, such as the permeability of that membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Now, we can also use them to basically deliver drugs and other things to patients."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "For instance, let's suppose a patient has some sort of tumor in their body, and a tumor is basically a collection of these cancerous cells."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And so we can build these liposomes, and we can direct these liposomes to the cancerous cells of the tumor."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And what happens is because the cells of the tumor are basic, also contain the same phospholipid bilayer membrane, these liposomes confuse with the cell membranes of those cancerous cells and that can in turn inject whatever drug is found inside the internal aqueous compartment into those cancerous cells and that can kill off those cancerous cells."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So the point is, liposomes can be used to study the properties of cell membranes or they can be used to deliver drugs to patients."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Now, the final thing I'd like to mention about liposomes is we can also actually build liposomes that contain proteins embedded inside the liposome."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And we can use these types of protein liposome structures to study the properties of the proteins that exist within the cells of our body, within the cell membranes of our body."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So how do we build, how do we actually embed these proteins into the bilayer membrane of liposomes?"}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "Well, all we have to do is we basically take the proteins of interest and we mix them with detergents, and then we mix that with that particular phospholipid solution in the aqueous solution we once again sonicate."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And that allows us to actually embed those proteins inside the liposome."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "And we can carry out many different types of experiments to basically study the properties of the proteins embedded inside the cell membrane."}, {"title": "Liposomes (Lipid Vesicles) .txt", "text": "So we see that we can actually use the natural properties of lipid molecules, their ability to basically spontaneously form these bilayer membranes, to actually build their useful structures, these lipid vesicles, known as liposomes."}, {"title": "Introduction to Human Skeletal System .txt", "text": "The human skeletal system is an endoskeleton."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And what that basically means is the entire structure of the skeleton is found inside our body and this is in contrast to the exoskeleton which contains the entire structure of the skeleton outside of the body."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the exoskeleton sheds as the organism grows but the endoskeleton does not heartshed, in fact it grows as the organism itself grows."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the human skeletal system consists of two types of connective tissue."}, {"title": "Introduction to Human Skeletal System .txt", "text": "We have bone and we have cartilage."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, when the human being is born we have 270 bones."}, {"title": "Introduction to Human Skeletal System .txt", "text": "But as the organism grows and eventually develops into an adult the number of bones decreases to 206."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And that's because some of these bones basically join together to form individual single bone structures."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, what exactly is the difference between bone and cartilage?"}, {"title": "Introduction to Human Skeletal System .txt", "text": "Well, cartilage is a much more flexible type of connective tissue and that's exactly why cartilage is found in those regions of the human body that require a bit more flexibility."}, {"title": "Introduction to Human Skeletal System .txt", "text": "For example, cartilage is found in the outer portion of the ear, in the nose, in the trachea as well as in our joints and other parts of the body."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now bone on the other hand is a much more rigid connective tissue and it is capable of resisting tensile and compressive forces."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And that's exactly why bone gives us our structure and provides us with support and gives us our shape and it serves many other purposes as we'll see in just a moment."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the skeletal system of the human body is broken down into two divisions."}, {"title": "Introduction to Human Skeletal System .txt", "text": "We have the axile division, the axile skeleton which consists of the skull, the spinal cord and the ribcage."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And we also have the apendicular skeleton that consists of the bones in the upper limbs, the arms in the lower limbs, our legs as well as our pelvic girdle and the pictorial girdle."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So the bone here and the bone here and these basically connect the axial skeleton to the apendicular skeleton."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now let's discuss the different types of functions of the human skeletal system."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So what roles does the skeletal system actually play?"}, {"title": "Introduction to Human Skeletal System .txt", "text": "So we have five important functions that we have to be aware of."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So we have a function in protection, in support, in movement, in storage and mineral homeostasis as well as in the production of blood cells known as hematopoasis."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So let's begin by briefly discussing the concept of protection."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So one of the many roles of the skeletal system of the human body is basically to protect the internal organs of our bodies such as the brain, the heart, the lungs and other organs."}, {"title": "Introduction to Human Skeletal System .txt", "text": "For example, the skull is part of the skeletal system and it protects the brain while the ribcage and the sternum basically protects the heart and the lungs and the vascular system found within this region."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So that basically means if someone hits us in the chest or in the brain these bones will basically absorb some of the impact some of the force so that our internal organs aren't actually damaged."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, what about the second function known as support?"}, {"title": "Introduction to Human Skeletal System .txt", "text": "So, the skeletal system supports the many organs of the body by basically creating a scalp folding system."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So we create a framework that maintains the shape of the body."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, it is also capable of resisting tensile and compressive forces."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And that's exactly what allows us to resist different types of forces that we feel as a result of outside stimuli."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, what about movement?"}, {"title": "Introduction to Human Skeletal System .txt", "text": "Well, one of the predominant functions of our skeletal system is basically bodily movements that are voluntary."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So the skeletal system coordinates with the muscular system, skeletal muscle, as well as with the nervous system to basically coordinate different types of voluntary movements such as walking, running, swimming, riding a bicycle and so forth."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So, anytime we can voluntarily move our body, this involves not only skeletal muscle and the nervous system, it also involves our skeletal system."}, {"title": "Introduction to Human Skeletal System .txt", "text": "In fact, our skeletal muscles are connected to bones via filaments known as our tendons."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And bones are connected to other bones via filaments, known as ligaments, that also consist in certain regions of joints that basically act to absorb some of that force, some of that shock."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So basically, the skeletal system, coupled with the skeletal muscle and together known as the musculoskeletal system, is responsible for voluntary movements such as walking."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Skeletal muscle is attached to bone via tendons, as shown in this diagram."}, {"title": "Introduction to Human Skeletal System .txt", "text": "We have the biceps, we have this tendon attached to our bone, we have a tendon on this side also attached to our bone, and our bone is attached to another bone via ligament."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the movement of this musculoskeletal system allows for a wide range of motion that is ultimately controlled by our nervous system."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So the nervous system coordinates with the musculoskeletal system to basically create this type of voluntary motion."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the fourth type of function is in storage as well as mineral homeostasis."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So basically, our bone contains special type of tissue known as adipose tissue."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And adipose tissue consists of cells known as adipose."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And these adipose, these adipose tissue basically stores our fatty acids in the form of triglycerides."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And these triglycerides can be used to break down and form ATP molecules in the mitochondria of the body."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the bone is also responsible for storing important types of minerals that are used by the body, by the cells."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And one example of the mineral stored is calcium."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So when the blood levels, if we find too much calcium in the blood, the bone is responsible for taking that calcium out of the blood and depositing the calcium into the bone."}, {"title": "Introduction to Human Skeletal System .txt", "text": "But if the blood level of calcium is low, then if the calcium level in the blood is low, that basically means the bone can actually release calcium into the blood and then the calcium can go to the cell that requires that calcium."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So remember, calcium is important."}, {"title": "Introduction to Human Skeletal System .txt", "text": "For example, in muscle contraction."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And if our muscle cells are low in calcium, the bone can basically release calcium to the blood that will eventually travel to those muscle cells."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So bone is responsible for storing important minerals such as calcium."}, {"title": "Introduction to Human Skeletal System .txt", "text": "It also contains adipose tissue that is responsible for storing triglycerides."}, {"title": "Introduction to Human Skeletal System .txt", "text": "Now, the final function of the skeletal system is producing our blood cells, and this process is known as hematopoasis."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And this takes place in a specialized type of structure within the bone known as the bone marrow."}, {"title": "Introduction to Human Skeletal System .txt", "text": "And we'll discuss the structure of the bone in the next lecture."}, {"title": "Introduction to Human Skeletal System .txt", "text": "So there are two important types of blood cells."}, {"title": "Introduction to Human Skeletal System .txt", "text": "We have red blood cells, which basically transport our oxygen using hemoglobin along the blood vessels, and white blood cells, which are important cells involved in the immunity of our body."}, {"title": "Introduction to Human Skeletal System .txt", "text": "We'll talk about white blood cells in more detail when we'll discuss the immune system of the human body."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So now that we discuss the processes of oygenesis and sperm manogenesis let's briefly focus on the anatomy of the male and the female reproductive organs."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And let's begin with the male."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Recall that the male gonads are known as the testes."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And inside the testes we have the seminar philosophy's where sperm cells are actually formed."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So we have the testes shown in brown."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "By the testes we have the seminfilosubules where spermatogenesis actually takes place."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now notice that the testes are enclosed in this saclike structure in a flap of skin known as the Scrotum."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And what the Scrotum does is it basically maintains a slightly lower temperature than the body core temperature."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "For example, if the normal body core temperature is about 37 degrees Celsius then the temperature of the scrotum is around 35 degrees Celsius."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "It's two Celsius degrees lower than the body core temperature."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now the reason for that is because the enzymes involved in producing the sperm cells within our testes function effectively and efficiently at a slightly lower temperature."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So that's exactly why the Scrotum functions to maintain a slightly lower temperature than our body core temperature."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now, once the sperm cells are actually formed in the sand monopoly's tubules of the testes those sperm cells travel into a highly convoluted tubule section found next to our testes known as the epididymis."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And what the epididymis does is it stores those sperm cells until ejaculation actually takes place for example during sexual intercourse."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And what the epidymus also does is it helps those sperm cells actually mature into mature sperm cells."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So let's suppose that during sexual intercourse this male individual ejaculates and what that means is the sperm cells will be released from the epididymus and they will travel along the following canal shown in blue and this canal is known as the VAS deference."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now the VAS deference ultimately empties out into a smaller canal shown in red known as the ejaculatory duct."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And the ejaculatory duct is found next to an accessory gland known as the seminal vesicle."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now what the seminal vesicle does is it releases a fluid substance that contain nutrients such as fructose and proteins that are needed by the sperm cells."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So when the sperm cells enter the ejaculatory duck they mix with that fluid that is produced by the seminal vesicle and then that fluid travels into our urethra."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "This canal shown in purple."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now notice we have this gland along the urethra known as the bulbourethro gland and we also have another gland known as the prostagland."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now these two glands both release a slightly basic solution, a slightly basic substance."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "The only difference is the bulba urethral gland releases that substance before ejaculation takes place while the prostate gland releases that substance during ejaculation."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And what the function of that slightly basic substance is is to neutralize the environment found inside the vaginal tract."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And that's because the sperm cells must the sperm cells require a slightly basic or neutral solution to actually survive, they cannot survive in an acidic environment."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So that's why these two glands produce that type of slightly basic solution and alkaline solution."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So we have these three different glands and when these glands release that fluid that fluid mixes with the sperm cells and eventually that fluid known as semen basically exits our urethra and exits our penis through the following hole."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And eventually it enters, let's say during sexual intercourse it enters the vaginal cavity."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So these are the different structures involved in the male reproductive organ."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And this is the pathway that is followed by the sperm cell before the sperm cell is ejaculated and after the sperm cell is ejaculated."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So they are produced in the seminar tubules."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Then they are stored inside the epididymus and during ejaculation they travel into the vast deference and into the ejaculatory duck where they mix with the fluid that comes from the seminal vesicle."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And then they travel into the urethra where they mix with the fluid that is produced by the prostate gland and the bulba urethral gland."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And finally that forms the semen."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And the semen basically exits the penis and eventually enters the vaginal cavity."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now let's move on to the female reproductive organ."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So let's focus on the following diagram."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So we have the ovary and each female contains two ovaries just like the male contains two testes."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So the ovary is the gonad of the female."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And what that means is this is where oogenesis actually takes place."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So this is where we produce our oicides, our exiles."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now when the woman actually reaches puberty she will begin to undergo the menstrual cycle every single month."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "She will basically produce and release a secondary oicide, our exile."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And the excel will exit the ovary."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "It will enter the peritoneal cavity and it will enter the fallopian tube."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And along the fallopian tube we basically have these smooth muscles that undergo the process of peristalsis and we also have cilia."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And together the process of peristalsis and the movement of the cilia moves propagates that ovum that exhale along this fallopian tube and eventually into the uterus."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So this is basically the uterus."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now if the sperm cell is present inside the fallopian tube so after sexual intercourse if the sperm cell makes its way into the fallopian tube eventually it fuses, it combines with that excel to produce a zygote and that zygote begins to move and eventually makes its way into this organ known as the uterus."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So the uterus is basically a pear shaped organ that is lined with a thick layer of smooth muscle."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "This layer right here that can basically contract during the process of childbirth."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And it also contains a layer known as the endometrium."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So a mucus layer, a mucous membrane known as the endometrium."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And during fertilization, when the sperm combines with the egg to form the zygote and the zygote makes its way into the uterus, the zygote will attach itself, it will implant itself onto the endometrium and it will begin to grow."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Because the endometrium is the structure that provides the nutrients, the minerals and the oxygen that is needed for the growth and development of that zygote."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "Now, notice we also have the cervix, which is basically the lower portion of our uterus."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And it connects our upper portion of the uterus into our vagina."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And this is the vagina."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "It's the vaginal cavity."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "The function of the vaginal cavity is to basically interact with the penis and it also acts as the birth canal."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "This is where the child actually moves from the uterus into the vaginal cavity and then out of the body."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So the vagina is an elastic muscular tube that connects the uterus to the outside environment."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "This is where the sperm injures the woman during sexual intercourse."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So essentially after sexual intercourse, once the semen actually is ejaculated into the vagina, it travels via the cervix, into the uterus and eventually travels into the fallopian tube."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And if it meets with that egg, with that ovum, they fuse to form the zygote and the zygote will move and implant itself onto that endometrium, the lining of our uterus."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "And the endometrium will basically provide the nutrients, the minerals needed for the growth and development of that zygote."}, {"title": "Anatomy of Reproductive Organs .txt", "text": "So these are the organs found in the male and the female reproductive system."}, {"title": "Affinity Chromatography.txt", "text": "So far."}, {"title": "Affinity Chromatography.txt", "text": "In our discussion on protein purification processes, we discuss four different methods."}, {"title": "Affinity Chromatography.txt", "text": "We begin by discussing the process of salting out, and in salting out, we separate the proteins based on their solubility and salt concentrations."}, {"title": "Affinity Chromatography.txt", "text": "Then we discuss dialysis in which we separate proteins from tiny molecules and ions by using a semipermeable membrane."}, {"title": "Affinity Chromatography.txt", "text": "We moved on to gel filtration chromatography, in which we separate the protein mixture based on their size."}, {"title": "Affinity Chromatography.txt", "text": "And finally, we discussed ion exchange chromatography, in which we separate the proteins based on their net charge."}, {"title": "Affinity Chromatography.txt", "text": "Now we're going to discuss a fifth method by which we can purify our protein mixture."}, {"title": "Affinity Chromatography.txt", "text": "And in this method, we also use a specific property of proteins."}, {"title": "Affinity Chromatography.txt", "text": "So many proteins inside our body have a specific high affinity to some type of molecule."}, {"title": "Affinity Chromatography.txt", "text": "And the general example of these proteins are enzymes."}, {"title": "Affinity Chromatography.txt", "text": "So enzymes are these proteins found inside our body that bind to specific substrate molecules and accelerate the reaction, basically increase the rate at which that reaction actually takes place."}, {"title": "Affinity Chromatography.txt", "text": "Enzymes are biological catalysts, and we have many different types of enzymes in our body."}, {"title": "Affinity Chromatography.txt", "text": "For example, just in our immune system alone, we have many, many, many proteins."}, {"title": "Affinity Chromatography.txt", "text": "These protective proteins we call antibodies."}, {"title": "Affinity Chromatography.txt", "text": "And our body manufactures these antibodies so that they bind to specific types of molecules we call antigens."}, {"title": "Affinity Chromatography.txt", "text": "So for every antigen, we have a specific type of antibody that can bind to that antigen and that antigen alone."}, {"title": "Affinity Chromatography.txt", "text": "Another example is the DNA polymerase molecule."}, {"title": "Affinity Chromatography.txt", "text": "So DNA polymerase is basically this enzyme complex that only binds to specific sequence of nucleotides on our DNA."}, {"title": "Affinity Chromatography.txt", "text": "And once the binding takes place, once the enzyme binds onto our DNA, that initiates the process of DNA replication."}, {"title": "Affinity Chromatography.txt", "text": "Another example is glucose oxidase."}, {"title": "Affinity Chromatography.txt", "text": "This enzymes bind specifically to glucose molecules, sugar molecules we call glucose."}, {"title": "Affinity Chromatography.txt", "text": "And we can go on and on."}, {"title": "Affinity Chromatography.txt", "text": "So we have many, many examples of these specific proteins, these proteins that bind to specific molecules and have high affinity for these molecules."}, {"title": "Affinity Chromatography.txt", "text": "So this is another property that we can use to separate proteins."}, {"title": "Affinity Chromatography.txt", "text": "And the method that uses this property is known as affinity chromatography."}, {"title": "Affinity Chromatography.txt", "text": "So a method called affinity chromatography basically separates, allows us to purify and isolate specific type of protein molecules from within a mixture of proteins based on their affinity to bind to specific molecules."}, {"title": "Affinity Chromatography.txt", "text": "Now, just like in gel filtration chromatography, an ion exchange chromatography, we also have the same exact setup in affinity chromatography."}, {"title": "Affinity Chromatography.txt", "text": "So we have a funnel."}, {"title": "Affinity Chromatography.txt", "text": "We place the funnel on top of a long, narrow column, and inside that column, we pack that column with these insoluble gel beads."}, {"title": "Affinity Chromatography.txt", "text": "Now, in the case of affinity chromatography, what we want to do is we basically want to modify those gel beads and we want to attach a specific type of group or molecule onto those gel beads."}, {"title": "Affinity Chromatography.txt", "text": "For example, if we zoom in on one of these gel beads, we get the following diagram and notice that to the gel bead."}, {"title": "Affinity Chromatography.txt", "text": "We basically attach a specific type of group we're going to call group Y."}, {"title": "Affinity Chromatography.txt", "text": "Now, what type of group that we want to attach?"}, {"title": "Affinity Chromatography.txt", "text": "Well, the type of group we want to attach basically corresponds to that substrate molecule that the protein that we want to actually isolate binds to it."}, {"title": "Affinity Chromatography.txt", "text": "And to see exactly what we mean, let's take a look at the following diagram."}, {"title": "Affinity Chromatography.txt", "text": "So let's zoom in onto the molecular level to a small section of this column."}, {"title": "Affinity Chromatography.txt", "text": "We basically get the following diagram."}, {"title": "Affinity Chromatography.txt", "text": "Now, in that column, we basically have these bees."}, {"title": "Affinity Chromatography.txt", "text": "Now, we also have a beaker that contains a crude mixture of proteins."}, {"title": "Affinity Chromatography.txt", "text": "So we have three proteins, and we only want to isolate one of those three proteins."}, {"title": "Affinity Chromatography.txt", "text": "Now, what we know about these three proteins is one of those proteins binds to a specific molecule, let's say a glucose molecule, and the other two enzymes, proteins, do not bind to enzyme molecules."}, {"title": "Affinity Chromatography.txt", "text": "So we have a green molecule, which is enzyme number one, that has a high affinity for glucose."}, {"title": "Affinity Chromatography.txt", "text": "So it basically has an active side that can accommodate a glucose molecule."}, {"title": "Affinity Chromatography.txt", "text": "We have enzyme number two in red that does not bind to glucose, and also enzyme number three in orange that also does not bind to glucose."}, {"title": "Affinity Chromatography.txt", "text": "So we take the beaker of these mixture proteins, we essentially dump them into our column, and they begin to move along our column."}, {"title": "Affinity Chromatography.txt", "text": "Now, only those enzymes that have the active side that can accommodate and bind onto the glucose will actually bind onto the glucose."}, {"title": "Affinity Chromatography.txt", "text": "And so only these green molecules will become trapped because they're bound onto the glucose of the bees."}, {"title": "Affinity Chromatography.txt", "text": "And the other two enzymes, enzyme two and three, will not interact with the glucose in any way."}, {"title": "Affinity Chromatography.txt", "text": "So they will simply continue traveling along and down our column."}, {"title": "Affinity Chromatography.txt", "text": "So when we pour the crude mixture proteins, the protein with affinity for glucose will bind to the beads."}, {"title": "Affinity Chromatography.txt", "text": "For example, that protein could be glucose oxidase that we spoke about earlier, or it could be some other protein that also binds to glucose."}, {"title": "Affinity Chromatography.txt", "text": "So the other molecules, however, these proteins here did not bind to the glucose on the beads, and so they continue traveling to the bottom of that column."}, {"title": "Affinity Chromatography.txt", "text": "So let's take a look at the following five diagrams that basically describes how this process actually takes place."}, {"title": "Affinity Chromatography.txt", "text": "So here we have our experimental setup."}, {"title": "Affinity Chromatography.txt", "text": "We have our column, we have the funnel, and this is our beaker that contains that crude mixture of three proteins."}, {"title": "Affinity Chromatography.txt", "text": "So we have the green enzyme one, the red enzyme two, and the orange enzyme three."}, {"title": "Affinity Chromatography.txt", "text": "And only enzyme one has a high affinity for glucose."}, {"title": "Affinity Chromatography.txt", "text": "So these are our beads."}, {"title": "Affinity Chromatography.txt", "text": "So we essentially pour our solution into our column."}, {"title": "Affinity Chromatography.txt", "text": "And so initially, at the initial moment we pour our solution, all of these proteins essentially congregate at the top of our column."}, {"title": "Affinity Chromatography.txt", "text": "Now, over time, what happens is because these two proteins have no affinity for the glucose on the beach, they will continue moving down our column as a result of the gravitational pull."}, {"title": "Affinity Chromatography.txt", "text": "But that protein, enzyme number one, that has the high affinity for glucose, will essentially bind onto that glucose molecule that is bound onto the beads."}, {"title": "Affinity Chromatography.txt", "text": "And this will happen ultimately at the beginning of our column."}, {"title": "Affinity Chromatography.txt", "text": "Now, some of these enzymes will make it farther down, but most of these enzymes bind in the beginning, towards the beginning of that column."}, {"title": "Affinity Chromatography.txt", "text": "So we have enzyme number one in this, and we have a bunch of enzymes number one throughout our beads, throughout the column."}, {"title": "Affinity Chromatography.txt", "text": "Now, enzyme two and three don't bind to any of the bees, and so they simply continue moving all the way to the bottom."}, {"title": "Affinity Chromatography.txt", "text": "So we see that the mixture of protein two and three will essentially be mixed together because none of them actually bind, none of them are attracted to those glucose molecules bound to our beets."}, {"title": "Affinity Chromatography.txt", "text": "And so in step four, we essentially turn the knob and we open up our hole."}, {"title": "Affinity Chromatography.txt", "text": "And so that allows the movement of these two proteins that we did not want to separate in the first place."}, {"title": "Affinity Chromatography.txt", "text": "And we basically place them in this beaker."}, {"title": "Affinity Chromatography.txt", "text": "And so now we can dump that out because we don't want to actually use this in our experiment, remember, our focus was basically to isolate protein number one and not protein number two or protein number three."}, {"title": "Affinity Chromatography.txt", "text": "Okay?"}, {"title": "Affinity Chromatography.txt", "text": "And finally, in the last step, so the question is, how do we get that protein number one out of that column?"}, {"title": "Affinity Chromatography.txt", "text": "Because the problem now is these proteins are bound to the beads found in that column."}, {"title": "Affinity Chromatography.txt", "text": "So in this particular case, what we can basically do is we can create a solution of glucose, and that glucose is essentially not bound to anything in that solution."}, {"title": "Affinity Chromatography.txt", "text": "So this is our glucose solution, and we wash that column down with the glucose solution."}, {"title": "Affinity Chromatography.txt", "text": "So what will happen is the glucose that is free to move in that solution will now compete for that active side found on that enzyme, enzyme number one, and it will outcompete that glucose that is bound onto the beads."}, {"title": "Affinity Chromatography.txt", "text": "And so once that glucose replaces the glucose that was bounced, the beads, that protein that was initially bounced, the bead, will essentially move away from that bead and will continue moving down our column because now it contains the active side that is filled with that glucose."}, {"title": "Affinity Chromatography.txt", "text": "And in this manner, we can basically wait until it goes all the way to the bottom."}, {"title": "Affinity Chromatography.txt", "text": "We can open up our knob, and so that will essentially be collected into some type of beaker or some type of test tube, as shown in the following diagram."}, {"title": "Affinity Chromatography.txt", "text": "And so now, following our affinity chromatography method, we have this solution that is purely one protein, protein one, the protein that we wanted to isolate in the first place."}, {"title": "Affinity Chromatography.txt", "text": "So we see that this method is only useful if we know what specific molecule that protein actually binds to, and if we also know that the other proteins in that mixture don't bind to that specific molecule, as we saw in this particular case."}, {"title": "Affinity Chromatography.txt", "text": "So if we know that these other two enzymes have no affinity or a very low affinity for our glucose while this one has a very high affinity, this method was useful because it allowed us to actually isolate our protein, number one."}, {"title": "Affinity Chromatography.txt", "text": "But if all of these proteins had a high affinity for glucose, then this would not have been a useful method because all of them would have been trapped in our column."}, {"title": "Affinity Chromatography.txt", "text": "And so we would have had no way of actually removing these two proteins that we don't want and isolate that protein, at least not with this affinity chromatography technique."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Red blood cells are formed inside the bone marrow of our body from special stem cells known as hematopoietic stem cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, once the red blood cells are formed, they are released into the blood plasma, into our blood circulation of our cardiovascular system."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, once the red blood cells are fully formed, they are terminally differentiated and that means they will not divide, they will not undergo mitosis again during their lifetime."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, the main function of red blood cells is to carry oxygen."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So red blood cells contain many, many hemoglobin proteins inside the cytoplasm."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And these hemoglobin proteins inside the red blood cells are responsible for picking up that oxygen inside the lungs and dropping, delivering that oxygen to the tissues of our body."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, as with any other cell in our body, these red blood cells age with time."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And what that means is, with time, as they collide with other cells of our blood, with the walls of the capillaries, and as they squeeze through the tiny capillaries of our body, they are damaged."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And eventually they must be destroyed."}, {"title": "Recycling of Red Blood Cells .txt", "text": "They must be broken down and they must be recycled in special areas of our body."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, there are three places where red blood cells are generally recycled and broken down."}, {"title": "Recycling of Red Blood Cells .txt", "text": "It's inside our liver, inside the lymph nodes and also inside an organ known as the spleen."}, {"title": "Recycling of Red Blood Cells .txt", "text": "The spleen is an organ found in close proximity to our stomach and it not only stores blood in our body, but it also breaks down the red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, recall that some factors that increase the rate of production of red blood cells in our body are exercise, exposure to high altitude hemolytic diseases, damage to the bone marrow, low hemoglobin concentration of content in our blood."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And all these things not only lead to the increase in production of red blood cells, but because we also produce more red blood cells, that implies we also have to break down more red blood cells as a result."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So these also can increase the rate of destruction of these red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So let's focus, let's discuss on how and where these red blood cells are actually broken down and what recycled components are formed as a result."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, red blood cells can generally live up to 120 days before they are damaged to the point where they must be recycled in our spleen, in our liver, or in our lymph nodes."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the rate at which the average rate at which our body breaks down recycles these red blood cells is about 2.5 million red blood cells every single second."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So every single second, our liver, our spleen and the lymph nodes break down and recycle 2.5 million red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, this actually seems like a lot, but it's not."}, {"title": "Recycling of Red Blood Cells .txt", "text": "If we remember that our body contains about 25 trillion red blood cells circulating in our blood circulation system."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, 90% of these red blood cells that are damaged are recycled in our spleen in our liver and in our lymph nodes by specialized white blood cells known as macrophages."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the remaining 10% of those red blood cells actually lice."}, {"title": "Recycling of Red Blood Cells .txt", "text": "They break open directly in the blood, in our blood circulation as a result of being damaged by some other type of factor."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So, for example, when our red blood cells age and when they become very fragile, if they are squeezed through that very tight capillary, they can actually lyse."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And by lysing, they release the components to the blood plasma of our cardiovascular system."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So about 10% of the red blood cells lyse and this process is known as hemolysis directly in our blood circulation."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Their remnants are eventually picked up by the macrophages, as we'll see in just a moment."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, the majority of the aged or damaged red blood cells end up in our spleen, in our liver, or in our lymph nodes."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the white blood cells we call macrophages, which are phagocytic cells, essentially engulfed, digest and recycle the different components of red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So to summarize what we describe and to discuss how this process takes place, let's take a look at the following diagram."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So, let's begin in region number one."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So this is our bone, this is the bone marrow."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And inside the bone marrow, our hemopoetic stem cells essentially form red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Those red blood cells mature, they end up being released into our blood plasma."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So red blood cells are released into our blood."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, after about 120 days of circling our cardiovascular system, they essentially are damaged to the point where they either lice directly in our blood or they go into our spleen, into our liver or end up in the lymph nodes."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the white blood cells engulf those damaged red blood cells and form this vacuole inside that combines with the lysosomes of the macrophage."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the lysosomes contain digestive proteolytic enzymes that can break down the red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, notice when hemolysis of the blood cell takes place inside our blood, the contents of our red blood cell is spilled into the blood plasma."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, what are the contents of the red blood cell?"}, {"title": "Recycling of Red Blood Cells .txt", "text": "Well, the red blood cell doesn't have any organelles, it doesn't have any nucleus."}, {"title": "Recycling of Red Blood Cells .txt", "text": "What it does have is a ton of hemoglobin proteins."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And so these hemoglobin proteins are released into our blood plasma."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, the hemoglobin proteins, as well as the remnants of the red blood cell that lies can be either picked up by the macrophage circulating in our blood plasma or it ends up being released by the kidneys to the outside environment."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So let's focus on the macrophage and what happens inside the macrophage."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So let's suppose the macrophage either engulfs the red blood cell or picks up the remnants of the lyst red blood cell that was found in the blood plasma."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Either way, the recycling process begins to actually take place."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So the main component of the red blood cell are these hemoglobin proteins."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So this describes the recycling of hemoglobin inside the macrophage."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So essentially what happens is our hemoglobin consists of a heme group that contains an iron atom and it also contains of the protein component, the globin."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So what happens is the globin protein component is broken down into its constituents, amino acids, and the heme group is broken down into the iron atom as well as that heme."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, the iron and the amino acids can either remain inside the cell and be used by that cell, or they go into our blood plasma and then travel back into the bone marrow, where the bone marrow reuses these recycled materials to form more red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, amino acids can actually travel in the blood plasma by themselves, but this iron has to be carried by special protein carrier known as a transferring."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So transferring carries the fe atom to the bone marrow, or if the fe remains in that cell, it can be used by that cell for some type of process."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Now, what about the heme group?"}, {"title": "Recycling of Red Blood Cells .txt", "text": "Well, the heme group is ultimately broken down and form and broken down and transformed into something called bilirubin."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And bilirubin eventually exits and enters the blood plasma, where it travels into the liver."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the liver either transfers that bilirubin into our kidneys or it combines it with the bile that is excreted into the intestines, where the bile combines with our remnants of whatever we ingest and eventually is excreted by the large intestine of our body."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So this is the process by which we produce our red blood cells."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And we also destroy those red blood cells and recycle those red blood cells so that we can reuse some of the components to form more red blood cells in our bone marrow."}, {"title": "Recycling of Red Blood Cells .txt", "text": "So, to summarize, red blood cells are formed in our bone marrow and they are recycled, they are broken down by macrophages and either the liver, the spleen, or our lymph nodes."}, {"title": "Recycling of Red Blood Cells .txt", "text": "About 90% of the red blood cells are engulfed by those macrophages."}, {"title": "Recycling of Red Blood Cells .txt", "text": "But about 10% of those red blood cells, as a result of some type of strain, some type of force or some type of pressure, for example, a collision with the wall of the capillary, that can cause about 10% of those red blood cells to actually lyse directly inside our blood plasma."}, {"title": "Recycling of Red Blood Cells .txt", "text": "And the remnants of that lysing process are picked up by the macrophage."}, {"title": "Recycling of Red Blood Cells .txt", "text": "Or the hemoglobin can actually travel to the kidneys, where the kidneys essentially excretes that hemoglobin."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So now that we have a general idea of what gluconeogenesis is and what it's and what it does and what it's used for, let's actually discuss the details of this process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And in this lecture we're going to focus on the first two steps of gluconeogenesis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So remember, gluconeogenesis is the process by which specific types of cells, so liver cells and kidney cells basically use Pyruvate to build glucose molecules."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So then the glucose molecules can be used by our body ourselves to actually carry out different types of processes."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, here we have two steps on the board."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "First step of gluconeogenesis and the second step of gluconeogenesis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And what the goal of these two steps are, or what the goal of these two steps is, is to basically bypass the last irreversible step of glycolysis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Because remember, gluconeogenesis is not simply the reverse of glycolysis and that's because glycolysis itself is a highly exergonic process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so, for instance, we know that in step ten of glycolysis we transform Pyruvate into phosphorino Pyruvate by using a very exergonic process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so if we simply reversed that step in gluconeogenesis, this reverse step would be very endergonic."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "It would require a large input of energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So to basically bypass that highly endergonic process, we create a different process, a different reaction pathway that bypasses it, and this is a much more favorable reaction."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So in a two step process, we're able to actually transform the Pyruvate molecule into a phosphate ENL Pyruvate by using a favorable reaction pathway."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So let's begin by focusing on step number one."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And in step number one, we basically want to carboxylate a Pyruvate molecule to form an oxalo acetate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, if we simply try to add a carbon dioxide onto the Pyruvate to form the oxyloacetate, that reaction in itself actually requires energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "It would be an endorganic process under cellular conditions."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "But what we do is we couple that process with the hydrolysis of ATP into ATP and pi orthophosphate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And because the hydrolysis of ATP is a highly exergonic process, we use that free energy to basically couple the endergonic process of carboxylating, that Pyruvate molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So together, this process, the coupling of these two processes, the hydrolysis of ATP and the carboxylation of Pyruvate, actually creates a relatively favorable process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now let's talk about this enzyme."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we essentially have a CO2 molecule that is attached onto the Pyruvate to form the oxyloacetate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "In the process, we hydrolyzed the ATP into orthophosphen ATP and we also form two H plus ions."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And this is our oxalo acetate intermediate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, the enzyme that catalyzes this reaction is the Pyruvate, because that's the substrate carboxylase, because this is a carboxylation process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And this enzyme consists of four identical but individual subunits."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now let's talk a bit about these important regions that exist on the enzyme on these subunits."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we have two very important regions."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "One of these regions, known as the biotin binding domain, actually contains this molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "This helper molecule we call biotin."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And biotin is actually used to bind that CO2 molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, another important site is a region that contains the area that binds an ATP molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so we have to use that ATP molecule to actually activate that CO2 molecule to make it much more reactive so that we can actually attach that molecule onto Pyruvate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Why?"}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Why do we have to activate the CO2?"}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Well, because we can't simply attach the CO2 because that would require an input of energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so we have to activate it, make it more reactive, and that's where that ATP comes into play."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So once again, Pyruvate carboxylase consists of four identical subunits that each have a domain that has a Covalently attached biotin prosthetic group."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So this helper group that helps to bind that CO2."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we call this group the biotin binding domain that is used to bind the CO2 molecule and bring it into the active site of the enzyme."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So basically the active side that contains that Pyruvate and we'll talk more about that in just a moment."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And we also have that domain that actually binds that ATP molecule that is used to make that carbon dioxide much more active."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, this process actually involves three individual steps, or we can call it many steps."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so these are the steps that I've listed on the board."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So let's begin with step number one."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, we know that inside our fluids of our body, we don't simply have a CO2 molecule dissolved because CO2 by itself is a very non polar molecule and so it cannot simply dissolve in our blood."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And we have an enzyme called Carbonic and Hydrate that is basically used to transform the CO2 into bicarbonate ions."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And this takes place in the cytoplasm of our red blood cells."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so we actually find bicarbonate ions dissolved in our cytoplasm and in our blood."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so in the first step, what we do is we essentially activate that bicarbonate molecule to form this carboxy phosphate intermediate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we transfer of a spoil group from the ATP onto this bicarbonate to form this carboxy phosphate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And the reason we have to carry this step out is to actually prepare that molecule to bind that CO2 molecule onto that biotin because without this step, the CO2 would simply not be able to bind onto that binding site of that enzyme."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So once again, recall that carbon dioxide exists as bicarbonate ions in the cytoplasm and in our fluids of the body."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And in the first step of this process, we essentially use an ATP molecule to activate the carbon dioxide to form the carboxy phosphate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "This is our carboxy phosphate complex."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so we form the ATP that we have here on the product side."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So now that we have an active CO2 molecule, it is ready to be attached onto the biotin component of that enzyme."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And that's exactly what happens in step two."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, I should mention that there is a requirement to attach that CO2 onto the biotin."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "This attachment only takes place if we have a coenzyme present attached onto that enzyme known as acetyl, coenzyme A or acetylCoA."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So this enzyme is required for the CO2 to actually bind onto that biotin."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And the coenzyme has to be bound onto that Pyruvate carboxylate for the step to actually take place."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we see that in the next step, the phosphorylated CO2 can now attach onto the biotin of the enzyme and form that carboxy biotin enzyme intermediate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So this intermediate here and so this bond that is formed between the carbon dioxide and the biotin that is bound onto the enzyme is actually a very reactive bond."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "It's a very high in energy bond."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And when we break that bond, that actually releases a certain amount of energy, that releases 20 kilojoules of energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so that's exactly why we call this an activated bond."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Because it's an activated bond, it's very reactive."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And in the final step, we're going to basically use this high energy in the bond to attach that molecule onto that Pyruvate to form the oxyloace."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So, once again, the bond holding the CO2 and the biotin enzyme together is quite unstable and quite reactive."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so when we cleave that in the next step, that will release 20 kilojoules of energy per mole that we actually use up."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So in the final step, we have the enzyme Biden CO2 complex that we basically formed here that is mixed with that Pyruvate molecule and that forms that oxalo acetate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we're able to actually use this very activated and reactive complex to attach that CO2 on the oxyloacetate molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so if we sum up these reactions, we essentially get this net reaction here."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And again, I have to emphasize that the coenzyme we call acetyl COA is required for the CO2 to bind to that binding."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And without it, that binding will not take place."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And actually, as we'll discuss in more detail in a future lecture, this actually creates a very important, a very important regulatory point of the process of glucosegenesis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So remember this point because we're going to cover it again in a future lecture when we discuss how we actually regulate the process of gluconeogenesis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, by the way, this entire process, step one, takes place entirely in the matrix of the mitochondria of our cell."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And that's because Pyruvate carboxylase is only found in the matrix of the mitochondria."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So the conversion of Pyruvate into the oxalo acetate intermediate by Pyruvate carboxylase."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So these three steps essentially take place in the matrix of the mitochondria."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, step two actually takes place in the cytoplasm."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So, as we might imagine, now we have to basically transport that oxalo acetate intermediate into the cytoplasm."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "But before we actually transport the oxalo acetate, we have to reduce it into a malate molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so what happens in the matrix of the mitochondria is an enzyme called malade dehydrogenase uses an NADH to reduce the oxalo acetate into malate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And we form the NAD plus in its oxidized form."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And now the malade can move across the two membranes of the mitochondria by using special proteins and eventually enter the cytoplasm."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And once it enters the cytoplasm before it can basically react in step two of Gluconeogenesis, that malade has to be transformed back into oxyloacetate by using that same enzyme malade malade dehydrogenase."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "But now, instead of using NADH, we're using NAD plus because we basically want to oxidize the malade back into oxyloacetate, producing that reduced version of the NAD molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So let's take a look at step two."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, remember, in step one, the entire goal was to use the highly exergonic process of the hydrolysis of ATP to basically drive the endergonic process of the attachment of the CO2 molecule onto that Pyruvate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we saw that the carboxylation process is actually an endergonic process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, that implies if carboxylation requires energy, that means decarboxylation actually releases energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And that's important in this step because what happens in this step is this oxalo acetate is transformed into phosphorinopyruvate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And in the process, there are two different things that take place."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Number one is we essentially undergo the process of decarboxylation where this CO2 group is actually released."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And number two, we also phosphorylate this oxyloacetate into this molecule."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, when we phosphorylate the molecule that actually requires energy."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so if this reaction just took place with phosphorylation, that would mean an energy input would be required."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "But because we essentially couple the exothermic, the exergonic decarboxylation with the endergonic phosphorylation, this process basically the sum of those processes basically creates a favorable reaction."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so in the second step, we see that an enzyme called phosphoenol Pyruvate, carboxy kinase or Pep carboxy kinase, converts the oxalo acetate into Pep."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "Now, carboxy kinase once again means we're coupling the decarboxylation reaction with the phosphorylation reaction."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So in this step, the highly energonic phosphorylation of this molecule is coupled with the highly exergonic decarboxylation process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So in two steps, we basically are able to create a pathway that is favorable, energetically."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so we form that phosphorinopyruvate in this two step process."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So we have step number one and step number two."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And if we sum up these two individual steps, this is the net reaction that we're going to get noticed."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "The Co twos will essentially cancel because they're intermediate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And so will these oxalo acetates cancel because they appear on both sides, they're intermediate."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So these two molecules cancel."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "The CO2 will cancel."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "And we sum up these two results and this is what we get."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So, a Pyruvate molecule in the presence of one ATP and one GTP in a water molecule forms that pep the phosphorinopyruvate, the ADP, GDP, the two plus ions."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "So, and these are the two steps in Gluconeogenesis."}, {"title": "Gluconeogenesis Steps 1-2.txt", "text": "The first two steps in Glucanogenesis."}, {"title": "Structure of the Nephron.txt", "text": "The nephron is the basic unit of structure of the kidneys."}, {"title": "Structure of the Nephron.txt", "text": "And each one of our kidneys contains over 1 million of these individual nephrons."}, {"title": "Structure of the Nephron.txt", "text": "Now, the function of the nephron is to basically filter our blood plasma."}, {"title": "Structure of the Nephron.txt", "text": "It secretes the waste products into our urine, which is eventually excreted by our body."}, {"title": "Structure of the Nephron.txt", "text": "Now, in this lecture, we're going to focus focus on the structure of the nephron."}, {"title": "Structure of the Nephron.txt", "text": "So let's begin by taking a look at this diagram that describes what an individual nephron actually looks like."}, {"title": "Structure of the Nephron.txt", "text": "Now recall that our kidney is divided into two regions."}, {"title": "Structure of the Nephron.txt", "text": "The outer portion of the kidney is known as the renal cortex, while the inner portion of the kidney is known as the renal medulla."}, {"title": "Structure of the Nephron.txt", "text": "And this dashed line basically separates the cortex from the medulla region in our kidney."}, {"title": "Structure of the Nephron.txt", "text": "So we see that the nephron actually encompasses both the cortex and the medulla of our kidney is found in the cortex as well as in aramidoula."}, {"title": "Structure of the Nephron.txt", "text": "So let's begin with our initial point on the nephron, which is found in the cortex."}, {"title": "Structure of the Nephron.txt", "text": "Now recall that the renal artery brings the blood to our kidney."}, {"title": "Structure of the Nephron.txt", "text": "The renal artery divides and subdivides and eventually divides into very tiny blood vessels known as the African arterios."}, {"title": "Structure of the Nephron.txt", "text": "And these are the blood vessels that carry not only the oxygenated and the nutrient filled blood, but also the blood that contain the waste products that must be excreted."}, {"title": "Structure of the Nephron.txt", "text": "And it brings that blood to our nephron."}, {"title": "Structure of the Nephron.txt", "text": "So this is the apharynt arteriol shown here, and it connects with a network of capillaries known as araglomerilus."}, {"title": "Structure of the Nephron.txt", "text": "This is Arglomerilus, shown here."}, {"title": "Structure of the Nephron.txt", "text": "So the African arterio is the blood vessels that ultimately comes from the renal artery and it brings the oxygenated and the nutrient filled blood to our nephron."}, {"title": "Structure of the Nephron.txt", "text": "Now, it also contains the multitude of different waste products such as urea."}, {"title": "Structure of the Nephron.txt", "text": "It brings it to our nephron for excretion."}, {"title": "Structure of the Nephron.txt", "text": "So basically, inside this glomerylus, we have a very high hydrostatic pressure."}, {"title": "Structure of the Nephron.txt", "text": "And that pressure forces some of that blood to be filtered into a region known as the Bowman's capsule."}, {"title": "Structure of the Nephron.txt", "text": "So the Bowman's capsule is this cup shaped region here that connects with araglomerilus."}, {"title": "Structure of the Nephron.txt", "text": "The Bowman's capsule contains many tiny pores that allow the movement of certain types of molecules across our capillary system known as the glomerulus."}, {"title": "Structure of the Nephron.txt", "text": "Now, the glomerulus and the Bowman capsule together is known as the renal corpusol."}, {"title": "Structure of the Nephron.txt", "text": "And we see that along the renal corpusol we have the process of filtration taking place."}, {"title": "Structure of the Nephron.txt", "text": "So the glomerulus is a network of capillaries that receives the blood from the African arterial filtration initiates in this section here, a high hydrostatic pressure in the glomerulus as a result of that movement of blood through these small capillaries forces relatively small and positively charged particles such as sodium, potassium, amino acids, glucose and so forth across this region and into a section known as the Bowman's capsule."}, {"title": "Structure of the Nephron.txt", "text": "Now, relatively large molecules such as protein molecules such as albumin, as well as things like red blood cells, are too large to actually pass across the pores that are found within this section."}, {"title": "Structure of the Nephron.txt", "text": "And so larger molecules do not actually pass across and into the Bowman's capsule."}, {"title": "Structure of the Nephron.txt", "text": "Now, about 20% of the blood plasma that enters this region, it's filtered into the Bowman's capsule."}, {"title": "Structure of the Nephron.txt", "text": "The rest of it, about 80%, enters this blood vessel known as the Ethernet Arterio."}, {"title": "Structure of the Nephron.txt", "text": "Now, the ephemeraterial carries the oxygenated and nutrient filled blood into a second network of capillaries shown here known as the Vasorecta."}, {"title": "Structure of the Nephron.txt", "text": "Now, the oxygenated blood found in these capillaries, in these blood vessels, supplied the nutrients to the cells found within this section of the kidney."}, {"title": "Structure of the Nephron.txt", "text": "And this capillary system also acts to basically absorb and secrete some of the things found between this vessel here, this cubial, and this blood vessel here."}, {"title": "Structure of the Nephron.txt", "text": "Now, once the oxygenated blood, or once the oxygen is taken up by the cells, the deoxygenated blood is carried away by these venues and eventually into our circulatory system."}, {"title": "Structure of the Nephron.txt", "text": "So only about 20% of the blood is filtered into the Bowman's capsule from the glomerulus."}, {"title": "Structure of the Nephron.txt", "text": "The rest goes into the efair and arterio and then travel to the second network of capillaries known as the Vasa rectan."}, {"title": "Structure of the Nephron.txt", "text": "Now, because we have two sets of different capillaries, the glomerulus and the Vasa rectum, this is an example of a portal system."}, {"title": "Structure of the Nephron.txt", "text": "So the kidney contains a network of two different capillaries."}, {"title": "Structure of the Nephron.txt", "text": "Now, the Bowman's capsule is this cup shaped structure shown that encloses the glomerulus."}, {"title": "Structure of the Nephron.txt", "text": "The first capillary network system of the nephron."}, {"title": "Structure of the Nephron.txt", "text": "Hydrostatic pressure in the glomerulus forces some of that blood plasma that was carried by the afairy arterial to enter the Bowman's capsule."}, {"title": "Structure of the Nephron.txt", "text": "And this filtered blood that enters Araboman's capsule is known as the glomerulus filtrate, or simply Arifiltrate."}, {"title": "Structure of the Nephron.txt", "text": "So from now on, when we refer to the blood found inside this region, that is Arifiltra, but the blood found here is known as simply the blood plasma or our blood."}, {"title": "Structure of the Nephron.txt", "text": "Now, this portion of the nephron is known as the Proximal convoluted tubule."}, {"title": "Structure of the Nephron.txt", "text": "And as our blood plasma travels, as our filter travels across the proximal convoluted tubule, reabsorption as well as secretion begin to take place."}, {"title": "Structure of the Nephron.txt", "text": "So certain molecules such as, for example, amino acids, sodium ions, as well as other things such as our glucose molecules, are reabsorbed from the filtrate and back into our blood plasma."}, {"title": "Structure of the Nephron.txt", "text": "But other waste products such as, for example, hydrogen ions and creatine molecules, are secreted from the blood plasma and into the lumen of the proximal convolute."}, {"title": "Structure of the Nephron.txt", "text": "Now, notice that the Proximal convolute, the entire renal corpusal, is found inside the cortex portion of our kidney."}, {"title": "Structure of the Nephron.txt", "text": "Now, the filtrate eventually travels from the Proximal convolute tubule and into this Ushaped tubule known as the Loop of Henley."}, {"title": "Structure of the Nephron.txt", "text": "And the Loop of Henley can be subdivided into different sections."}, {"title": "Structure of the Nephron.txt", "text": "And each one of these sections serves its own purpose, as we'll see in the next several lectures."}, {"title": "Structure of the Nephron.txt", "text": "We have the descending loop of Henley that is basically permeable to water."}, {"title": "Structure of the Nephron.txt", "text": "So water exits the descending loop of Henley."}, {"title": "Structure of the Nephron.txt", "text": "And we have the thin ascending loop of Henley and the thick ascending loop of Henley that becomes impermeable to water."}, {"title": "Structure of the Nephron.txt", "text": "And the entire function of the loop of Henley is to basically increase the concentration of solution in our renal medulla."}, {"title": "Structure of the Nephron.txt", "text": "And that basically Increases the Osmotic pressure inside our medulla."}, {"title": "Structure of the Nephron.txt", "text": "Now the entire Loop of Henley is found in our medulla."}, {"title": "Structure of the Nephron.txt", "text": "Now, the filtrate eventually travels up into this section known as the distal convoluted tubule."}, {"title": "Structure of the Nephron.txt", "text": "And just like the proximal, the distal convoluted tubule is down entirely inside Our Renal Cortex, as shown in this diagram."}, {"title": "Structure of the Nephron.txt", "text": "Now, the distal convoluted tubule is a portion of the nephron that reabsorbs some of the sodium as well as our calcium, while at the same time secreting potassium as well as the hydrogen ions into our filtrate."}, {"title": "Structure of the Nephron.txt", "text": "Now, in the presence of certain hormones, such as the antiduretic hormone ADH, this becomes permeable to water, and it reabsorbs the water from that filtrate back into our blood plasma."}, {"title": "Structure of the Nephron.txt", "text": "Finally we have this section known as the Collecting duct."}, {"title": "Structure of the Nephron.txt", "text": "And the collecting duct is found in the medulla portion of our kidneys."}, {"title": "Structure of the Nephron.txt", "text": "Just like the vase erecta and our loop of Henley."}, {"title": "Structure of the Nephron.txt", "text": "Now the collecting duct is permeable to sodium."}, {"title": "Structure of the Nephron.txt", "text": "It absorbs some of that sodium back into our blood plasma."}, {"title": "Structure of the Nephron.txt", "text": "Now, normally, it is not very permeable to water."}, {"title": "Structure of the Nephron.txt", "text": "But in the presence of certain hormones, such as, once again, ADH, this becomes permeable to water."}, {"title": "Structure of the Nephron.txt", "text": "And it reabsorbs some of that water, concentrating our urine."}, {"title": "Structure of the Nephron.txt", "text": "This is basically done to preserve the amount of water found in our blood plasma."}, {"title": "Structure of the Nephron.txt", "text": "So these are the different structures found inside Our Nephron."}, {"title": "Structure of the Nephron.txt", "text": "In the next several Lectures, we're going to focus on the function of each one of These structures."}, {"title": "Structure of the Nephron.txt", "text": "Now, by the way, I also forgot to mention that we have a very important structure known as the Juxta Glomeryl Apparatus."}, {"title": "Structure of the Nephron.txt", "text": "And what this is, is a collection of three types of cells that are found in this section on top of the distal convolute tubule, next to the a fairing arterial."}, {"title": "Structure of the Nephron.txt", "text": "And what the purpose of these cells are, is to control and regulate the function of Our Nephron."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Inside our body and inside our cells, there are many different types of enzymecatalyze reactions that can be generalized by the following chemical equation."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So we have an enzyme that basically takes two different substrate molecules, A and B and transforms them into these products, C and D. And these types of enzyme catalyze reactions are known known as multiple substrate or bi substrate reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And we can categorize these bi substrate reactions into two types."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "We have sequential reactions and we have double displacement reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And in both of these reactions, the enzymes active side can basically accommodate both of these different types of substrate molecules A and B."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, let's begin by focusing on sequential reaction."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So what do we mean by sequential reaction?"}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Well, in a sequential reaction, the defining property of a sequential reaction is basically the presence of a ternary structure."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And a ternary structure is a structure in which the active side of the enzyme is filled with the two substrate molecules A and B."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So the defining property of sequential reactions is that all the substrates, the two substrates A and B, have to bind to the active site of the enzyme to form the ternary structure that consists of the enzyme and the two substrates before the catalysis process can actually take place."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And we can convert those reactants into the products."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, we can further subdivide sequential reactions into two types."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "We have ordered sequential reactions, and we have random sequential reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And let's begin by focusing on the ordered sequential reaction."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So in this ordered sequential reaction, the order at which the two substrate molecules the two reactants bind onto the active side, as well as the order at which the two products are released by the active side, actually matters."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And one common example that describes an order sequential reaction is a reaction that takes place in the process of glycolysis."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So remember, in Glycolysis, the ultimate goal is to basically produce pyruvate molecules and NADH molecules."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, in the process of anaerobic respiration, we basically take the pyruvate molecules and we reduce the pyruvate molecules into lactate by using NADH."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "The NADH acts as a coenzyme, and it basically is transformed into NAD plus."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And the enzyme that catalyzes this reaction is known as lactate dehydrogenase."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So how exactly is this reaction an ordered sequential reaction?"}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So to see what we mean by that, let's take a look at the following five diagrams."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So, in diagram A, we basically have the active side."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "This crevice is the active side of the lactate dehydrogenase."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And what must happen is this coenzyme, the NADH, will bind into the active side of that enzyme first before the pyruvate actually binds."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Only then, only when we bind the NADH into the active side, can the pyruvate actually move into the active side and bind into the active side."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And once the pyruvate moves in, we form this ternary structure in which we have the pyruvate and the NADH inside the active side."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Of that enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Once again, ternary simply means we have three molecules, the enzyme and the two substrate molecules."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, once we form this complex, only now can we actually transform the Pyruvate into lactate and the NADH into the NAD plus."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And once we form the two products, so lactate in this case is product C and NAD plus E is product D. Once we form these two products, only then can they be released from the active side of that enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And because this is an ordered sequential reaction, the order at which these two products are released also matters."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And in this particular reaction, we're always going to find that it's the lactate that leaves first, followed by that NAD plus molecule."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So in an order sequential reaction, to actually catalyze the transformation of the reactants into the products, we have to form the termary structure, this complex in which the active site contains those two substrates."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And we also have to basically bind these two reactants into the active site in a specific order."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And once we form the products, those two products must be released also at a specific order."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And this is in contrast to random sequential reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So now let's focus on random sequential reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Unlike in order sequential reactions, in random sequential reactions, the order at which the two reactants bind into the active side and the order at which the two products are released from the active side does not actually matter."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "It takes place completely at random."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, to demonstrate a random sequential reaction, let's discuss a specific reaction that is catalyzed by an enzyme known as a creatine kinase."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So creatine kinase is this enzyme that essentially transforms ATP molecules and creatine molecules into phosphoriaine and ATP molecules, it basically catalyzes the formation of a high energy molecule that is used by the muscle cells of our body."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So to demonstrate how this reaction takes place, let's take a look at the following four diagrams."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So this green structure is the active side of the creatine kinase."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And what happens is we have these two substrate molecules, the ATP is our A and the Creatine is our B."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And notice in this particular reaction, because we're dealing with a random sequential reaction, the order at which these two reactors, the two substrates, actually bind onto the active side does not matter."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "We can either have the ATP bind first, followed by the creatine, or we can have the creatine bind first followed by the ATP."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "But because this is a sequential reaction, just like in the order sequential reaction case, we have to actually form that ternary structure, that structure that contains the enzyme bound to the two substrate molecules, in this case ATP and creatine."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Only when we form this three molecule complex can we begin the process of catalyzation."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And only now can we transform the ATP into the ATP and the Creatine into the phosphorine."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So basically what the enzyme does is it catalyzes the transferring of the phosphate group from the ATP onto that Creatine molecule to create the high energy phosphor Creatine that can be used by the muscle cells as a high energy source."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, once we form these two products, now these two products can be released from the active side, but because we're dealing with a random sequential reaction, unlike in this case, in this case it doesn't matter which one of these products is released first."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "We can either have the ADP come out first, followed by the phosphor Creatine, or we can have the phosphorus Creatine released first followed by that ADP."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So either ATP or Creatine can insert the active site first."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Once both of those reactants the substrates into the active site, only then can we actually transform the two reactants into the two products."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And once we form the two products, the order at which the two products actually depart does not matter."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So this is the difference between ordered sequential reactions and random sequential reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And the underlying fact about these two reactions is that the two substrate molecules have to bind to the active side before that reaction actually takes place."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So we have to form this three molecule structure known as the ternary structure."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now let's move on to the double displacement reaction, also sometimes known as a ping pong reaction."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So what exactly is the major difference between the sequential reaction and the double displacement reaction?"}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Well, just like the sequential reaction, this is the equation that generalizes the double displacement reaction."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "But unlike in the sequential case in which these two molecules, A and B, have to bind into the active side together for that reaction to take place, in this particular case, in a double displacement reaction, what happens is first, one of these molecules, let's say A binds onto the active side of that enzyme and a group on A is transferred into that enzymes active side and that modifies that enzyme and it also transforms our reactant A into, let's say product C. And then product C is released."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And once product C is released, we now have that modified enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And only now can the second substrate B actually bind onto the active site of that modified enzyme to form an intermediate between the enzyme and that reactant B."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And now that group that was transferred into the active site of the enzyme by A is transferred onto this reactant B and that transforms that reactant B into product D and that basically ultimately releases that product D from the active site of the enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And now the enzyme, the original enzyme in its original form is released by that reaction."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So the major difference between the sequential reaction and the double displacement reaction is for the reaction to actually take place in a sequential reaction, both have to be bound onto the active side."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "But in this case, only one has to be bound for that reaction to actually take place."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And in fact, the two substrates bind and are catalyzed at different times inside the active side of the enzyme that follow these double displacement reactions."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So to see what we mean, let's take a look at the following general case."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So in these reactions, the first substrate binds and changes the enzyme to produce an enzyme substrate intermediate complex."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And this can be seen in the following diagram."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So let's suppose we have substrate A that binds onto the active side of the enzyme to produce this intermediate."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "What happens next is some type of group."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "For example, a phosphoryl group from the molecule A can be transferred onto the active side of that enzyme and that modifies that enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And that's why we have this asterisk the start symbol on top of this intermediate."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So in this intermediate, once we transfer the group onto the enzyme, we transform A into product C. And now the product C can be released from that complex."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And so now we have this modified complex E with the star on top."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "Now, next, the second substrate B goes and binds into the active side of that enzyme to form this intermediate."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "And now that group that was transferred by A into the active side of E is transferred onto that molecule B and that transforms the second substrate B into the product D. And finally, this intermediate in this intermediate D is released from that enzyme and that reforms our original enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So notice in this reaction, like in any enzyme catalyze reaction, even though the enzyme might be modified intermediately at the end, that enzyme is produced and exists in its original, unchanged form."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So the defining property of this reaction is that the first substrate is converted to the product and then released before the second substrate binds to the active side of the enzyme."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "In addition, we see that the enzyme is actually modified in its intermediate stages, but even though it's modified at the end, it is released unmodified unchanged."}, {"title": "Sequential and Ping Pong Reactions .txt", "text": "So these are the two types of reactions, sequential reactions and double displacement reactions that commonly take place inside our cells and which can be generalized by using the following equation in which we have these two reactants two substrate molecules and the enzyme catalyzes the transformation of these two substrates into these two products."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "In order to describe the way that hemoglobin binds oxygen in a cooperative fashion, we came up with two different models."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "One of these models became known as the concerted model, and the other model became known as a sequential model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, the first question you might be thinking is, why do we need two different models to describe a single phenomenon in nature?"}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Well, as it turns out, each of these models alone does not correctly describe some aspect of the way that oxygen binds onto hemoglobin in a cooperative fashion."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And where one model basically fails, the other model succeeds and vice versa."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And that's exactly why we have to combine these two models to correctly describe the mechanism by which hemoglobin binds oxygen cooperatively."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So let's begin with the concerted model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And this is a diagram that describes the concerted model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, the big point about the concerted model is hemoglobin can only exist in two states."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "It can either exist in the t state, the ten state, or it can exist in the r state, the relaxed state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And by binding oxygen onto that hemoglobin molecule, all we're doing according to this model is shifting the equilibrium between the two states."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And to see what we mean, let's take a look at the left side of this diagram."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So on the left side, right here, none of the heme groups on the hemoglobin actually contain oxygen."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And so what that means is the error going this way will be much longer than the error going this way."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And what that means is, in this particular situation, when we have deoxy hemoglobin, when none of the heme groups contain an oxygen, the structure will be predominantly and almost exclusively in the t state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, what happens when we bind a single oxygen onto that hen group?"}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So, for example, when we fill this oxygen, what happens is the error going this way becomes ever so slightly longer."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And what that means is the equilibrium shifts slightly towards this side, towards the r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "But in this particular case, our structure will still be predominantly in the t state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, if we add one more oxygen so that two of these heaton groups are filled, what we see happen is the arrow becomes longer going this way."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And now these two arrows are equal in size."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And what that means is both of these states will exist in the same proportion."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So 50 50."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, if we add one more oxygen, what we see happen is the equilibrium now shifts towards the arc state, and this arrow becomes longer than this arrow."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And so now what we see happen is this is the structure, the state of the hemoglobin that will predominate."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And finally, if we add one more oxygen, what happens is we shift our equilibrium almost entirely towards the r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And now this state will exist exclusively as our r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "This hemoglobin molecule will exist exclusively in that r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now let's take a look at the following diagram."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So, what this diagram basically describes is the oxygen binding curve for the T state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And it is described by this shallow curve here."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And this R state is described by this steep curve right over here."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And to actually obtain that Sigmoidal curve that we actually see for the hemoglobin oxygen binding, we have to combine these two curves to basically get this Sigmoidal curve."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So the Sigmoidal curve for hemoglobin is formed from the combination of the T state curve, this curve here, the shallow one, and the steep one, the R state curve."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, the final thing I'd like to discuss about the Concerted model is what's the limitation of the Concerted model?"}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "What is the problem?"}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Well, the problem is the following."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Let's take a look at the following diagram."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "What this diagram basically describes is when our oxygen binds onto one of the heme groups of hemoglobin, this is the state that will predominate."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, according to the Concerted model, this structure of this polypeptide that contains the bound oxygen does not change its conformation."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "It initially is a square, and it still is a square."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, we know experimentally in nature, as soon as that oxygen binds onto that hemegroom of that polypeptide, that changes the confirmation of that polypeptide."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And this simply is not what we see according to this diagram."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "In fact, what we also see in nature is when one of the heme groups binds that oxygen, the adjacent heme groups are also affected."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "They increase their affinity for oxygen because they change their shape as well."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And this is something that we don't see according to this model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So the problem with this model is if we examine this particular diagram here, even though we have one oxygen bound, and even though this is the state that will predominate, this structure here should technically have a slightly different shape, a slightly different conformation, which is not something that we see based on this model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And so, to compensate for that limitation, we came up with a second model that we call the sequential model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So let's take a look at what the sequential model actually tells us."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So, in the Sequential model, what we see happen is as soon as one of these heme groups, for example, this one binds the oxygen, that heme group completely changes its shape, and that changes the shape of the entire polypeptide that contains the heme group."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And that's why, when going from this structure to this structure, this entire square becomes a circle, because it changes its conformation."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And not only that, but the nearby polypeptide chains will also change their confirmation slightly."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And that tells us that their affinity for oxygen, which will also increase, which is what we see happening in nature."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So if we add one more oxygen, this will basically change our shape."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And this nearby structure will also change its polypeptide chain."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "If we add one more oxygen, we get this."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And finally, if this one is filled, we get the r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So the major difference between the concerted model and the sequential model is in the concerted model, we only have either the t state or the r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "But in this particular case, we have the T state, we have the r state, and we also have these three intermediate, intermediate one, intermediate two, and intermediate three."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So in the sequential model, the binding of the oxygen stimulates a conformational change in that polypeptide, and that in turn, induces a conformational change in this nearby and this nearby polypeptide chain."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And that tells us that because the conformation changes, that will increase the affinity of that heme group for the oxygen molecule."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Now, what's the problem with this sequential model?"}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Well, the problem with the sequential model is the following."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Based on this model, the only time we have the r state is when all these four different hein groups are completely filled with oxygen."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So according to our sequential model, this is the only time that our structure will exist in the art state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And we know that is not true."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "We know in nature."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "What we see experimentally is when three of those heme groups are filled with oxygen, the structure of the hemoglobin will exist predominantly in the r state, which is exactly what we see according to our concerted model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Based on the concerted model, when three of these heme groups are filled with oxygen, our r state will predominate."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So this arrow will be longer than this arrow, which is basically the correct description of what actually happens in nature."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "But according to this diagram here, if three of these groups are filled with oxygen, our molecule still exists in some intermediate state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "It will not exist in the r state."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So that is the limitation of the sequential model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And notice that this is compensated by the concerted model."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "And that's exactly why we have to use both of these models to basically correctly describe the mechanism by which hemoglobin actually binds oxygen."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So, in conclusion, neither model can describe the cooperative nature of hemoglobin alone."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "Instead, we have to combine these two models to actually correctly describe the mechanism by which hemoglobin binds oxygen."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "That is, the sequential model succeeds where the concerted model fails, and vice versa."}, {"title": "Concerted and Sequential Model for Hemoglobin.txt", "text": "So these two models can be used to basically describe the way that hemoglobin binds oxygen in a cooperative fashion."}, {"title": "Protein Kinase A .txt", "text": "Protein kinases are these enzymes found inside our body which are responsible for catalyzing phosphorylation reactions?"}, {"title": "Protein Kinase A .txt", "text": "And as we discussed previously, phosphorylation is an example of covalent modification."}, {"title": "Protein Kinase A .txt", "text": "And this is a mechanism that our cells use to basically regulate and control the activity of enzymes and the functionality of proteins."}, {"title": "Protein Kinase A .txt", "text": "Now, we can categorize protein kinases into two groups."}, {"title": "Protein Kinase A .txt", "text": "On one side we have a group called dedicated protein kinases and on the other side we have a group known as multifunctional protein kinases."}, {"title": "Protein Kinase A .txt", "text": "Now, what exactly is the difference between these two groups?"}, {"title": "Protein Kinase A .txt", "text": "Well, dedicated protein kinases basically phosphorylate either a single substrate molecule or a set of closely related substrate molecules."}, {"title": "Protein Kinase A .txt", "text": "On the other hand, multifunctional protein kinases have the capability of actually catalyzing the phosphorylation of many different types of enzymes and many different types of protein molecules."}, {"title": "Protein Kinase A .txt", "text": "Now, the first question I'd like to address is what exactly determines the specific nature of protein kinases?"}, {"title": "Protein Kinase A .txt", "text": "What exactly determines the ability of a protein kinase to actually bind and catalyze a specific location on some enzyme on some substrate molecule?"}, {"title": "Protein Kinase A .txt", "text": "Well, for a catalyzation reaction to actually take place, logically speaking, that substrate molecule has to be able to fit into the active side of that protein kinase."}, {"title": "Protein Kinase A .txt", "text": "And not only that, the substrate molecule has to have a high enough affinity so that it remains long enough in the active side for that phosphorylation reaction to actually take place in the first place."}, {"title": "Protein Kinase A .txt", "text": "And so what that means is to have a high affinity between the substrate molecule and the protein kinase."}, {"title": "Protein Kinase A .txt", "text": "The sequence of amino acids around the side, around the amino acid, which is about to be phosphorylated, has to be correct because if the sequence of amino acids on the substrate molecule is not correct, that active side will not be able to bind onto that substrate molecule."}, {"title": "Protein Kinase A .txt", "text": "So we conclude that the specificity of protein kinases depends on the amino acid sequence that directly surrounds that target residue that is about to be phosphorylated."}, {"title": "Protein Kinase A .txt", "text": "Now, to actually see what that means, let's discuss a specific example of a specific protein kinase that exists inside our body."}, {"title": "Protein Kinase A .txt", "text": "And this is protein kinase A or simply PKA."}, {"title": "Protein Kinase A .txt", "text": "So what exactly is the importance?"}, {"title": "Protein Kinase A .txt", "text": "What is the functionality of protein kinase a?"}, {"title": "Protein Kinase A .txt", "text": "When does our body actually use protein kinase A?"}, {"title": "Protein Kinase A .txt", "text": "Well, in dangerous or exciting or stressful situations, recall that it's the sympathetic division of our nervous system that kicks in and initiates the flight or fight response."}, {"title": "Protein Kinase A .txt", "text": "And what happens is the sympathetic nervous system basically stimulates the adrenaline dula to release a hormone we call epinephrine."}, {"title": "Protein Kinase A .txt", "text": "And as epinephrine travels through our cardiovascular system, it basically stimulates our cells to transform ATP molecules into another molecule known as cyclic adenosine monophosphate or simply camp."}, {"title": "Protein Kinase A .txt", "text": "Now, what canp does is it's an allosteric regulator of protein kinase a and as we'll see in just a moment, it binds onto the inactive version of protein kinase A and it activates protein kinase A and protein kinase A."}, {"title": "Protein Kinase A .txt", "text": "Once it's activated, it becomes responsible for activating many different types of enzymes via the process of phosphorylation."}, {"title": "Protein Kinase A .txt", "text": "And it phosphorylates one of two types of residues either the serine residue or the Thurianine residue."}, {"title": "Protein Kinase A .txt", "text": "Now, the question is on any given substrate enzyme molecule we have many different types of serene and three an amino acids."}, {"title": "Protein Kinase A .txt", "text": "So let's suppose we have a sequence of 200 amino acids and let's say 20 of them are actually serene or three Anion amino acids."}, {"title": "Protein Kinase A .txt", "text": "The question is how does protein kinase A actually know which Serine or three an amino acid to actually bind to?"}, {"title": "Protein Kinase A .txt", "text": "What determines the specificity of that protein kinase A?"}, {"title": "Protein Kinase A .txt", "text": "So it's exactly what we said before."}, {"title": "Protein Kinase A .txt", "text": "It's the sequence of amino acids that is found around the side that residue that is about to be phosphorylated that determines the ability of that protein kinase Apka to actually bind onto that substrate molecule."}, {"title": "Protein Kinase A .txt", "text": "Now, what is the sequence?"}, {"title": "Protein Kinase A .txt", "text": "Well, the sequence known as the consensus sequence is shown on the board."}, {"title": "Protein Kinase A .txt", "text": "So basically, if the substrate molecule contains arginine, arginine, x, serene, three or three ending and y, where X is basically any small amino acid for instance glycine and y is basically any large hydrophobic amino acid."}, {"title": "Protein Kinase A .txt", "text": "This is basically where that protein kinase will buy to and it will phosphorylate this target side, the serine or thyrionine."}, {"title": "Protein Kinase A .txt", "text": "Now, of course, we can also change the arginine to lysine and that will also allow the protein kinase to bind onto this sequence."}, {"title": "Protein Kinase A .txt", "text": "But if these are changed to Lysine, the Affidavit will not be as good as in the case where these two are arginine molecule arginine amino acids."}, {"title": "Protein Kinase A .txt", "text": "So we see that the consensus sequence that is recognized by protein kinase A is shown to the left."}, {"title": "Protein Kinase A .txt", "text": "And this means that enzymes, substrate molecules that contain serene or threeamine surrounded by this specific sequence will be recognized by the protein kinase A and the protein kinase A will bind onto this section and will phosphorylate this target side."}, {"title": "Protein Kinase A .txt", "text": "And by phosphorylate it can basically change the activity and the functionality of that target substrate molecule."}, {"title": "Protein Kinase A .txt", "text": "Now, earlier we said that it's a cyclic ANP molecule that actually binds and activates protein kinase A."}, {"title": "Protein Kinase A .txt", "text": "Now, the first question is what exactly is the quarterly structure of protein kinase A when it is not bound to the cyclic Amp?"}, {"title": "Protein Kinase A .txt", "text": "What is the inactive quarter structure of protein kinase A?"}, {"title": "Protein Kinase A .txt", "text": "So this is basically shown on the board."}, {"title": "Protein Kinase A .txt", "text": "So in its inactive form, PKA consists of two types of subunits."}, {"title": "Protein Kinase A .txt", "text": "So just like aspartate transcarbomolase atcase consists of catalytic and regulatory subunits, our PKA also consists of catalytic and regulatory subunits."}, {"title": "Protein Kinase A .txt", "text": "Now, the catalytic subunit contains the active side while the regulatory subunit contains that allosteric side that binds onto the cyclic Amp."}, {"title": "Protein Kinase A .txt", "text": "So in the absence of the allosteric effect of the cyclic adenosine monophosate molecule the coronary structure consists of two catalytic sites and these are shown in green as well as two regulatory sites."}, {"title": "Protein Kinase A .txt", "text": "And these are shown in light brown."}, {"title": "Protein Kinase A .txt", "text": "So this is basically one of these regulatory subunits and this is the other regulatory subunit."}, {"title": "Protein Kinase A .txt", "text": "And so we have two catalytic and two regulatory subunits."}, {"title": "Protein Kinase A .txt", "text": "And so we represent the inactive form of PKA with the following format."}, {"title": "Protein Kinase A .txt", "text": "So R two, C two complex basically means we have two regulatory subunits one, two and two catalytic subunits one and two."}, {"title": "Protein Kinase A .txt", "text": "So as we mentioned previously, under stressful situations the Adrian medulla is stimulated and it releases the epinephrine hormone."}, {"title": "Protein Kinase A .txt", "text": "And the epinephrine hormone basically stimulates the production of cyclic adenosine monophosphate camp."}, {"title": "Protein Kinase A .txt", "text": "And it's the Tamp that is the allosteric regulator of PKA."}, {"title": "Protein Kinase A .txt", "text": "The question is how exactly does it regulate the activity and how does it activate this enzyme?"}, {"title": "Protein Kinase A .txt", "text": "So what happens is, if we examine a single one of these regulatory chains each regulatory chain contains one, two allosteric sites."}, {"title": "Protein Kinase A .txt", "text": "So we have one, two, and two here."}, {"title": "Protein Kinase A .txt", "text": "So we have 1234 of these regulatory sites that the cyclic adenosine monophosphate can actually bind to."}, {"title": "Protein Kinase A .txt", "text": "Now, once that CMP binds onto all of these regulatory sites so we have four CMP molecules binding to four of these sites."}, {"title": "Protein Kinase A .txt", "text": "What happens is that creates a conformational change that allows the R two complex."}, {"title": "Protein Kinase A .txt", "text": "So this entire brown section to actually dissociate from these two green sections."}, {"title": "Protein Kinase A .txt", "text": "And so what happens is these active sites which are occupied in the inactive form basically become unoccupied."}, {"title": "Protein Kinase A .txt", "text": "They become free."}, {"title": "Protein Kinase A .txt", "text": "And once the active sites are free these catalytic subunits and we have two of them can basically go on and catalyze all these different types of target enzymes via the process of phosphorylation."}, {"title": "Protein Kinase A .txt", "text": "So once again, cyclic adenosine monophosate binds to allosteric sites found on the regulatory chains."}, {"title": "Protein Kinase A .txt", "text": "This stimulates the dissociation of the regulatory subunes from the catalytic subunits."}, {"title": "Protein Kinase A .txt", "text": "And once the catalytic subunits basically dissociate those active sites become free."}, {"title": "Protein Kinase A .txt", "text": "And now the substrate molecules can go on and buy onto those active sites."}, {"title": "Protein Kinase A .txt", "text": "And by the way, this is the active site here and this is the active site here for this second green subunit."}, {"title": "Protein Kinase A .txt", "text": "And in this inactive form, both of these active sites are basically occupied by regions of the regulatory subunits."}, {"title": "Protein Kinase A .txt", "text": "And the sequence of amino acids found on the regulatory subunit that binds onto the active side is known as the pseudosubstrate sequence."}, {"title": "Protein Kinase A .txt", "text": "So in this R two C two complex it's the pseudosubstrate sequence of the R subunits that binds onto the active side and occupies that active side."}, {"title": "Protein Kinase A .txt", "text": "And because that active side is occupied, it cannot bind to substrate molecules and so it is not active."}, {"title": "Protein Kinase A .txt", "text": "But if our concentration of cyclic Amp inside our body begins to increase, what happens is those CMP molecules will begin to bind onto these allosteric sites."}, {"title": "Protein Kinase A .txt", "text": "And once bound to all four allosteric sites, that creates conformational changes that causes these pseudosubra sequences to dissociate from the active sites and that produces this R two complex."}, {"title": "Protein Kinase A .txt", "text": "So notice that these two regulatory R subunits do not actually dissociate."}, {"title": "Protein Kinase A .txt", "text": "They remain bound together."}, {"title": "Protein Kinase A .txt", "text": "But these two green catalytic subunits basically dissociate."}, {"title": "Protein Kinase A .txt", "text": "And so now they're activated."}, {"title": "Protein Kinase A .txt", "text": "Because these active sites are free, they can go on and bind to all sorts of different types of substrate enzyme molecules."}, {"title": "Protein Kinase A .txt", "text": "And once the substrate molecule binds onto the active side of that catalytic subunit, what happens is this catalytic subunit, which actually consists of these two lobes."}, {"title": "Protein Kinase A .txt", "text": "So we have lobe number one, lobe number two."}, {"title": "Protein Kinase A .txt", "text": "Once that active side becomes bound onto the substrate molecule, those two lobes essentially close off."}, {"title": "Protein Kinase A .txt", "text": "And as they close off, they basically create a perfect conformation between the substrate molecule and this catalytic submit, and that allows the phosphorylation reaction to actually take place."}, {"title": "Structure and Function of Penicillin .txt", "text": "In our discussion on irreversible inhibitors, we briefly mentioned penicillin."}, {"title": "Structure and Function of Penicillin .txt", "text": "And we said that penicillin is an example of a suicide inhibitor."}, {"title": "Structure and Function of Penicillin .txt", "text": "It's basically a molecule that binds until an enzyme found bacterial cells and inhibits the activity of that enzyme."}, {"title": "Structure and Function of Penicillin .txt", "text": "It prevents the enzyme from actually forming the peptidoglycan cell wall found around the membranes of bacterial cells."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now recall from biology that peptaglycan cell walls basically give that bacterial cell the ability to resist a high osmotic pressure."}, {"title": "Structure and Function of Penicillin .txt", "text": "And it's because of that peptaglycan cell wall that once the bacterial cells enter our body that they don't actually immediately lice."}, {"title": "Structure and Function of Penicillin .txt", "text": "So once again, that peptiglycan cell wall that we're going to discuss in just a moment basically allows that cell to resist a high osmotic pressure."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, what we want to focus on in this lecture is the structure of penicillin and the actual mechanism by which penicillin acts on that bacterial enzyme."}, {"title": "Structure and Function of Penicillin .txt", "text": "So let's begin with the structure of penicillin."}, {"title": "Structure and Function of Penicillin .txt", "text": "So penicillin consists of three important components."}, {"title": "Structure and Function of Penicillin .txt", "text": "Component number one is the five membered ring we call thiozolidine."}, {"title": "Structure and Function of Penicillin .txt", "text": "So thiozolidine consists of this five member ring here."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, we also have a fourmember ring here that's called the Betalactum."}, {"title": "Structure and Function of Penicillin .txt", "text": "And it's the instability and the high energy of the beta lactamb that actually gives that penicillin a reactive nature and allows it to actually react in the first place."}, {"title": "Structure and Function of Penicillin .txt", "text": "In fact, it's this red carbon in the betalactam ring that allows it to react as we'll see towards the end of the lecture."}, {"title": "Structure and Function of Penicillin .txt", "text": "And finally, the final component of penicillin is this r group."}, {"title": "Structure and Function of Penicillin .txt", "text": "So it's the r group, it's the variable r group that basically gives that penicillin its unique structure."}, {"title": "Structure and Function of Penicillin .txt", "text": "So penicillin is actually a group of many related molecules that all contain the thiozolidine ring, the Betalactum ring, as well as that unique variable r group."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, how exactly did we discover the fact that penicillin actually acts indirectly on the peptidoglycan cell wall?"}, {"title": "Structure and Function of Penicillin .txt", "text": "Well, in the late 1950s, scientists carried out the following experiment."}, {"title": "Structure and Function of Penicillin .txt", "text": "They basically took bacterial cells, they placed them into a hypertonic environment, and then they added penicillin."}, {"title": "Structure and Function of Penicillin .txt", "text": "And what they found was, even though we had penicillin, those cells did not actually lice."}, {"title": "Structure and Function of Penicillin .txt", "text": "They did not actually die."}, {"title": "Structure and Function of Penicillin .txt", "text": "So if we took bacterial cells and grew them in the presence of penicillin in a hypertonic solution, those cells did not actually die off."}, {"title": "Structure and Function of Penicillin .txt", "text": "So what do we mean by hypertonic environment?"}, {"title": "Structure and Function of Penicillin .txt", "text": "So on the outside of the cell, we have a high concentration of solutes."}, {"title": "Structure and Function of Penicillin .txt", "text": "On the inside, we have a low concentration."}, {"title": "Structure and Function of Penicillin .txt", "text": "So what that means is water is going to flow from the inside to the outside."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so on the inside the cell, we're going to have a low osmotic pressure."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, when the scientists took those cells and placed them into a medium that we would typically find inside our body, what they found was water basically rushed into the cell that enlarged the cell, and the cell eventually lysed."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, they knew that if the cell contained peptidoglycan cell wall, it would not lice."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so what that means is that penicillin molecules somehow acted on that peptigly and cell wall."}, {"title": "Structure and Function of Penicillin .txt", "text": "So again, this experiment basically led to the conclusion that penicillin prevents the formation of the peptidoglycan cell wall because it's the peptidoglycan cell wall that gives the cell stability structure and give the ability to actually withstand or resist a high estimate pressure that can exist once the cells are placed into the environment that is found inside our body."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now the next question is how exactly does penicillin act on these peptidoglycan cell walls?"}, {"title": "Structure and Function of Penicillin .txt", "text": "Well before we answer that question, let's discuss the structure of peptiglycan and then let's discuss how the bacterial cells actually build this peptiglycan cell wall."}, {"title": "Structure and Function of Penicillin .txt", "text": "So if we examine this specific strain of bacterial cells, this is the type of peptaglycan structure that we're going to see."}, {"title": "Structure and Function of Penicillin .txt", "text": "So basically peptaglycan means we have a peptide component and we have a glycogen component."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so these purple molecules are sugar molecules and they basically line up to form a linear polysaccharide chain."}, {"title": "Structure and Function of Penicillin .txt", "text": "And we have one chain, we have two chain, a third chain, a fourth chain and so forth."}, {"title": "Structure and Function of Penicillin .txt", "text": "And some of these sugar components basically are attached to short peptides."}, {"title": "Structure and Function of Penicillin .txt", "text": "So we have this 1234 amino acid tetrapeptide and we also have these 12345 so pentapeptides."}, {"title": "Structure and Function of Penicillin .txt", "text": "And we see that these tetrapeptides are connected to the tetrapeptides of the adjacent linear polysaccharide chain by these pentapeptides."}, {"title": "Structure and Function of Penicillin .txt", "text": "And these linkages are known as cross linkages and they're the green linkages shown in this diagram."}, {"title": "Structure and Function of Penicillin .txt", "text": "So the peptaglyc and cell wall consists of long sugar chains that are connected by cross linkages between the short peptides."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this blue peptide here is connected to this blue peptide of the Jason polysaccharide chain via this five peptide."}, {"title": "Structure and Function of Penicillin .txt", "text": "So the pentapeptide short protein component."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now the question is what exactly is the reaction by which the bacterial cells actually build these cross linkages in the first place?"}, {"title": "Structure and Function of Penicillin .txt", "text": "Well this is the reaction that is described on the board."}, {"title": "Structure and Function of Penicillin .txt", "text": "So we have the pentapeptide, so let's say the pentaglycine."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is glycine one, glycine two, glycine three, glycine four, and the terminal glycine that we basically drew out."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now it's the nitrogen of this pentaglyne."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is the pentaglycine shown here."}, {"title": "Structure and Function of Penicillin .txt", "text": "It's this nitrogen that's going to form a bond with this carbon here."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is an adjacent short peptide and the terminal amino acid E is the D alanine."}, {"title": "Structure and Function of Penicillin .txt", "text": "And the next one in line is also the D alanine."}, {"title": "Structure and Function of Penicillin .txt", "text": "And what this nitrogen does is it bonds with this carbon and once it forms a bond, it basically kicks off that terminal dalanine."}, {"title": "Structure and Function of Penicillin .txt", "text": "And that's exactly what forms this green cross linkage that we basically show here."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this connects to this carbon that kicks off this terminal dalanine and that forms the green cross linkage between this terminal glycine on the pentaglycine molecule and this dalanine."}, {"title": "Structure and Function of Penicillin .txt", "text": "The second carbon, the second D alanine, the carbon of that second D alanine."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is the reaction that takes place, that forms the cross linkages inside bacterial cells."}, {"title": "Structure and Function of Penicillin .txt", "text": "And the enzyme that catalyzes speeds of this particular reaction inside bacterial cells is known as glycopeptide transpeptidase."}, {"title": "Structure and Function of Penicillin .txt", "text": "So in bacterial cells, this cross linking is catalyzed by an enzyme we call glycopeptide transpeptidase."}, {"title": "Structure and Function of Penicillin .txt", "text": "And if we examine the active site of this enzyme, the catalytic amino acid, the catalytic residue that catalyzes this reaction is serine."}, {"title": "Structure and Function of Penicillin .txt", "text": "So let's focus on how this actually takes place inside the active side of this transpeptidase enzyme."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is a portion of the active side and this is that catalytic residue, that Serene molecule."}, {"title": "Structure and Function of Penicillin .txt", "text": "So what happens is we take this blue molecule that we have here that is basically attached to, let's say, the linear polysaccharide chain here."}, {"title": "Structure and Function of Penicillin .txt", "text": "And what happens is this Serene molecule, the oxygen, basically binds onto this carbon and that kicks off this first dalanine to basically form the astle intermediate as well as this individual D. Alanine that was removed."}, {"title": "Structure and Function of Penicillin .txt", "text": "And now what happened is we basically prepare this section here."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this molecule here to form that cross linkage between this carbon here and this nitrogen here."}, {"title": "Structure and Function of Penicillin .txt", "text": "So in the next step, this pensaclyne would basically move into the active side and the enzyme would catalyze the formation of that cross linkage between this nitrogen here and this carbon here."}, {"title": "Structure and Function of Penicillin .txt", "text": "So this is how that catalyzation process actually takes place normally in the absence of penicillin."}, {"title": "Structure and Function of Penicillin .txt", "text": "Now, what happens when we add penicillin?"}, {"title": "Structure and Function of Penicillin .txt", "text": "Well, as we discussed in our discussion on Irreversible inhibitors, we said that penicillin is an example of a suicide inhibitor."}, {"title": "Structure and Function of Penicillin .txt", "text": "And what that basically means is what penicillin does is it moves into the active side of this enzyme, the glycopeptide transpeptidase, and it tricks the active side, the enzyme, it tricks it into thinking that the penicillin is actually a substrate."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so this enzyme is going to treat the penicillin as if it was a substrate."}, {"title": "Structure and Function of Penicillin .txt", "text": "It's going to begin the catalyzation process."}, {"title": "Structure and Function of Penicillin .txt", "text": "But as soon as it begins the catalyzation process, what happens is because of the reactive nature of the penicillin."}, {"title": "Structure and Function of Penicillin .txt", "text": "So remember, from organic chemistry, whenever we have a structure, a ring that consists of four atoms, so four member ring that creates a lot of steric hindrance and that increases the energy of that ring, and it makes it very reactive."}, {"title": "Structure and Function of Penicillin .txt", "text": "In fact, that's precisely why this carbon will be very reactive."}, {"title": "Structure and Function of Penicillin .txt", "text": "And what will happen is when penicillin actually enters the active side of that glycopeptic glycopeptide transpeptidase, this Serene will react, the oxygen will react with the carbon, and that will break this bond and that will relieve some of that stereotyinderrance that existed as a result of this high reactivity of this fourmember ring."}, {"title": "Structure and Function of Penicillin .txt", "text": "So the betalactam."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so once this bond is broken, those two electrons in that bond will grab an H atom and will basically form this intermediate structure."}, {"title": "Structure and Function of Penicillin .txt", "text": "And as soon as we form this intermediate structure, that serine residue is no longer able to actually further catalyze that reaction because we now block and inhibit that activity of that serine residue."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so this is A suicide inhibitor because it essentially tricks that active site into thinking it's a substrate."}, {"title": "Structure and Function of Penicillin .txt", "text": "It begins the catalysis process, but somewhere down the line, it forms an intermediate that inhibits the activity of that transpeptidase."}, {"title": "Structure and Function of Penicillin .txt", "text": "And once it binds, because it binds covalently and tightly, it will not let go."}, {"title": "Structure and Function of Penicillin .txt", "text": "And so now that will inactivate the active side of the glycopeptide transpeptidase, and those cross linkages Will not be able to form, and that will basically break apart the structure of the peptoglycan cell wall, and the bacterial cell Will now lack that peptoglycan cell wall."}, {"title": "Structure and Function of Penicillin .txt", "text": "And this is precisely how penicillin Actually acts."}, {"title": "Structure and Function of Penicillin .txt", "text": "So, penicillin acts as a suicide inhibitor."}, {"title": "Structure and Function of Penicillin .txt", "text": "It basically acts on that enzyme that is responsible for forming the cross linkages that hold the sugar components inside the peptidoglycan cell wall of bacterial cells."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Amino acids are the building blocks of proteins."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And inside our body, we have 20 different types of amino acids."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, what exactly distinguishes one amino acid from another one?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, it's the side chain group that not only differentiates the amino acid from other amino acids, but it's also that side chain group that gives the amino acid its properties and its chemical reactivity."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So in this lecture, we're going to focus on 15 of these amino acids."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And the next lecture, we're going to focus on the remaining five."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we're going to categorize these amino acids based on their hydrophobic and hydrophilic properties based on their side chain groups."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So let's begin by focusing on those amino acids that contain non polar, non reactive hydrophobic side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we have eight of these."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "We have Alanine Vallene."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Leucine Isolucine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "We have methionine, we have Phenylalanine tryptophan, and we have tyrosine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So let's begin by focusing on these four right over here."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So notice that what these four have in common is each one of these side chain groups, which are shown in the colored region, are basically hydrocarbon molecules."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And hydrocarbon molecules contain carbonate atoms, and they're non polar."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that makes them hydrophobic and non reactive."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, as we go from left to right, the hydrocarbon group increases inside."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we essentially add two carbon atoms here."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "We add one more carbon atom compared to this one here."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And in this particular case, we take this methyl group and we place it onto this carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So these two amino acids are more hydrophobic than Valene, and valine is, in turn, more hydrophobic than aline, because the more carbon H atoms we have, the more hydrophobicity found within that particular amino acid."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So that's exactly why valine is more electronegative than Alanine and so forth."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, what distinguishes Leucine from isolucine?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, it's the fact that this carbon here contains this methyl group, and that makes this carbon a chiral carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So this is chiral, and that means it contains a mirror image."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, inside the proteins of our body, this is the only nantomer of isolucine that we actually find when this H atom is coming out of the board, as shown in the following diagram."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, let's move on to methionine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So what exactly is the difference between these here and methionine?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, unlike these, the methionine side chain contains a sulfur atom."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, what's the electronegativity of sulfur as compared to the carbon?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So the electronegativity of carbon is 2.55, and the electronegativity of sulfur is 2.58."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And those values and those values are essentially the same."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that's exactly why these bonds are non polar."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so this side chain of methionine is also non polar, it's non reactive, and it's hydrophobic."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, what about these remaining three?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "What exactly do Phenylalanine, Tyrosine, and tryptophan have in common?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, let's take a look at their side chain groups."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Notice that their side chain groups all contain ring structures."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "In this case, we have a benzene."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "In this case, we have a benzene that contains a hydroxyl group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And in this case, we have a group known as an indul group that essentially consists of these two fused rings."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, all of these are hydrophobic."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "All of them are nonpolar, but some of them are less hydrophobic than others."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So which ones?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, this one here contains a benzene ring and nothing else."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And a benzene ring contains carbon and H atoms."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so it makes this very hydrophobic and very nonreactive."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, if we look at tyrosine and tryptophan tyrosine contains the relatively electronegative oxygen and the relatively electronegative nitrogen."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that's exactly why these are slightly less hydrophobic and slightly more reactive than the phenyl Alameine because of the presence of these relatively electronegative atoms."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "But because we have these relatively large ring structures, these are still hydrophobic, they're still relatively non reactive as compared to these other amino acids, as we'll see in just a moment."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So these are our eight hydrophobic side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And what that means is because we have these non polar side chain groups, these non polar side chain groups tend to pack together and aggregate."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so in the protein, these are the side chains that will point into that protein structure because they will not want to interact with the polar water molecules that are usually found in solution that are usually found in or outside that protein."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So remember, inside the cells of our body and inside our body in general, our solutions are made predominantly of polar water molecules."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And these proteins are usually found inside the polar molecules."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so as a result, all these amino acids that contain these hydrophobic side chain groups are going to display the hydrophobic effect and they're going to basically create this pack structure that will be found inside that protein as compared to outside."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now let's move on to the uncharged hydrophilic polar side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So these are the amino acids that essentially contain electric dipole."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "nomins, they contain a certain polar nature."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And because of their polar nature, they will be found on the outside of that protein structure interacting with the polar water solvent molecules."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we have Celine, we have three Anine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "We have Asparagine glutamine, and we also have cysteine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now notice that Serene basically contains this hydroxyl group that is attached to our carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now remember, our oxygen is much more electronegative than our H atom."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So this will gain a partial negative charge."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "This H atom will have a partial positive charge."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so we have a dipole moment that essentially points from this positive end to this negative end."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so this will be a relatively polar side chain, but it is still uncharged."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that's why we label this as uncharged polar side chain."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So this polar side chain will basically be able to interact with the water molecules found in our solvent and that will basically determine or help determine the structure of our protein."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, we also have threeanine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And the major difference between thyrene and Serene is that this carbon contains, instead of one of the age groups, it contains a methyl group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so, just like isolucine, this Threatening contains a second CHYL carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And just like isolucine, this is the only nantomer of Threatening that is found in our proteins found inside our body."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, notice that Serene is almost like Alanine, except one of the H atoms bound to this carbon is replaced with the hydroxyl group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And thyanine is almost like Vallene, except one of these methyl groups is replaced with a hydroxyl group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "But because we have this electronegative atom, this is partially negative, this becomes partially positive."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so we have this dipole moment, and that makes this a relatively polar side chain and so a relatively polar amino acid."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, let's now look at Asparagine and glutamine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So these are basically the same, or these are very, very similar."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "The only difference is, in this particular case, we have one additional ch two group compared to this case."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So on the terminal end of the side chain, we have this carboxy amide group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we have the carbon attached to our oxygen, and the carbon is also attached to our nitrogen."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so what we see is this is partially negative."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "This is partially negative, this is partially positive."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So the carbon is partially positive because it's less electronegative than the oxygen."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And the nitrogen is more electronegative than H and more electronegative than the carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so the nitrogen will also have a partial negative charge."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so we have this polarity that exists on these side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so these are also polar, and they will be much more reactive than any of these hydrophobic side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So generally, our polar side chains are more reactive than the hydrophobic side chains."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Finally, we have cysteine."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, cysteine is not only polar, but it's also very special because is responsible for forming these very important bonds known as disulfide bonds or disulfide bridges."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And these are covalent bonds that exist within protein structures."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And they play an important role in actually determining the three dimensional structure of our protein."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So cysteine is structurally similar to Serene, except it has a thyl group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So Serene is polar and reactive in forming disulfide bridges."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So if we compare these two, this is almost the same as this."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "The only difference is we replace the oxygen in this case with a sulfur in this case."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "But cysteine is actually sometimes known as a special side chain or a special amino acid because of its importance in forming those disulfide bridges."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So, as we said earlier, Asparagin and glutamine contain polar carboxyamide groups."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now let's focus on two special cases that contain special side chain groups."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So we have the simplest type of amino acid that is actually a chiral."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that's because the side chain group is nothing more than an H added."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And so this is an acyl carbon, it will not have an enantomer because of these two identical H atoms found attached to our carbon."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, because of this very small H atom, because it doesn't have that ch three group like, let's say this one has, this one is not really labeled as a hydrophobic side chain, but because of its small size, it can easily interact with other hydrophobic side chains and it can also interact with hydrophilic side groups."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So Glycine is the smallest amino acid."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "It is a chiral."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And because it's minimally invasive, because of that tiny H atom, it can fit into either hydrophobic or hydrophilic environments."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And finally, let's take a look at another special case known as proline."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, proline is technically a hydrophobic side chain, but because of its special structure of that side chain, we label it as a special side chain."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So what's so special about the proline?"}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Well, if we examine our side chain, this is the only side chain that connects not only to the alpha carbon, but also to that nitrogen."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And we form this five membered ring."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, because of this five member ring, this molecule is structurally restrictive."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And that means this actually helps play a very, very important role in determining the structures of special types of proteins, as we'll see in future lectures."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So all the proline is hydrophobic, and technically, it should belong to the hydrophobic side chain group."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "It is special in that it contains a side group that is bound to the alpha carbon and the nitrogen."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So this is bound to this carbon here, as well as this nitrogen here."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "Now, the five member ring of Proline makes it structurally restrictive, allowing it to greatly influence the structure of special types of proteins."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "So these are 15 of the 20 different types of proteins found inside of our body."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "The other five proteins we're going to focus in the next lecture."}, {"title": "Nonpolar and Uncharged Polar Amino Acids .txt", "text": "And these other five proteins are also polar, but they actually contain full charges on their side chains, as we'll see in the next lecture."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "The oxygen hemoglobin dissociation curve is a graph that describes the ability of hemoglobin to actually bind to oxygen at specific partial pressure values."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, it turns out that the ability of hemoglobin to bind to oxygen is affected by several important factors."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And one of these factors is the PH of our blood."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So we when the PH of our blood changes, the hemoglobin's ability to bind to oxygen also changes."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this ultimately changes the oxygen hemoglobin dissociation curve."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this effect, as we'll see in just a moment, is known as the Bohr effect, which was named after the scientist who essentially described it, Christian Bohr."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, let's begin by discussing what actually affects the PH of our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Well, recall that inside our cells of our tissues, the cells undergo many type of metabolic processes, for example, cellular respiration."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And when cells undergo these processes, the major byproduct waste byproduct that is produced is carbon dioxide."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, carbon dioxide is, of course, non polar."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And that's because carbon dioxide consists of two polar bonds that point in opposite directions."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And so because the dipole moments cancel out, the carbon dioxide has a net dipole moment of zero."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And so that's why it is a non polar molecule."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, because carbon dioxide is non polar and because our blood plasma consists mostly of water, a polar molecule, that implies that carbon dioxide will not actually dissolve in our blood plasma very easily."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So how exactly do we solve this problem?"}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Well, the way that our body solves this problem is by transforming the carbon dioxide into a slightly different form to make it more soluble in our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So when the cells of our tissue are exercising, they're producing a bunch of CO2 gas molecules."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And those CO2 gas molecules dissolve or diffuse across the cell membrane and enter the extracellular matrix."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And then the CO2 is moved across the capillary walls."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "It diffuses across the capillary wall, our walls, and enters the red blood cells found inside the blood plasma of our capillaries."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And once inside the red blood cells, inside the red blood cells, we have a special type of catalytic enzyme known as our carbonic anhydrase."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And what carbonic anhydrase does is it combines a single water molecule with a single carbon dioxide gas molecule to produce H, two Co three in the aqueous state."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is our carbonic acid."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, because carbonic acid is a weak acid, it will dissociate into these two ions, into an H plus ion and into bicarbonate."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And because these two ions have a charge, they will be soluble in our water, in our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And so we see that inside our body, we actually store carbon dioxide in the form of this equation because these are essentially soluble in our water while carbon dioxide is not."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So once again, exercising tissue has a high rate of metabolism and therefore produces a large number of carbon dioxide."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Waste byproducts these carbon dioxide, because they are not soluble in our blood plasma, are ultimately moved into the red blood cells where we use carbonic anhydrates to transform the carbon dioxide into H plus ions and bicarbonate ions, which are soluble in our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, recall from basic chemistry that what determines the PH of anything of our blood plasma, in this case, is the concentration of H plus ions of hydrogen ions inside our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the more carbon dioxide molecules we have inside the blood plasma, the more of these H plus ions we will have inside our blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So when the tissue is exercising, it produces more CO2 molecules, which ultimately ends up with produces more H plus ions."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And because we have a higher concentration of H plus ions, that will make our blood plasma more acidic, thereby lowering the PH of the blood plasma."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this effect is known as the Bore Effect."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So it basically affects our hemoglobin's ability to bind to oxygen."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "The next question is how exactly does the presence of carbon dioxide and H plus ions affect hemoglobin's ability to bind to oxygen?"}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Well, basically, hemoglobin has a special site we call the allosteric site."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And these H plus ions and CO2 ions can actually bind to the allosteric site found on hemoglobin."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And once they bind, they create a conformational change, a change in the three dimensional structure of hemoglobin."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And what this does is it decreases the ability of hemoglobin to actually bind to oxygen."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And by decreasing our hemoglobin's ability to bind to oxygen, we ultimately shift the entire oxygen hemoglobin dissociation curve to the right, as seen in the following diagram."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is known as the Bore Effect."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So by increasing the concentration of carbon dioxide, we ultimately increase the concentration of H plus ions, and that makes our blood more acidic."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So we decrease our PH, and this causes a decrease in our hemoglobin's ability to bind to oxygen, thereby shifting the entire curve to the right side with respect to the original curve shown in blue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the blue curve is the oxygen hemoglobin dissociation curve when the PH is 7.4."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So when our tissue is not exercising, but if the tissue begins to exercise, that means we produce more H plus ions, and that shifts the entire curve to the right."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the red curve, which describes the PH of, let's say, 7.2, so slightly lower, is shifted to the right side with respect to our blue curve."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is what we call the Bore Effect."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So let's take a look at the following curve at the following diagram and describe exactly how our hemoglobin's ability to oxygen actually decreases."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So, let's begin with number one."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So recall that on average, the partial pressure of oxygen inside our tissues is around 40 mercury."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the Y axis is the percent saturation of hemoglobin."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "It's the percent of hemoglobin that is fully saturated with our oxygen."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So we range from 0% to 100%."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, the X axis is the partial pressure of oxygen in our surrounding tissue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is given in millimeters of mercury."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the range begins at zero to about 100 mercury."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So recall that at 100 mercury we are in our lungs and at 40 we are in our tissue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So notice what these two curves actually tell us."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "At about our 40 mercury partial pressure, which is the partial pressure of oxygen inside our tissues, the value for how much of hemoglobin is actually saturated differs for these two PH."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "At a PH of 7.4 it's around 70% saturation and at a PH of 7.2 it's around 60% saturation of hemoglobin."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So there is this difference of about 10%."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And what that tells us is when our cells of the tissue are exercising and therefore producing more H plus ions and so we have a lower PH."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "What the lower PH means is our hemoglobin will be more likely to actually unload that oxygen into those exercising cells inside our tissue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So the average partial pressure of oxygen in our tissues is around 40 mercury."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, at lower PH values, when the cells of our tissue are exercising, we shift the curve to the right and this means we make the hemoglobin much more likely to actually dissociate and unload that oxygen into the exercising tissue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So this in turn will deliver more oxygen to those tissues because those cells of the exercise tissue will need more oxygen to produce more ATP in the process of cellular respiration."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So even from this curve we see that at a PH of 7.4, on the blue curve we see that at a 40 mmhd partial pressure we have a 70% saturation of hemoglobin."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "But at the same exact partial pressure inside our exercising muscles, inside our exercising tissue, at a PH of 7.2 we have a lower percent saturation, means more of the hemoglobin have unloaded that oxygen."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So about 40% of the hemoglobin actually exists in its dissociated form because all that oxygen has been unloaded."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is important because we want to ensure that the cells in our body that have a higher rate of metabolism receive that oxygen that is needed to produce ATP for the cell to actually function correctly and efficiently."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Now, from this graph, we also see another important point."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "Notice that at a partial pressure of about 100 mercury, which is the partial pressure inside the alveoli of our lungs, our percent saturation of hemoglobin for both curves at both PH values is approximately the same."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "And this is important point because even if our cells of the body are exercising, we don't want that to actually affect hemoglobin's affinity for oxygen inside our lungs because we want to basically make sure that the hemoglobin inside the lungs continually accept those oxygen molecules and brings those oxygen molecules to the exercising tissue."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So notice that a change in PH does not really affect the affinity of hemoglobin at high partial pressure value."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So physiologically, this is beneficial because we do not want hemoglobin to bind less oxygen in our lungs."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "We see that both curves, the blue curve and the red curve, show that at a partial pressure of 100 mercury, the percent of hemoglobin that is fully saturated with oxygen is about 98%."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So even though the PH decreases when our cells are exercising and producing more carbon dioxide, our hemoglobin binds the same exact percentage of oxygen inside our lungs."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "But once the hemoglobin actually brings that oxygen into the exercising tissue, this is where we see the bore effect really take its place."}, {"title": "Hemoglobin and Bohr Effect.txt", "text": "So we basically see a difference in about 10% of unloading in our tissue when we have a partial pressure of about 40 mercury."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Detail about this reaction."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "This reaction describes a bimolecular second order chemical reaction and that's because this is the rate of the reaction V Naught, KCAD divided by Km, that's the reaction rate constant."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And these are our two substrates and they each have an exponent of one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So the order of this is one and the order of this is one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so the total order of the reaction is two."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So this is a typical bimolecular second order chemical reaction that takes place inside our body under enzyme catalyzed conditions."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now, according to this equation, we see that the enzyme catalyze reactions, when they take place inside our cells, the rate of the enzyme, the rate at which the enzyme actually catalyzes that reaction depends on three different things."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Number one, it depends on the concentration of that substrate."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Number two, it depends on the concentration of that enzyme."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And number three, it depends on the rate constant, KCAD divided by Km."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now, A makes sense because if we have more substrate, more substrate is going to bind on the active side and more that substrate will basically be transformed into the product as a result."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Likewise, if we increase the concentration of the enzyme we have more active sites and so more likelihood that the substrate will be transformed into the product."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And finally, what about KCAD divided by Km?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "What exactly is the meaning behind KCAD divided by Km, the rate constant of this reaction?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Well, it turns out that this is what we actually use to measure the catalytic efficiency of enzymes."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So how enzymes or how efficient are enzymes in catalyzing a certain type of substrate?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So let's remember what Kcat means and let's remember what Km means because if we remember what these two quantities mean individually, we can then basically decipher what the meaning is behind this ratio."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So let's begin with Kcat."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So Kcat, as we discussed in the previous lecture, is known as the turnover number."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And Kcat basically describes how many of the substrate molecules are transformed into the product molecules per unit time, per single active site, per single enzyme."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So KCAD, the turnover number, tells us how many substrate molecules are transformed into product molecules by single active side per unit time, usually per second."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "What about Km?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Well, Km has two meanings."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "One meaning of the Km basically tells us it's the substrate concentration that gives us rate of VMAX divided by two."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "But the other meaning of Km, basically Km describes how attracted that enzyme the active side is to that substrate."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So if we have a very high Km value, what that means is that active side is not very likely to bind onto that substrate."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "But if the Km value is low, that means there will be a very good binding that takes place between the substrate and that particular active side."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So if we take a look at the following ratio a very high Km value basically means this ratio will be small."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so the velocity, the rate of that reaction will be small."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And that makes sense, because if Km is small, that means the substrate is not going to bind very well to that active side."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And if it can't bind well, it will not spend long enough time to basically be catalyzed into that product."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "On the other hand, if Km is low, this ratio is high."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so v not is high."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so if Km is low, that means the affinity for that substrate and active site is high."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so that substrate will be able to spend enough time to catalyze it into that product."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And likewise, if Kcat is high, that means this ratio is high and this velocity will be high."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So we see that ultimately, the ratio of Kcat divided by Km, which is the rate constant in this reaction here, basically can be used as a measure of how well that enzyme actually catalyzes that particular substrate."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now, the final question I'd like to answer is what exactly is the limit of this quantity of this ratio?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "How high can this ratio actually be for this particular reaction here?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So can it be infinitely large, or is there some finite value that this ratio can actually take?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Well, to answer this question, let's actually define what KCAD divided by Km means in equation form."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So remember from this discussion that Km is equal to k minus one plus KCAD divided by k one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So we have KCAD divided by Km."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And now if we replace Km with this ratio and rearrange a little bit, this is what we get."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So k one divided by k minus one plus Kcat, and the whole thing is multiplied by Kcat."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now let's bring the Kcat to this side and take out the k one, so that we get the following rearranged version of this same ratio."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So KCAD divided by Km is equal to KCAD divided by k one plus Kcat, and the whole thing is multiplied by k one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now notice what this ratio is."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "The ratio is some number given by Kcat divided by that same number, kcat plus some positive number."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so if we have a number divided by some positive number plus Kcat plus itself, this will basically be a ratio that is less than one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Now, what is the maximum value of this ratio?"}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "Well, the maximum number of this ratio is basically reached when this value approaches zero."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So when this quantity approaches zero, that basically means we have Kcat divided by Kcat, and that gives us one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So the maximum, the highest possible value of this ratio in parentheses is one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And when this is equal to one, then we see that this ratio is simply equal to k one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And so the highest possible value that can be achieved by KCAD divided by Km is equal to k one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And mathematically, this is how we express that."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So if we take the limit as k minus one, this approaches zero."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So if we plug in a zero here, this divided by this gives us one, and the limit is simply equal to K one."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "And what that means is that physical limit that determines how high this ratio can get is basically the rate constant for this reaction, where K one is simply the rate constant that describes the formation of that enzyme substrate complex."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So the limiting fact that that basically limits how high this ratio can get is how quickly we actually form that enzyme substrate complex in the first place."}, {"title": "Catalytic Efficiency of Enzymes Part II .txt", "text": "So ultimately, if K minus one is very small, and what that means is this reaction doesn't take place very quickly, if that is true, then this entire ratio here, the rate constant for this reaction, will essentially approach K one, which is the rate constant of the formation of the enzyme substrate complex from the enzyme and its substrate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Aside from having active sites, enzymes also contain an additional site or sites known as allosteric sites."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And those enzymes that contain these allosteric sites are known as allosteric enzymes."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, why would an enzyme want to have these allosteric sites?"}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Well, basically these allosteric sites is a method by which we can control or regulate them."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Activity of our enzymes."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And certain types of molecules or ions known as effector ions can bind to the allosteric sites of enzymes and either activate the activity of enzymes or deactivate inhibit the activity of our enzymes."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And this method of regulation of enzymes is known as allosteric regulation."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, the method by which allosteric regulation actually takes place is usually the feedback mechanism method."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, to see what this mechanism actually involves, let's take a look at the following hypothetical series of enzymatic reaction."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So let's suppose we want to convert A into D. And the way that we basically convert A into D is by following these series of steps."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So enzyme one takes our molecule A and transforms it into intermediate B."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Then enzyme two takes B, transforms it into intermediate C and enzyme three then takes C and transforms it into our product D. Now, in this process of feedback mechanism, we basically have one of these intermediates or products moves back and binds to the allosteric sites of one of these enzymes."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And that either inhibits or activates the activity of that enzyme."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And depending on whether we have inhibition or activation, we have these two types of feedback mechanism processes."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "We have negative feedback inhibition and positive feedback which is basically our activating process."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So let's begin with the negative feedback inhibition."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So if the effector molecule binds to the allosteric site of the enzyme and inhibits its activity, this effector molecule is known as the inhibitor."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And one example of this negative feedback inhibition process is in glycolysis."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So in our cells, in our body, our glucose basically is broken down into pyruvate molecules."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And this concept, this process is known as glycolysis."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, glycolysis involves many different enzymes and one important enzyme in glycolysis is Hexokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Hexokinase basically catalyzes the transformation of glucose into glucose six phosphate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, as the concentration of glucose six phosphate builds up, that glucose six phosphate basically binds to an allostericide on that enzyme, our hexokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And that deactivates it inhibits the activity of that enzyme."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So let's suppose A is glucose and enzyme one is our hexokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So as hexokinase converts A into B, then binds onto enzyme A and that inactivates our enzyme."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And the reason we want to regulate this is to basically make sure that our intermediate B, the glucose six phosphate, doesn't build up in concentration."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So this is a method by which we basically make sure that we don't have too much of our intermediate in this reaction."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So this is another diagram of this particular negative feedback inhibition mechanism."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So we have our enzyme E, which is basically the hexokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And these blue molecules are the glucose molecules."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So our hexokinase transforms these glucose molecules shown in blue to these green molecules which are the glucose six phosphate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Eventually, when we build up the concentration of these green molecules, one of these green molecules act as an inhibitor."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "It binds to an allosteric site on the enzyme that is different than this active side and that deactivates or inhibits the activity of our enzyme."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So this is an example of negative feedback inhibition."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now what about the positive feedback?"}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So in some instances the effector molecule that binds to the allosteric site of the enzymes doesn't actually deactivate it, but it activates the activity of that enzyme and these effective molecules are known as activated and this process is known as positive feedback."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, in the same way that glycolysis has negative feedback inhibition, it also has positive feedback."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And to see our example, let's take a look at the following paragraph."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So basically another important enzyme in our glycolysis process is known as phosphorptokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "What phosphorptokinase does is it basically transforms a molecule known as fructose six phosphate into fructose one six biphosphate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So let's take a look at the following diagram and see what's taking place."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So we have this enzyme which is our phosphate fructokinase."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And these blue molecules are the fructose six phosphate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now when the concentration of fructose six phosphate is very high, what happens is fructose six phosphate transforms into the purple molecule known as fructose two six biphosphate and fructose two six by phosphate the purple molecule binds to the allosteric site of this enzyme, the phosphorptokinase and that activates the activity of that enzyme."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So now the phosphor fructosekinase can take the glucose six phosphate shown in blue and it can transform that molecule into the final product in this particular reaction known as our fructose one six by phosphate."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So we see that in this process when the intermediate goes back and binds to our enzyme, it actually activates that enzyme and this phenomenon is known as positive feedback."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now one other type of regulation that I'd like to discuss that also deals with allosteric sites is known as enzyme Cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So basically certain enzymes can also display this phenomenon known as Cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And before we define what this actually is, let's take a look at an example at a biological enzyme that displays this concept of Cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So this enzyme is hemoglobin."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So hemoglobin is a protein that consists of four subunits and each one of these subunits contains a heme group that is capable of binding a single diatomic oxygen molecule so that a hemoglobin can bind a total of four individual diatomic oxygen molecules."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now when our hemoglobin binds one of the oxygen onto one of the subunits by binding that first oxygen molecule, that increases the affinity for oxygen for the other three different subunits."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So basically by binding one of the oxygen to only one of the subunits, that increases definitive of the other subunits for oxygen."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And this cooperative behavior is known as positive cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So, hemoglobin, for example, contains four individual subunits that can each bind an oxygen molecule."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "When the first oxygen molecule binds to one of the hemoglobin subunits, the affinity of the other three subunits to oxygen increases greatly."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And this behavior of our enzyme is known as positive cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, hemoglobin not only displays positive cooperativity, it also displays something called negative cooperativity, which is basically the opposite of positive."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So a molecule known as two three biphosphoglycerate, or simply two three BPG can bind to hemoglobin at a specific allosteric site at low oxygen concentrations."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And by binding to our hemoglobin, what the two three BPG essentially does is it decreases definitive to our oxygen molecules by basically changing the three dimensional shape of hemoglobin."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Now, why in a world when our two three BPG want to actually lower the activity of hemoglobin for oxygen?"}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "Well, at low concentrations of oxygen, we basically want to make sure that all the oxygen ends up in our tissues of the body."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So that means we do not want our hemoglobin to actually bind that oxygen very strongly."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And that's exactly why, at low concentrations of oxygen, that two, three BPG binds to the allosteric side of hemoglobin."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "And that basically makes sure that it doesn't take that oxygen and it gives that oxygen off to with the tissues of our body."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So this cooperative behavior is known as negative cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So we have positive and negative cooperativity."}, {"title": "Allosteric Regulation of Enzymes .txt", "text": "So these are basically the methods by which we can use allosteric sites on enzymes to regulate and control the activity of our enzymes."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "In the previous lecture, we define a quantity used in biochemistry known as the sedimentation coefficient."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And we define this mathematically."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we define it by using an equation, the following equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, the sedimentation coefficient of a particle inside a test tube that is rotating with some angular velocity is equal to m, the mass of that particle multiplied by one minus V bar multiplied by Rho, where V bar is the partial specific volume."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "It's the reciprocal of the density of that particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And row is the density of that medium, the fluid in which that particle is moving inside our test tube."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And we divide the product by F, the frictional coefficient of that particle with respect to the fluid in which that particle is in."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, the question that we want to ask ourselves in this lecture is where exactly does this equation actually come from?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we want to derive this equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, in biochemistry, this equation is used to describe or tell us the rate at which our object or particle sentiments inside our test tube as it rotates in a centrifuge."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's begin by imagining our picture."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So what is taking place within our test tube as it rotates with some angular velocity?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, let's suppose this is our test tube."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "The blue particle is some particle given by mass M. And this entire structure, the entire test tube, is rotating in the following direction with a given angular velocity of Omega."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, the distance from that particle to the axis of rotation is given by R. So this is the radius of the circle that is circumscribed by this rotating particle shown in blue."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, before we begin our derivation, we want to ask ourselves what are all the forces that are acting on that blue particle as it is rotating inside our test tube?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have three forces acting on the particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, let's suppose this is the x axis."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Going this way is the positive direction, and going that way is the negative direction."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have two negative forces and one positive force."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "The positive force is the centrifugal force, and that causes our object to move in this direction."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, let's suppose that the other direction is the negative direction, and we have two forces pointing in that negative direction."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "We have the force that is created by that fluid that basically pushes on that particle, and that is the bone force that is FB."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And we also have the frictional force that is due to the electrostatic repulsion between the charges found on the fluid particles and this particle that we are examining and that also opposes motion points in the opposite direction."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So these two forces oppose motion, and that's why they point in the opposite direction of motion, because our particle is moving in this direction as our test tube rotates."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So the first question is, or the first step is, in our derivation, what equation do we want to use?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Well, we want to use the equation of motion in classical physics, and that is the second law of motion."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we know that the sum of all the forces acting on that particle along the x axis is equal to the mass of that particle multiplied by its acceleration."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, let's suppose that the velocity of that object, that particle, is constant."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And what that means is if the velocity is constant, then the acceleration is essentially equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And so that implies that the thumb of the forces acting on that object along the x axis is equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, with that in mind, let's actually see what the left side of this equation is."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's take a look at all the forces acting on the object."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this is the Positive Force and these are the two Negative Forces."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's use red for that positive force."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have this force here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "It's positive minus."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And these are the two negative forces."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we're going to put them both in parentheses and set that equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this implies that that is true."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have our force of Buoyancy and then we have the frictional force."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have the Buoyancy force, the Frictional force."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "We put a positive here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Because this when we open up our parentheses, the negative will make these negative."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So that's why we put the positive inside."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have our single positive force and we add the two negative and we add the two negative forces and then we subtract the two values."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this is step number one."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, step number two is to actually figure out what these three forces are."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Well recall from classical physics that we can represent the centrifugal force as simply."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So our centrifugal force is equal to so the red force, F subscript C is equal to the mass of that object, the particle, the blue particle, which is assumed to be m multiplied by its acceleration."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "In this particular case, because we're undergoing angular motion, our acceleration is omega squared multiplied by R. Now, what is FB?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "What is the Boin Force?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Well, once again, from classical physics, we know that the boine force is equal to not the mass of that particle, but the mass of the fluid that is displaced by that particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So it's the mass of the fluid that is displaced by that particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we're going to designate that as M. This where this is displaced and it's multiplied by the acceleration, which is once again omega squared multiplied by R. Now, what is the force?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Frictional."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Well, the Force frictional is simply equal to the coefficient multiplied by the velocity of that object."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have the frictional force is equal to the coefficient of friction multiplied by the velocity of that object."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So these three forces are given by the following three equations."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And now in step two, we basically want to replace all these forces with the right side of these equations."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this becomes we have m omega squared r minus in parentheses."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "We have misplaced multiplied by omega squared r plus this quantity here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So the coefficient of friction multiplied by V, and the sum is equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, the question is what exactly is the mass displaced?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "How else can we represent the displaced mass of that fluid that is displaced by that particle?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Well, from fluid dynamics, we know that the mass displaced is equal to."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So the mass displaced or the mass of the fluid that is displaced by that object is equal to the product of the mass of that object multiplied by the ratio of the density of the fluid to the density of that object."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's call it a particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, let's, let's represent the bar, because that is used in this equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "The bar is equal to one divided by the density of the particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And if this is how we want to represent the density of the particle, then we can basically rewrite the following equation in the following way."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So the mass, this is equal to the mass of that object multiplied by the top."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this stays here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So multiplied by row."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And let's just leave row as row and not row fluid."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So row basically means row fluid."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And then, because we're rewriting one divided by the dense of the particle as v bar, we simply multiply by the V bar."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this is equal to this here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, if we go back to this equation, we can rewrite the MDIS in the following form."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's make that step three."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So in step three, we have mass multiplied by omega squared r minus."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's keep that in parentheses."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Actually, you know what, let's open up the parentheses."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we open up our parentheses."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this becomes negative and this becomes negative."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And we also want to replace MDIS with the following representation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, we have the mass multiplied by the density of the fluid multiplied by V bar, which is simply one over the density of the particle multiplied by omega squared multiplied by R minus FV."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And the minus comes because we open up those parentheses and we set that equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this is a bit crooked."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So it's M omega squared R. Okay."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So the next step is to basically collect the terms that appear on this term and this term."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, we have M and m, we have our omega squared, and we have the R. So this can be rewritten in the following method."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we have m omega squared r multiplied by one minus v bar multiplied by rho minus FV is equal to zero."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So, once again, if we multiply this out, we get back this equation here, and that's why these are essentially equivalent."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, in the next step, we want to bring this term f multiplied by v to the right side."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And so we get m multiplied by omega squared multiplied by R multiplied by one minus v bar, the density of the fluid is equal to is equal to F multiplied by v. Now, if we keep the velocity on this side and bring the F to this side, we basically get the following results."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So m omega squared r multiplied by one minus v bar rho is equal to v, and this is divided by no, not rho, but F, which is a frictional coefficient of that particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Okay?"}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And the last step is, well, our goal is to make this equation look like the right side of this equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So notice that the right side of this equation has m one V bar Rho and F, but it doesn't have the omega and R. So we want to bring the omega squared multiplied by R to the other side."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Of the equation, and we basically obtain so we have v divided by omega squared r is equal to m one minus v bar rho divided by f. And so this right side of this equation is the same as the right side of this equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we see, because they're equal, we see that s, the sedimentation coefficient is equal to v, the velocity of that object divided by Omega squared, where Omega is the angular velocity multiplied by r, where r is this distance right over here."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So we see that s is equal to v divided by Omega squared r, which is equal to m one minus v bar row divided by F. And this is basically our derivation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, sometimes we express this in a slightly different way."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So if we multiply this ratio top and bottom by some number, we're not going to change the value of it."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's multiply top and bottom by Avogadro's number."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So remember, Avogadro's number is given by uppercase NA, and this gives us Avogadro's number of molecules."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So basically 6.2 times ten to 23 molecules, this is Avogadro's number."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So if you multiply top and bottom by Avogadjo's number, we won't change our result."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "And we get an A multiplied by m multiplied by one minus v bar, the density divided by an a multiplied by F. So this doesn't change because we can simply cross this out and we get back our result."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Now, notice that Avogadro's number multiplied by the mass of that object gives us the molar mass of that object."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "Remember, the molar mass of some particle is basically the mass of Avogadro's number of particles."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So if we take this particle and we collect Avogadro's number, we get a mass value that is equal to NA multiplied by m. So this is another way of basically describing that same equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So let's rewrite this with uppercase m, where uppercase m is our molar mass and the bottom stays as NA multiplied by F. So this is another equation that gives us that same sedimentation coefficient given by s. So these two equations here are equal to one another."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "The only difference is in this case, we don't have Avagado's number."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "We have the lowercase m, where m is the mass of that single particle."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "But in this case, uppercase is the mass of Avogadro number of particles."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So 6.02 times ten to the 23."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "So this is how you basically derive this equation."}, {"title": "Derivation of Sedimentation Coefficient Equation.txt", "text": "It comes from basic physics."}, {"title": "Primary Structure of Proteins (II).txt", "text": "Those rotations will actually lead to stereo kinderance."}, {"title": "Primary Structure of Proteins (II).txt", "text": "So not all of these angles can actually rotate in specific ways."}, {"title": "Primary Structure of Proteins (II).txt", "text": "Not all of these bonds can rotate in specific ways."}, {"title": "Primary Structure of Proteins (II).txt", "text": "And that's actually a good thing."}, {"title": "Primary Structure of Proteins (II).txt", "text": "Because what that means is if there are a limited number of ways that our rotations of these two Torsion angles can actually take place, that means the polymer, the linear polymer amino acids, has to go through less number of these rotations to eventually end up with that final three dimensional structure of our protein."}, {"title": "Primary Structure of Proteins (II).txt", "text": "So what we conclude is that every protein contains a primary structure, which is basically a specific sequence of nucleotides, specific sequence of amino acids that is unique to that specific protein."}, {"title": "Primary Structure of Proteins (II).txt", "text": "And it's the sequence of amino acids that ultimately determines what the three dimensional structure of that protein is."}, {"title": "Implantation of Blastocyst .txt", "text": "Following fertilization which takes place inside the fallopian tube of the female reproductive system that zygodat is formed, begins to move along the fallopian tube and towards the cavity of the uterus."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, as it moves along the blastocyst, it begins to divide in a process known as cleavage."}, {"title": "Implantation of Blastocyst .txt", "text": "And eventually it forms a structure known as a morala."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, a morala consists of of these individual, tiny identical cells known as blastomirs."}, {"title": "Implantation of Blastocyst .txt", "text": "And eventually that morala will make its way to the cavity of the uterus."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, inside the uterus, we have the lining of the uterus known as the endometrium."}, {"title": "Implantation of Blastocyst .txt", "text": "And the endometrium contains these special glands that secrete a nutritious fluid."}, {"title": "Implantation of Blastocyst .txt", "text": "And that fluid, which is found inside the cavity of the uterus is used to basically initiate the process known as blastulation."}, {"title": "Implantation of Blastocyst .txt", "text": "So once the moral is inside that cavity of the uterus, it undergoes blastulation to form a blastocyst."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, recall that a blastocyst consists of three important structures."}, {"title": "Implantation of Blastocyst .txt", "text": "We have the blastoceal, which is the hollow cavity inside the blastocyst that contains a nutritious fluid that is needed by that developing embryo to actually develop further."}, {"title": "Implantation of Blastocyst .txt", "text": "We also have a structure known as the trophy blast and the inner cell mass."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, the cells part of the trophy blast eventually give rise to a structure known as the corian, as well as the placenta, while the cells of the inner cell mass eventually give rise to the actual organism itself."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, following the formation of the blastocyst, the blastocyst finds itself inside the fluid found inside the cavity of the uterus."}, {"title": "Implantation of Blastocyst .txt", "text": "What exactly happens next?"}, {"title": "Implantation of Blastocyst .txt", "text": "Well, for the blastocyst to develop further, it must actually implant itself onto the endometrium, the lining of the uterus."}, {"title": "Implantation of Blastocyst .txt", "text": "And in this lecture, we're going to focus on this process of implantation and we're going to discuss how it takes place and what happens after implantation actually takes place."}, {"title": "Implantation of Blastocyst .txt", "text": "So let's begin by taking a look at the following diagram."}, {"title": "Implantation of Blastocyst .txt", "text": "Diagram A."}, {"title": "Implantation of Blastocyst .txt", "text": "In diagram A, we basically describe the lining of the uterus we call the endometrium."}, {"title": "Implantation of Blastocyst .txt", "text": "So we have connective tissue and we have vascular tissue."}, {"title": "Implantation of Blastocyst .txt", "text": "We have these cells shown in light pink as well as the red cells that make up the epithelium of that endometrium."}, {"title": "Implantation of Blastocyst .txt", "text": "And we also have these blood vessels that carry the oxygen and the nutrients and so forth along this endometrium."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, this is the actual blastocyst."}, {"title": "Implantation of Blastocyst .txt", "text": "So we have the dark purple cells is the trophy blast."}, {"title": "Implantation of Blastocyst .txt", "text": "And these light purple cells are the inner cell mass."}, {"title": "Implantation of Blastocyst .txt", "text": "And this inside and this inner cavity is the blastoceal."}, {"title": "Implantation of Blastocyst .txt", "text": "It contains that fluid."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, notice that our blastocyst implants itself along the section of the trophy blast that is adjacent to the inner cell mass."}, {"title": "Implantation of Blastocyst .txt", "text": "And that's because the inner cell mass needs to be as close to the vascular tissue of the endometrium because it's the inner cell mass that eventually gives rise to that individual, to that organism."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, as soon as attachment actually takes place, the cells of the trophy blast, these dark purple cells begin to release digestive enzymes."}, {"title": "Implantation of Blastocyst .txt", "text": "And what these digestive, digestive enzymes do is they dig a hole inside the endometrium that can accommodate that implanting embryo."}, {"title": "Implantation of Blastocyst .txt", "text": "So the embryo slowly begins to make its way into the endometrium of that uterus."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, implantation takes place on about the 7th day following fertilization."}, {"title": "Implantation of Blastocyst .txt", "text": "Now, what happens next?"}, {"title": "Implantation of Blastocyst .txt", "text": "Well, by about the 10th day, that entire implanting embryo is found entirely inside the endometrium, as shown in the following diagram."}, {"title": "Implantation of Blastocyst .txt", "text": "And notice that these cells continue to secrete these digestive enzymes that even further break down this area surrounding that implanting embryo."}, {"title": "Implantation of Blastocyst .txt", "text": "Notice what also happens because these digestive enzymes come in close proximity with these blood vessels, that blood vessels are also actually broken down."}, {"title": "Implantation of Blastocyst .txt", "text": "And what happens is this creates a temporary source of nutrition, of oxygen and nutrients such as glucose and so forth."}, {"title": "Implantation of Blastocyst .txt", "text": "And this eventually will develop into something called the placenta."}, {"title": "Implantation of Blastocyst .txt", "text": "So we have these blood vessels that now are in slight contact with this region of our embryo."}, {"title": "Implantation of Blastocyst .txt", "text": "So by the way, this is what eventually forms the corian."}, {"title": "Implantation of Blastocyst .txt", "text": "So in a way, this is our corion."}, {"title": "Implantation of Blastocyst .txt", "text": "Notice what we also form is something called the umbilical vesicle."}, {"title": "Implantation of Blastocyst .txt", "text": "And the umbilical vesicle will eventually become part of the umbilical cord."}, {"title": "Implantation of Blastocyst .txt", "text": "Now we have these inner cell mass that eventually opens up and creates this cavity inside known as the amniotic cavity."}, {"title": "Implantation of Blastocyst .txt", "text": "And this will eventually is the place."}, {"title": "Implantation of Blastocyst .txt", "text": "This will eventually be the place where that embryo is actually found, where that individual is actually found, as we'll see in just a moment."}, {"title": "Implantation of Blastocyst .txt", "text": "Now notice another thing that actually happens is we form this surrounding layer of epithelial cells around that embryo that implanted."}, {"title": "Implantation of Blastocyst .txt", "text": "So basically in this case, we have the breaking of these cells so that the embryo can actually make its way."}, {"title": "Implantation of Blastocyst .txt", "text": "But once it makes its way into the endometrium, we have blood clots that are formed within this area and eventually these new epithelial cells reform this epithelium and now the entire embryo is found entirely inside the endometrium."}, {"title": "Implantation of Blastocyst .txt", "text": "Now what happens next?"}, {"title": "Implantation of Blastocyst .txt", "text": "Well, after about 25 days following fertilization, we have something like this."}, {"title": "Implantation of Blastocyst .txt", "text": "Basically what happens is now we no longer have a temporary connection between the mother's blood vessels and the coriane portion of the embryo."}, {"title": "Implantation of Blastocyst .txt", "text": "Now we have a direct connection between the Coryon and the uterine blood vessels."}, {"title": "Implantation of Blastocyst .txt", "text": "And so what that means is we have this continual source of nutrition and oxygen that comes from the mother."}, {"title": "Implantation of Blastocyst .txt", "text": "We also form the embryonic stock that eventually becomes that umbilical cord."}, {"title": "Implantation of Blastocyst .txt", "text": "And this connection between the corian and the blood vessels of the mother eventually forms the placenta."}, {"title": "Implantation of Blastocyst .txt", "text": "Now notice this is our umbilical vesicle that eventually becomes part of the umbilical cord."}, {"title": "Implantation of Blastocyst .txt", "text": "We also have this amniotic cavity that eventually grows in size in order to accommodate that embryo, that organism that develops inside, as shown in the following diagram."}, {"title": "Implantation of Blastocyst .txt", "text": "So this is the amnioc, this is the amniotic cavity."}, {"title": "Implantation of Blastocyst .txt", "text": "Inside the amniotic cavity, we have the fluid that basically acts as a nutritious source for that embryo."}, {"title": "Implantation of Blastocyst .txt", "text": "It also absorbs some of that shock that the embryo can actually experience."}, {"title": "Implantation of Blastocyst .txt", "text": "And this entire section is the coreonic cavity."}, {"title": "Implantation of Blastocyst .txt", "text": "It is also filled with a fluid that not only provides nutrition to the cells surrounding, but it also acts as an absorbent."}, {"title": "Implantation of Blastocyst .txt", "text": "It absorbs the forces and the shocks that the embryo can actually experience."}, {"title": "Implantation of Blastocyst .txt", "text": "So this is the process of implantation and these describe what happens following implantation."}, {"title": "Implantation of Blastocyst .txt", "text": "In the next lecture, we're going to discuss something called gastrelation."}, {"title": "Gel Filtration Chromatography.txt", "text": "In order to be able to purify and separate a mixture of proteins, we have to know a certain property about the proteins that differs between the different proteins that we want to actually separate."}, {"title": "Gel Filtration Chromatography.txt", "text": "So one common type of property that we use is the size of the proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "And that's because inside our body, we have a great diversity of proteins, and they vary in size."}, {"title": "Gel Filtration Chromatography.txt", "text": "For example, we have various tiny proteins, such as insulin, which is only 51 amino acids in length."}, {"title": "Gel Filtration Chromatography.txt", "text": "But we also have very, very large proteins, such as titan, also known as connectin, which is over 27,000 amino acids in length."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we have these proteins that vary in size, and we can use this property of size to basically separate and purify mixture of proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "And one technique that we developed over the years to help us purify mixture of proteins based on size is gel filtration chromatography, also known as molecular exclusion chromatography."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's begin by taking a look at the setup."}, {"title": "Gel Filtration Chromatography.txt", "text": "The setup is relatively simple."}, {"title": "Gel Filtration Chromatography.txt", "text": "We have this funnel, and we place the funnel on top of this long column."}, {"title": "Gel Filtration Chromatography.txt", "text": "And inside the column, we have these gel beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, what's so special about these spherical gel beads?"}, {"title": "Gel Filtration Chromatography.txt", "text": "Well, these gel beads consist of a hydrated polymer, such as, for example, dexterin, which is a carbohydrate."}, {"title": "Gel Filtration Chromatography.txt", "text": "And even though this molecule, this bead, is insoluble, it doesn't dissolve in aqueous solutions."}, {"title": "Gel Filtration Chromatography.txt", "text": "It contains these tiny holes, these tiny pores, and that allows small molecules to pass through those tiny pores."}, {"title": "Gel Filtration Chromatography.txt", "text": "So this is our setup."}, {"title": "Gel Filtration Chromatography.txt", "text": "We have the funnel inside."}, {"title": "Gel Filtration Chromatography.txt", "text": "The funnel is placed on top of our column, and inside the column, we have these pores gel beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so, as our fluid flows along our gel beads, that water doesn't actually dissolve our beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "So those beads are in soluble, but things can actually pass across those beads as a result of those tiny pores."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's actually zoom in onto the molecular level and see what's taking place on the molecular level as we pour our mixture of proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's take a look at the following diagram."}, {"title": "Gel Filtration Chromatography.txt", "text": "Let's suppose we have a mixture of three different proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we pour the proteins into our funnel, and it travels into this column section that contains our beats."}, {"title": "Gel Filtration Chromatography.txt", "text": "What exactly will happen?"}, {"title": "Gel Filtration Chromatography.txt", "text": "Well, let's suppose we have three proteins of varying sizes."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we have a small green protein, we have an intermediate size red protein, and we have a large protein."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, those tiny proteins, because of their small size, they will be able to fit into the internal structure of these beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so what that means is these tiny green proteins will be able to fit into the crevices, the pores inside our bead, and they will spend more time traveling inside our bead, these red intermediate proteins, because of their slightly larger size, sometimes they will be able to fit into the pores, but sometimes they will not."}, {"title": "Gel Filtration Chromatography.txt", "text": "And as a result, because they spend less time moving inside the crevices of our bees, they will travel quicker along our column as compared to these tiny proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "And if we examine this very large protein, shown a purple, these proteins will not be able to fit into the tiny pores, into the internal structure, the volume of those beets."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so they will never travel inside the bead and always move around the bead."}, {"title": "Gel Filtration Chromatography.txt", "text": "And as a result, they will emerge first at the bottom of that column."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, one analogy that I can give is, let's suppose we have a patch of grass and we have a race between an ant and a beetle."}, {"title": "Gel Filtration Chromatography.txt", "text": "So an ant is a very tiny insect, and because of its very small size, it will have to take all the different pathways inside that grass."}, {"title": "Gel Filtration Chromatography.txt", "text": "So it cannot take any shortcuts because of its very small size, but because of the size of the beetle, because the beetle simply cannot fit through the different tiny pathways where the end can fit, that beetle will make its way further to the end of that grass, the patch of grass, because of its larger size."}, {"title": "Gel Filtration Chromatography.txt", "text": "And in the same analogous way, these larger proteins, because they can't fit in the tiny pores, they can take all those different pathways that our small protein can."}, {"title": "Gel Filtration Chromatography.txt", "text": "These large proteins will make their way to the end, to the bottom of that column first."}, {"title": "Gel Filtration Chromatography.txt", "text": "So, once again, as a mixture of proteins travels through our column, the small proteins into the porous beads, but the larger proteins cannot fit into the internal volume of those beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "And as a result, those large proteins will end up at the bottom first, while the small proteins will emerge less."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's see how we can actually carry out this experiment with these three different proteins by using gel filtration chromatography."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's take a look at the following three diagrams."}, {"title": "Gel Filtration Chromatography.txt", "text": "So let's begin with diagram one."}, {"title": "Gel Filtration Chromatography.txt", "text": "In diagram one, we have the beaker."}, {"title": "Gel Filtration Chromatography.txt", "text": "Inside that beaker, we have our solution, the mixture of three different proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we have the small green protein, intermediate red protein, and the large purple protein."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we pour it into the funnel, and the funnel essentially exits through this tiny little hole and ends up in the column."}, {"title": "Gel Filtration Chromatography.txt", "text": "So what happens is, when we move on to step two, in step two, at the top of our column, we have this collection, the mixture of three different types of proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "So initially, they have not yet separated because they have not yet traveled through the section of our column through the beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, as we begin to wait, what happens is these proteins begin to travel."}, {"title": "Gel Filtration Chromatography.txt", "text": "They are pulled by the force of gravity."}, {"title": "Gel Filtration Chromatography.txt", "text": "So as they travel, those tiny proteins, the green proteins, will travel slowest because they have to travel through the tiny pores of those beads, while the red proteins will travel slightly quicker, because sometimes they get stuck inside the beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "And have to travel through the beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "But other times, they make their way around the beads, and so they will be found somewhere in the middle as compared to the green, which will be found at the top."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, these large proteins essentially never make their way into those beads because they simply cannot fit into the internal volume of those beads."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so what happens is they will emerge first, they will be found at the bottom relative to these two other proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we have the protein, this protein number one."}, {"title": "Gel Filtration Chromatography.txt", "text": "We have this protein number two."}, {"title": "Gel Filtration Chromatography.txt", "text": "And we have here this protein number three."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so in the final step, what we can actually do is we can take three test tubes."}, {"title": "Gel Filtration Chromatography.txt", "text": "And as we see this protein reaching the bottom, we can essentially open up this open up this knob or turn the knob, and this basically this protein enters our test tube number one."}, {"title": "Gel Filtration Chromatography.txt", "text": "And then we can wait for this to get to the bottom."}, {"title": "Gel Filtration Chromatography.txt", "text": "We open up our knob, and so it enters test tube number two."}, {"title": "Gel Filtration Chromatography.txt", "text": "And then when this reaches the bottom, once again, we turn a knob, open up this hole, and so this will elude into this test tube number three."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so now we have these three different separate test tubes that contain those isolated proteins, protein number one, protein number two, and protein number three."}, {"title": "Gel Filtration Chromatography.txt", "text": "Now, I should emphasize that gel filtration chromatography only works if there is a relatively large difference in size between our proteins."}, {"title": "Gel Filtration Chromatography.txt", "text": "If we use three proteins that are of the same size, this is not a very useful technique because these proteins will basically have the same exact rate of movement down our beats."}, {"title": "Gel Filtration Chromatography.txt", "text": "And so we will not be able to separate them with this method."}, {"title": "Gel Filtration Chromatography.txt", "text": "So we only use gel filtration chromatography if we know that there is a large size difference between the proteins in the mixture that we actually want to separate."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "The skeletal system of the human body, which consists of bone and cartilage is a very important component because it doesn't only protect our organs, store important minerals and create blood cells, but it also creates an overall framework of our body that allows us to actually move."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now bone does not actually initiate voluntary motion."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Motion, bone is actually associated with, it interacts with skeletal muscle and it's the contraction of the skeletal muscle that causes the movement of our bone and which creates our voluntary motion as we know it's a motion that we can actually consciously control."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So it's the interaction between our bone and the skeletal muscle, which is ultimately controlled by our nervous system, that allows us to move in any way that we wish to actually move."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now skeletal muscle does not actually attach directly to bone."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Our skeletal muscle attaches to our tendons and it's the tendons that consist of collagen fibers that actually attach to our bone."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now tendons should not be confused with ligaments."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Ligaments are those fibers that connect bone to other bones, but tendons are those fibers that connect our skeletal muscle to bone."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So tendons and muscles basically work together to move our bones and that ultimately controls the movement of our body."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "It allows us to move in a wide range of different ways."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now there are many examples of muscle bone systems in our body and the example we're going to look at is the movement of our arm."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And this involves two very important types of muscles, the biceps muscle and the triceps muscle as well as all these bones as shown in the diagram."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So basically this is our bicep muscle, this bone is the humerus bone and the muscle behind the humerus bone is our tricep muscle."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now when we actually create this motion, what happens is the humorous muscle does not actually move or the humorous bone does not actually move."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And this bone is known as our immovable bone."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "While the bone inside this portion of the arm do actually move with respect to our body."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the bones inside this are the radius bone and our ulna."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So this entire bone is the humerus bone."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In the back we have the triceps, in the front we have the bicep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "This is our radius, this is our owner."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And these two bones are the movable bones."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "They are the bones that actually move when that muscle contraction actually takes place."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now the point where the muscle actually attaches to our bone that does not move and the attachment takes place via our tendons."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "This is known as the origin."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And this side where the origin is located is known as our proximal end while the other end is known as our distal end."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And this location is known as our insertion."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the point where the muscle attaches to our movable bone via the tendon, that is known as our insertion."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the radius and the ulna are the movable bones."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Our humerus is the immovable bone and this is our proximal end."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "It contains the origin, this is the distal end, it contains our insertion."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now of course, we actually have the joints that allow the movement of these bones with respect to each other."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So we have the joint that connects our humerus to our shoulder bone, the flat bone known as the scapula, and we have the joint in our elbow as shown."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now, one of these muscles is known as an agonist, the other muscle is known as an antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And these roles basically change with respect to the type of motion that we are actually creating."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And we'll see what that means in just a moment."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the biceps triceps system works together in an autogenous manner."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the triceps biceps system is controlled antagonistically."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And what that basically means is when one of these muscles contracts, the other muscle actually stretches, it elongates and vice versa."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So let's take a look at diagram A and diagram B."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So let's suppose I have my arm oriented as shown and I wish to pull it, so I wish to flex my arm and pull it towards my body."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So basically what's happening is the central nervous system is creating an electrical signal."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Our brain initiates an electrical signal, it passes through the motor neuron found in the somatic nervous system that actually innervates our bicep muscle."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And that creates a contraction that initiates an action potential which creates the muscle contraction in the bicep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So as I'm pulling these two movable bones, my radius and my owner, towards my body, the bicep is increasing in thickness, it's contracting."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And at the same time that the radius is decreasing between this bone and our hinge, our joint, our muscle in the back, our tricep muscle is actually elongating."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "It's stretching out, it's extending."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And the muscle that contracts is known as our agonist, while the muscle that is elongating is known as our antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So when the angle is decreasing and when I'm pulling my bones closer to my body, our bicep contracts, it's the agonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "While this, our tricep, is elongating, it's our antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "On the other hand, let's look at diagram B in which the opposite is taking place."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So now I want to increase my angle between these bones and my joint hinge."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And I basically want to move these two movable bones away from my body."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And basically for this to actually take place, the electrical signal now must basically cause the contraction of the tricep muscle."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the tricep muscle thickens, it basically shortens as a result of that contraction of the contraction of the sarcomeres inside the skeletal muscle."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "At the same time the bicep is stretching out, it's basically elongating."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And you can see that as this motion takes place, this muscle basically stretches out."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "This muscle is the muscle that contracts."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case, this muscle is our antagonist, while this muscle, our contracting muscle, is our agonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So basically the bicep can act as the agonist but it can also act as our antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So in diagram A the somatic nervous system carries that electrical signal that was created by the brain and it brings it to our bicep muscle which causes the contraction of that muscle."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So as this muscle contracts, it causes this muscle to basically stretch out and it elongates as seen in the following diagram."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In diagram B, the tricep muscle fibers contract and move the radius and the ulna bone, the movable bones away from the body."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "This cause the fibers in the bicep to actually stretch out and lengthen."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So we have contraction elongation, elongation contraction."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now the muscle that contracts is known as the agonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case it's the bicep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case it's the tricep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "The muscle that elongates is known as our antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case it's the tricep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case it's the bicep."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now we have many other muscles involved in this motion and these muscles, these other muscles that help the bicep and the triceps are known as our synergist muscles."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So we also have synergist muscles that are involved in aiding in aiding the agonist antagonist muscles."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Now we can also refer to these muscles in a different way."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "We also have flexor muscles and extensor muscles."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So the flexor muscle is the muscle that contracts and decreases the angle at the joint with respect to our moveable bone while the extenter is the muscle that lengthens and increases the angle at the joint."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So in this particular case, our bicep is acting as our flexor because it is decreasing that angle with respect to the joint and our arm that is moving."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "In this case, the bicep is acting as the extensor because as we are extending our arm the angle basically increases."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And that's exactly why our bicep is an extensor in this case."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So we see any given muscle can act as an agonist but it can also act as an antagonist."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "By the same token, it can act as an extensor but it can also act as a flexor in other cases."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So when we flex, this acts as our flexor."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "When we extend this act as our extensor as described just a moment ago."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "So we see muscles by themselves do not actually create the motion."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "Muscles actually contract and cause the bones to actually move."}, {"title": "Agonist-Antagonist Muscle Pairs .txt", "text": "And so it's the interaction between our nervous system, our bone system and our skeletal muscle that creates our movement that we are consciously in control of."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Changing the PH of our blood plasma is not the only factor that actually influences and affects hemoglobin's ability to bind to oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Another factor is temperature."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So increasing or decreasing the temperature of our blood plasma can affect hemoglobin's ability to bind to oxygen and therefore affect the oxygen hemoglobin."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "This association curve."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And this will be the focus of this lecture."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, before we actually discuss how increasing or decreasing the temperature effect hemoglobin, let's discuss where this increase in temperature actually comes from."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, inside the cells of our exercising tissue, these exercising cells are carrying out more metabolic processes such as cellular respiration."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And what that means is more thermal energy is produced as a byproduct."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Thermal energy is energy that cannot be used to do any useful work."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so what the cells actually do is they release that energy into the blood plasma of the nearby capillary."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So let's take a look at the following diagram to see what exactly we mean."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, we have the exercising cells found within our tissue, and this is the nearby capillary that is carrying our blood plasma that contains the red blood cells and the hemoglobin within those red blood cells."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, as these exercising cells are carrying out metabolic processes at a higher rate, they produce more thermal energy."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that thermal energy transfers from a higher temperature to a lower temperature via the process of heat."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly why we sometimes refer to this thermal energy simply as heat."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, as the blood plasma receives more energy from the cells, more thermal energy, it essentially increases in temperature, because the particles and molecules and cells within our blood plasma gain more kinetic energy."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So we increase the temperature of the blood plasma within our capillary."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, now that we know where the increase in temperature actually comes from, let's discuss how our increase in temperature actually affects the ability of hemoglobin to bind to oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So the question is, what would we expect to happen to hemoglobin's ability to bind to oxygen when we increase the temperature of the blood plasma that contains the red blood cells that are carrying those hemoglobin molecules?"}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Well, when these exercising cells are carrying out more metabolic processes, that means they actually require more oxygen to create the ATP molecules via the process of cellular respiration."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So that implies when these exercising muscles produce more ATP, they use more ATP."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So that means they need more oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so the hemoglobin inside the blood plasma must be able to unload and release that oxygen with a greater likelihood."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So that also means that the hemoglobin must bind to oxygen much less likely in order for the oxygen to actually get into these exercising cells."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly why when we have a higher temperature of the blood plasma, the hemoglobin becomes less likely to actually bind to oxygen and much more likely to release and unload that oxygen into this exercising tissue."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, when these cells are carrying out more metabolic processes at a greater rate, we produce thermal energy."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that thermal energy essentially stimulates the hemoglobin to become much less likely to bind to oxygen so that they can unload that oxygen at a greater rate so that the cells can receive the oxygen they need to continue carrying out the metabolic processes."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, the next question is how will this affect the oxygen hemoglobin dissociation curve?"}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Well, let's take a look at the following diagram."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "The Y axis is the percent saturation of hemoglobin and it ranges from zero to one ZeroZero."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, the X axis is the partial pressure of oxygen within our tissue given in millimeters of mercury."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, the blue curve describes our oxygen hemoglobin dissociation curve at a normal body temperature of about 37 36.7 degrees Celsius."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "But the red curve describes the same exact curve, but at a slightly higher temperature."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And notice that the red curve is shifted to the right compared to our left curve compared to our blue curve."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly what happens when we increase the temperature of our blood plasma."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "We shift the entire curve to the right."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "The question is why?"}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Well, recall that at 100 mercury that is the partial pressure of our alveoli within the lungs."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "But at a partial pressure of 40 mercury, this is the partial pressure within our tissue."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Notice what the red curve tells us."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "It tells us that at a higher temperature given by the red curve, if we look at the value for the Y axis this gives us a percentage of about 60% saturation."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "But the blue curve describes a percentage that is equal to about 70."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So the red curve describes hemoglobin that is less likely to bind to oxygen and more likely to unload and release that oxygen to the exercising tissue."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly why our shift takes place to the right when we increase our temperature."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So a higher temperature shifts entire oxygen hemoglobin dissociation curve to the right."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "This means that more oxygen will be delivered to the exercising tissue because hemoglobin will be more likely to unload the oxygen and less likely to actually bind to that oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Now, what happens if we decrease our temperature?"}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "Let's suppose our cells are now exercising less than they normally do."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And what that means is they are producing less thermal energy."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so the temperature within the blood plasma of the capillary actually drops."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And what that means is if the cells are exercising less, they need less oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so the hemoglobin will be less likely to release and unload that oxygen and more likely to actually bind to that oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly why, in such a case, when we decrease the temperature we shift the entire curve to the left side with respect to the original blue curve."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So in this diagram, the blue curve is our normal temperature curve, but the red curve is the lower temperature."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so we shifted entirely to the left side and at a pressure of 40 mercury inside our tissue."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "At a lower temperature, the cells will carry out metabolic processes at a lower rate."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "They will therefore require less oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And so hemoglobin will be less likely to actually unload that oxygen."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And that's exactly why the red curve describes a greater percentage of saturation of hemoglobin about 80% compared to the 70% for our normal temperature."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "So, once again, a decrease in temperature has the opposite effect."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "As in this particular case, it causes the hemoglobin to bind to oxygen more strongly, and this decreases the likelihood that it will unload the o two into those tissues."}, {"title": "Effect of Temperature on Hemoglobin Dissociation Curve.txt", "text": "And this shifts the oxygen hemoglobin curve to the left side with respect to this original blue curve."}, {"title": "Classical Pathway of Complement System .txt", "text": "The complement system is basically part of our immune system."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what the complement system aims to do is it basically aims to protect our healthy cells of our body from different types of pathogens and different types of toxic substances that can get into our body and infect and cause damage to those healthy cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, generally speaking, the complement system can be broken down into two pathways, into two major mechanisms."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have the classical pathway that we're going to focus on in this lecture and we have another pathway known as the alternative pathway, which we're going to focus on in the next lecture."}, {"title": "Classical Pathway of Complement System .txt", "text": "So what exactly is the classical pathway?"}, {"title": "Classical Pathway of Complement System .txt", "text": "Well, let's recall the relationship between antibodies and antigens."}, {"title": "Classical Pathway of Complement System .txt", "text": "So remember, antigens are those pathogenic molecules, usually pathogenic proteins that come from foreign pathogenic cells and which eventually end up in the bloodstream or the tissues of our body, while antibodies are those protein molecules that are produced by the immune cells of our body which eventually are complementary and bind to those antigens."}, {"title": "Classical Pathway of Complement System .txt", "text": "And once the antibody binds onto the antigen and forms the antibody antigen complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, what exactly happens following the formation of the antibody antigen complex?"}, {"title": "Classical Pathway of Complement System .txt", "text": "So usually once the antibody antigen complex is formed, that's when we activate the classical pathway of the complement system."}, {"title": "Classical Pathway of Complement System .txt", "text": "So what triggers the classical pathway is the formation of the antibody antigen complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So what exactly happens once we form that antibody antigen complex to initiate the classical pathway?"}, {"title": "Classical Pathway of Complement System .txt", "text": "Well, as it turns out, the complement system actually consists of over 30 inactivated proteins that are found circulating in the bloodstream of our body."}, {"title": "Classical Pathway of Complement System .txt", "text": "And these proteins are only activated when we actually form the antibody antigen complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So the antigen antibody or the antibody antigen complex goes on and activates all these inactivated proteins found in our bloodstream, as we'll see in just a moment."}, {"title": "Classical Pathway of Complement System .txt", "text": "And then those activated proteins go on and create a cascade of events, many different processes that eventually label those antigens for destruction and kill off those pathogenic agents that created those antigens in the first place."}, {"title": "Classical Pathway of Complement System .txt", "text": "So to see exactly what we mean by that, let's discuss some of these proteins that are part of the classical pathway that are part of the complement system."}, {"title": "Classical Pathway of Complement System .txt", "text": "And let's begin with the first protein known as complement One, or simply C One."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, C One is actually a protein complex that consists of three different protein subunits."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have C one Q, we have C one S and C one R. And to be more specific, we have six molecules of C one Q here shown in blue."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we have 123456 C, one Q molecules."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have two molecules of C one S. So one, two, and then we have two molecules of C one R shown in red one and two all the way in the back here."}, {"title": "Classical Pathway of Complement System .txt", "text": "And this entire complex is the C One protein that is part of the classical pathway."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, this is in its inactive form."}, {"title": "Classical Pathway of Complement System .txt", "text": "But to be activated, what must happen is the constant region of the antibody that is bound to its complementary antigen has to bind onto this C One Q complex of C One."}, {"title": "Classical Pathway of Complement System .txt", "text": "So basically, to be more specific, we have five different types of antibodies in our body."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have five different types of immunoglobulins."}, {"title": "Classical Pathway of Complement System .txt", "text": "And two of these immunoglobulins that are capable of binding to this C One complex are immunoglobulin M and immunoglobulin G. So let's suppose immunoglobulin M. This antibody finds its complement antigen, it binds to it, and then that complex goes on and binds onto the C One Q portion of the C One protein."}, {"title": "Classical Pathway of Complement System .txt", "text": "And then that activates C one R, and then that activates C one S. Now, C one X is actually C one S is actually a serene protease."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what that means is it can go on and activate other proteins that are part of the classical pathway by cleaving them at specific amino acid sequences."}, {"title": "Classical Pathway of Complement System .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Classical Pathway of Complement System .txt", "text": "So this is the entire C One complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "When the C one complex binds onto the antibody antigen complex, it basically is activated."}, {"title": "Classical Pathway of Complement System .txt", "text": "And then the C one S portion, these two proteins here basically go on and they cleave the C two and the C four proteins also part of the classical pathway."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we cleave the C two into C two a and C two b."}, {"title": "Classical Pathway of Complement System .txt", "text": "And we cleave the C four into C four a and C four B."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, C two A and C four A basically diffuse away."}, {"title": "Classical Pathway of Complement System .txt", "text": "They swim away while C two B and C four B create a non covalent bond and they form a complex known as C four B C two B complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what this complex does is it goes on to activate two other proteins, as we'll see in just a moment."}, {"title": "Classical Pathway of Complement System .txt", "text": "One of the proteins is known as C Three."}, {"title": "Classical Pathway of Complement System .txt", "text": "And that's exactly why sometimes the C four B C two B complex is known as the C Three convertes."}, {"title": "Classical Pathway of Complement System .txt", "text": "And the other protein that this can activate is the C Five, as we'll see in just a moment."}, {"title": "Classical Pathway of Complement System .txt", "text": "So let's begin with the C Three."}, {"title": "Classical Pathway of Complement System .txt", "text": "So here we have the inactive form of C Three that is moving around, circulating in the bloodstream."}, {"title": "Classical Pathway of Complement System .txt", "text": "And eventually, once we form this, this complex activates this by cleaving it into C three B and C three A."}, {"title": "Classical Pathway of Complement System .txt", "text": "So what exactly is the function of C three A?"}, {"title": "Classical Pathway of Complement System .txt", "text": "Well, C three A is a molecule known as an anaphylatoxin."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what an anaphyllotoxin does is it goes on and bind onto the membrane of either mass cells or onto basin."}, {"title": "Classical Pathway of Complement System .txt", "text": "And it basically stimulates those two types of cells to release a chemical immune chemical known as histamine."}, {"title": "Classical Pathway of Complement System .txt", "text": "So recall that histamine dilates the blood vessels leading to that infection and it also makes the capillaries much more permeable to fluid."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what that means is the blood flow will increase to that infected area."}, {"title": "Classical Pathway of Complement System .txt", "text": "And so the immune cells and immune chemicals will be able to get to that infected area much more quickly."}, {"title": "Classical Pathway of Complement System .txt", "text": "So C three A basically increases the rate at which we can protect our body from these different types of pathogenic infections."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now."}, {"title": "Classical Pathway of Complement System .txt", "text": "What about C?"}, {"title": "Classical Pathway of Complement System .txt", "text": "Three B?"}, {"title": "Classical Pathway of Complement System .txt", "text": "Well, C three b has two different functions."}, {"title": "Classical Pathway of Complement System .txt", "text": "One of its function is to act as a molecule known as obsonin."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, what Opsinin does is it carries out a process known as obsonization."}, {"title": "Classical Pathway of Complement System .txt", "text": "And that basically means it stimulates phagocytic cells of our immune system."}, {"title": "Classical Pathway of Complement System .txt", "text": "It calls upon these phagocytic cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "So C three B goes on and binds onto a special glycoprotein found on the membrane of that particular pathogenic cell."}, {"title": "Classical Pathway of Complement System .txt", "text": "And once bound, it acts in a process known as oxygenization, meaning it calls upon these phagocytic cells, for example, macrophages or neutrophils."}, {"title": "Classical Pathway of Complement System .txt", "text": "And then these phagocytic cells come nearby and basically phagocytes, they engulfed these pathogenic agents."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, the other function of C three B is to basically go on and bind onto an allosteric site found on a C Five protein."}, {"title": "Classical Pathway of Complement System .txt", "text": "And by binding to the C Five protein, it basically creates a conformational change and it prepares it for cleavage by the C four B C two B complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "Remember, this complex doesn't only activate C three, it also activates C Five."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we have this very complex mechanism where many different proteins activate other proteins."}, {"title": "Classical Pathway of Complement System .txt", "text": "And that's why we call this a cascade of events."}, {"title": "Classical Pathway of Complement System .txt", "text": "In fact, the complement system is also sometimes known as the complement cascade system because we have so many events taking place and so many proteins are being activated."}, {"title": "Classical Pathway of Complement System .txt", "text": "So let's see exactly how the C Five is activated."}, {"title": "Classical Pathway of Complement System .txt", "text": "Basically, the C three B binds onto the allosteric side and C Five creating a conformational change in its structure."}, {"title": "Classical Pathway of Complement System .txt", "text": "And then the C four B C two B complex goes on and cleaves the C five to form the C five A and C five B Now, C five A doesn't only act as an anaphyla toxin and stimulates the release of histamine."}, {"title": "Classical Pathway of Complement System .txt", "text": "But the C five A also acts in a process known as chemotaxis."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what chemotaxis means is the stimulation of other cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "It calls upon other cells such as, for example, neutrophil."}, {"title": "Classical Pathway of Complement System .txt", "text": "So chemotaxis is the process by which cells use chemicals to basically communicate with one another and call upon one another."}, {"title": "Classical Pathway of Complement System .txt", "text": "So C five A basically acts in this process of chemo taxes."}, {"title": "Classical Pathway of Complement System .txt", "text": "Now, what C five B does, the other component of the cleavage of C Five is is it basically acts as the foundation to produce a special complex known as the membrane attack complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So C five B acts as an anchor to basically stimulate the formation of this complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we call upon C six, C seven, C eight we form the complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "And this complex goes on to a cell membrane of that pathogenic cell and it stimulates the formation of a channel inside that membrane that basically lysis that cell."}, {"title": "Classical Pathway of Complement System .txt", "text": "So what happens is this complex forms or stimulates another complex that is composed of C nine molecules."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we have as many as 18 C nine molecules basically arrange themselves and form a water channel inside that cell membrane."}, {"title": "Classical Pathway of Complement System .txt", "text": "And once we form the water channel with the guidance of this complex, this protein complex water basically moves via osmosis down its concentration gradient and the water molecules move into the cell that blows up the cell eventually the cell lysis."}, {"title": "Classical Pathway of Complement System .txt", "text": "And so what the membrane attack complex consists of is this entire complex that guides the formation of this type of channel that eventually lysis and destroys that pathogenic cell."}, {"title": "Classical Pathway of Complement System .txt", "text": "That's what we mean by the membrane attack complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So this is basically the classical pathway."}, {"title": "Classical Pathway of Complement System .txt", "text": "And to initiate that classical pathway, part of the complement system, we need the antibody to actually bind onto that antigen to form the antibody antigen complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So that we activate this C one and then the C one goes on to activate C two and C Four to form this complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "And this complex can either go on to activate C three or go on to activate C five which activates the membrane attack complex."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we have different types of mechanisms that are in play in the classical pathway."}, {"title": "Classical Pathway of Complement System .txt", "text": "So for one thing, we have the cell lysis process that kills off those pathogenic cells and the cells that carry those antibodies that are balanced to the antigens."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have the process of chemo toxic taking place."}, {"title": "Classical Pathway of Complement System .txt", "text": "So we said that the C Five A protein, for example, is a chemical that can communicate with other immune cells and call upon other immune cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "We have the process of oxidization which basically is the process by which we stimulate the process of phagocytosis."}, {"title": "Classical Pathway of Complement System .txt", "text": "We call upon these phagocytic cells such as macrophages and neutrophils."}, {"title": "Classical Pathway of Complement System .txt", "text": "And we also have the process of aggloutnation taking place."}, {"title": "Classical Pathway of Complement System .txt", "text": "And what agglutination means is it's when many of these antibody antigen complexes get together and they basically inhibit that pathogenic agent from acting and infecting our cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "And so eventually that conglomerate of antibody antigen complexes is engulfed by our phagocytic cells."}, {"title": "Classical Pathway of Complement System .txt", "text": "And finally we also have the promotion of formation of antibodies."}, {"title": "Classical Pathway of Complement System .txt", "text": "So I didn't discuss this."}, {"title": "Classical Pathway of Complement System .txt", "text": "But also what happens is once the C three B ceases to exist, sees it to function, the C three B is basically degraded."}, {"title": "Classical Pathway of Complement System .txt", "text": "And some of the fragments that are produced when we degrade C three B go on to basically activate cells such as derivative cells, which then go on to activate plasma cells to basically produce antibodies."}, {"title": "Classical Pathway of Complement System .txt", "text": "And all these processes are in play in the classical pathway which is a pathway of the complement system."}, {"title": "Classical Pathway of Complement System .txt", "text": "So in the next lecture, we're going to focus on the alternative pathway of the complement system."}, {"title": "Fertilization.txt", "text": "Fertilization is the process by which the sperm cell that came from the male parent fuses with the xcel, the ovum that came from the female parent to produce a specialized type of cell known as the zygote."}, {"title": "Fertilization.txt", "text": "Now, the process of fertilization has two important functions."}, {"title": "Fertilization.txt", "text": "Firstly, what it does is it restores the deployed number of chromosomes of that particular organ organism."}, {"title": "Fertilization.txt", "text": "In the case of the human organism, we have 23 chromosomes that are found in the sperm cell, in the nucleus of the sperm cell, and this is a haploid number."}, {"title": "Fertilization.txt", "text": "Likewise, the egg that came from the female parent contains 23 chromosomes, a haploid number in the nucleus."}, {"title": "Fertilization.txt", "text": "And when these two cells, the sperm and our egg, fuse, the number of chromosomes is restored."}, {"title": "Fertilization.txt", "text": "23 plus 23 gives us 46, a deployed number of chromosomes."}, {"title": "Fertilization.txt", "text": "What fertilization also does is it activates the egg, it transforms the egg into the zygote."}, {"title": "Fertilization.txt", "text": "And this begins several processes, metabolic processes, that eventually lead to and initiate embryological development, as we'll see in the next several lectures."}, {"title": "Fertilization.txt", "text": "Now, let's actually discuss and focus on the process of fertilization and how it actually takes place."}, {"title": "Fertilization.txt", "text": "So fertilization is the interaction between sperm cell and our egg cell."}, {"title": "Fertilization.txt", "text": "The sperm cell is shown in blue and the egg cell is this entire structure."}, {"title": "Fertilization.txt", "text": "So notice the sperm cell contains a tail, that is the flagellum."}, {"title": "Fertilization.txt", "text": "It allows our cell, our sperm cell, to move within the fluid."}, {"title": "Fertilization.txt", "text": "And it also contains a head that contains the cytoplasm, the organelles such as the mitochondria and the nucleus that is shown in blue."}, {"title": "Fertilization.txt", "text": "And it also contains a specialized structure known as the acrosome, found on the tip of the head, that contains special digestive enzymes that are responsible for digesting a hole in the membrane surrounding our excel, as we'll see in just a moment."}, {"title": "Fertilization.txt", "text": "Now, if we look at our XL, the XL also contains its own nucleus that contains a haploid number of chromosomes."}, {"title": "Fertilization.txt", "text": "This is the cytoplasm of our cell and it also contains organelles that are not shown."}, {"title": "Fertilization.txt", "text": "We have the plasma membrane of the xcel shown in purple."}, {"title": "Fertilization.txt", "text": "And we have these cortical granules, these vesicles that contain special enzymes that help initiate the process known as the cortical reaction."}, {"title": "Fertilization.txt", "text": "And we'll discuss what that is in just a moment."}, {"title": "Fertilization.txt", "text": "Now, surrounding the plasma membrane of the egg cell, we have a layer of glycoproteins known as the zona pellucida."}, {"title": "Fertilization.txt", "text": "And the first contact that takes place between the sperm cell and our exile takes place at the zona pellucida."}, {"title": "Fertilization.txt", "text": "So when the sperm cell contacts the egg, it interacts first with this layer of glycoproteins known as the zona pellucida."}, {"title": "Fertilization.txt", "text": "And what happens is the acrosome structure found on the apex, on the tip of that sperm cell releases these digestive enzymes that begin digesting a hole in the zona pellucida."}, {"title": "Fertilization.txt", "text": "And when this happens, two important processes take place."}, {"title": "Fertilization.txt", "text": "First of all, the plasma membrane of the excel begins to depolarize and that's because we have many ion channels along the plasma membrane of the xcel that begin to open up."}, {"title": "Fertilization.txt", "text": "For example, sodium ion channels begin to open up and sodium ions begin to flow into the cell and that depolarizes the plasma membrane."}, {"title": "Fertilization.txt", "text": "What also happens is calcium ions also flow into our cytoplasm as a result of the opening of those channels, ion channels."}, {"title": "Fertilization.txt", "text": "And when calcium concentration increases inside the cytoplasm of the cell these granules, these vesicles we call cortical vesicles begin to fuse with the membrane of our excel."}, {"title": "Fertilization.txt", "text": "And via this exocytosis process the enzymes within these cortical granules are released into the zonapolucida."}, {"title": "Fertilization.txt", "text": "And what these enzymes do is it essentially reinforces that zonapalucida membrane."}, {"title": "Fertilization.txt", "text": "It changes the composition of zonapolucida and it forms the fertilization membrane."}, {"title": "Fertilization.txt", "text": "And this is shown in the following diagram."}, {"title": "Fertilization.txt", "text": "And what the fertilization membrane does is it prevents other sperm cells from actually entering that excel and so this prevents polyspermy from taking place."}, {"title": "Fertilization.txt", "text": "Now, this reaction that I just described, in which these cortical granules fuse with the membrane releasing these enzymes that change the composition of the zona pollucida and form the fertilization membrane is known as the cortical reaction."}, {"title": "Fertilization.txt", "text": "And it's the cortical reaction that prevents other sperm cells from actually entering that egg."}, {"title": "Fertilization.txt", "text": "Now, let's take a look at the following section of the diagram."}, {"title": "Fertilization.txt", "text": "So in this section, we see that once we actually drill a hole in the zona palusa eventually that sperm cell will make its way to the membrane of that excel and the membrane of the sperm cell and the membrane of the xcel will begin to fuse."}, {"title": "Fertilization.txt", "text": "And as they begin to fuse, we have this opening where the nucleus of that sperm cell will make its way into the cytoplasm of that egg cell and eventually that sperm nucleus will make its way to the egg nucleus."}, {"title": "Fertilization.txt", "text": "We have the fusion of these two nuclei and we restore the deployed number of chromosomes."}, {"title": "Fertilization.txt", "text": "We combine 23 chromosomes from the male parent and 23 chromosomes from the female parents who produce 46 chromosomes which is the deployed number of chromosomes in the human organism."}, {"title": "Fertilization.txt", "text": "So once the fusion of the two nuclei takes place we have different types of metabolic processes such as, for example, protein synthesis and other processes that eventually lead to embryological development."}, {"title": "Fertilization.txt", "text": "And we'll discuss different types of embryological development processes in the next several lectures."}, {"title": "Gene Library.txt", "text": "Now let's focus on how to build a genetic library."}, {"title": "Gene Library.txt", "text": "So we're going to use the concept that we learned in the previous lecture."}, {"title": "Gene Library.txt", "text": "We're going to use something called a restriction enzyme to build a genetic library."}, {"title": "Gene Library.txt", "text": "Now what exactly is a genetic library?"}, {"title": "Gene Library.txt", "text": "Well, a genetic library for some given organism is basically a collection of all the different types of genes that are are found on the DNA molecule for that particular organism."}, {"title": "Gene Library.txt", "text": "So let's take a look at the following seven steps that basically describe how to build a genetic library."}, {"title": "Gene Library.txt", "text": "And for simplification purposes, we're going to examine a hypothetical organism that has a DNA that only consists of four different types of genes."}, {"title": "Gene Library.txt", "text": "So let's take the following DNA of some hypothetical organism that consists of gene one shown in green, gene two shown in purple, gene three shown in red and gene four shown in orange."}, {"title": "Gene Library.txt", "text": "So as always, we're dealing with a double helix DNA molecule that consists of these two individual single strands that run an antiparallel direction."}, {"title": "Gene Library.txt", "text": "So the first step in building our genetic library is to use these restriction enzymes that we spoke of in the previous lecture."}, {"title": "Gene Library.txt", "text": "So we basically pick a special type of restriction enzyme that is capable of cleaving of cutting this DNA molecule exactly at the locations where each gene begins and the other gene ends."}, {"title": "Gene Library.txt", "text": "So we cleave it right here, we cleave it right here as well as right here."}, {"title": "Gene Library.txt", "text": "So at the end, we basically produce the following four individual genes."}, {"title": "Gene Library.txt", "text": "So step number one, we cut our DNA molecule of that organism with a restriction enzyme."}, {"title": "Gene Library.txt", "text": "Now the next step is to basically take a plasmid."}, {"title": "Gene Library.txt", "text": "So the next goal is to take some sort of vector, some sort of carrier that can actually hold on to that gene."}, {"title": "Gene Library.txt", "text": "And the vector carrier we're going to use in this lecture is a bacterial plasma."}, {"title": "Gene Library.txt", "text": "So we take a bacterial plasma and we place it, we mix it with these genes and we make sure that we also mix the plasmids with the same exact restriction enzyme."}, {"title": "Gene Library.txt", "text": "And the reason we want to mix those plasmids with the same restriction enzyme is to make sure that the sticky ends that are produced are complementary to the sticky ends that are produced within this particular case."}, {"title": "Gene Library.txt", "text": "So that once we mix the bacterial plasmids with these genes, those genes can basically use their complementary sticky end and attach onto that bacterial plasma."}, {"title": "Gene Library.txt", "text": "And at the end we also add DNA ligase to basically make sure that our bonds are fully formed between these genes and our plasmids."}, {"title": "Gene Library.txt", "text": "So at the end of step two, we now have these four different types of plasmids where each one of these plasmids carries its own gene."}, {"title": "Gene Library.txt", "text": "So this carries the green gene, this carries the purple gene, this carries the red gene and this carries our orange gene."}, {"title": "Gene Library.txt", "text": "Where these sections here are our genes and these brown sections are the rest of the DNA sequence of that particular plasmid."}, {"title": "Gene Library.txt", "text": "Now also notice that the plasmid comes with a special blue section."}, {"title": "Gene Library.txt", "text": "And what the blue section is, it's a special gene that codes for a special protein that gives the bacterial cell resistance to drugs, resistance to antibiotics."}, {"title": "Gene Library.txt", "text": "And that will become important in just a moment in step four, as we'll see in just a moment."}, {"title": "Gene Library.txt", "text": "So let's move on to step three."}, {"title": "Gene Library.txt", "text": "Once we form these plasmids, we now want to insert these plasmids into actual bacterial cells."}, {"title": "Gene Library.txt", "text": "So what happens is we take these plasmids, we mix them with bacterial cells, and some of these bacterial cells uptake these plasmids via the process of transformation."}, {"title": "Gene Library.txt", "text": "So what happens at the end of step three is we have this collection of bacterial cells and some of these cells will have the plasma and some of them will not."}, {"title": "Gene Library.txt", "text": "Now another thing that I should mention about these bacterial cells is these bacterial cells do not actually have resistance to antibiotics unless they have a plasma that has the gene that codes for protein that gives that cell resistance to drugs."}, {"title": "Gene Library.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Gene Library.txt", "text": "So this cell, this cell and this cell and this cell, they all took up those plasmids, but this cell did not take up the plasmid."}, {"title": "Gene Library.txt", "text": "Now because these cells have the plasmids and each plasma contains that blue gene, these four cells will all have resistance to antibiotics."}, {"title": "Gene Library.txt", "text": "But this last cell that did not take up the plasmid, it will not have resistance to drugs."}, {"title": "Gene Library.txt", "text": "And so if we expose this last cell to antibiotics, it will die off."}, {"title": "Gene Library.txt", "text": "In fact, that's exactly what we do in the next step in step four."}, {"title": "Gene Library.txt", "text": "So in the next step, what we want to basically do is we want to be able to distinguish between those bacterial cells that did take up those plasma and the ones that did not."}, {"title": "Gene Library.txt", "text": "And so what we do is we take all these plasmids and we take them and place them onto a special petri dish that contains not only a nutritious fluid but also antibiotic medium."}, {"title": "Gene Library.txt", "text": "And so what that means is once we place all these cells onto this antibiotic containing medium, those cells that took up these plasmids will have that blue gene that gives it resistance to those drugs and so they will not die off."}, {"title": "Gene Library.txt", "text": "But on the other hand, those cells that did not take up those plasmids will die off because they won't have that special blue gene."}, {"title": "Gene Library.txt", "text": "So this cell, this cell and this cell, because they did not take the plasmids, they will basically die off."}, {"title": "Gene Library.txt", "text": "But this cell, this cell, this cell and this cell, because they have these blue genes that gives them the resistance to antibiotics, they will not die off."}, {"title": "Gene Library.txt", "text": "They will survive."}, {"title": "Gene Library.txt", "text": "So now we basically have all these cells and we know that all these cells carry the plasma."}, {"title": "Gene Library.txt", "text": "The next step is to basically take each one of these types of cells."}, {"title": "Gene Library.txt", "text": "So let's suppose we take this cell that carries this plasmid and we take this cell and we place it onto a petri dish that has a nutritious substance."}, {"title": "Gene Library.txt", "text": "And what happens is this cell now divides via binary fission, producing millions and millions of these bacterial cells that have identical copies of these plasmids."}, {"title": "Gene Library.txt", "text": "And we follow the same exact step with the second type of cell that contains the second plasmid."}, {"title": "Gene Library.txt", "text": "Then we follow that with the third cell that contains the third plasmid and the fourth cell that contains this fourth plasmid."}, {"title": "Gene Library.txt", "text": "And so at the end of the step, what we have is a colony that consists of millions of millions of these identical plasmids."}, {"title": "Gene Library.txt", "text": "And we have a colony for each and every one of these different types of cells."}, {"title": "Gene Library.txt", "text": "So once we form the colony of cells in each one of these petri dishes, so now we have four different petri dishes, we can basically lyse the cells and by lysing the cells, we basically release those plasmids."}, {"title": "Gene Library.txt", "text": "And now we can expose the plasmids to these same restriction enzymes."}, {"title": "Gene Library.txt", "text": "And what that does is it breaks down the restriction enzymes and it releases each one of these genes."}, {"title": "Gene Library.txt", "text": "And now we're dealing with not a single gene, but we have millions of each of one of these genes."}, {"title": "Gene Library.txt", "text": "So we have many, many of these green genes, we have many of these purple genes, we have many of the red genes and we have many of these orange genes."}, {"title": "Gene Library.txt", "text": "And so now we have a collection of these genes that constitute the DNA for this particular organism."}, {"title": "Gene Library.txt", "text": "And that's exactly what we mean by a genetic library."}, {"title": "Gene Library.txt", "text": "A genetic library is basically a collection of all the different genes that are found within that particular organism's DNA."}, {"title": "Gene Library.txt", "text": "And this is how we basically create a gene library."}, {"title": "Gene Library.txt", "text": "Now, once we create the gene library, now we have the collection of all these genes and we can conduct many different types types of experiments, as we'll see in the next several lectures."}, {"title": "Composition of Nucleic Acids .txt", "text": "So now that we have a general idea of what nucleic acids are let's take a more detailed look at the components of nucleic acids."}, {"title": "Composition of Nucleic Acids .txt", "text": "So, as we discussed previously, a nucleic acid is a linear polymer."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, linear simply means we have a beginning and we have an end."}, {"title": "Composition of Nucleic Acids .txt", "text": "And this is in contrast to circular nucleic acids that don't have a beginning and don't have an end."}, {"title": "Composition of Nucleic Acids .txt", "text": "The polymer means we have these individual subunits that link together to make up the nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "And in nucleic acids, these monomers these subunits are known as nucleotides."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, every one of these nucleotides consists of three different groups."}, {"title": "Composition of Nucleic Acids .txt", "text": "We have a sugar molecule, we have a phosphate group and we have a nitrogenous base."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's begin by discussing the sugar molecule found in our nucleic acids."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, we have two types of nucleic acids."}, {"title": "Composition of Nucleic Acids .txt", "text": "We have RNA and DNA."}, {"title": "Composition of Nucleic Acids .txt", "text": "And these two different types of nucleic acids contain two different types of sugar molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "In fact, the RNA and DNA nucleic acids get their name from the type of sugar that is found within the nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's begin with RNA."}, {"title": "Composition of Nucleic Acids .txt", "text": "So RNA contains the ribo sugar and that's why we call RNA ribonucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "On the other hand, DNA contains the deoxyribar."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that's exactly why we call DNA deoxyribonucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, let's take a look at these two sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "Let's compare them and let's contrast them."}, {"title": "Composition of Nucleic Acids .txt", "text": "So each of these sugars contain six carbon atoms."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have carbon atom number one."}, {"title": "Composition of Nucleic Acids .txt", "text": "So one, prime carbon number two, two, prime carbon number three, three, prime carbon number four, prime and carbon number five, five, prime."}, {"title": "Composition of Nucleic Acids .txt", "text": "And the only difference between these two sugars is the fact that on the ribosugar we have this hydroxyl group attached to carbon number two."}, {"title": "Composition of Nucleic Acids .txt", "text": "But in the deoxyribosugar, deoxy means we don't have that hydroxyl group attached to the second carbon."}, {"title": "Composition of Nucleic Acids .txt", "text": "So although both DNA and RNA molecules contain sugar components in their nucleotides DNA contain DNA contain a deoxyribosugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "And what that means is it's simply a ribosugar that does not have a hydroxyl group attached to that second carbon."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, what exactly is the meaning behind the absence of this hydroxyl group?"}, {"title": "Composition of Nucleic Acids .txt", "text": "Well, it turns out that because that hydroxyl group is not present in deoxyribosugar, that actually stabilizes our structure of DNA because it makes it much more resistant to hydrolysis by different types of nucleophiles."}, {"title": "Composition of Nucleic Acids .txt", "text": "And we'll talk more about that in just a moment."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the absence of the hydroxyl and second carbon of the sugar molecule found on DNA makes DNA more stable and more resistant to hydrolysis than the RNA molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now let's move on to something called a backbone."}, {"title": "Composition of Nucleic Acids .txt", "text": "So, previously, when we introduced nucleic acids we said that a certain part of the nucleic acid is known as the backbone."}, {"title": "Composition of Nucleic Acids .txt", "text": "So before we discuss what the backbone is let's actually discuss how the different nucleotides are actually linked together in our polymer."}, {"title": "Composition of Nucleic Acids .txt", "text": "So, remember, just like in proteins, we have these monomers known as amino acids, linked together by these special bonds known as peptide bonds."}, {"title": "Composition of Nucleic Acids .txt", "text": "In nucleic acids, we have these monomers, our nucleotides, linked together by special bonds known as three to five phosphol diaster bonds or phosphol diaster linkages."}, {"title": "Composition of Nucleic Acids .txt", "text": "Okay, so what exactly is a three to five or three prime to five prime phosphol diastolinkage?"}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's take a look at the following subsection of our nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now notice because this sugar doesn't have a hydroxyl group on that second carbon."}, {"title": "Composition of Nucleic Acids .txt", "text": "So this is carbon number one, carbon number two, three, four and five."}, {"title": "Composition of Nucleic Acids .txt", "text": "Because there is no oxygen here, that means this must be a DNA nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have a single strand of DNA and notice how these sugars are actually connected to one another."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's begin with this sugar here."}, {"title": "Composition of Nucleic Acids .txt", "text": "This sugar contains carbon number three, that contains our oxygen."}, {"title": "Composition of Nucleic Acids .txt", "text": "And this oxygen attached to carbon number three is attached to a phosphate group."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that phosphate group is in turn attached to this oxygen here that is linked to carbon number five of this adjacent sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that's exactly what a three to five linkage actually means."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have this oxygen on the third carbon, is linked to this oxygen on the fifth carbon of that adjacent sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, what do we mean by phosphol diaster?"}, {"title": "Composition of Nucleic Acids .txt", "text": "So phosphol means we have this phosphate group in between these two aster bonds."}, {"title": "Composition of Nucleic Acids .txt", "text": "So these two bonds are the asterbonds."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that's why we have the dye, because we have these two aster bonds that are linked together by the phosphate group that in turn link together these two sugar molecules in a three to five fashion."}, {"title": "Composition of Nucleic Acids .txt", "text": "So that's what a three prime to five prime phosphodite as the linkage is."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the hydroxyl group on the third carbon of one sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "So this third carbon, this is the hydroxyl, the oxygen of that hydroxyl is connected to the hydroxyl group on the fifth carbon of the adjacent sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "So this carbon here, this is the oxygen of that hydroxyl group and they're connected by this phosphate group."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that's exactly what we mean by three prime to five prime phosphodi as the linkage."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, this entire chain, as we can see, basically consists of these repeating units that are composed of a phosphate group and a sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have phosphate sugar, phosphate sugar, phosphate sugar."}, {"title": "Composition of Nucleic Acids .txt", "text": "And this continues until that nucleic acid ends."}, {"title": "Composition of Nucleic Acids .txt", "text": "And this is what we call the backbone of that sugar, of that nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the backbone of that nucleic acid consists of a chain of repeating sugar phosphate units as shown in the following diagram."}, {"title": "Composition of Nucleic Acids .txt", "text": "And by the way, these are the bases, the third component of a nucleotide attached to this carbon number one of each one of these sugars."}, {"title": "Composition of Nucleic Acids .txt", "text": "And we'll discuss what these nitrogenous bases are in just a moment."}, {"title": "Composition of Nucleic Acids .txt", "text": "These bases are not part of that backbone of the nucleic acid because unlike these, the bases do actually change as we go from one nucleotide to another nucleotide."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the backbone that does not consist of these bases, but consists of these repeating units, does not change and remains constant throughout that entire nucleic acid."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, what else can we say about this backbone?"}, {"title": "Composition of Nucleic Acids .txt", "text": "So notice that because the backbone contains these repeating phosphate groups and because the phosphate groups carries a negative charge, that makes this part of the backbone hydrophilic."}, {"title": "Composition of Nucleic Acids .txt", "text": "So water loving, that's because we have a dipole moment that exists as a result of the charge that is delocalized among these two oxygen atoms within our phosphate group."}, {"title": "Composition of Nucleic Acids .txt", "text": "So notice that the phosphate group contains a negative charge."}, {"title": "Composition of Nucleic Acids .txt", "text": "And this means two important things."}, {"title": "Composition of Nucleic Acids .txt", "text": "Number one, when we place our DNA or RNA molecule into an aqueous solution, which is a solution found in our cells and inside the nuclei of our cells, the structure of that DNA molecule and RNA molecule will basically exist in such a way as so as to make sure that these phosphate groups actually interact with the polar water molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "And as we'll see in our discussion on the double stranded helix structure of DNA molecules, these phosphate groups actually are found on the surface of that double helix because they are able to interact with the hydrophilic water molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "So once again, this means that in an aqueous environment, these hydrophilic regions, these hydrophilic phosphate groups will interact with the polar water molecules to stabilize the structure of DNA."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, that's not the only thing that these phosphate groups actually do."}, {"title": "Composition of Nucleic Acids .txt", "text": "What they also do is they actually increase the resistance of the DNA molecules to hydrolysis."}, {"title": "Composition of Nucleic Acids .txt", "text": "So remember, anytime we have an Esther Bond, that Esther bond can undergo the process of hydrolysis in which a nuclearphile essentially attacks that bond and breaks that bond."}, {"title": "Composition of Nucleic Acids .txt", "text": "But in this particular case, because we have negative charges on these phosphate groups, these negative charges will repel the negative charge found on the nucleophile."}, {"title": "Composition of Nucleic Acids .txt", "text": "And because of this electrostatic repulsion, that will stabilize the structure of the DNA molecule and increase its resistance to hydrolysis in the same exact way as this, the absence of this oh, on the deoxyribo sugar also increase the resistance of the DNA to hydrolysis."}, {"title": "Composition of Nucleic Acids .txt", "text": "So these two effects increase and stabilize the structure of DNA."}, {"title": "Composition of Nucleic Acids .txt", "text": "And so that's exactly why DNA molecules are generally much more stable than RNA molecules and are able to resist hydrolysis with a much higher potential."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we see that the fact that we have these phosphate groups does two things."}, {"title": "Composition of Nucleic Acids .txt", "text": "It essentially dictates what that three dimensional shape of that DNA molecule, an RNA molecule is in an aqueous environment and it also increases the resistance of our DNA molecule to hydrolysis."}, {"title": "Composition of Nucleic Acids .txt", "text": "So it makes it much less susceptible to hydrolysis."}, {"title": "Composition of Nucleic Acids .txt", "text": "So this process does not generally take place because these two negative charges essentially repel one another as a result of electrostatic repulsion."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, the final components that we have to discuss, have left to discuss are the bases."}, {"title": "Composition of Nucleic Acids .txt", "text": "So remember, any nucleotide consists of a phosphate group, a sugar molecule and a base."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's take a look at what these nitrogenous bases actually are."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, unlike in the backbone, where these essentially repeat throughout the entire nucleic acid, these bases do change when we go from one nucleotide to another nucleotide."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that's exactly what allows these bases and allows the DNA to ultimately store genetic information, as we'll see in just a moment."}, {"title": "Composition of Nucleic Acids .txt", "text": "So although the backbone does not change, the bases in the nucleotides do vary from one monomer, one nucleotide to the next nucleotide."}, {"title": "Composition of Nucleic Acids .txt", "text": "And there are two categories of bases."}, {"title": "Composition of Nucleic Acids .txt", "text": "We have purines and we have pyrimidines."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's begin with purines."}, {"title": "Composition of Nucleic Acids .txt", "text": "So in DNA and RNA we only have two types of purines."}, {"title": "Composition of Nucleic Acids .txt", "text": "And a purine is basically a molecule that consists of two fused rings."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have adenine and we have guanine."}, {"title": "Composition of Nucleic Acids .txt", "text": "So adenine is given by A and guanine is given by g and these are the two molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have two fused rings."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the difference between these two molecules is the presence of different types of groups."}, {"title": "Composition of Nucleic Acids .txt", "text": "So in this particular case, we have this nitrogen containing group and in this case we have an H. In this case we have a nitroge containing group."}, {"title": "Composition of Nucleic Acids .txt", "text": "But in this case we have a carbon oxygen double bond."}, {"title": "Composition of Nucleic Acids .txt", "text": "And that will play an important role in determining the types and the number of interactions that are formed between the different bases in the double stranded DNA molecule, as we'll see in our discussion of the double helix."}, {"title": "Composition of Nucleic Acids .txt", "text": "So in RNA and DNA, these are the two purines that are common that exist."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now."}, {"title": "Composition of Nucleic Acids .txt", "text": "What about the pyrimidines?"}, {"title": "Composition of Nucleic Acids .txt", "text": "Well, this is where our RNA and DNA molecules differ."}, {"title": "Composition of Nucleic Acids .txt", "text": "In DNA molecules."}, {"title": "Composition of Nucleic Acids .txt", "text": "We have two pyrimidines."}, {"title": "Composition of Nucleic Acids .txt", "text": "One of them is thiamine and the other one is thin cytosine."}, {"title": "Composition of Nucleic Acids .txt", "text": "But in RNA we have the cytosine, but the Thiamine is replaced with uracil."}, {"title": "Composition of Nucleic Acids .txt", "text": "So let's take a look at the following three diagrams."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have cytosine, which is found in both RNA and DNA nucleic acids."}, {"title": "Composition of Nucleic Acids .txt", "text": "In DNA."}, {"title": "Composition of Nucleic Acids .txt", "text": "We have thiamine."}, {"title": "Composition of Nucleic Acids .txt", "text": "But in RNA the Thiamine is replaced with uracel."}, {"title": "Composition of Nucleic Acids .txt", "text": "And notice that the only difference between Thiamine and uracil is the presence of this methyl group."}, {"title": "Composition of Nucleic Acids .txt", "text": "So in Thiamine we have the methyl group here, but in uracel we have the H atom that is replaced."}, {"title": "Composition of Nucleic Acids .txt", "text": "So we have this methyl group that is replaced by the H atom."}, {"title": "Composition of Nucleic Acids .txt", "text": "Now, what's the importance of these bases?"}, {"title": "Composition of Nucleic Acids .txt", "text": "Well, one importance is a double helix structure."}, {"title": "Composition of Nucleic Acids .txt", "text": "These bases are used to basically hydrogen bond with respect to one another and they form that double helix as we'll discuss eventually."}, {"title": "Composition of Nucleic Acids .txt", "text": "But the more important reason, the more important fact about these bases is that because it's these bases that essentially change as we go from one nucleotide to another, it's the sequence of these bases that essentially determine the type of genetic information that is stored within that DNA molecule."}, {"title": "Composition of Nucleic Acids .txt", "text": "So the sequence of these bases is unique to the nucleic acid that we're studying."}, {"title": "Composition of Nucleic Acids .txt", "text": "And because it is the basis that varies from one nucleotide to the next along that linear nucleic acid, it's the sequence of these bases that ultimately allows the DNA to actually store genetic information that can be used to basically synthesize many different types of proteins."}, {"title": "Composition of Nucleic Acids .txt", "text": "And we'll discuss that in much more detail when we'll touch upon the genetic code."}, {"title": "Somatic Nervous System .txt", "text": "The nervous system of the human is broken down into two categories."}, {"title": "Somatic Nervous System .txt", "text": "We have the central nervous system which contains the brain and the spinal cord and the peripheral nervous system."}, {"title": "Somatic Nervous System .txt", "text": "Now, the peripheral nervous system is made up of neurons and support cells that are found outside of the central nervous system outside of the brain and a spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So the peripheral nervous system system is further divided into the autonomic nervous system and the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "So in this lecture, we're going to focus on the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "Now, the somatic nervous system consists of two divisions."}, {"title": "Somatic Nervous System .txt", "text": "We have the motor division that consists of only motor neurons also known as epharic neurons and we have the sensory division which consists of only sensory neurons also known as Afaric neurons."}, {"title": "Somatic Nervous System .txt", "text": "Now recall that a motor neuron is basically a neuron that accepts an electrical signal from the central nervous system and sends it away to some type of target organ gland, muscle tissue, and so forth."}, {"title": "Somatic Nervous System .txt", "text": "While the sensory neuron picks up that electrical signal from some type of outside stimulus and sends that electrical signal to the central nervous system where it's integrated as well as processed."}, {"title": "Somatic Nervous System .txt", "text": "Now, the somatic nervous system is responsible for innervating and controlling skeletal muscles, skeletal tissue which basically means the somatic nervous system is ultimately responsible for voluntary movement."}, {"title": "Somatic Nervous System .txt", "text": "So if I want to actually, for example, bend and extend my arm this requires the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "So it's the brain that actually creates or initiates that electrical signal but it's the somatic nervous system that actually extends my arm as we'll see in just a moment."}, {"title": "Somatic Nervous System .txt", "text": "So let's begin with our motor division."}, {"title": "Somatic Nervous System .txt", "text": "So let's discuss the motor neurons found in the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "So as I mentioned earlier, motor neurons are those neurons that accept our signals from the central nervous system so the brain or the spinal cord and send these signals to the target tissue gland, organ, muscle, et cetera."}, {"title": "Somatic Nervous System .txt", "text": "In the case of the somatic nervous system the target organ is always our skeletal muscle."}, {"title": "Somatic Nervous System .txt", "text": "So in the somatic nervous system the dendrites and the cell body of the motor neuron always begin, always originate in the spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So let's take a cross section of the spinal cord as shown in the following diagram."}, {"title": "Somatic Nervous System .txt", "text": "We have the white matter and we have the gray matter."}, {"title": "Somatic Nervous System .txt", "text": "So the cell body and the dendrites of the motor neuron in the somatic nervous system always begin within our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So let's suppose I want to actually move my bicep."}, {"title": "Somatic Nervous System .txt", "text": "What happens is my brain initiates creates that electrical signal in the form of an action potential and that action potential travels and eventually ends up on the dendrites of our somatic motor neuron."}, {"title": "Somatic Nervous System .txt", "text": "And that dendrite picks up that signal and once the signal is picked up by the dendrites it sends it through the axon of our body."}, {"title": "Somatic Nervous System .txt", "text": "So the axon of the somatic motor neuron."}, {"title": "Somatic Nervous System .txt", "text": "Now, notice the body of this neuron, the axon, not the body, the cell body, is within the central nervous system."}, {"title": "Somatic Nervous System .txt", "text": "But notice our axon of the motor neuron is located entirely in the peripheral nervous system."}, {"title": "Somatic Nervous System .txt", "text": "So our electrical signal, the action potential, travels and eventually ends up at our axon terminal."}, {"title": "Somatic Nervous System .txt", "text": "Now, the axon terminal is right next to our cell membrane of the muscle cell."}, {"title": "Somatic Nervous System .txt", "text": "In this case, let's say it's a skeletal muscle found inside my bicep."}, {"title": "Somatic Nervous System .txt", "text": "So if we zoom in on a synapse, this is basically our neuromuscular junction."}, {"title": "Somatic Nervous System .txt", "text": "It's the synapse between our neuron, the motor neuron, and our cell membrane of that muscle."}, {"title": "Somatic Nervous System .txt", "text": "So if we zoom in, we basically get the following picture."}, {"title": "Somatic Nervous System .txt", "text": "So, we have the axon terminal of our somatic motor neuron, and we have the cell membrane of the skeletal muscle inside our biceps muscle."}, {"title": "Somatic Nervous System .txt", "text": "So notice that the cell membrane contains these receptor proteins, and the axon terminal contains these synaptic vesicles that carry special neurotransmitters."}, {"title": "Somatic Nervous System .txt", "text": "Now, in the case of the motor division of the somatic nervous system, these neurotransmitters are always acetylcholine."}, {"title": "Somatic Nervous System .txt", "text": "So as the action potential travels and eventually ends up on the exxon terminal, it basically causes the release of these synaptic vesicles, and that releases our acetylcholine."}, {"title": "Somatic Nervous System .txt", "text": "The acetylcholine eventually binds onto these receptor proteins that create an action potential."}, {"title": "Somatic Nervous System .txt", "text": "And that action potential ultimately causes the contraction of our biceps muscle."}, {"title": "Somatic Nervous System .txt", "text": "So in this way, it's the brain that generates that electrical signal, but it's the motor neuron of the somatic nervous system that actually causes that movement, that voluntary movement in the first place."}, {"title": "Somatic Nervous System .txt", "text": "Now, one more thing we have to notice about the motor neurons is when they actually leave, when they actually exit the spinal cord, they always exit from the front side, from the ventral side of our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So if this is the back and this is the front, notice they always leave from the front side of our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "Now, one more thing we have to notice is we have a single axon leaving this spinal spinal cord, and the axon eventually ends up exactly at our effective target."}, {"title": "Somatic Nervous System .txt", "text": "So our effective organ, in this case, our biceps tissue, the biceps muscle."}, {"title": "Somatic Nervous System .txt", "text": "So basically, we have a single axon traveling all the way to the target tissue, the target muscle."}, {"title": "Somatic Nervous System .txt", "text": "Now let's move on to our sensory neuron."}, {"title": "Somatic Nervous System .txt", "text": "So sensory neurons are those neurons that connect to receptors."}, {"title": "Somatic Nervous System .txt", "text": "These receptors basically pick up stimuli, and this stimulus is transformed into an electrical signal by those sensory neurons of the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "So these somatic sensory neurons then carry our electrical signal via a single axon, as in this case, and they carry that signal to the backside, which is our dorsal side of our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So the motor neurons leave from the front side, the ventral side."}, {"title": "Somatic Nervous System .txt", "text": "But the sensory neurons pick up those signals and carries them through the backside into our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "The backside is the dorsal side."}, {"title": "Somatic Nervous System .txt", "text": "Now, one major difference between the sensory neurons and the motor neurons of our somatic system is the cell body of our motor neuron is found inside our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "But the cell body here is found close in the backside, so close to the backside of our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So this region where we find the cell body of the sensory neuron is known as the dorsal or backside, so dorsal root ganglia, where ganglia simply means neurons outside of the spinal cord and the brain."}, {"title": "Somatic Nervous System .txt", "text": "So let's see how this signal actually takes place."}, {"title": "Somatic Nervous System .txt", "text": "So let's suppose I apply pressure onto my finger."}, {"title": "Somatic Nervous System .txt", "text": "As I apply the pressure, the dendrites of our sensory neuron contains special pressure receptors."}, {"title": "Somatic Nervous System .txt", "text": "And when I apply these receptors are basically these receptors basically create a force."}, {"title": "Somatic Nervous System .txt", "text": "That force creates the oscillation, the movement of our ions, and that ultimately creates our electric current, the action potential."}, {"title": "Somatic Nervous System .txt", "text": "And so the action potential travels, our electric current travels through the axon."}, {"title": "Somatic Nervous System .txt", "text": "Eventually that creates an action potential at this section, the axon terminal, which is down inside our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "And then that sends the electric signal up to the spinal cord into the brain."}, {"title": "Somatic Nervous System .txt", "text": "And the brain basically senses that pressure."}, {"title": "Somatic Nervous System .txt", "text": "Now, sensory neurons and motor neurons."}, {"title": "Somatic Nervous System .txt", "text": "So these pathways that we discussed so far involve voluntary movement."}, {"title": "Somatic Nervous System .txt", "text": "So if I want to move my hand, if I want to extend it or bend it, this is basically a result of the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "The more division and the sensory division, now we are in complete control of this voluntary motion."}, {"title": "Somatic Nervous System .txt", "text": "But the somatic nervous system doesn't only control voluntary movement of skeletal muscle, it also controls reflex arcs that we are not in control of."}, {"title": "Somatic Nervous System .txt", "text": "So reflex arcs are basically those reflexes, those responses that we have no control over."}, {"title": "Somatic Nervous System .txt", "text": "So they simply take place and we cannot do anything about them."}, {"title": "Somatic Nervous System .txt", "text": "So the somatic nervous system is also responsible for reflex arcs."}, {"title": "Somatic Nervous System .txt", "text": "These are quick and automatic responses that cannot be controlled voluntarily."}, {"title": "Somatic Nervous System .txt", "text": "And they basically are a result of outside stimuli."}, {"title": "Somatic Nervous System .txt", "text": "So let's suppose I place my hand on a hot stove."}, {"title": "Somatic Nervous System .txt", "text": "So without even knowing, my hand will basically move away."}, {"title": "Somatic Nervous System .txt", "text": "Now, eventually I'm going to feel that, but initially, I have no control over the fact that my hand will automatically move."}, {"title": "Somatic Nervous System .txt", "text": "And this is known as a reflex arc."}, {"title": "Somatic Nervous System .txt", "text": "And our somatic nervous system controls this reflex arc, and it involves both sensory and motor neurons."}, {"title": "Somatic Nervous System .txt", "text": "So we have two types of reflex arcs."}, {"title": "Somatic Nervous System .txt", "text": "We have monosynaptic and polysynaptic."}, {"title": "Somatic Nervous System .txt", "text": "So monosynaptic simply means we have a single synapse between our motor neuron and a sensory neuron."}, {"title": "Somatic Nervous System .txt", "text": "But polysynaptic means we have more than one synapse."}, {"title": "Somatic Nervous System .txt", "text": "So to see what we mean, let's take a look at these two diagrams."}, {"title": "Somatic Nervous System .txt", "text": "So, in diagram one, this is our spinal cord."}, {"title": "Somatic Nervous System .txt", "text": "So let's suppose my stimulus is that hot stove."}, {"title": "Somatic Nervous System .txt", "text": "So I place my hand on a hot stove."}, {"title": "Somatic Nervous System .txt", "text": "That stimulus is transformed into an electrical signal that is picked up by our sensory neuron of the somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "It travels from the backside, the dorsal side of our spinal cord, and let's say it basically synapses first with an inter neuron."}, {"title": "Somatic Nervous System .txt", "text": "If it's synapses with an inter neuron, that means we have one synapse here."}, {"title": "Somatic Nervous System .txt", "text": "Now, eventually, the inter neuron shown in brown, found inside the spinal cord will synapse with our motor neuron of a somatic nervous system."}, {"title": "Somatic Nervous System .txt", "text": "And that electro signal will basically travel back into my hand and it will tell my hand to basically move that hand."}, {"title": "Somatic Nervous System .txt", "text": "So this is known as a polysynaptic reflex because it contains one, two synapses."}, {"title": "Somatic Nervous System .txt", "text": "So more than one synapse."}, {"title": "The Motor Unit .txt", "text": "The human body organizes neurons and muscles into units we call motor units."}, {"title": "The Motor Unit .txt", "text": "Now simply put, a motor unit consists of the motor neuron as well as all the muscle cells that that particular motor neuron innervate."}, {"title": "The Motor Unit .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "The Motor Unit .txt", "text": "So let's suppose we have a single muscle cell as shown in red."}, {"title": "The Motor Unit .txt", "text": "So the muscle cell is also known as the muscle fiber or the myocides."}, {"title": "The Motor Unit .txt", "text": "So we have a single motor neuron that comes from the central nervous system and it basically connects its synapses with our muscle cell."}, {"title": "The Motor Unit .txt", "text": "So this is the axon of the motor neuron that's coming from the central nervous system and it basically splits in its synapses with our muscle cell."}, {"title": "The Motor Unit .txt", "text": "And at the given synapse we have the neuromuscular junction where our neurotransmitter acetylcholine basically transfers the action potential from the neuron to our muscle cell."}, {"title": "The Motor Unit .txt", "text": "So basically this muscle cell shown in red as well as the motor neuron is our motor unit."}, {"title": "The Motor Unit .txt", "text": "And in this particular case, the motor unit only consists of a single muscle cell and a single motor neuron."}, {"title": "The Motor Unit .txt", "text": "Now a single motor neuron always consists of a single neuron but it can have thousands of muscle cells."}, {"title": "The Motor Unit .txt", "text": "So we have thousands of these different types of muscle cells in a bundle and that is our motor neuron."}, {"title": "The Motor Unit .txt", "text": "Now, within the muscle cell we have many of these fibers known as myofibrils."}, {"title": "The Motor Unit .txt", "text": "And these myofibrils themselves consist of the Sarcomir units."}, {"title": "The Motor Unit .txt", "text": "So Sarcomir units consist of the myosin and the actin protein."}, {"title": "The Motor Unit .txt", "text": "Now in our body we have many of these motor units."}, {"title": "The Motor Unit .txt", "text": "Now, whenever we're carrying out an activity that basically requires a very small force, we only use several or few of these motor units."}, {"title": "The Motor Unit .txt", "text": "But if we're conducting some activity that requires a large force we have to use many of these motor units."}, {"title": "The Motor Unit .txt", "text": "And motor units can basically work together to carry out a motion in a coordinated and smooth fashion."}, {"title": "The Motor Unit .txt", "text": "So many different motor units can work together to create smooth and coordinated motion."}, {"title": "The Motor Unit .txt", "text": "If a certain activity requires a small force, a small number of motor units are actually used."}, {"title": "The Motor Unit .txt", "text": "On the other hand, if the activity requires a relatively large force when for example, we're lifting some type of heavy object, many motor neurons are actually used."}, {"title": "The Motor Unit .txt", "text": "Now, typically small muscles like the muscles found in our fingers require few motor units while large muscles like the muscles in our legs require a larger number of motor units."}, {"title": "The Motor Unit .txt", "text": "So let's take a look at the following diagram to see what we mean by a motor unit."}, {"title": "The Motor Unit .txt", "text": "So let's suppose we have the biceps muscle, the triceps muscle and this is the central nervous system, our spine as well as our brain."}, {"title": "The Motor Unit .txt", "text": "So we have one motor neuron, the second motor neuron and the third motor neuron."}, {"title": "The Motor Unit .txt", "text": "Now every one of these motor units or every one of these motor neurons begins in the central nervous system."}, {"title": "The Motor Unit .txt", "text": "And that means each one of these motor neurons, their dendrites and the cell bodies originate begin at the central nervous system."}, {"title": "The Motor Unit .txt", "text": "Now the axon of the motor neuron basically extends and the axon terminal of each one of these motor neurons basically ends up at the muscle cells that they control."}, {"title": "The Motor Unit .txt", "text": "So motor neuron number one, as well as all the muscle cells that motor neuron number one controls is known as motor unit number one."}, {"title": "The Motor Unit .txt", "text": "The same thing goes for number two."}, {"title": "The Motor Unit .txt", "text": "We have motor unit number two that consists of motor neuron number one and the muscle cells that it controls."}, {"title": "The Motor Unit .txt", "text": "And the same thing is true for motor neuron number three."}, {"title": "The Motor Unit .txt", "text": "Motor neuron number three creates motor unit number three that consists of this neuron as well as the muscle cells that it actually controls."}, {"title": "The Motor Unit .txt", "text": "Now there are three things that actually affect the magnitude, the quantity of force that is produced by arrow muscles."}, {"title": "The Motor Unit .txt", "text": "So let's discuss what these three things are."}, {"title": "The Motor Unit .txt", "text": "And let's begin with bullet point number one, the size of the motor unit."}, {"title": "The Motor Unit .txt", "text": "Now what do we mean by the size of the motor unit?"}, {"title": "The Motor Unit .txt", "text": "So earlier we said that a single motor unit can consist of thousands of muscle cells."}, {"title": "The Motor Unit .txt", "text": "So basically those motor units that have more muscle cells will create a greater force than those that have less muscle cells."}, {"title": "The Motor Unit .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "The Motor Unit .txt", "text": "So in this diagram in blue, we have our motor neuron."}, {"title": "The Motor Unit .txt", "text": "And this is basically a fascicle."}, {"title": "The Motor Unit .txt", "text": "So recall that a fascicle is basically a bundle."}, {"title": "The Motor Unit .txt", "text": "It's a collection of many of these muscle cells, of many of these muscle fibers."}, {"title": "The Motor Unit .txt", "text": "So this is one muscle cell."}, {"title": "The Motor Unit .txt", "text": "Now we have 1234-5678."}, {"title": "The Motor Unit .txt", "text": "We have eight of these muscle cells in this given fascicle."}, {"title": "The Motor Unit .txt", "text": "So this motor unit consists of a single motor neuron and only eight muscle cells."}, {"title": "The Motor Unit .txt", "text": "But if we examine this larger motor unit, this consists of many more of these muscle cells of many more of these muscle fibers inside the entire fascicle."}, {"title": "The Motor Unit .txt", "text": "And so because this motor unit consists of many more of these muscle cells, this larger motor unit will be able to exert a larger force."}, {"title": "The Motor Unit .txt", "text": "So that's what we mean by the size of the motor unit affects the magnitude of the force that is produced by that particular motor unit."}, {"title": "The Motor Unit .txt", "text": "Now let's move on to number two."}, {"title": "The Motor Unit .txt", "text": "So number two states that the number of motor units involved also affects the magnitude of the force that is produced."}, {"title": "The Motor Unit .txt", "text": "That means if we have more of these motor units that are involved in creating that motion, we're going to produce a greater force."}, {"title": "The Motor Unit .txt", "text": "Likewise, if we have less of these motor units involved we're going to produce a smaller force."}, {"title": "The Motor Unit .txt", "text": "Now to see what we mean, let's take a look at the following diagram once more."}, {"title": "The Motor Unit .txt", "text": "So let's suppose I take the following marker and I try to curl my hand."}, {"title": "The Motor Unit .txt", "text": "So I tried to basically raise the marker."}, {"title": "The Motor Unit .txt", "text": "I tried to exert a force that basically does work against the force of gravity which is pulling down on this marker."}, {"title": "The Motor Unit .txt", "text": "Now because the marker has a small mass that basically means I'm going to have to apply a small force to actually move this marker against the force of gravity."}, {"title": "The Motor Unit .txt", "text": "So that means because I'm going to have to apply a smaller force, I'm only going to have to use a small number of motor neurons."}, {"title": "The Motor Unit .txt", "text": "So let's suppose I'm only using motor unit number one, that involves motor neuron number one as well as these muscle cells that it actually innervates."}, {"title": "The Motor Unit .txt", "text": "Now instead, let's suppose instead of raising this marker I take some type of weight."}, {"title": "The Motor Unit .txt", "text": "And that weight let's suppose has a very large mass."}, {"title": "The Motor Unit .txt", "text": "So now because I'm trying to lift a very large mass I'm going to have to use many more motor units."}, {"title": "The Motor Unit .txt", "text": "And so now let's suppose I'm using all three of these motor neurons and that means I'm using all three of these motor units."}, {"title": "The Motor Unit .txt", "text": "And this as a result of me using more of these motor units I will produce a greater force because more of these motor units contain more of these muscle cells and so I will exert a greater force."}, {"title": "The Motor Unit .txt", "text": "So if we stimulate many motor units to carry out a certain activity this will produce a greater force than if we use a smaller number of motor units."}, {"title": "The Motor Unit .txt", "text": "And this is simply because more motor units means we're using many more muscle fibers, many more muscle cells."}, {"title": "The Motor Unit .txt", "text": "And finally, let's move on to number three."}, {"title": "The Motor Unit .txt", "text": "So the thickness of the muscle cells also influences the force, the magnitude of the force that we're creating."}, {"title": "The Motor Unit .txt", "text": "And this is exactly what happens when we exercise."}, {"title": "The Motor Unit .txt", "text": "So let's take a look at the following muscle cell."}, {"title": "The Motor Unit .txt", "text": "So this individual single muscle cell, single muscle fiber consists of many of these myofibrils found inside the cytoplasm of that muscle cell."}, {"title": "The Motor Unit .txt", "text": "Now these myofibrils basically are made up of adjacent units we call sarcomeres."}, {"title": "The Motor Unit .txt", "text": "And these sarcomeres themselves are composed of meiosin and actin."}, {"title": "The Motor Unit .txt", "text": "Now when we continually exercise on a daily basis, what happens is we actually increase the number of myosin and the number of actin inside each sarcomere."}, {"title": "The Motor Unit .txt", "text": "And that in turn increases the thickness, increases our diameter of each one of these myofibrils."}, {"title": "The Motor Unit .txt", "text": "And over time, because our thickness of each of these myofibrils is increased the entire thickness and diameter of the muscle cell will increase as well."}, {"title": "The Motor Unit .txt", "text": "And because it's the actin and the myosin that basically move along each other to produce our force, it's these that create the force in the first place."}, {"title": "The Motor Unit .txt", "text": "A thicker muscle cell means we're essentially producing a larger force."}, {"title": "The Motor Unit .txt", "text": "So when we exercise often we increase the thickness of the individual myofibus down inside each muscle cell by increasing the number of actin and myosin in those myofibus."}, {"title": "The Motor Unit .txt", "text": "This in turn increases our thickness, our diameter of that muscle cell."}, {"title": "The Motor Unit .txt", "text": "A muscle cell with a larger thickness, a larger diameter will exert a greater force than one with a smaller one."}, {"title": "The Motor Unit .txt", "text": "So this basically concludes our discussion on the motor unit."}, {"title": "The Motor Unit .txt", "text": "So the motor unit is nothing more than the motor neuron as well as all the muscle cells that that particular motor neuron actually controls."}, {"title": "The Motor Unit .txt", "text": "And we have different types of motor units found inside our body body."}, {"title": "The Motor Unit .txt", "text": "And these motor units basically work together to create a coordinated and smooth motion."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we know that when glucose is broken down an aerobic cell respiration, we produce ATP molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So some number are produced in glycolysis and then we generate the remaining ATP molecules in a citric acid cycle and on the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "But the question is, what is the number of ATP molecules that we actually generate when a single glucose is broken down in in aerobic cell respiration?"}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So this is what I'd like to discuss in this lecture."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And let's begin with glycolysis."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So glycolysis takes place entirely in the cytoplasm of the cell."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so let's suppose this is the cytoplasm and this is the mitochondrion."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now, a single glucose is broken down into two Pyruvate molecules in glycolysis."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And in the process, we also generate two ATP molecules and we produce two NADH molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now, the ATP molecules can be used directly by the cell to power some type of biological process in that cell."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "But to produce ATP molecules from NADH, the NADH must move onto the electron transfer chain found on the inner membrane of the mitochondrion."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we have the outer membrane, the inner membrane, we have electron transport chain, and this is the matrix of the mitochondria and this is the intermembrane space."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now the question is how many ATP molecules do we actually form when a single NADH is transported onto the electron transport chain from the cytoplasm?"}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Well, the answer to that question basically depends on the type of shuttle that the cell actually uses."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Some cells, such as skeleton muscle cells, use a shuttle known as the glycerol threephosphate shuttle."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And in this particular case, the high energy electrons are transported onto complex three of the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so what that means is we bypass complex one."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And in this particular case, 1.5 ATP molecules will be formed when a single NADH produced in glycolysis moves onto the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So that means because we form two NADH molecules, two multiplied by 1.5 is three."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so three ATP molecules will be formed per two NADH molecules produced in glycolysis in cells that utilize the g three P shuttle to actually move the NADH onto the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So where do we get that number?"}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Well, when the two electrons from NADH are ultimately transported onto complex three, we know that complex three of the electron transport chain actually moves a net amount of two H plus ions."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so actually, we're moving them from the matrix into the intermembrane space so it's in this direction."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And then when the electrons are moved on to this particular complex, complex four, we move a net quantity of four H plus."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so we basically create a proton gradient where we move six H plus ions."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so when these six H plus ions will move from the intermembrane space back into the matrix, this ATP synthase complex five will use them to actually generate the ATP molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And remember, we need four H plus ions so four H plus ions have to move through complex five to actually generate a single ATP molecule."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And what that means is when the six plus H ions move through ATP synthase we need four of them to actually generate a single ATP molecule."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so six divided by four gives us 1.5 ATP molecules are generated when the six H plus ions move when a single NADH is oxidized by the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now, what about the other shuttle?"}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So cells such as cardiac muscle cells, so the heart cells and liver cells utilize a slightly different shuttle known as malate aspartate shuttle."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And the thing about this shuttle is the high energy electrons produced by or found on the NADH produced in the glycolytic pathway ultimately end up being transported onto complex one."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And complex one essentially pumps a net amount of four H plus ions into the intermembrane space."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so here we have four plus two plus four."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "That gives us a total of ten."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so ten divided by four gives us 2.5."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so what that means is the NADH molecules produced in glycolysis in cells that utilize the malade aspartage shuttle basically generate a net amount of 2.5 ATP molecules per single NADH that is oxidized by the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so in cells that utilize malate aspartate shuttle we produce two multiplied by 2.5."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So five ATP molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So this is the number of ATP that we produce in glycolysis."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So the two ATP molecules are produced directly and then we also form the ATP via the oxidative phosphorylation that takes place on the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And this ranges anywhere from three to five ATP depending on the type of shuttle that the cell actually uses."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now the two Pyruvate molecules produced in the cytoplasm then move into the matrix of the mitochondria."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And in the matrix we have Pyruvate decarboxylation that transforms the two Pyruvate into two acetyl coenzyme A molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And in the process we also generate the two NADH molecules and the two NADH molecules because they're produced directly in the matrix of the mitochondria, they move directly onto complex one."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so a single NADH oxidized by the electron transport chain in the matrix goes through all these complexes."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so we pump out these ten H plus ions and that means a single NADH oxidized by the electron transport chain produced in Pyruvate carboxylation produces 2.5 ATP molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And because we have two of these, two multiplied by 2.5 gives us five ATP molecules produced from this process."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now the majority of the NADH are produced in the citric acid cycle."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we have a net result of two GTP, six NADH and two Fadh, two molecules that are produced when two of these acetyl coenzyme A molecules are fed into the citric acid cycle."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now the two GTP are basically catalyzed by special enzyme into two ATP molecules."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so those are the two ATP molecules shown here."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now the six NADH because they're produced directly in the matrix of the mitochondria."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Each one of these nadhs produces 2.5 ATP molecules and six multiplied by 2.5 gives us 15."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Now, recall that when a single fadh two is oxidized by the electron transport chain, it is oxidized by complex two."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so we bypass complex one."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And that means when a single fadh two is oxidized by complex two, complex two doesn't actually pump any protons."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so those electrons extracted from fadh two ultimately end up being transported onto complex three."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we bypass complex one."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so six protons total are pumped."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so six divided by four gives us 1.5."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so 1.5 ATP molecules are produced per single fadh two that is oxidized by the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "And so because we have two of them, two multiplied by 1.5 gives us three."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So to summarize, we have anywhere from two plus three, five to two plus five, seven ATP molecules produced from glycolysis."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "That includes the two ATP and the Nadhs that are basically oxidized by the electron transport chain."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "We have a net amount of five ATP produced by Pyruvate carboxylation when the Nadhs are oxidized by the electron transport chain and the total for the citric acid cycle."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we have two, three and 15, that's 20."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So 20 plus five, that's 25."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So we have two and three."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So 25 plus five, that gives us 30."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "Or in the case of the mallet, aspartage shuttle, we have 32."}, {"title": "ATP Yield of Aerobic Cell Respiration .txt", "text": "So a net result of 30 to 32 ATP molecules are formed from one glucose molecule that is metabolized broken down in aerobic cell respiration."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "From physics we know that whenever a fluid is moving inside a pipe, that fluid will create a force on the walls of that pipe and that will create pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And we define pressure to be the force per unit area."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, in the same analogous way, when we have blood moving inside a blood vessel, that blood will create a force on the walls of that blood vessel and our blood pressure is simply the force per unit area."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So let's suppose we have this blood vessel, we have blood moving inside the blood vessel."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Inside that blood we have many individual molecules, ions."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "We have cells, we have different particles."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And when these things collide with the walls of the container, that will create a force on the walls."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, if we sum all those individual forces in this particular region of the blood vessel and we divide it by the area of the walls of the blood vessel, within that particular section, we get our measurement called the blood pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, in our cardiovascular system we have different types of blood vessels."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "We have large and small arteries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "We have large and small veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "We also have capillaries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now the question is why is there a pressure variation between one location and a different location inside our blood vessel system?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we're going to discuss why there is a difference in pressure between arteries, veins and capillaries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And let's begin with arteries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now remember that arteries are basically those blood vessels that connect directly to the ventricle chamber of our heart."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And these arteries always carry blood away from the ventricle of the heart and to the organs, the tissues and the cells of our body."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now let's take a look at the following diagram."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we have the heart and we also have the surrounding vessels, blood vessels."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now let's focus in on the left ventricle."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The left ventricle contains a very thick layer of muscle and that is shown in black."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we have the thickest layer of muscle within the left ventricle as shown."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now that's because it's the ventricle that creates that hydrostatic pressure in the first place that forces all that blood to move into our blood vessel."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And the blood vessels that connect directly to the left ventricle are these blood vessels."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "It's our order which is the largest artery in our body."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So this left ventricle forces all that blood to quickly fill this blood vessel."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that's exactly why this large artery contains a very high pressure because it's connected directly to that pump that establishes that high pressure in the first place."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "In fact, if we study the anatomy, the structure of the artery, arteries are made specifically to withstand these high pressures."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "They have a very thick layer of muscle within our tunica media layer of that artery."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So large arteries and smaller arteries, they basically have a relatively high hydrostatic pressure because of this reason."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, if we take a look at the following diagram, this is exactly what the diagram describes."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The y axis is the pressure given in millimeters of mercury and the x axis basically are the different types of blood vessels."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So if we look at our largest artery array order and the smaller ones are arteries this is where our pressure is at a highest value."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, when we go from the arteries to the tiniest arteries called arterioles we have a very sharp drop in blood pressure as shown by the slope of this line."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The question is why?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Why is there a drop in blood pressure when we go from the arteries to the arterios and what is the benefit of that to our body?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So the reason there is a drop in blood pressure is because our arterios have a relatively high area to volume ratio."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And what that means is the volume of blood that travels inside our arterios interacts with much more of the surface area of the wall."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And what that basically means is we have a much higher resistance and that decreases our pressure and it also decreases the velocity with which the blood actually moves along our arterios."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, the question is why is that beneficial?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So the velocity of the blood flow decreases."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "But why is this actually beneficial?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Well, the answer lies in our capillaries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The arterios empty out that blood directly into our capillaries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And capillaries are these really specialized blood vessels that are very thin."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "In fact, they're only a single cell layer thick."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that means they are not actually built to withstand any high pressure like our arteries are built."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And in fact, because within the capillaries we have an exchange of nutrients and waste products taking place."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "That basically means is for that exchange to take place efficiently the flow of the blood within the capillaries has to be relatively slow."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So the reason that we need a drop in pressure is to make sure that the pressure and the rate at which our fluid is flowing within the capillaries is low so that the capillaries don't actually pop and so that the capillaries can actually exchange those nutrients and waste products effectively and efficiently."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, one quick way that I can explain why the velocity within the capillaries is low is by using something called the continuity equation."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The continuity equation, Q equals AV, comes from fluid dynamics, comes from physics."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So within our entire cardiovascular system our Q remains constant."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Q is simply the flow of blood within our system."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The flow of blood doesn't actually change because we have a closed cardiovascular circuit, a closed cardiovascular system."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, what does change within the blood vessels is the A the cross sectional area and B the velocity of that fluid."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, it turns out that if we take the sum of all the cross sectional areas of all the individual capillaries it will be much greater than the cross sectional area of the arteries and of the veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So that cross sectional area, the total cross sectional area for the capillaries is the greatest."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, as we increase the A to keep the Q the same, the V must decrease."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that's exactly why within the capillaries the velocity of blood flow is the lowest because the total cross sectional area of the capillaries is basically the greatest."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we see that within the aorta and the large and smaller arteries we have a high pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "But then as we go into the arterials the resistance to flow increases, the velocity of the blood flow decreases and the pressure also drops."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that's to ensure that the capillaries don't break as a result of any high pressure and that the flu exchange, the nutrient exchange can take place within our capillaries."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, the veins connect to our capillaries on the other side."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So the capillaries basically take the de oxygenated blood and dump it out into the small veins known as the Venuels."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And then we go into small veins and large veins and finally into our vena CaveA."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So once the blood travels through the capillaries it enters the Venuels and the veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now let's recall what the structure is of our vein."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The vein also contains a three layer system just like the artery but it has a very thin layer called the tunica media."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So it has a very thin layer of muscle."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And what that means is our veins are inelastic."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "They do not recoil."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So they can easily expand when the blood enters these veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And because they can easily expand, that decreases our pressure within the veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "On top of that, what also decreases is our flow, the velocity with which our blood actually flows."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And on top of that, because veins have to move that blood against the force of gravity that will additionally decrease the flow velocity of our blood within veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So that's exactly why within veins we also have a low pressure and we also have a low velocity with which our blood actually moves."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now of course we have things like the valve system inside the vein and the skeletal muscle that allow that movement to actually take place."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "But that's a different story."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So let's take a look at this diagram once again."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The pressure is the Y axis."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "As we go from the large artery to the smaller arteries we have this very high pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "But then we have a drop taking place between the arterials and our arteries right over here."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And eventually when we get to the capillaries that ensures that the capillaries don't have a high pressure and have a low velocity of blood flow."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Then we have the Venuels, the veins and our vena cava and then the cycle basically repeats."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, this describes the diagram only for our systemic cardiovascular system."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The pulmonary circulation looks very similar except the pressure within our pulmonary artery is smaller than the pressure within our order which is this one right here."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, the way that we actually measure blood pressure inside our body is by first calculating our blood pressure within our aorter."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "This blood vessel right here, the largest artery during cystille."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Cystily is the point when our left ventricle actually contracts and creates that hydrostatic pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So as soon as the left ventricle contracts, it creates that pressure within our order, and that is cystily."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "That is about 120 mmhg normally."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Likewise, we also measure our pressure during relaxation."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "That is known as a diastoli."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Diastoli refers to the process when our left atrium fills the left ventricle."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that's when our blood vessel basically relaxes and the ventricle relaxes."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And the normal value for that is about 80 Mercury."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So the way that we measure pressure is by taking the ratio of the largest to the smallest."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we have contraction, our cystily 120 and relaxation 80."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So it's 120 over 80 is the normal blood pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Now, the last thing I'd like to briefly discuss is why there is a pressure difference pressure gradient in the first place."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Notice in the arteries, we have a large pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "In the veins, we have a small pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "The question is, why does that actually exist?"}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "Well, one good analogy is the movement of an object when you let go."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So if you let go of an object, it will travel down to the surface of the Earth."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And that's because it's moving from a high potential gravitational potential to a low gravitational potential."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "It's moving down its potential gradient."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "In the same exact way."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "We have a high pressure, we have a low pressure."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So we establish a pressure gradient."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "And blood always moves from a high pressure to a low pressure, that is, from our arteries to our veins."}, {"title": "Blood Pressure in Arteries, Veins, and Capillaries.txt", "text": "So it's because we have a pressure gradient inside our blood vessel system that the blood can actually move in the first place from the arteries to the veins and continue moving as our pump continues pumping that blood."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "The amino terminal groups of the four polypeptide chains."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So, to see what that actually forms, let's take a look at the following equation."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So this is the carbon dioxide, the nonpolar carbon dioxide, and this is the terminal residue, the amino terminal residue."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So, in the presence of a special enzyme, this is basically transformed into the following group known as the carbonate."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So this carbonate contains a negative charge."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "And just like we form salt bridges, in this case, this can also form, the carbonate can also form a salt bridge, thereby stabilizing the entire T state structure of the deoxy hemoglobin."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "And by the same token, the stabilization of the deoxy hemoglobin's T state also shifts the curves to the right side, thereby decreasing the affinity of hemoglobin for oxygen and allowing to actually unload more o two molecules to the exercising tissue of our body."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So this entire discussion basically is known as the Bore effect."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "So the Bore effect is basically the effect that is observed when hydrogen ions and carbon dioxide ions together create the PH effect and the carbon dioxide effect, and basically shift the curve to the right side."}, {"title": "The Bohr Effect and Hemoglobin (Part II) .txt", "text": "And that means they decrease the affinity of hemoglobin for oxygen, allowing the hemoglobin to release more oxygen to the rest of tissues, as well as to the exercising tissues of our body."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So far in our discussion on proteases, we focused on seren proteases, and we discussed three examples of serum proteases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So we discussed chimera, Trypton, trypsin and elastics."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now, we said these three serum proteases all use the same catalytic triad."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So in their active side, they have this collection of three amino acids that work together to basically promote the hydrolysis of peptides side bonds."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And out of these three amino acids, it's the serine that acts as the nucleophilic agent."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now, what about the other categories of proteases?"}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So remember, we not only have seren proteases, but we also have cysteine proteases aspertal proteases metalloprotiases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And we have other examples of proteases that we're not going to focus on in this lecture."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So the question is, what exactly is the mechanism of these other proteases?"}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And how does the mechanism differ or how does it compare to the mechanism inside seren proteases?"}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So let's begin by briefly discussing cysteine proteases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So in cysteine proteases, we also have amino acids in the active side that work together to basically catalyze the cleavage of peptide bonds."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "But unlike encryption, proteases insisteine proteases, it's the cysteine residue found on the active side that acts as that nucleophilic agent that will cleave that peptide bond."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And to see how that actually works, let's take a look at the following diagram."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So, we have a cysteine residue in the active side of some particular cysteine protease."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now, in the form that we have cysteine here, cysteine is not a strong enough nucleophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So the sulfur, as shown here, is not a strong enough nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And it will not be able to attack the carbon of that carbonyl group on that substrate molecule because this simply isn't a good enough nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So what must happen is another residue must work together with the cystine to basically transform it into a better nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So how does that actually take place?"}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Well, in a similar way to how it takes place in seren proteases, so we have a nearby residue, for example, a histidine."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And on that histidine, we have this nitrogen, which contains a lone pair of electrons."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "On top of that, the nitrogen can also have or also has a partial negative charge because it's more electronegative than the nearby carbon atoms."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now, if we examine this H on the sulfur, we see that the age contains a partial positive charge because the sulfur is more electronegative and the sulfur contains a partial negative charge."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So what we see happening is before the substrate actually enters the active side, what begins to happen is the nitrogen, because of its higher electron density, begins to pull on this H ion."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And as the H ion is being pulled away onto the nitrogen, as shown in this particular diagram, these two electrons in the sigma bond move closer to the sulfur atom, and that increases the electron density, the electron cloud around the sulfur, and that increases its ability to act as a nucleophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So as the H atom is being pulled away onto the nitrogen of the nearby histidine residue, we see that these two electrons move closer to the sulfur and the electron density on the sulfur increases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so as we have this incoming substrate molecule these two electrons attack nucleophilically the carbon on the carbonyl and that displays the pi bond."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so once the step takes place twice we form the same type of tetrahedral intermediate that we formed in the serene protease reaction mechanism."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And just like in Seren proteases we can have an oxyanion hole that stabilizes the negative charge on that oxygen."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Once we form the tetrahedral intermediate in cysteine proteases we can also have a similar type of oxygenine hole that stabilizes that relatively unstable and high energy tetrahedral intermediate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now of course eventually the tetrahedral intermediate will collapse and after a few processes we're going to basically break that peptide bond in a similar way to how we broke the peptide bond in Serine proteases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now two examples of cysteine proteases are cat spaces."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "These are those enzymes involved in the process of programmed cell deposit apatosis as well as cathypsons, which are involved in immunity."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now let's move on to aspartate proteases, also known as aspertyl proteases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now the major difference between cysteine proteases and aspirations is the following."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "In cystine proteases as well as the serum proteases we see that one of the residues inside the active side of the enzyme acts as a nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "But in aspital protease, the residues don't actually act as nuclear files."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Instead it's the water that will ultimately act as the nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now the similarity between, let's say cysteine protease and aspirin protease is we still have to transform the water into a good nuclear file in the same way that we had to transform the cysteine into a strong nuclear file before the nuclearphilic attack took place."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "In this particular case we see that we're going to have residues that will transform the water into a better nuclear phile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now if we examine the active side of aspir proteases we're going to find two residues."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "One of these residues will be aspartic acid and the other one will be aspartate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So this is basically the same thing as this but this is in the deprovinated state and this is in the proteinated state."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So we have aspartate, we have aspartic acid."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now when water moves into the active side the negative charge on the aspartate will interact with a positive charge on one of the H atoms."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So we have a partial positive charge here because the oxygen contains a partial negative charge."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so by the same analogy here when the nitrogen pulls away the H it gives the electrons to the sulfur and so the electron density on the sulfur increases and it becomes a better nucleophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Here when the negative charge the oxygen pulls away the H, it makes the oxygen a better nucleophile because we essentially transform water into a hydroxide and the hydroxide is a much stronger nucleophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "At the same time, what happens is the other residue, the spartic acid, uses its H to basically interact with the oxygen of the Carbonal."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So the oxygen here contains a partial negative charge and the H here contains a partial positive charge."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so, as they interact here, what begins to take place is we basically make the carbon of the carbonyl a better electrophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So the ultimate reason why we have these two different we have the aspartate and the spartic acid is because one transforms the water into a better nuclear file and the other one transforms the incoming substrate into a better electrophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And now we can have our reaction take place."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "The similar reaction, the same type of reaction that took place here, we have this bond breaking, forming a bond with carbon, attacking the carbon nucleophilically, displacing the pi bond, forming that same type of tetrahedral intermediate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Except now, instead of having a bond between this residue and the carbon, we have a bond between the oxygen of the water and this carbon."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So inside the active side of these proteins is a pair of aspartic acid residues."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "They work together to transform water into a good nuclear file so that it can hydrolyze that peptide bond."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So what happens is the deprotonated aspartic acid, the aspartate shown here, uses its negative charge to transform the water into a better nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So we essentially create a hydroxide and then the protonated version of the residue, the spartic acid, uses the partially positive hydrogen to basically interact with that partially negative oxygen of the carbonyl."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And that creates a good electrophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And now the reaction can take place at a relatively high rate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Now, two examples of aspartate proteases that we're going to focus on in future lectures is Renmin, and this is basically the enzyme that is used to control blood pressure as well as pepsin."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And this is one of the digestive enzymes that is found in our digestive system."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And finally, let's take a look at metalloprotiases."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So, just like the name implies, this has to do with the fact that inside the active side of metalloproteases, we actually have a metal atom, and usually the metal atom is zinc."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So what's the point of the metal atom?"}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Well, for the same exact reason that we have this residue to basically transform the water into a better nuclear file here, we also have a metal atom to actually bind the water and transform it into a better nuclear file so that the water can basically hydrolyze that peptide bond."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So if we examine the active side, as shown here, let's say we have the zinc metal atom that is actually bound to the active side of that enzyme."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so what it does is it interacts with the oxygen as a result of this being partially negative and this having a positive charge."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So they form this bond at the same time, some type of nearby residue acts as a base and usually the residue is glutamate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So this acts as a base and basically grabs off the h. It pulls the h away from this oxygen and that transforms the oxygen into a much better nuclear file."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So it creates that hydroxide."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And now this can act as a nucleophile attacking the carbon of the carbonyl and once again forming a tetrahedral intermediate."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And then following several steps, we basically collapse and break apart that tetrahedral intermediate and eventually we hydrolyze that peptide."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Bond now, one example of a metalloprotease that is found inside our body is carboxy peptidase a."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And this is once again another example of a digestive enzyme."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "So we see that even though we have many different groups, many different types of proteases, we have seren proteases, cysteine proteases aspertal proteases metalloprotiases and so forth, all these different types of proteases basically function in a very similar way."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "What they ultimately do is they transform a bad nucleophile into a good nucleophile and they transform a bad electrophile into a better electrophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And so that ultimately we have a strong nucleophile attacking a very good electrophile."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "And that's exactly what increases the rate of that reaction, the rate of the hydrolysis of that peptide."}, {"title": "Cysteine, Apsratyl and metalloproteases.txt", "text": "Bond."}, {"title": "NMP Kinases .txt", "text": "So far in our discussion on enzymes, we focus on two types of enzymes."}, {"title": "NMP Kinases .txt", "text": "We discuss proteases and carbonic and hydrates."}, {"title": "NMP Kinases .txt", "text": "Now we're going to focus on a third type of enzyme found in our body known as nucleotide monophosphate kinases or simply an MP kinases."}, {"title": "NMP Kinases .txt", "text": "Now, Nmpkinases catalyze the transfer of a phosphoryl group from some type type of nucleotide triphosphate, for example, ATP molecule onto another molecule, namely the nucleoside monophosphate or NMP."}, {"title": "NMP Kinases .txt", "text": "And to basically show what that means, let's take a look at the following general chemical equation."}, {"title": "NMP Kinases .txt", "text": "So we have two reactants, two substrate molecules and this reaction is catalyzed by some type of NMP kinase."}, {"title": "NMP Kinases .txt", "text": "Now in this particular case, because I'm using ATP as a specific nucleuside triphosphate, the name of the NMP kinase molecule is adenylate kinase."}, {"title": "NMP Kinases .txt", "text": "And so adenylate kinase will catalyze the transfer of this purple terminal phosphoryl group from the ATP molecule onto this region of the nucleocide monophosphate and we ultimately form the nucleocide diphosphate and the adenosine diphosphate."}, {"title": "NMP Kinases .txt", "text": "So this loses a phosphoryl group and this gains a phosphoryl group."}, {"title": "NMP Kinases .txt", "text": "So in this reaction we have two substrate molecules, the ATP as well as the MMP."}, {"title": "NMP Kinases .txt", "text": "Now what do we have to know about nucleotide monophosphate kinases?"}, {"title": "NMP Kinases .txt", "text": "Well, there are three things that you have to keep in mind about these enzymes and let's begin by discussing the first one."}, {"title": "NMP Kinases .txt", "text": "So NMP kinase molecules, for example adenylate kinase or guanylate kinase."}, {"title": "NMP Kinases .txt", "text": "So guanylate kinase basically catalyzes the transfer of the phosphoryl group from GTP onto some type of NMP."}, {"title": "NMP Kinases .txt", "text": "So if we study the three dimensional structure of all these different types of NMP kinases, for example, these two, we're going to see a region that is conserved."}, {"title": "NMP Kinases .txt", "text": "It remains the same when we go from one molecule, one enzyme, one kinase to another kinase."}, {"title": "NMP Kinases .txt", "text": "And this is the region shown here."}, {"title": "NMP Kinases .txt", "text": "So if we begin at the beginning of the polypeptide chain, this is where we're going to be."}, {"title": "NMP Kinases .txt", "text": "And so we basically move along the polypeptide chain."}, {"title": "NMP Kinases .txt", "text": "And this is the first beta sheet that we come across."}, {"title": "NMP Kinases .txt", "text": "And then we continue moving and we move through this colored loop."}, {"title": "NMP Kinases .txt", "text": "And this colored loop is known as the P loop structure."}, {"title": "NMP Kinases .txt", "text": "And we'll see why we call it the P loop in just a moment."}, {"title": "NMP Kinases .txt", "text": "Then we have the first alpha helix and then we continue."}, {"title": "NMP Kinases .txt", "text": "We have the second beta sheets, then we continue, we have the second alpha helix, we continue, we have the third beta sheet and so forth and we continue all the way until we get to the end."}, {"title": "NMP Kinases .txt", "text": "Now what's so special about this colored loop?"}, {"title": "NMP Kinases .txt", "text": "Well, this loop is known as the P loop."}, {"title": "NMP Kinases .txt", "text": "And the reason we call it the P loop is because this polypeptide section is the section that contains the amino acids that are responsible for actually binding to and interacting with the ATP molecule."}, {"title": "NMP Kinases .txt", "text": "And more specifically, it will interact with the negative charges on this triphosphate group of that ATP molecule."}, {"title": "NMP Kinases .txt", "text": "And if we study the sequence of nucleotides among the different types of NMP kinases on that p loop, this is what we're going to see."}, {"title": "NMP Kinases .txt", "text": "So it's relatively conserved."}, {"title": "NMP Kinases .txt", "text": "So we have a glycine followed by four x's, where the x basically describes some type of arbitrary amino acid."}, {"title": "NMP Kinases .txt", "text": "And then we have glycine and lycine."}, {"title": "NMP Kinases .txt", "text": "Now, what we see happen is the NH groups that are basically found on the backbone of this pilot will interact, will form hydrogen bonds with the negative charges of these oxygen on the triphosphate."}, {"title": "NMP Kinases .txt", "text": "And likewise, if we have any residue that contains a positive charge."}, {"title": "NMP Kinases .txt", "text": "So if we have basic residues such as lysine and arginine found on a PLOOP, those will also form interactions with this triphosphate."}, {"title": "NMP Kinases .txt", "text": "And so it's the p loop structure found inside this domain of the enzyme that actually is responsible for binding and interacting with this substrate molecule, the triphosphate group of that particular nucleotide triphosphate."}, {"title": "NMP Kinases .txt", "text": "So in the case of adenylate kinase, it's the triphosphate group of the ATP that the p loop actually interacts with."}, {"title": "NMP Kinases .txt", "text": "Now, the second thing you have to know about nucleoside monophosphate kinases is they use a specific mechanism of enzyme catalysis known as metal ion catalysis."}, {"title": "NMP Kinases .txt", "text": "Now, we actually discussed metal ion catalysis previously when we discussed proteases and carbonic and hydrates."}, {"title": "NMP Kinases .txt", "text": "But the major difference between that type of metaline catalysis and the metaline catalysis that takes place within an MP kinases is here that metal ion doesn't actually interact with the active sites enzyme, but it interacts with the substrate molecule itself."}, {"title": "NMP Kinases .txt", "text": "So we see that NMP kinases require the presence of a metal atom such as magnesium or a manganese."}, {"title": "NMP Kinases .txt", "text": "And so we have to have some type of divalent metal atom."}, {"title": "NMP Kinases .txt", "text": "Divalent simply means it has a charge of positive two."}, {"title": "NMP Kinases .txt", "text": "So to demonstrate why this is so, let's suppose we have the ATP molecule as our substrate."}, {"title": "NMP Kinases .txt", "text": "So this is the ATP."}, {"title": "NMP Kinases .txt", "text": "So we have our adenine base, the sugar component, and the triphosphate group."}, {"title": "NMP Kinases .txt", "text": "And so the reason we need that magnesium or the manganese, the reason we need a divulge positive metal ion is because the positive metal ion will interact with the negative charges on the oxygen molecule on the oxygen atoms of the triphosphate."}, {"title": "NMP Kinases .txt", "text": "And by interacting with the oxygen, they will create a conformational change in that substrate molecule."}, {"title": "NMP Kinases .txt", "text": "And by inducing that conformational change, they will create a shape."}, {"title": "NMP Kinases .txt", "text": "They will give the ATP molecule a shape that is appropriate for the shape of that active side."}, {"title": "NMP Kinases .txt", "text": "So we need the divilus metal atom to basically give the ATP substrate molecule the appropriate shape so that it can actually interim bind to the active side of that nucleocide monophosphate kinase."}, {"title": "NMP Kinases .txt", "text": "So before the NTP substrate, in this particular case, ATP can bind onto the active side of that kinase, the NTP must bind to a dive of metal atom such as magnesium or manganese."}, {"title": "NMP Kinases .txt", "text": "So what happens is two oxygens on this triphosphate interact with our magnesium atom so we have the alpha oxygens, we have the beta oxygens, these two, and then we have these are the gamma oxygens because this is the alpha phosphorus atom, the beta phosphorus atom and the gamma phosphorus atom."}, {"title": "NMP Kinases .txt", "text": "And so the magnesium can either interact with the alpha and beta oxygens or with the alpha and gamma oxygens or as in this particular case, the beta and gamma oxygens."}, {"title": "NMP Kinases .txt", "text": "And each time the magnesium interacts with two different oxygens that creates its own unique conformation."}, {"title": "NMP Kinases .txt", "text": "And so different enzymes require a different interaction because different enzymes require a different shape."}, {"title": "NMP Kinases .txt", "text": "And in this particular case, for adenylate kinase the magnesium must interact with these two oxygen atoms to give it the proper orientation and shape to basically be able to bind into the active side of that and MP kinase."}, {"title": "NMP Kinases .txt", "text": "Now, not only will the magnesium interact with two oxygen atoms of the triphosphate of the substrate, but the magnesium will also be stabilized by four different water molecules and that will give a stabilizing octahedral arrangement."}, {"title": "NMP Kinases .txt", "text": "So these are the two oxygens that come from the triphosphate group and these are the four oxygens."}, {"title": "NMP Kinases .txt", "text": "And so the partially negative oxygen of these water molecules will form bonds, coordinate bonds with this magnesium atom and this will stabilize that structure and create a conformational change that will basically bridge that active side structure and the structure of this particular substrate molecule."}, {"title": "NMP Kinases .txt", "text": "So the magnesium will interact with two oxygen atoms on the ATP molecule as well as four water molecules and the interaction will hold that substrate in a well defined conformation, a well defined shape that is suitable for the shape of the active side found in that enzyme."}, {"title": "NMP Kinases .txt", "text": "And so ultimately, we see that the metal ion serves as a bridge between the substrate molecule and the enzyme."}, {"title": "NMP Kinases .txt", "text": "Without that metal ion the substrate would not be able to bind into the active side because it would not have the proper orientation."}, {"title": "NMP Kinases .txt", "text": "And so ultimately, it's the ATP metal ion complex that is the substrate of that active side because only when the metal atom binds with the ATP molecule will the interactions between the active side and the substrate be perfect and very stabilizing interactions."}, {"title": "NMP Kinases .txt", "text": "Now, the final thing that I'd like to mention about MP kinases is that they not only use the metal ion catalysis, but they also use catalysis by proximity and orientation."}, {"title": "NMP Kinases .txt", "text": "And to see what we mean by that, let's take a look at the structure of our NMP kinase, namely the adenolid kinase."}, {"title": "NMP Kinases .txt", "text": "And so this is the domain that we basically spoke of earlier and this is our P loop."}, {"title": "NMP Kinases .txt", "text": "So what happens is once the magnesium binds onto the ATP molecule, that creates a correct conformation and then the ATP magnesium complex can move into the active side of this molecule and bind with that P loop structure."}, {"title": "NMP Kinases .txt", "text": "And once it binds with the P loop structure, that creates a localized change in conformation."}, {"title": "NMP Kinases .txt", "text": "And that localized chain creates a more extensive change in the entire structure of that particular enzyme."}, {"title": "NMP Kinases .txt", "text": "And in particular if we examine the purple region, this is known as the lid domain of the kinase."}, {"title": "NMP Kinases .txt", "text": "As it binds onto the pilot, this basically closes down just like a lid closes on top of a can."}, {"title": "NMP Kinases .txt", "text": "And so, in the same way, this lid basically closes down and it induces a conformational change that traps that ATP molecule in the proper orientation so that now the other substrate, the NMP, can bind onto the active side."}, {"title": "NMP Kinases .txt", "text": "And it binds in such a way so that the terminal phosphoryl group of the ATP is in close proximity and in the proper orientation with respect to this and MP molecule."}, {"title": "NMP Kinases .txt", "text": "And that's exactly what we mean by catalysis by proximity and orientation."}, {"title": "NMP Kinases .txt", "text": "What the active side does is it induces this change that brings these two substrate molecules in close proximity and arranges them in a proper orientation which basically decreases the energy of transition and it basically catalyzes the transfer of this phosphoryl group from ATP onto the NMP."}, {"title": "NMP Kinases .txt", "text": "In addition, because these two substrate molecules are essentially trapped in the active side, nothing else can actually come in because this entire lid domain closes off."}, {"title": "NMP Kinases .txt", "text": "And so other molecules, for example, water molecules, will not be able to enter the active side and that means the water molecules will not be able to hydrolyze this section."}, {"title": "NMP Kinases .txt", "text": "And so that will decrease the likelihood that any competing reaction will take place."}, {"title": "NMP Kinases .txt", "text": "Because remember, the problem is if we don't have the NMP kinase and these two molecules are in the presence of water, water will be very likely to actually hydrolyze and break this bond here."}, {"title": "NMP Kinases .txt", "text": "And what that means is instead of transferring the phosphoryl group onto the NMP, that phosphoryl group will be transferred onto the water molecule."}, {"title": "NMP Kinases .txt", "text": "And so what the enzyme does is it utilizes catalysis by proximity."}, {"title": "NMP Kinases .txt", "text": "It closes off the active side and keeps away the water molecules and so no competing reactions can actually take place."}, {"title": "NMP Kinases .txt", "text": "So once again, as the ATP magnesium substrate binds to the P loop, as this complex binds into this P loop here, it induces a local conformational change in the section and that causes a more extensive change."}, {"title": "NMP Kinases .txt", "text": "And so the lid domain essentially closes off and then the binding of that second substrate, the NMP molecule into the active side creates additional changes and this causes catalysis by proximity."}, {"title": "NMP Kinases .txt", "text": "So these changes in confirmation hold the two substrates close together so in close proximity and gives them the proper orientation that basically promotes the transfer of the phosphoral group."}, {"title": "NMP Kinases .txt", "text": "So it decreases the energy of the transition state, decreases the activation energy barrier and prevents any competing reactions from actually taking place."}, {"title": "NMP Kinases .txt", "text": "So NMP kinases do not only utilize the metal iron catalysis mechanism but they also utilize catalysis by proximity and orientation."}, {"title": "Peptide Bond Formation.txt", "text": "We now know that the building blocks of proteins are amino acids."}, {"title": "Peptide Bond Formation.txt", "text": "And inside our body, we only have 20 different types of amino acids that constitute the different types of proteins."}, {"title": "Peptide Bond Formation.txt", "text": "Now, the next question is, how exactly are these amino acids held together inside any given protein?"}, {"title": "Peptide Bond Formation.txt", "text": "So what is the type of bond that holds our amino acids together?"}, {"title": "Peptide Bond Formation.txt", "text": "Well, this bond is actually a special type of covalent bond known as a peptide bond or an AmiB."}, {"title": "Peptide Bond Formation.txt", "text": "So let's begin by taking a look at the following reaction that basically describes the reaction that forms this peptide bond."}, {"title": "Peptide Bond Formation.txt", "text": "So let's suppose we're on the reactant side, and on the reactant side, we have amino acid A and amino acid B."}, {"title": "Peptide Bond Formation.txt", "text": "Now, amino acid A contains a side chain group given by R one, and this one contains a different side chain group given by R two."}, {"title": "Peptide Bond Formation.txt", "text": "And any one of these amino acids can be any one of the 20 amino acids found inside our body."}, {"title": "Peptide Bond Formation.txt", "text": "For example, this can be Glycine and this can be Lysine and so forth."}, {"title": "Peptide Bond Formation.txt", "text": "Now, under certain conditions, these two reactants will react, and they will produce the following product."}, {"title": "Peptide Bond Formation.txt", "text": "Now, product C is a dipeptide, and a dipeptide simply means we have two amino acids connected by a peptide bond that is shown in green."}, {"title": "Peptide Bond Formation.txt", "text": "So this carbon on product C is this carbon on reactant A, and this nitrogen on product C is this nitrogen on reactant B."}, {"title": "Peptide Bond Formation.txt", "text": "So basically, this carbon forms a bond with this nitrogen shown in green, and that is our peptide bond between these two amino acids A and B."}, {"title": "Peptide Bond Formation.txt", "text": "Now, whenever we react a certain type of reactants, and whenever a chemical reaction takes place, we know that the number of atoms is always conserved because we have the conservation of mass."}, {"title": "Peptide Bond Formation.txt", "text": "Now, let's take a look at this carbon and then compare to this carbon."}, {"title": "Peptide Bond Formation.txt", "text": "In this particular case, the carbon contains a single oxygen atom."}, {"title": "Peptide Bond Formation.txt", "text": "But in this particular case, the carbon contains one two oxygen atoms."}, {"title": "Peptide Bond Formation.txt", "text": "So somewhere in this reaction, there was a loss of an oxygen atom."}, {"title": "Peptide Bond Formation.txt", "text": "Likewise, if we take a look at the nitrogen and compare it to this nitrogen, in this particular case, we have three H atoms."}, {"title": "Peptide Bond Formation.txt", "text": "In this particular case, we only have one."}, {"title": "Peptide Bond Formation.txt", "text": "So when we basically combine A and B to form C, we basically lose two H atoms and one oxygen, and that is a water molecule."}, {"title": "Peptide Bond Formation.txt", "text": "So in the process of forming this peptide bond, we always release a water molecule."}, {"title": "Peptide Bond Formation.txt", "text": "And that's why this reaction is known as a dehydrolysis reaction or a condensation, because we release a water molecule."}, {"title": "Peptide Bond Formation.txt", "text": "So we have amino acid A and B react to form a dipeptide C, and we also release a water molecule."}, {"title": "Peptide Bond Formation.txt", "text": "So going this way, we have a dehydrolysis a condensation reaction."}, {"title": "Peptide Bond Formation.txt", "text": "But if we go in reverse, if this bond breaks by using a water molecule that is known as a hydrolysis reaction."}, {"title": "Peptide Bond Formation.txt", "text": "Now, let's take a look at the arrows."}, {"title": "Peptide Bond Formation.txt", "text": "So the arrow going this way is smaller than the arrow going in reverse."}, {"title": "Peptide Bond Formation.txt", "text": "And what that basically means is the reactants A and B are thermodynamically more stable than the products C and D. And so if we plot this reaction on the following graph, the energy graph where the y axis is the energy state and the x axis is the reaction progress, this is what we're going to get."}, {"title": "Peptide Bond Formation.txt", "text": "And notice that the energy values of these reactants is lower than the energy values of these products."}, {"title": "Peptide Bond Formation.txt", "text": "And that's exactly what we mean by our reactants being thermodynamically more stable than our products."}, {"title": "Peptide Bond Formation.txt", "text": "Now, what exactly does that actually mean about our reaction?"}, {"title": "Peptide Bond Formation.txt", "text": "Well, what it means is for this reaction to actually take place and for us to go from a lower energy level to a higher energy level."}, {"title": "Peptide Bond Formation.txt", "text": "So for us to go from this energy level right over here to this energy level, let's say right over here, we have the input a certain amount of energy."}, {"title": "Peptide Bond Formation.txt", "text": "So that means that the peptide bond formation is a process that requires energy."}, {"title": "Peptide Bond Formation.txt", "text": "Now where does that energy come from in our body?"}, {"title": "Peptide Bond Formation.txt", "text": "Well, the energy comes from using ATP molecules."}, {"title": "Peptide Bond Formation.txt", "text": "So it turns out that to actually form a peptide bond, we have to use ATP molecules as a result of the fact that the reactants are thermodynamically more stable than our products."}, {"title": "Peptide Bond Formation.txt", "text": "So once again, notice that the four reaction which is a dehydrolysis reaction, is thermodynamically unfavorable."}, {"title": "Peptide Bond Formation.txt", "text": "And this means that to form a peptide bond we actually have to input a certain amount of energy and that energy comes from the ATP molecules found inside our body."}, {"title": "Peptide Bond Formation.txt", "text": "Now the next question is if these products are higher in energy than these reactants here, why exactly do these bonds not spontaneously break inside our body?"}, {"title": "Peptide Bond Formation.txt", "text": "So why don't the bonds inside the protein holding our amino acids actually break spontaneously?"}, {"title": "Peptide Bond Formation.txt", "text": "And the answer is because of a high activation energy."}, {"title": "Peptide Bond Formation.txt", "text": "So if we take a look at the following reaction going backwards, this here is the activation energy, the barrier energy that is needed, that we must overcome to actually go from the product side to the reactant side."}, {"title": "Peptide Bond Formation.txt", "text": "So even though this reaction here, so going from the products to our reactants is thermodynamically favorable, it is not kinetically favorable."}, {"title": "Peptide Bond Formation.txt", "text": "And what that means is we have to input a lot of energy to actually overcome this reverse activation barrier."}, {"title": "Peptide Bond Formation.txt", "text": "And we simply don't have that much energy under normal conditions inside our cells at a PH of seven and at the normal body temperature, we don't have enough energy for this reaction to actually take place."}, {"title": "Peptide Bond Formation.txt", "text": "In fact, to actually break the peptide bond inside our body, we have to use special enzymes that basically decrease this activation barrier."}, {"title": "Peptide Bond Formation.txt", "text": "So once again, if the dipeptide bond, if the dipeptide formation as described in this diagram is energetically unfavorable, why doesn't the reverse reaction take place spontaneously?"}, {"title": "Peptide Bond Formation.txt", "text": "And naturally in our body."}, {"title": "Peptide Bond Formation.txt", "text": "Well it turns out that the activation energy is simply too high, it's simply too great."}, {"title": "Peptide Bond Formation.txt", "text": "And at the conditions of our body temperature and neutral physiological PH, this reaction simply does not take place."}, {"title": "Peptide Bond Formation.txt", "text": "So we conclude the following three facts about peptide bonds and the biosynthesis of peptide bonds."}, {"title": "Peptide Bond Formation.txt", "text": "So peptide bonds form via a dehydrolysis reaction."}, {"title": "Peptide Bond Formation.txt", "text": "And what that means is at the end of forming a single peptide bond we always release a water molecule."}, {"title": "Peptide Bond Formation.txt", "text": "Now we can also say that the breaking of a peptide bond is a hydrolysis reaction."}, {"title": "Peptide Bond Formation.txt", "text": "So we have to use a water molecule to actually break this peptide bond to give back this carbon its oxygen and this nitrogen its two H atoms."}, {"title": "Peptide Bond Formation.txt", "text": "Now fact number two is peptide bond formation."}, {"title": "Peptide Bond Formation.txt", "text": "The biosynthesis of peptide bonds is a thermodynamically unfavorable process."}, {"title": "Peptide Bond Formation.txt", "text": "And what that means is we always have to input energy."}, {"title": "Peptide Bond Formation.txt", "text": "We have to take energy away from ATP to basically form the peptide bonds that hold these amino acids together inside protein molecules."}, {"title": "Peptide Bond Formation.txt", "text": "And fact number three is the reason that inside our cells these proteins don't spontaneously break apart."}, {"title": "Peptide Bond Formation.txt", "text": "And these peptides don't spontaneously break apart is because this reaction here is kinetically unfavorable and this reaction is kinetically favorable."}, {"title": "Peptide Bond Formation.txt", "text": "And what that means is there's simply too much energy in the activation barrier for us to actually go in reverse from the products to our reactants."}, {"title": "Peptide Bond Formation.txt", "text": "So peptide bonds are kinetically stable."}, {"title": "Peptide Bond Formation.txt", "text": "We would have to increase, increase the temperature to a high temperature or we would have to use an enzyme that decreases that activation energy to actually break the peptide bond and go back to these individual constituent amino acids."}, {"title": "Peptide Bond Formation.txt", "text": "So these are the bonds that hold our amino acids together inside protein molecules."}, {"title": "cDNA Library.txt", "text": "One of the major differences between prokaryotic DNA and Eukaryotic DNA is that Eukaryotic DNA consists of introns and exxons while prokaryotic DNA only contains exons."}, {"title": "cDNA Library.txt", "text": "Remember, an intron is a segment on that DNA that does not code for any useful protein."}, {"title": "cDNA Library.txt", "text": "Now what happens inside signed Eukaryotic cells is when transcription takes place we form a pre mRNA molecule that contains introns and exons."}, {"title": "cDNA Library.txt", "text": "But then what happens inside the Eukaryotic cell is we have a process that takes place that removes those intros from the mRNA to form an mRNA molecule that only consists of the exons."}, {"title": "cDNA Library.txt", "text": "And this is a fully functional mRNA molecule that can now be used to form proteins."}, {"title": "cDNA Library.txt", "text": "So if we are to use bacterial cells to form different types of eukaryotic proteins from Eukaryotic genes we have to first remove these introns from the genes of those Eukaryotic DNA molecules."}, {"title": "cDNA Library.txt", "text": "So once again Eukaryotic genes contain noncoding segments called introns."}, {"title": "cDNA Library.txt", "text": "And when Eukaryotic genes are transcribed the pre mRNA molecule that is formed contains those intron segments."}, {"title": "cDNA Library.txt", "text": "What happens inside the eukaryotic cells is these intron segments are removed because the eukaryotic cells contain the proper proteins and the proper machinery inside the cell to actually carry out the process."}, {"title": "cDNA Library.txt", "text": "But this does not exist inside prokaryotic cells such as bacterial cells."}, {"title": "cDNA Library.txt", "text": "And this is a problem because if we take a Eukaryotic gene so let's suppose this is Eukaryotic DNA molecule and this colored portion is the gene within that eukaryotic DNA molecule that codes for some particular protein."}, {"title": "cDNA Library.txt", "text": "The question is can we take this eukaryotic DNA, place it inside that prokaryotic bacterial cell in this form and expect that bacterial cell to be able to actually form any useful protein from this particular DNA?"}, {"title": "cDNA Library.txt", "text": "And the answer is no."}, {"title": "cDNA Library.txt", "text": "And that's because once we take this molecule and place it inside that bacterial cell we have these intro sections shown in orange and these exxon sections shown in blue."}, {"title": "cDNA Library.txt", "text": "And when this is found inside that bacterial cell the bacterial cell will be able to use special types of proteins to transcribe the DNA into this premRNA but it will not be able to take out these RNA sections, these intron sections from this mRNA."}, {"title": "cDNA Library.txt", "text": "And so because it's only these blue sections that are necessary to form that particular protein and because the bacterial cell has no way of removing these orange sections and splicing together the blue sections that bacterial cell will not be able to form any useful protein."}, {"title": "cDNA Library.txt", "text": "Now the question is can we somehow fix this problem?"}, {"title": "cDNA Library.txt", "text": "Can we somehow create a eukaryotic gene that does not contain these intro sections, these intron sections here?"}, {"title": "cDNA Library.txt", "text": "Because if we can somehow create a Eukaryotic gene, if we somehow can take this Eukaryotic DNA and remove these introns just simply splice together the blue sections, then we'll form a gene that doesn't contain these useless intron sections."}, {"title": "cDNA Library.txt", "text": "And then we take that gene, place it into that bacterial cell, and that bacterial cell won't have to worry about removing these introns, and so it can easily form that eukaryotic protein."}, {"title": "cDNA Library.txt", "text": "So this is called building a complementary DNA library."}, {"title": "cDNA Library.txt", "text": "So a complementary cDNA library is a library that consists of eukaryotic genes in which we have removed all these different introns."}, {"title": "cDNA Library.txt", "text": "So to see how we can build a cDNA library, let's take a look at the following five steps."}, {"title": "cDNA Library.txt", "text": "So let's suppose we take this same eukaryotic DNA molecule that contains these introns and these exons."}, {"title": "cDNA Library.txt", "text": "So this is our DNA library shown here."}, {"title": "cDNA Library.txt", "text": "So we have these introns, we have the exons and this is our gene, the eukaryotic gene."}, {"title": "cDNA Library.txt", "text": "So the first step is to allow that eukaryotic cell to transcribe this DNA molecule into the single stranded pre mRNA molecule."}, {"title": "cDNA Library.txt", "text": "And pre simply means it has not yet been processed by that eukaryotic cell."}, {"title": "cDNA Library.txt", "text": "Now, instead of taking out the premrina molecule, let's keep the prem RNA molecule inside that eukaryotic cell."}, {"title": "cDNA Library.txt", "text": "And what that means is this eukaryotic cell will use the premrina molecule and because it is a eukaryotic cell, it has the proper machinery to remove these intros and basically combine these exons."}, {"title": "cDNA Library.txt", "text": "So we basically take the premna, we remove these orange sections, we modify the mRNA in other ways."}, {"title": "cDNA Library.txt", "text": "For example, we add a polyatail and then we finalize and we form that fully processed mRNA molecule that only consists of these exon sections and not of these intron sections."}, {"title": "cDNA Library.txt", "text": "Now, once we form the fully processed mRNA molecule that no longer contains those intron sections, we now take and mix it with a special enzyme known as reverse transcriptase."}, {"title": "cDNA Library.txt", "text": "Now, what reverse transcriptase does is it uses the mRNA molecule to form the DNA molecule."}, {"title": "cDNA Library.txt", "text": "And so we take this mRNA, mix it with reverse transcriptase and we form a DNA molecule that is complementary to that mRNA molecule that has been fully processed and which no longer contains those introns."}, {"title": "cDNA Library.txt", "text": "And because this DNA is complementary to the mRNA, this complementary DNA will no longer contain these orange sections, these intron sections, it will only contain the sequence of nucleotides that corresponds to these exons sections."}, {"title": "cDNA Library.txt", "text": "So now we heat this double stranded molecule and we separate the mRNA and the DNA."}, {"title": "cDNA Library.txt", "text": "Remember, this DNA is complementary to this mRNA."}, {"title": "cDNA Library.txt", "text": "And so if we take this DNA molecule and we place it inside a eukaryotic cell, it will be able to use this complementary DNA molecule to synthesize the proteins because it won't have to worry about those introns, because those introns were removed in this process inside the eukaryotic cell."}, {"title": "cDNA Library.txt", "text": "Now, because single stranded DNA molecules are less stable than double stranded DNA molecules, what we have to do is we have to take the single stranded DNA molecule, mix it with DNA polymerase to form the more stable double stranded complementary DNA molecule."}, {"title": "cDNA Library.txt", "text": "Now, this process is done with a single eukaryotic gene, but we can carry out with many different types of genes within that eukaryotic organism."}, {"title": "cDNA Library.txt", "text": "And so at the end, what we end up producing is this library of genes for that particular eukaryotic organism."}, {"title": "cDNA Library.txt", "text": "And inside every single gene, every single DNA molecule, we essentially removed all these introns and only kept the exons."}, {"title": "cDNA Library.txt", "text": "And now if we take any one of the genes within the cDNA library and place it inside the eukaryotic bacterial cell, that bacterial cell will easily be able to take that DNA molecule, the gene create the mRNA molecule that is already fully processed, because the complementary DNA molecule is complementary to that fully processed mRNA molecule."}, {"title": "cDNA Library.txt", "text": "And now, by using that fully processed mRNA molecule, because there are no introns, that bacterial cell can easily create the protein of interest, the eukaryotic protein of interest that corresponds to that particular gene that came from that cDNA library."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So, now that we discussed the details of the eight steps of the citric acid cycle, let's actually summarize our results."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So, we have the citric acid cycle, also known as the trichrobacylic acid cycle, TCA cycle, and also known as the crept cycle."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we have three different names for the single process that takes place entirely in the matrix of the mitochondria of our cell."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, before this process can actually begin, we have to break down glucose molecules into pyruvate molecules in the process we call glycolysis, and that takes place in the cytoplasm of the cell."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So once we form the pyruvate molecules, if we have plenty of oxygen present in the cell, then the pyruvate molecules will move into the matrix of the mitochondria via special type of protein found in the membrane of the mitochondria known as pyruvate translocase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And once the pyruvate moves into the matrix of the mitochondria, before it begins the citric acid cycle, we have to transform that pyruvate into acetyl coenzyme a."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So, ultimately, a two carbon component from the pyruvate is transferred onto a carrier molecule known as coenzyme a, or simply COA."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so once we form the CETL coenzyme A molecule in the pyruvate decorboxylation process, only then can the citric acid cycle actually begin."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so let's focus on step one."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In step one, we have a water molecule, this acetyl coenzyme a, as well as an oxyloacetate, react to ultimately produce a six carbon molecule known as citrate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So notice we begin with the oxyloacetate of four carbon molecules, so 1234."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And we begin with this acetyl coenzyme a, that contains this two carbon component."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so ultimately, what happens in step one is the enzyme known as citrate synthase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Synthase catalyze."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "The transfer of this acetyl group from the CETO coenzyme ain onto this oxalo acetate, and that forms this citrate molecule."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So citrate is actually a conjugate base of citric acid, and that's why we call this the citric acid cycle."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, this is also an example of a trichrobaxylic acid, and that's why this is sometimes known as the TCA cycle, trichrobic silic acid cycle."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, this step is an exergonic step, and under physiological cell conditions, it releases about negative 31.4 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And this step, as we discussed previously, actually consists of two different steps."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "The first step is an aldo condensation."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "The second step is a hydration reaction."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "But ultimately, we form the citrate molecule from the oxyloacetate and this acetyl coenzyme a."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, once we form the citrate molecule, it must be transformed into its isomer molecule known as isocitrate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Well, because only the isocitrate can actually undergo the decarboxylation step that takes place in step three."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So, in step two, we have an isomerization reaction that is catalyzed by a connotase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And what a connotase does is it basically transfers this hydroxyl group, shown in orange, from this carbon onto this carbon here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So that's the only difference between this citrate molecule and the isomer isocytrate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "But now this molecule is actually activated, and it's ready to undergo the decryptoxylation step that takes place in step three."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, by the way, I forgot to mention, if we go back to this citrate molecule here, notice that we color coded this molecule."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And that's because this violet region basically comes from this section here, and this second oxygen comes from this water molecule shown in blue."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, I color coded this orange because this is the molecule that is ultimately being transferred onto this carbon here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So the only difference between citrate and isocytrate is the position of this hydroxyl group."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "It is moved from this location onto this location here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, once we form the isocytrate, which, by the way, is actually an endergonic reaction, we essentially use up about 6.3 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, once we actually form this isocitrate, now it is ready to actually undergo the first oxidative decarboxylation step that takes place in the citric acid cycle."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So what we mean by an oxidative decarboxylation step is we actually have two reactions taking place."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have an oxidation reduction reaction, and we have a decarboxylation step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And this step three is catalyzed by the enzyme known as isocytrade, because that's the substrate molecule to the dehydrogenase enzyme."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So isositrade dehydrogenase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And remember, whenever you hear the word dehydrogenase, what that means is we're going to have an oxidation reduction reaction, which electrons are going to be transferred onto a carrier molecule, in this particular case, the nicotine amide at any dinucleotide NAD plus."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So in step three, we basically reduce the NAD plus into NADH and the H ion."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And the two electrons essentially come from this molecule here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So this is the Hydride ion that is transferred onto the NAD plus to form the NADH."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In the process, we essentially oxidize the isocitrate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So if this is reduced, then this is oxidized, and we form the alpha key to gluterate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And also in the process, this entire component, this carbon dioxide region, is basically released."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And this H atom, or the hion attached to this oxygen, is basically released as well."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so we formed the carbonyl group between this carbon shown here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so the alpha ketoglutrate is now basically ready to undergo the next step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So in the next step, what happens is, once again, we owe and by the way, the amount of energy that is released."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And step three is equal to negative 8.4 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And actually, the formation of the alpha ketoglutrate is the rate determining step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And we'll see why we'll talk about that in much more detail in a future lecture."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, once we form the alpha key to gluorate, it now undergoes a second oxidative decorboxylation step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Remember, in a citric acid cycle, we have two oxidative decurboxylation steps, and this is the second one."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So in step four, we take the alpha key to glutrate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We essentially reacted with coenzyme A, the same coenzyme A that we released in this particular case."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And we also have the NAD plus the carrier for the electron."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So in this step, what we want to do is we want to essentially kick off this carbon dioxide shown in blue and replace that with a coenzyme a, which is what we have in this particular case."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In the process, we also abstract our electrons a hydride IoT and we place it onto the NADH or the NAD to form the NADH."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So the NAD is reduced and the alpha key to gluten rate is oxidized."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We release the carbon dioxide and an H plus I and notice we attach the coenzyme A."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we form this very high energy bond known as the Thio ester bond."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So this is essentially the same bond that we have here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we have that shown here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And the key here is, because we form this thio ester bond, it will be very unstable, high in energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And when we cleave this bond, it will release a certain amount of free energy that will allow us to actually carry out step five."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, let's go back to step four in a moment, for a moment, because we didn't mention the enzyme that catalyzes this step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we have the substrate molecule is alpha ketoglutrate, and the enzyme is basically a dehydrogenase complex."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So alpha ketoglutterate, dehydrogenase complex."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And it's a complex because we actually have three different enzymes involved in this process."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And this complex is very similar to the complex that we spoke about in our discussion on Pyruvate decorboxylation."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So once we form this molecule, this molecule that contains the high energy thioester bond is known as succinct coenzyme a."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And what happens next is we essentially cleave this high energy bond that releases a certain amount of energy, and the energy that is released is used to basically drive this reaction here the addition of the orthophosphate onto the GDP to form the GTP."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In the process, we release the coenzyme a."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, by the way, step four releases negative 30.1 kilojoules per mole of energy, while step five releases negative 3.3 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And we also produce the GTP."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So step five is the only step of the citric acid cycle that actually generates this high energy purine nucleuside triphosphate molecule, the GTP."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, the GTP can either be transformed into ATP or it can actually be used by, for instance, a g protein to carry out some type of specific process in the cell, for instance, a signal transduction pathway."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, the product molecule of step five is succinate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And notice that even though we had all these color coded atoms in these steps here, we don't have the color coded atoms in this step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And that's because now this molecule is symmetric."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Look, we have both of these ends contain the c O negatively charged group, and then we have the methylene group in between."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so this is a completely symmetrical molecule."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And that's why we no longer actually use these color coded atoms."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, once we form the succinate, the next reaction, step six, or actually, I should generalize once we formed the succinate molecule, notice that we lost the carbon dioxide, two of them."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so we went from a six carbon molecule to a four carbon molecule."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And now, in step six, seven, and eight, the entire point is truth, to transform this four carbon succinate into a four carbon oxalo acetate so that the citric acid cycle can basically begin all over again."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So that's the goal in step six, seven, and eight."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So step six is actually a hydration react or oxidation reaction."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Oxidation reduction reaction."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "This is a hydration reaction, and this is another oxidation reduction reaction."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And ultimately, we transform this methylene group into this Carbonal group and going from this molecule to this molecule in these three steps."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So let's focus on step six."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Step six is catalyzed by succinate dehydrogenase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And what this does is it ultimately abstracts two H atoms."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And those two H atoms are then carried by the Fad."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we form the Fadh two."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we essentially reduce the Fad into this, and we oxidize this molecule into fumerate, which has a double bot."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So ultimately, one H atom and one H atom here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So these two H atoms are basically abstracted, and they are placed onto the Fad."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so then we form the double bond between these two carbons to form that fumar rate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And this process actually is at equilibrium."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "It has a Gibbs free energy value of zero kilojoules per mile under the conditions that we find in ourselves."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, in step seven, this is a hydration step, and it's catalyzed by fumarase."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And what fumarase does is it basically attaches a hydroxyl group from water onto this side, and the H ion is attached onto this side."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so we form the L isomer of malate."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And once malate is formed, and this reaction releases negative 3.8 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And once we form the malate, now the final enzyme, Malade dehydrogenase, is able to actually reduce the NAD plus into NADH, releasing an H plus ion."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In the process, we oxidize the malade into oxyloacetate, and now we regenerate this same molecule that we began with, and we can use this same oxalo acetate to basically carry out that same process all over again."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So if we sum up all these steps and by the way, this final step, an oxidation reduction reaction, is a very endergonic reaction."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "It requires about 29.7 kilojoules per mole of energy."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Now, if it's so endergonic, why does it actually take place?"}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Well, because it produces the NADH molecule that then goes on into the electron transport chain."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And when this is oxidized by the proteins of electron transport chain, that process is exergonic."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And that process helps drive this process here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In addition, once we form the oxyloacetate, it goes on to carry out step one."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And step one is a very exergonic process."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So these two steps, the oxidation of NADH into NAD plus along the electron transport chain and step one of the citric acid cycle helps drive this final step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "That is a very energonic step."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So if we sum up all these reactions, this will be the net equation, net reaction of the citric acid cycle."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "So we input an acetyl coenzyme A."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "In step one."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have three NAD plus molecules."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "One here, one here and one here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have a single fad molecule here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have a GDP and an inorganic orthophosphate and two water molecules, one here and one here."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And so ultimately, we produce the coenzyme A."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Basically."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "Here we have the three nadhs."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "One in step three, one in step four and one in step eight."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have the fadh two, one in step six."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "We have the GTP that is produced in step five."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "And we have the two carbon dioxides and the two H plus ions."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "These two carbon dioxides are produced."}, {"title": "Overview of Citric Acid Cycle .txt", "text": "One is produced in step three and the other one is produced in step four."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Previously we discussed the small intestine and we said that in the small intestine we have digestion and absorption taking place."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So we break down the many macromolecules into their constituent units and then the interacy, the cells of the small intestine absorb those nutrients and transport those nutrients into the bloodstream and into our lymph system of our body."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now in this lecture we're going to focus on the proteolytic digestive enzymes that are produced by the small intestine as well as by the pancreas."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And we're also going to discuss several important hormones that basically stimulate the process of digestion that are released by the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So let's begin with the proteolytic digestive enzymes of the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So as soon as our acidic kind actually leaves the stomach and enters our small intestine, it stimulates the small intestine to secrete specialized proteolytic enzymes."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So two categories are disaccharidases and peptidases."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And both of these proteolytic enzymes are found at the brush border at the Villai of our small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So disaccharidases are those proteolytic digestive enzymes that break down our disaccharides."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So sugars that consists of two individual monomers."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So three important types of disaccharidases that you should be familiar with is Maltase which breaks down maltose."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "We have Succeeds which breaks down sucrose and we have Lactase, which breaks down lactose."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now peptidases are basically those proteolytic enzymes that break down our peptides."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And a specific type of peptidase that is found at the brush border is Dipeptidase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Dipeptidase is a proteolytic enzyme that breaks the peptide bonds in a peptide that only consists of two amino acids."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And both of these categories of enzymes are found at the brush border of our villi in the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, deep in our villi of the small intestine we have these exocrine glands that are known as the crypts or glands of Librechine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And they secrete and produce a special type for proteolytic enzyme known as Antera kinase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And what interkinase does is it basically Cleaves, a specialized type of zymogen known as Tripsinogen."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And it activates trypsinogen and transforms it into trypsin."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And trypsin is a very important type of proteolytic enzyme as we'll see in just a moment."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "That ultimately not only cleaves peptide bonds but it also activates many other proteolytic enzymes in our digestive system."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now let's discuss the three important types of hormones that are produced by the small intestine and which actually stimulate the process of digestion."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Let's begin with a peptide hormone known as secretin."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So secretin is yet another peptide hormone that is released by our exocring, by our glands found in the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And what Secretin basically does is it stimulates the pancreas to release the pancreatic juice which consists of many proteolytic enzymes as we'll see in just a moment."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now another type of peptide hormone that is released by the small intestine is CCK which stands for Colocysticina."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, colocysticina is a peptide hormone that doesn't only stimulate the pancreas to release the pancreatic juice but it also stimulates the liver to produce the bile that is necessary to emulsify our fat to break down the surface area."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Of the fat, to increase the surface area of the fat and to allow the lifepace, the proteolytic enzymes, to break down that fat efficiently and effectively."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And finally, we have another hormone that is involved in the breakdown of fat."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "This is known as antero gastrone."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So this is our hormone that is stimulated by the presence of fat and lipids inside the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And what intergastrone does is it basically causes a decrease in the movement of the chime along our small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And that gives the lipase and other proteolytic enzymes more time to break down the macromolecules, especially the fats and lipids found inside the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So these are the different types of proteolytic enzymes produced by the small intestine, and these are the hormones produced by the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, let's move on to the pancreas."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So, the pancreas is basically an accessory gland that produces specialized proteolytic enzymes that are needed in digestion."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So we have this combination of proteolytic enzymes as well as a solution of bicarbonate that forms the pancreatic juice."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And when stimulated, the pancreas releases the pancreatic juice into the pancreatic duct, which basically connects with the common bile duct."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And this combination of bile and the pancreatic juice empties into the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So the question is, what is the purpose of bicarbonate?"}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So, bicarbonate is that molecule that ultimately neutralizes the acidity that comes along with the chime that comes from our stomach."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And what the bicarbonate does is it increases the basicity of our solution, it gives our solution inside the lumen of the small intestine a PH of about 8.5."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, we have three important types of categories of enzymes that are produced in the pancreas."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So we have the pancreatic amylase and the pancreatic lipase, not to confuse them with the amylase and the lipase that are produced in the oral cavity in our mouth."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, pancreatic amylase is responsible for breaking down alphagly acidic linkages, so that means it breaks down starch as well as glycogen into their individual monomers."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, we also have pancreatic lipase, which is responsible for breaking down fats and lipids into fatty acids, which can then be absorbed by denterics of the small intestine."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And finally, we have the pancreatic peptidases."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So we have three important types of peptidases that we should be familiar with."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "We have tryptogen, we have china trypsinogen, and we have our carboxy peptidase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So trypsinogen is this xiaomogen that we spoke of earlier."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So our pancreas produces our trypsinogen."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And when our interkinase mixes with trypsinogen, it cleaves it and it forms the active form known as trypsin."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And trypsin doesn't only cleave peptides at specific peptide buns, but it also activates other enzymes, as we'll see in just a moment."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So let's move on to chymo trypsinogen."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Chimotrypsinogen is yet another type of peptidase that is produced by the pancreas and Chimotryptinogen is activated by trypsin."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So trypsin actually activates chimotryptinogen into chimotrypsin."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And what Chimotrypsin does is it breaks down our peptide bonds and aromatic amino acids."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And now let's move on to the third type of proteolytic peptidase, produced by the pancreas, known as the carboxy peptidase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So carboxy peptidase is a proteolytic enzyme that breaks down peptide bonds at the carboxy end of our peptide of our polypeptide."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So these are the three different types of peptidases that are released by the pancreas."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So, let's summarize what we just discussed."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So basically, as the acidicine moves into our lumen of the small intestine, it basically activates the release of our secretin and CCK the kylo cystic ianin by the small intestinal glands found in the villi deep along the villi of our small intestine so secrete and stimulates the release of the pancreatic juice, which includes pancreatic amylase, pancreatic lipase and the pancreatic peptidases."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Our trypsinogen, which is activated into trypsin by interkinase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "We have the chinamatripsinogen, which is activated into chiama tryptin by trypsin, and we have carboxy peptidase."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "Now, the kylo cysticionin basically activates and stimulates the liver to release the bile."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And the bile is a collection, it's a mixture of water and cholesterol fat as well as bile salts."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And this causes fat emulsification, it breaks down our fat, it increases the surface area of that fat so that our line phase can actually break down chemically those bonds that hold the lipids together."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "And we also have the stimulation of these types of proteolytic enzymes that are found at the brush border."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So we have the production of di sacrodases such as Maltase succeeds and lactase, and we have the production of dipeptidases, which break down our proteins or peptides that only consists of two amino acids."}, {"title": "Digestive Enzymes of Small Intestine and Pancreas .txt", "text": "So these are our proteilitic enzymes produced by the small intestine, these are the ProtoLytic enzymes produced by the pancreas, and these are the hormones produced by the small intestine that are involved in the process of digestion."}, {"title": "Ovaries.txt", "text": "The female gonads are known as ovaries."}, {"title": "Ovaries.txt", "text": "Now a gonad is basically a structure that produces gametes."}, {"title": "Ovaries.txt", "text": "And that means that our ovaries are the reproductive organs of the female and they are responsible for producing the female gametes known as excels or ovum."}, {"title": "Ovaries.txt", "text": "Now not only that, but the ovaries also act as endocrine gland lands."}, {"title": "Ovaries.txt", "text": "They produce and release special types of hormones known as the female sex hormone."}, {"title": "Ovaries.txt", "text": "So they produce estrogen as well as progesterone."}, {"title": "Ovaries.txt", "text": "Now before we discuss what these two hormones are and what their function is, let's briefly discuss the structure of our female reproductive system."}, {"title": "Ovaries.txt", "text": "So we have two ovaries inside our female reproductive system."}, {"title": "Ovaries.txt", "text": "We have one and we have the second one."}, {"title": "Ovaries.txt", "text": "So inside the ovary, we basically have the maturation and the production of the excels, our ovum."}, {"title": "Ovaries.txt", "text": "So once our ovum is basically mature, it will undergo a process known as ovulation."}, {"title": "Ovaries.txt", "text": "And the ovary will release that XL, that ovum into a cavity known as our peritoneal cavity."}, {"title": "Ovaries.txt", "text": "And that ovum, the excel, will then travel from the parrot neal cavity into a canal known as our fallopian tube."}, {"title": "Ovaries.txt", "text": "So the fallopian tube basically connects our ovary to the uterus."}, {"title": "Ovaries.txt", "text": "Now eventually the ovum will make its way to our uterus, which is this section here."}, {"title": "Ovaries.txt", "text": "And if we have the presence of sperm cells inside the female reproductive system, then the sperm cell can combine with our ovum in a process known as fertilization and that produces our diploid cell, the zygote."}, {"title": "Ovaries.txt", "text": "And once the zygote is inside the uterus, it implants onto, it attaches onto the outer membrane the lining of the uterus known as the endometrium."}, {"title": "Ovaries.txt", "text": "And what the endometrium does is it supplies the developing zygote with the nutrients that it needs to actually develop further."}, {"title": "Ovaries.txt", "text": "Now, if there is no sperm cells found in our female reproductive system, then when the exile actually reaches our uterus, what happens is the exile, the ovum, along with the lining of the uterus, the endometrium is released into the surrounding environment."}, {"title": "Ovaries.txt", "text": "And this process takes place about a month in the female human organism."}, {"title": "Ovaries.txt", "text": "So this process is known as the menstrual cycle."}, {"title": "Ovaries.txt", "text": "So let's zoom in on our zygote, on our ovary, we basically get the following diagram."}, {"title": "Ovaries.txt", "text": "So this diagram basically describes the process by which our follicles mature into our ovum, into our excel."}, {"title": "Ovaries.txt", "text": "So we begin with these tiny little dots known as the primary follicles."}, {"title": "Ovaries.txt", "text": "They mature into the oocide, then they become the secondary follicle."}, {"title": "Ovaries.txt", "text": "And that secondary follicle eventually undergoes the process of ovulation."}, {"title": "Ovaries.txt", "text": "This is the release of the secondary follicle."}, {"title": "Ovaries.txt", "text": "It's the release of the mature ovum, the mature excel, into the cavity known as the parrotmeal cavity."}, {"title": "Ovaries.txt", "text": "And then once released into our parrotmeal cavity, it travels into our fallopium tube and eventually into our uterus."}, {"title": "Ovaries.txt", "text": "Now the remaining portion of our secondary follicle, the remaining portion of the ovarian follicle, which is the basic unit of structure of our ovary, this remaining portion that is left behind in the ovary eventually becomes a structure known as the corpus luteum."}, {"title": "Ovaries.txt", "text": "And this is a very important structure in both our menstrual cycle as well as pregnancy."}, {"title": "Ovaries.txt", "text": "And we'll see what its function is in just a moment."}, {"title": "Ovaries.txt", "text": "So let's discuss these two hormones."}, {"title": "Ovaries.txt", "text": "Let's begin with estrogen and then let's move on to progesterone."}, {"title": "Ovaries.txt", "text": "So estrogen is a steroid hormone that means it's lipid soluble."}, {"title": "Ovaries.txt", "text": "So that means it can easily travel across a cell membrane and it basically binds to the protein receptor inside that cell and eventually it enters, estrogen enters our nucleus of the cell and it acts on the cell on a transcriptional level, it influences the transcription of our cell."}, {"title": "Ovaries.txt", "text": "Now, estrogen itself is stimulated by our luteinizing hormone as well as the follicle stimulating hormone that are released by the interior pituitary gland."}, {"title": "Ovaries.txt", "text": "And FSH as well as LH are both stimulated by the gonadotropin releasing hormone released by the hypothalamus."}, {"title": "Ovaries.txt", "text": "So estrogen is basically released by two structures."}, {"title": "Ovaries.txt", "text": "So estrogen is initially released by our ovarian follicle, this structure here."}, {"title": "Ovaries.txt", "text": "Now, once our ovulation process actually takes place and we form the corpus luteum, then the corpus Lewdium begins to release our estrogen."}, {"title": "Ovaries.txt", "text": "So we have two structures inside our ovary that are capable of releasing our estrogen hormone."}, {"title": "Ovaries.txt", "text": "So estrogen is released by the ovarian follicle, which is the basic unit of the structure inside the ovary."}, {"title": "Ovaries.txt", "text": "It is also released by the corpus luteum, which is the portion of the follicle that is left behind in the ovary."}, {"title": "Ovaries.txt", "text": "Following the release of our ovum, the mature female gaming into our Peric mule cavity and eventually into the fallopium tube."}, {"title": "Ovaries.txt", "text": "Now, what exactly is the purpose of estrogen?"}, {"title": "Ovaries.txt", "text": "So basically, when the secondary follicle is still inside our ovary, estrogen is released by that follicle."}, {"title": "Ovaries.txt", "text": "And what it basically does is it generates our endometrium."}, {"title": "Ovaries.txt", "text": "It is responsible for generating and thickening the endometrium, which is the layer of membrane in the uterus that serves as the binding side for our zygote."}, {"title": "Ovaries.txt", "text": "The zygote is the combination of the sperm and our egg."}, {"title": "Ovaries.txt", "text": "This process of combining is known as fertilization."}, {"title": "Ovaries.txt", "text": "Now, the second purpose of estrogen is basically to promote the development of female secondary sex characteristics such as our enlargement of breasts, as well as the growth of body hair in different parts of the body."}, {"title": "Ovaries.txt", "text": "It also is responsible for increasing the muscle mass and bone mass of women."}, {"title": "Ovaries.txt", "text": "Now, let's move on to the other type of female sex hormone known as progesterone."}, {"title": "Ovaries.txt", "text": "So progesterone is also a steroid hormone that means it's formed from cholesterol and it is lipid soluble."}, {"title": "Ovaries.txt", "text": "It passes across the cell membrane and it binds onto protein receptors inside the target cell."}, {"title": "Ovaries.txt", "text": "Now, progesterone is stimulated by the luteinizing hormone LH that is released by the anterior pituitary gland."}, {"title": "Ovaries.txt", "text": "So as our amount of LH in the blood increases, the amount of progesterone released also increases."}, {"title": "Ovaries.txt", "text": "Now progesterone is initially released by the corpus luteum."}, {"title": "Ovaries.txt", "text": "So after ovulation takes place and the ovum is released into our parrot meal cavity, the corpus luteum eventually forms and that corpus luteum begins to release our progesterone hormone."}, {"title": "Ovaries.txt", "text": "Now, once our corpus luteum actually degenerates during the process of pregnancy, our placenta, the structure that basically supplies the growing fetus with nutrients, begins to release our progesterone."}, {"title": "Ovaries.txt", "text": "So we have two structures that are capable of releasing progesterone."}, {"title": "Ovaries.txt", "text": "Initially it's the corpus luteum, but eventually when the corpus luteum degenerates during the process of pregnancy, it's the placentha that releases our progesterone."}, {"title": "Ovaries.txt", "text": "Now, what exactly is the function of progesterone?"}, {"title": "Ovaries.txt", "text": "So it has many important functions and one of the most important functions is the maintenance of the endometrium."}, {"title": "Ovaries.txt", "text": "So it's the estrogen that generates and thickens that endometrium, but it's progesterone that maintains the endometrium as our ovum travels through the fallopian tube and during the process of pregnancy."}, {"title": "Ovaries.txt", "text": "So progesterone is used to maintain the endometrium during the menstrual cycle as well as during pregnancy if the sperm actually combines with our egg."}, {"title": "Ovaries.txt", "text": "Now, it also inhibits the process of lactation during pregnancy and it also decreases the ability of the smooth muscle inside the uterus to basically contract."}, {"title": "Ovaries.txt", "text": "And this is important because we don't want our muscles in the uterus to contract too early during the process of pregnancy."}, {"title": "Ovaries.txt", "text": "So this is our ovary."}, {"title": "Ovaries.txt", "text": "So once again, the ovary is the female gona that acts as an endocrine gland and forms two important female sex hormones, the estrogen and progesterone."}, {"title": "Ovaries.txt", "text": "And both of these play an important role in not only the female menstrual cycle, but also in the process of pregnancy."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "The next topic that we're going to focus on will be fatty acid metabolism."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So, in this lecture, I'd like to discuss what fatty acids are and what the cells of our body actually use fatty acids for."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And I'd also like to introduce the processes of fatty acid breakdown in fatty acid synthesis."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So what are fatty acids?"}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Well, fatty acids are these biological molecules that consist of a long hydrocarbon chain and a terminal carboxylate group."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, the terminal carboxylate group gives the molecule hydrophilic polar properties, while the long hydrocarbon chain gives the fatty acids hydrophobic nonpolar properties."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So what do our cells use fatty acids for?"}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Well, fatty acids have four important functions inside our cells."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Number one is fatty acids are fuel molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And as we'll shortly see, our cells can break down fatty acids to actually generate high energy ATP molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Number two is fatty acids are actually used to build molecules that exist within cell membranes."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So things like lycolipids and phospholipids are built from fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Number three is we can modify proteins by attaching fatty acids onto them."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And what this does is it increases and diversifies the functionality of the proteins."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Number four is molecules such as hormones and other intracellular messenger molecules are built from fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we have many hormones which are built from fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now let's discuss the breakdown and the synthesis of fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And as we'll see in just a moment, these two processes are essentially mirror images of one another."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "They're the reverse of one another."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And let's begin by discussing the breakdown of fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So the breakdown of fatty acids basically consists of four steps."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "We have an oxidation step, we have a hydration step, we have another oxidation step, and we have a cleavage."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And so these four processes together make up one cycle of fatty acid breakdown."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And this process is, in fact, an oxidative process."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So what we're essentially doing is we're extracting electrons, and we ultimately want to basically cleave a Sigma bond."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And by cleaving that Sigma bond, we're essentially shortening that fatty acid chain by two carbon."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So each cycle removes two carbon component molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we begin with an activated fatty acid."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And activated simply means we've done something to the fatty acid."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "We attached a specific group onto that fatty acid to make it more reactive."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And in this particular case, the group we attached is the Rprine group, and this is usually the coenzyme molecule, and that makes it more active."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we take the activated fatty acid and we allow it to undergo an oxidation step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And here, we're essentially extracting electrons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "More specifically, we extract an H atom from this carbon, an H atom from this carbon, and electrons left over on these two carbons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "We have one electron left over here, one electron left over here that is used to actually generate a pi bond."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So going from this molecule to this molecule, we ultimately form a double bond."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, once we form the double bond, the next step is a hydration step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And what that ultimately tries to achieve is to attach a hydroxyl group onto this carbon here."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So going from here to here, we break that pi bond and we also attach that hydroxyl group, as shown here."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So this gives us an alcohol group in the next step, which is once again, an oxidation step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Just like this step, we essentially want to extract electrons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "In the process, we want to transform this hydroxyl group into a carbonyl group."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And once we form that carbonyl group, we basically form the ketone."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And now we can undergo a cleavage process in which Coenzyme A is basically used to cleave this bond and we form these two product molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, one of these two product molecules is the two carbon component that we basically removed, and this is this activated acetyl unit."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So acetyl simply means we have one, two carbons, and activated means we still have this Coenzyme A molecule, which is given by R prime."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, this is the activated Acyl unit."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And if this molecule has a fully saturated hydrocarbon chain and it contains an even number of carbon atoms, then this process can basically take place again and again and again until we break down that absolute unit into these acetyl units."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So if the fatty acid that were breaking down is fully saturated and it contains an even number of carbon atoms, then this process can cycle over and over and over until we completely break down that fatty acid into these acetyl units."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, once we form the acetyl units, they can then enter the citric acid cycle, and that can ultimately be used to generate high energy ATP molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So, once again, to summarize, the breakdown of fatty acids is an oxidative process that releases activated acetyl coenzyme A units, thereby shortening or decreasing the size of that hydrocarbon chain by two carbons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And once we form the activated Coenzyme A units, they can enter the citric acid cycle, where they're ultimately used to actually generate the high energy ATP molecules."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, what about fatty acid synthesis?"}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "What if we actually want to synthesize fatty acids?"}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Why would we want to synthesize fatty acids?"}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Well, if we have plenty of ATP molecules we don't want to form anymore, our cells will essentially take these acetyl units and we'll synthesize fatty acids from them."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Or if we want to build some type of hormone or modify a protein or build up our cell membrane, we can also build up these fatty acids and use them in those processes."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, as we'll see in just a moment, the synthesis is actually the opposite of the breakdown."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "They are mere images."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And to see exactly what we mean, let's take a look at this process here."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So here we have an oxidation reaction."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Here we have a reduction reaction."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So the first step in this process, the first step in the breakdown process is an oxidation step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "The last step in the synthesis process is a reduction step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now, the second process, the second step in the breakdown process is a hydration."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And the second to last step is the dehydration."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Then we have an oxidation, we have a reduction, and then we have a cleavage here, and we have a condensation."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we see that this process is the reverse of this process."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "This is the reverse of this process."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "This is the reverse of this process, and this is the reverse of this process."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "On top of that, all the steps are actually reversed in this synthesis process."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And that's what we mean by these processes being mere images of one another."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So in this particular case, we want to actually synthesize these fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "We begin with the activated Acyl units and the activated melonial units, or Malanol units."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Now we take the activated melanol units, and we basically undergo a condensation reaction with this activated Acyl unit."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And what that does is it helps us generate that sigma bond."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And once we generate that sigma bond, we essentially generate that same molecule that we had in this particular case."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "The next process is a reduction step, because that's the opposite of this oxidation step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we're going this way here, and that means we essentially want to add an extra number of electrons along with h atoms."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And so we generate we transform this ketone group into this alcohol group."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Once we form that, we want to remove that hydroxyl."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And the way that we remove that hydroxyl is via dehydration step."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So we form this pi bond."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And in the final step, we once again want to reduce this."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "We want to add the h atoms along with our electrons, and we generate the activated fatty acid."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And so we see that in this particular case, one cycle of the breakdown of fatty acids basically shortens that carbon chain by two carbons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "But in this particular case, it increases that carbon chain by two carbons."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "So once again, the synthesis process is a reductive process that builds up the hydrocarbon chain of fatty acids."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "Beginning with the activated acid units and the malanol units, the reverse processes of fatty acid degradation are followed in the opposite order."}, {"title": "Introduction to Fatty Acid Metabolism.txt", "text": "And we'll talk about the details of these individual steps in the lecturer to Come."}, {"title": "Placenta .txt", "text": "The placenta is a very important organ that begins to develop as soon as the zygote implants onto the endometrium of the uterus of the mother."}, {"title": "Placenta .txt", "text": "Now that means our placenta actually develops and exists during pregnancy."}, {"title": "Placenta .txt", "text": "And what it does is it ultimately connects our thesis to the walls of the uterus of the mother."}, {"title": "Placenta .txt", "text": "And the placenta serves as for important functions."}, {"title": "Placenta .txt", "text": "So it plays a role in nutrition, in excretion, in immunity, and also acts as an endocrine gland."}, {"title": "Placenta .txt", "text": "So it basically allows the movement of our glucose, the amino acids and fatty acids from the mother to our fetus because the fetus needs these nutrients to basically produce that energy to grow and develop."}, {"title": "Placenta .txt", "text": "Now as our fetus actually develops and grows, it produces many unwanted wasteful byproducts."}, {"title": "Placenta .txt", "text": "And what the placenta allows the fetus to do is basically excrete those wasteful byproducts to the mother that can ultimately excrete those products to the surrounding environment."}, {"title": "Placenta .txt", "text": "It also plays a role in immunity and that means it can actually fight off infections."}, {"title": "Placenta .txt", "text": "And finally we have this endocrine ability of the placensa to basically produce hormones and release those hormones into the bloodstream."}, {"title": "Placenta .txt", "text": "And in this lecture we're going to focus on the endocrine capabilities of the placenta's."}, {"title": "Placenta .txt", "text": "So we're going to focus on six different types of hormones that are produced and released by the placenta."}, {"title": "Placenta .txt", "text": "Now previously we discussed two of these hormones."}, {"title": "Placenta .txt", "text": "We discussed progesterone and estrogen."}, {"title": "Placenta .txt", "text": "So these two hormones are basically steroid hormones and what that means is they're lipid soluble, they cannot dissolve in the blood and so they need a protein carrier."}, {"title": "Placenta .txt", "text": "And because they're lipid soluble, they can easily cross the plasma membrane of the target cell, which means they bind onto protein receptors found inside our cell."}, {"title": "Placenta .txt", "text": "Now progesterone is initially produced by the corpus lutein that is found in the ovaries."}, {"title": "Placenta .txt", "text": "Now eventually the corpus lutein begins to break down, it begins to degenerate and what happens is our placenta takes over the role of producing our progesterone."}, {"title": "Placenta .txt", "text": "So initially it's the corpus luteum that produces our progesterone, but eventually our placenta takes over that job because the corpus luteum degenerates, it breaks down."}, {"title": "Placenta .txt", "text": "Now there are two important functions of progesterone."}, {"title": "Placenta .txt", "text": "First it is basically used to actually maintain that endometrium layer inside the uterus."}, {"title": "Placenta .txt", "text": "And the second role is to basically inhibit the contraction of our smooth muscle in the uterus to basically prevent premature labor."}, {"title": "Placenta .txt", "text": "Now let's move on to estrogen."}, {"title": "Placenta .txt", "text": "So estrogen is initially released by the ovarian follicle, but when ovulation takes place, it's the corpus luteum that begins to release our estrogen."}, {"title": "Placenta .txt", "text": "And finally, as the corpus luteum begins to break down, it's the placenta once again that takes over the role of releasing our estrogen."}, {"title": "Placenta .txt", "text": "Now estrogen has many important functions during pregnancy, so its first important function is to actually generate the endometrium."}, {"title": "Placenta .txt", "text": "But during pregnancy it serves three functions."}, {"title": "Placenta .txt", "text": "It basically acts to actually enlarge our breasts of the woman, to basically prepare the woman for the process of lactation that takes place following birth."}, {"title": "Placenta .txt", "text": "It also enlarges our uterus."}, {"title": "Placenta .txt", "text": "And that's because as our fetus grows, the uterus must enlarge with our fetus."}, {"title": "Placenta .txt", "text": "So it enlarges the uterus to accommodate the growing fetus."}, {"title": "Placenta .txt", "text": "And finally, it plays a role in relaxing our joints and ligaments that are found in the women's pelvic region."}, {"title": "Placenta .txt", "text": "And this is basically to prepare our women for birth."}, {"title": "Placenta .txt", "text": "Now, let's move on to the third type of hormone, which is a glycoprotein."}, {"title": "Placenta .txt", "text": "This is our human Coriana gonadotropin, or HCG."}, {"title": "Placenta .txt", "text": "Now, this is a glycoprotein and that means it's water soluble, it can easily dissolve in the blood and it binds onto the membrane of our plasma cells, of our target cells, plasma membrane, and it basically creates some type of response inside that cell."}, {"title": "Placenta .txt", "text": "Now, there are two important functions of our human corianic, natotropin, and this hormone is released as soon as our zygote actually implants onto the endometrium of the uterus of the mother."}, {"title": "Placenta .txt", "text": "Now, there are two important purposes."}, {"title": "Placenta .txt", "text": "Firstly, it basically stimulates the corpus luteum found in the ovary to release progesterone and estrogen until the placenta can actually take over that job and begin releasing these hormones on its own."}, {"title": "Placenta .txt", "text": "And this is required to basically maintain the development of the endometrium during the process of pregnancy."}, {"title": "Placenta .txt", "text": "It also acts to actually suppress the immune system of the mother."}, {"title": "Placenta .txt", "text": "So remember, what the immune system does is it basically attacks any foreign object that is found inside our body."}, {"title": "Placenta .txt", "text": "And technically speaking, the fetus as well as our placenta are two foreign objects."}, {"title": "Placenta .txt", "text": "And so what this hormone does is it suppresses the maternal immune system, the mother's immune system, to ensure that the immune cells do not actually attack the placenta or the growing fetus."}, {"title": "Placenta .txt", "text": "Now, the human corianic Tropin is produced strictly and only by our placenta, by the mother's placenta."}, {"title": "Placenta .txt", "text": "And what that means is one way we can test whether or not a woman is pregnant is by testing the blood level of this hormone found inside the woman's blood."}, {"title": "Placenta .txt", "text": "Now, let's move on to the next type of hormone known as the human placental oxygen or HPL."}, {"title": "Placenta .txt", "text": "Now, this is also a peptide hormone."}, {"title": "Placenta .txt", "text": "That means it's water soluble and it bonds onto the membrane of the target cell."}, {"title": "Placenta .txt", "text": "Now, this is produced by the placenta and it plays two very important functions."}, {"title": "Placenta .txt", "text": "Firstly, it basically controls and regulates the concentration, the level of glucose, fatty acids and amino acids in the blood plasma of the mother."}, {"title": "Placenta .txt", "text": "And this is done to basically ensure that the fetus has a constant supply of energy that it basically needs to grow and develop."}, {"title": "Placenta .txt", "text": "And it also stimulates the enlargement of the memory glands, which are the glands that basically produce and secrete the milk that the child needs following childbirth."}, {"title": "Placenta .txt", "text": "Now, let's move on to the fifth type of hormone, which is once again a peptide hormone."}, {"title": "Placenta .txt", "text": "This is relaxant."}, {"title": "Placenta .txt", "text": "Now, Relaxant is not only released by aroplacenta, it is also produced by the corpus luteum as well as other structures and is also produced in males now in females and during pregnancy."}, {"title": "Placenta .txt", "text": "What relaxant does is basically serves two important functions."}, {"title": "Placenta .txt", "text": "Firstly it increases the flexibility of the joints and ligaments found inside our pelvic region of the women which is similar to what estrogen does."}, {"title": "Placenta .txt", "text": "And relaxin also basically makes the pubic synthesis, the bone in this region, very relaxed."}, {"title": "Placenta .txt", "text": "And this prepares the mother for labor, for childbirth."}, {"title": "Placenta .txt", "text": "And secondly, it also increases the blood rate as well as the rate at which our heart actually pumps blood."}, {"title": "Placenta .txt", "text": "And this is important because the mother needs to be able to pump more blood because now it has this growing organism, the fetus, inside the uterus."}, {"title": "Placenta .txt", "text": "And finally, we also have a hormone known as corticotropic releasing hormone or corticotropic releasing factor."}, {"title": "Placenta .txt", "text": "Now this is a peptide hormone just like these hormones here and it is not only released by the placenta, it is also produced by the neurons found inside the hypothalamus."}, {"title": "Placenta .txt", "text": "So this is a peptide hormone produced by the hypothalamus and arop placenta."}, {"title": "Placenta .txt", "text": "Now because CRH the level the concentration of this hormone increases in concentration towards the end of pregnancy this basically suggests that this hormone might be involved in stimulating the smooth muscle contraction so it stimulates the release of special gonadotropin molecules that basically stimulate the contraction of smooth muscles inside the uterus of the mother."}, {"title": "Placenta .txt", "text": "So these are the six different important hormones that are produced by the placenta that play a role in pregnancy."}, {"title": "Emulsification of Fats .txt", "text": "Emulsification is a process that takes place in a small test of our body."}, {"title": "Emulsification of Fats .txt", "text": "So in this lecture, we're going to focus on what emulsification is, how it is actually carried out and what it does."}, {"title": "Emulsification of Fats .txt", "text": "Now recall that fats are hydrophobic and that means fats will not dissolve in water."}, {"title": "Emulsification of Fats .txt", "text": "Now the solution found in the lumen in the cavity of the small intestine as well as the solution of the kind is mostly water."}, {"title": "Emulsification of Fats .txt", "text": "It consists predominantly of water."}, {"title": "Emulsification of Fats .txt", "text": "And that means the solution is polar."}, {"title": "Emulsification of Fats .txt", "text": "It's hydrophilic."}, {"title": "Emulsification of Fats .txt", "text": "And that's exactly why fats or lipids will not easily mix with the kind nor will they easily mix in the solution of the small intestine."}, {"title": "Emulsification of Fats .txt", "text": "And that's exactly why because the fats and lipids cannot mix with anything else."}, {"title": "Emulsification of Fats .txt", "text": "They will aggregate together to form very large molecules known as fat globules."}, {"title": "Emulsification of Fats .txt", "text": "So if we examine the following section of the small intestine this is the lumen of the small intestine."}, {"title": "Emulsification of Fats .txt", "text": "These are arabili of the small intestine."}, {"title": "Emulsification of Fats .txt", "text": "The red section is the smooth muscle that contracts and creates the motion of peristalsis."}, {"title": "Emulsification of Fats .txt", "text": "And these individual spherical molecules are the fat globules."}, {"title": "Emulsification of Fats .txt", "text": "So fat globules are basically nothing more than the aggregation of cholesterol, triglycerides and other lipids that we ingest into our body."}, {"title": "Emulsification of Fats .txt", "text": "Now these very tiny blue regions, these structures are basically the pancreatic lipase, the proteolytic enzymes that break down our fats, the lipids into our fatty acids and glycerol."}, {"title": "Emulsification of Fats .txt", "text": "Now, lipase are water soluble and that means they cannot actually mix with the fat globules."}, {"title": "Emulsification of Fats .txt", "text": "Now the problem here is because of the very large size of the fat globules our livease molecules cannot actually access the inside portion of the fat globules because they cannot dissolve into these fat globules."}, {"title": "Emulsification of Fats .txt", "text": "And that means they cannot actually cleave the majority of the ester bonds that basically hold the triglycerides, the lipids together."}, {"title": "Emulsification of Fats .txt", "text": "In other words, the pancreatic lipase can only cleave the bonds the lipids found on the surface of the fat globules and they have no way of actually getting inside those fat globules."}, {"title": "Emulsification of Fats .txt", "text": "Now this makes the efficiency and the rate at which lipase actually cleans the bonds very, very low."}, {"title": "Emulsification of Fats .txt", "text": "And what happens is in order to increase the rate and efficiency at which our lipase molecules actually break those ester bonds to form fatty acid and glycerol the liver produces a special type of fluid known as bile."}, {"title": "Emulsification of Fats .txt", "text": "So bile consists of amphipatic molecules such as phospholipids and bile salts and it also consists of hydrophobic molecules such as cholesterol."}, {"title": "Emulsification of Fats .txt", "text": "Now, antipatic simply means these molecules do not only have a hydrophobic section, they also have a hydrophilic section."}, {"title": "Emulsification of Fats .txt", "text": "Now, when bile is produced by the liver it is stalled in the gallbladder."}, {"title": "Emulsification of Fats .txt", "text": "It is stored in the gall bladder and eventually it is released via the common bile duct into the small intestine."}, {"title": "Emulsification of Fats .txt", "text": "Now, once the bile is inside the lumen of the small intestine it basically mixes very well with the fat globules because it contains hydrophobic molecules and this is what breaks down the fat globules into smaller molecules we call emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "In this process by which the bile mixes with the fat globules and breaks them down to smaller emulsion droplets, is known as emulsification."}, {"title": "Emulsification of Fats .txt", "text": "Now, emulsification breaks down the fat globules, and it greatly increases the area on which the light pace can actually act on."}, {"title": "Emulsification of Fats .txt", "text": "And digestion begins on the surface of these emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "So digestion takes place at these emulsion droplets on the surface of these droplets, and emulsification greatly increases the surface area on which lipase can actually act on."}, {"title": "Emulsification of Fats .txt", "text": "So this increases the efficiency and the rate at which the lipase molecules can cleave those ester bonds."}, {"title": "Emulsification of Fats .txt", "text": "So, this is our fat globule."}, {"title": "Emulsification of Fats .txt", "text": "When we mix it with bile, emulsification takes place, and we break down the fat globule into these individual molecules we call emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "Inside these emulsion droplets, we still have many of these triglycerides molecules that we actually have to break down."}, {"title": "Emulsification of Fats .txt", "text": "But now the surface area greatly increases, and these pancreatic light based molecules can actually attach onto the surface of these emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "Now, the question is, if our emulsion droplets are hydrophobic, and since our pancreatic lipase is hydrophilic, how exactly does the lipase bind onto the surface of our emulsion droplets?"}, {"title": "Emulsification of Fats .txt", "text": "Well, basically, with the help of a special type of molecule known as colepase cholipase is amphithetic."}, {"title": "Emulsification of Fats .txt", "text": "It has a hydrophobic and a hydrophilic region."}, {"title": "Emulsification of Fats .txt", "text": "The hydrophilic region binds onto the lipase, while the hydrophobic region binds onto the surface of this emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "And as soon as the lipase binds, it begins our digestion."}, {"title": "Emulsification of Fats .txt", "text": "It begins the breakdown of the triglycerides found on the surface into fatty acids and our glycerol."}, {"title": "Emulsification of Fats .txt", "text": "Now, as soon as we break down, the emulsion droplet into these fatty acids."}, {"title": "Emulsification of Fats .txt", "text": "The fatty acids themselves are hydrophobic, so they cannot exist in the solution of the lumen by themselves."}, {"title": "Emulsification of Fats .txt", "text": "So what happens is the amphithatic phospholipids and the bile salts that are secreted with the bile basically create a spherical structure around those fatty acids, and the structure is known as a myosphil."}, {"title": "Emulsification of Fats .txt", "text": "So, once again, let's take one of these emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "As shown, this blue section is the pancreatic lipase."}, {"title": "Emulsification of Fats .txt", "text": "This orange section is the colipase that allows the lipase to bind onto our surface."}, {"title": "Emulsification of Fats .txt", "text": "And over time, this pancreatic lipase breaks down the molecules, our triglycerides, into many fatty acids."}, {"title": "Emulsification of Fats .txt", "text": "Now, if we zoom in on any one of these tiny dots, we basically get the following diagram."}, {"title": "Emulsification of Fats .txt", "text": "So, we have a myosil, and the membrane of the myosil is formed as a result of the member of the phospholipids that come from the bile."}, {"title": "Emulsification of Fats .txt", "text": "Now, the outside portion of phospholipids is hydrophilic, and the inside portion is hydrophobic."}, {"title": "Emulsification of Fats .txt", "text": "And enclosed inside the myosil, we have the fatty acid that was broken down from our triglycerides found in sizing Molsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "Now, what's the big deal with these myocyls?"}, {"title": "Emulsification of Fats .txt", "text": "Well, myosils are 200 times as small as these emulsion droplets, and that allows these very tiny myosils to actually get very close to our membrane, bind to that membrane of the intricacy found on our villi, and that allows our fatty acids to get inside our cytoplasm of the cell."}, {"title": "Emulsification of Fats .txt", "text": "And ultimately, that cell transports the fatty acid into the lactial that connects to our lymphatic system."}, {"title": "Emulsification of Fats .txt", "text": "So we see that the process of emulsification takes this very large hydrophobic fat globule, and it breaks it down into much smaller emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "This increases the surface area on which the pancreatic lipase can actually act on."}, {"title": "Emulsification of Fats .txt", "text": "And so the pancreatic lipase, with the help of colepase, binds onto the surface of these emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "So we see that digestion and breakdown of these lipids and fats actually takes place on the surface of these emulsion droplets and not on the surface of the fat globule."}, {"title": "Emulsification of Fats .txt", "text": "So each one of these emulsion droplets is eventually broken down into our fatty acids."}, {"title": "Emulsification of Fats .txt", "text": "And each one of these fatty acids is surrounded by this membrane that is formed from either biosolids or the biophospholipids."}, {"title": "Emulsification of Fats .txt", "text": "And these tiny myocells are much smaller than these emulsion droplets."}, {"title": "Emulsification of Fats .txt", "text": "And these myosomes can easily approach the membrane of the nteroside."}, {"title": "Emulsification of Fats .txt", "text": "They can bind on our membrane, and that allows our fatty acids to enter the cytoplasm of our antarxide found inside the small intestine."}, {"title": "Emulsification of Fats .txt", "text": "So this is the process by which we actually increase the efficiency and the rate at which the pancreatic light base can break down the fats and lipids inside our body."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Ribosomes are the machinery of the cell that are responsible for synthesizing our polypeptides via a process known as translation."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And translation itself, as we discussed previously, involves three important stages."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "We have initiation, the elongation, and the termination stage."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, in eukaryotic cells, ribosomes begin to synthesize the polypeptide chain in the cytosol of aracel."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And such ribosomes that are found in the cytosol and which are not attached to any organelle are known as free ribosomes."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, if the growing polypeptide chain that is being synthesized by the free ribosome is destined to remain inside the cytoplasm of the cell, in such a case, the free ribosome will remain a free ribosome."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "It will not attach to any organelle inside the cell during the entire process of translation."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "However, if the growing polypeptide chain that is being synthesized by the free ribosome is destined to be either secreted by the cell or to be embedded into the plasma membrane of the cell, in such a case, the free ribosome as well as the growing polypeptide chain will go on to attach onto the membrane of the endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And now the free ribosome becomes a membrane bound ribosome."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So a free ribosome is a ribosome that synthesizes polypeptides that are destined to remain inside a cytoplasm."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "But the membrane bound ribosomes are those ribosomes that are responsible for forming proteins that are either secreted by the cell or which remain inside the membrane of that cell."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, the question that we want to discuss in this lecture is the following."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "If all polypeptides initially begin in the free ribosomes, how exactly do the free ribosomes know to attach onto the membrane bound organelle our endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So basically, the polypeptides contain a special type of sequence of amino acids known as the signal sequence."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And it's the signal sequence, as we'll see in just a moment, that directs the free ribosomes to actually bind onto the membrane of the endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, the process by which our growing polypeptide chain is transported from the cytoplasm and onto the membrane of the endoplasmic reticulum along with the ribosome is known as translocation."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And this is what we're going to discuss in this lecture."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So let's begin by looking at the following diagram."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So, we have the mRNA molecule that is being read by the ribosome as shown."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And as it's being read, our ribosome is producing our polypeptide chain as shown."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So the signal sequence is a special sequence of amino acids that are found at the beginning, at the end terminus of the polypeptide chain."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And if the polypeptide chain actually contains the signal sequence, what happens is a special complex of molecules known as the signal recognition particles or SRP, which are basically a complex of RNA and protein molecules, will bind onto the signal sequence."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And once they bind onto the signal sequence, they will basically transport this entire complex, known as the SRP ribosome complex, onto the membrane of the endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So once again, polypeptides variedestine for secretion or to be embedded in the cell membrane, begin synthesis in the free ribosome."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "However, shortly after the synthesis actually begins, it stops, because the ribosomes are transported into the cytoplasmic side of the endoplasmic reticulum's membrane and the polypeptide synthesis then resumes and the growing polypeptide chain extends into the er lumen."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, the question is, what exactly is the mechanism by which the ribosome knows to migrate onto the endoplasmic reticulum?"}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So this should be not ribosome, but endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So let's designate this as Er."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So what distinguishes the polypeptides destined to remain inside the side of plasma, the cell, compared to those that are ultimately secreted or end up being inside the plasma membrane of that cell?"}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So, basically, it's the sequence of amino acids known as the signal sequence."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So a polypeptide that is destined for secretion or to be inside the cell membrane contains a special sequence of amino acids beginning at the beginning of that growing polypeptide chain, at the end terminus."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And as soon as the ribosome synthesizes the signal sequence, a group of molecules known as the signal recognition particles, or SRP, can recognize that sequence."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So as soon as the signal sequence is synthesized by the free ribosomes, the signal recognition particles, the complex of proteins and RNA molecules, binds to the signal sequence and moves the ribosome to the er membrane."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, how exactly does the binding between the SRP ribosome complex and the membrane of our endoplasmic reticulum actually take place?"}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So let's take a look at our Er membrane."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So, this is the phospholipid bilayer of the Er membrane."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So inside that Er membrane, we have a set of proteins that are known as the SRP receptor, where SRP stands for the signal recognition particles."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So what happens is this entire SRP and SRP ribosome complex binds to the SRP receptor."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And when that takes place, another type of membrane, known as another type of protein in the er membrane, known as translocon, basically opens up."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So adjacent to the SRP receptor is a protein channel known as the translocan."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And the translocan is normally closed."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "But upon binding of the SRP ribosome complex to the SRP receptor on the er membrane, the channel opens up."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And at this point, the synthesis of the growing polypeptide chain commences."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So it basically resumes and the growing polypeptide chain will extend into the endoplasmic reticular lumen of that organelle."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So basically, in step number one, our free ribosome synthesizes the signal sequence that is found at the beginning of the growing polypeptide chain."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And what the signal sequence means is the polypeptide that is produced will ultimately either be secreted by that cell or will be placed, will be embedded into the plasma membrane."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Once the signal sequence is synthesized, the signal recognition particle SRP binds onto the signal sequence, forming the SRP ribosome complex."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And then this entire complex goes on and binds onto the SRP receptor, where a series of processes basically opens up this protein channel known as translocan."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And then once our translocan channel opens up, our growing polypeptide chain extends into the er lumen, as shown, and then synthesis of that polypeptide chain basically resumes and continues."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And it will continue."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And as it continues, our growing polypeptide chain will extend into the er lumen."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So this is the cytoplasm, this is the er lumen, and this is the membrane that separates the cytoplasm and the er lumen."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Now, as soon as termination takes place, what happens is our ribosome dissociates from the growing polypeptide chain."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Then the growing polypeptide chain basically goes into the er lumen."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "Our ribosome dissociates and detaches from the translocan, and the translocan basically shuts close, so it closes, and that basically completes the process of translation."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And now this polypeptide chain can undergo further post translational modification processes."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "It can fold, and eventually it is basically secreted by the cell or will end up being embedded inside the membrane of that cell."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So basically, this process by which our growing polypeptide chain is transported from the cytoplasm onto the membrane of the endoplasmic reticulum, is known as translocation."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And the mechanism by which it actually takes place involves the signal sequence and the signal recognition particles."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So those growing polypeptides, those proteins that actually are destined to be secreted by the cell or remain in the plasma membrane, contain this signal sequence."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And it's the signal sequence that basically allows the signal recognition particles to recognize it, to bind to it, and to bring the entire growing polypeptide chain, as well as the free ribosome, and bring that ribosome onto the membrane of the endoplasmic reticulum."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "And once that binding takes place, the free ribosome becomes a membrane bound ribosome."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "So these membrane bound ribosomes are responsible for synthesizing proteins that are ultimately and that ultimately end up being secreted by the cell or being embedded inside the plasma membrane of the cell."}, {"title": "Signal Sequences and Signal-Recognition Particles.txt", "text": "But those ribosomes that remain inside the cytoplasm and do not attach to the membrane of the endoplasmic reticulum, those ribosomes are known as free ribosomes, and they synthesize those proteins that end up staying inside the cytosol of our cells."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "The isoelectric point of an amino acid or protein is the PH value at which the net charge on that molecule is zero."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, we already know how to calculate the isoelectric point of individual amino acids."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "But how do you calculate the isoelectric point, the pi value of proteins that consists of two or more amino acids?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Well, this is what we want to focus on in this life."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We want to find out how to calculate the isolectric point of proteins."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, the general rule is to follow the following two steps."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "In step one, we basically want to guess."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We want to estimate what the PH value is at which that protein would have a net charge of zero."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And then in the next step, we want to use that estimated PH value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "In the second step, we want to find the average of the two PKA values right above and right below that estimated PH that we obtained in part one."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, to actually see these two rules, these two steps in action, let's take a look at these two examples, beginning with example one."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So find the pi value, the isoelectric point of the tripepptide, aspartate glycine and glutamate."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's begin by drawing our structure for this tripeptide."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So on the left side, we have this amino acid."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have our amino group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have h, three n, and this is bound to the central carbon."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "The central carbon contains an h atom going into the board and the r group, the side chain coming out of the board."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And and for aspartate, we have the following side chain group, and then we finish off this amino acid with our carbanal group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, glycine, so glycine has a very simple side chain, and the side chain of glycine is simply an h atom."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So here we have an h atom, and we have an h atom."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And now we finish off this glycine, and we move on to our glutamate."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Glutamate has a very similar side chain to this first amino acid."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have our h going to the board and our side chain group coming out of the board."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And the only difference here is it has one more carbon group than in that particular case."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have actually, let's draw it in a slightly different manner, show the resonance stabilized form."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay, so now we finish off this group by finishing off with the alpha terminal carboxyl group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay, so this is our tripeptide."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, once we draw our tripepptide, we now have to find and label all those groups on our peptide that can readily lose or gain an h atom."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And we have to write down their PKA values."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's begin on our side."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So on this side, we have this terminal amino group, and it has a PKA value of eight."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So 8.0 for this particular case."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "This group here, the PKA value is about 3.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have, let's make this neater 8.03.1 and then we have to look at the side chain group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So for Glycine, this cannot lose an H atom, so it doesn't have a PK value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "But these two groups can gain and lose an H atom, and it happens at a PKA value of around 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So PKA for both of these is around 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, once again, your textbook or your teacher might give you slightly different PKA values."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And that's because under different conditions, for example, if the temperature is different, these PKA values will be slightly different."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So that's okay because this method still works for those values as well."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a PK of eight, 4.14.1 and three."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's begin by applying these rules in rule number one."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Step number one, we estimate the PH at which the net charge and the protein would be zero."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, at least in the beginning, before we gain intuition about how to solve these problems, we have to actually guess."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's suppose our guess is PH of seven."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, that guess might be wrong, and the only way to find out is to actually solve the problem."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Let's suppose that our guess is a PH of seven."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "At a PH of seven, the charge will be zero."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So at a PH of seven, what will be the charge on this group here?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Well, because the PKA is eight and it's above seven, our guess, that means this will have a positive charge, right?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Remember, this will only lose an H atom and become neutral at this PH or above."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And because we're below, because our guess has a PH of seven, this will be a positive charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Let's move on on to this one."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So what this PK tells us is this group will lose an H atom at this th or higher."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And because we're at a PH of seven, that means this will have a negative charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a negative charge on this group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And the same thing is done with these two groups here."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So because we're at 4.1, which is below seven, that means these will lose the H atom."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And so we'll have a negative charge will exist in the form as shown on the board."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And now what we have to do to find the net charge is we sum up all the charges."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a positive one, negative one, those cancel out, and then we have negative one and negative one."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we see that the net charge on the protein is negative two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And what that means is our estimate, our guess, was incorrect."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "At a PH of seven, this protein will have a charge of negative two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, do we go up or do we go down?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So basically, because we have a charge of negative two, that means we want to decrease the amount of negative charge we have on our protein."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, if we go higher, if we go above eight, we will remove this positive charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And make our peptide more negative."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So that means instead of going above seven, we have to go somewhere below seven to basically remove some of that negative charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And so to remove the negative charge, right, we have to remove two negative charges because our charge at seven is negative two, we have to go below a PH of 4.1, because below a PH of 4.1, these two groups will gain an H atom and so will neutralize themselves."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's go below 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Let's say 3.5."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So our second guess is a PH of so we said PH of seven does not work."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Let's try PH of 3.5."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Let's see if that works."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we basically continue with the same exact type of procedure."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We write down our pluses and negatives."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So at a PH of 3.5, this will be negative because this value is lower than this."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a negative here, we have a positive value here."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And for these particular groups, we're going to have a neutral charge because this PH is below 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And that means these will gain an H atom at a PH of below this."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a positive, a negative and two neutral."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And what that means is our net charge is in fact zero."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So this is the correct guess, the correct estimate."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And now we can move on to step two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Step two tells us to take this PH value and to find the PKA right above it, right below it, sum them up, divide them by two and find the average."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So the PKA value right above this PH is basically 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "The PK value right below it is 3.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we take 4.1 and 3.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have 4.1 plus 3.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Divide that by two, and that gives us so we have 7.2 divided by two, and that gives us 3.6."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So this is our pi, the isoelectric point for this particular tripeptide."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's move on to example number two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So, once again, let's begin by drawing our peptide."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "In this case, we have four amino acids."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So the first amino acid is cysteine."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we begin with our h amino group, h three N. Then we have our central carbon, the h. And then we have our cysteine, the side chain."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And cysteine is this side chain shown here."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Then we have our carbanogroup."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Then we go on to the second amino acid."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So the second amino acid in this particular case is glycine."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So just like in that case, we have a simple h. And this finishes off the second amino acid."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "The third amino acid is glutamate or glutamic acid."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have our side chain group, the same as in that particular case, right?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We have ch two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Ch two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Then we have a C and we have our group as shown here."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Then we finish off this amino acid with our Carbonal group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And finally we have Lysine."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have lysine."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now, what does the side chain of lysine look like?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Well, it looks something like this."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We essentially have four carbons in a row."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And then at the bottom, we have this amine group that has a positive charge at a specific PH value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now we finish it off with our terminal group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay, so the same exact procedure holds here."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We have to begin by labeling all those groups and their respective PKA values."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So let's begin on this end."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Once again, this has a PKA value of 8.0."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "This has a PKA value of 3.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "This has a PKA value of PKA of 10.8."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "This has a PKA value we saw from previous example of about 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "What else?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Glycine has no PKA value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And this, what is it?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Cystine has a PKA value of 8.3."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay, so we have this value, this value, this value, this value, and this value that we now have to consider."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So once again, we have to begin with our guess."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So as always, let's suppose our guess is a PH of seven."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we don't know if it's correct until we actually try."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So at a PH of seven, what will be the charge on that molecule?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Right."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Okay, so at a PH of seven, this one will have a positive charge because it only loses that H and becomes neutral at or above this PKA value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So what about this one?"}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Well, this one will have a neutral charge because it will only lose that H and gain a negative charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "At or above this PH value, this one has a lower PKA value, so it will be negative."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a negative charge coming from this side chain group."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And in this particular case, we're above, we're below this 10.8 value."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So this will have a positive charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And then we're at this particular location, so that means we're above it."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So this will have a negative charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now in this particular case, we see that if we add up these charges, two positive and two negative, they work out just fine."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And at a PH of around seven, at the estimated PH of seven, we have a net neutral charge."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "Now we move on to step two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "We find a PTA value above and below."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have a PH of seven, and the one above it, directly above it is."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we have 8.310.8 and eight."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So this is the closest one to seven from above."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And so that means we have to add 8.0."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And the one right below seven is well, we have 3.1 and 4.1."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "This is the one right below it."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "And so that means we add 8.1 and we add eight and 4.1 and divide that by two."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So the numerator is 12.1, denominator is two, and this gives us 6.5."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we see that the isoelectric point, the pi value for this peptide that consists of four amino acids is 6.05."}, {"title": "Calculating Isoelectric Point of Proteins .txt", "text": "So we see that these are the two steps that basically give us a general, a general rule of how to find the isoelectric point value of our proteins."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Protein structure has different levels and so far we focused on three of these levels."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we begin our discussion on primary structure and we said that primary structure is the sequence of amino acids within that polypeptide chain."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Then we moved on to the secondary structure and we said that secondary structure is the spatial arrangement of those amino acids."}, {"title": "Quaternary Structure of Proteins .txt", "text": "It's the interaction of those amino acids that are found in close proximity on that polypeptide chain."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And we said that secondary structure consists of these regular patterns we call alpha helixes, betappleated sheets, beta turns and omega loops."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And finally, in the previous lecture we discussed tertiary structure and we said that tertiary structure is the interaction, it's the spatial arrangement of those amino acids that are found far away on that polypeptide chain."}, {"title": "Quaternary Structure of Proteins .txt", "text": "In this lecture we're going to focus on the final level of protein structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So all proteins contain primary structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "The majority of proteins contain secondary and tertiary structure and some proteins also contain a fourth and final level of structure known as quaternary structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So a protein is said to have quarter structure if that protein actually consists of two or more individual polypeptide chains and the quarterliary structure is basically the interaction of these polypeptide chains with respect to one another."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, the simplest type of quaternary structure is a dimer."}, {"title": "Quaternary Structure of Proteins .txt", "text": "In a dimer we have two individual polypeptide chains and these polypeptide chains can interact usually via non covalent bonds but sometimes we have covalent bonds such as disulfide bridges disulfide bonds that also hold those individual polypeptide together."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, generally speaking, whenever we have quotinary structure those individual polypeptide chains are also known as subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So for example, in a dimer we have two subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "In a trimer we have three subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "In a tetrimer we have four subunits and so forth."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, these subunits can be different or they can be identical."}, {"title": "Quaternary Structure of Proteins .txt", "text": "It really depends on the type of protein that we're discussing."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, all the different types of proteins inside our body can usually be categorized into two categories."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have a type of protein known as a fibrous protein also called structural proteins and we also have globular protein."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So let's begin by focusing on fibrous protein."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So what is a fibrous protein?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "Well, a fibrous protein or a structural protein basically consists of these long fibers that play a structural role in the cell and in our body."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So some examples are intermediate filaments found in our cytoskeleton."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We have collagen found in our connective tissue such as bone and we have carotene found in the hair and in our nails as well as in the wool of animals in the horns and in the claws of different kinds of animals."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So in this lecture we're briefly going to focus on a specific type of keratin known as alpha carotene."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So alpha carotene is the type of fibrous protein that is found in our hair and in our nails."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, alpha carotene consists of these two individual and long fibers."}, {"title": "Quaternary Structure of Proteins .txt", "text": "These polypeptide chains as shown in the following diagram."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And both of these polypeptide chains essentially are composed of these right handed alpha helixes and these right handed alpha helixes together intertwined to form a left handed coil known as the alpha coiled coil."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, how exactly are these polypeptide chains?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "How exactly are these two subunits actually held together?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "So notice because we have two subunits in the alpha carotene, this is an example of a dimer."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So a quarterinary protein that contains coordinate structure that is actually a dimer because it consists of two subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So how are these two subunits actually held together?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "Well, they're held together by Covalent and non Covalent interactions."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have Vanderwal's forces that are basically the London dispersion forces between the non polar side chains of the amino acids found on these two opposing subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We also have ionic bonds which are basically the bonds between the negatively charged side chains and the positively charged side chains."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We also have hydrogen bonds and we have a type of Covalent bond known as a disulfide bond or a disulfide bridge."}, {"title": "Quaternary Structure of Proteins .txt", "text": "This is a covalent bond that is formed between two adjacent 15 amino acids."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, the more disulfide bonds we have inside the alpha carotene, the stronger and the more rigid that molecule is that protein is."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now."}, {"title": "Quaternary Structure of Proteins .txt", "text": "What about globular proteins?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "Well, Globular proteins have a very, very wide range of functions."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We see that fibrous proteins are responsible mainly in giving our cells in our body structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "But these Globular proteins have a wide range of functionality as we'll see in just a moment."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So unlike these fibrous proteins or structural proteins that consist of long fibers, these Glybla proteins have a relatively spherical shape."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, what are some examples of Glibula protein?"}, {"title": "Quaternary Structure of Proteins .txt", "text": "So hormones, for example, insulin is a type of hormone that is a Glibular protein."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have Glybla proteins that play a role as hormones."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We also have many enzymes in our body that are Globular proteins."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have these membrane bound proteins, transfer proteins that essentially allow the movement of different types of ions and molecules across the cell membrane."}, {"title": "Quaternary Structure of Proteins .txt", "text": "These are also globular proteins."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So DNA polymerase is basically this protein molecule that contains coronary structure, that contains many subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And this DNA polymerase is a Glybla protein."}, {"title": "Quaternary Structure of Proteins .txt", "text": "It allows the replication of the DNA during the process of mitosis and meiosis."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, the type of Glibla protein we're going to focus on in this lecture is hemoglobin."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And hemoglobin is the oxygen carrier inside our blood."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So hemoglobin essentially picks up oxygen in the lungs and it moves the oxygen via the blood, the circulatory system into the cells and tissues of our body that need the oxygen to synthesize ATP molecule."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And hemoglobin has quadnary structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "In fact, it is a tetromer."}, {"title": "Quaternary Structure of Proteins .txt", "text": "It consists of four individual polypeptide subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have polypeptide subunit one, subunit two, subunit three and subunit four."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have two alpha and two beta subunits to form this tetromer molecule."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, inside each one of these subunits we have a helper prosthetic group we call the heme group."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And the heme group is responsible for actually binding the oxygen via an oxidation reduction reaction."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have heme group one, hemegroup two, heme group three and heme group four."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And these heme groups can bind a single oxygen molecule each."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And that means because we have four subunits and each one of these carries one heme group we can bind four oxygen molecules per hemoglobin molecule."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So once again, hemoglobin is a tetrimer that consists of four individual subunits."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Each subunit is equipped with a heme group that is capable of binding oxygen molecules."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, slight changes to the coronary structure of our hemoglobin can actually increase or decrease definitive of the hemoglobin molecule to oxygen as we'll see when we discuss the hemoglobin molecule in much more detail."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we see that there are four levels of structure in protein."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So we have primary structure which is a sequence of our amino acids."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We have the secondary structure which are basically these regular patterns that are formed so alpha, helixes, beta sheets, beta turns and omega loops."}, {"title": "Quaternary Structure of Proteins .txt", "text": "We have our tertiary structure which basically consists of these amino acids that are far away from one another and they interact with one another to give that tertiary structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "And finally, we also have those proteins that contain a fourth level quadinary structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "This means that protein consists of two or more polypeptide chains."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, not all proteins will contain quarterly structure."}, {"title": "Quaternary Structure of Proteins .txt", "text": "For example, an important type of protein in our muscle is myoglobin."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So myoglobin, like hemoglobin, carries oxygen inside our muscle."}, {"title": "Quaternary Structure of Proteins .txt", "text": "So hemoglobin carries oxygen inside our blood while myoglobin carries oxygen inside our muscle."}, {"title": "Quaternary Structure of Proteins .txt", "text": "Now, unlike hemoglobin, myoglobin only contains tertiary structure and that's because it consists of a single polypeptide chain and not four polypeptide chains like the case was in the hemoglobin molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "The three major types of monosaccharides that we ingest into our bodies that are part of the human diet are glucose, fructose and galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, when we ingest glucose and glucose makes its way to the side of plasma cells, our cells begin the glycolytic pathway and this breaks down that glucose into ATP molecules and Peruvian molecules and other molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "But what happens when fructose or galactose actually make their wings the cytoplasm of our cells?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So fructose we typically obtain from plants, and galactose we typically obtain from milk or dairy products."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, it turns out that unlike glucose, which actually has its own catabolic pathway in our cells, these two sugars do not have their own individual breakdown pathways."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so when these two sugars monosaccharides actually make their way into the cells of our body, these sugars must be transformed into molecules, into metabolites that are part of that glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And once that happens, we can basically incorporate those glycolytic metabolites into the glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So let's begin by discussing fructose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, depending on what type of cell that fructose actually ends up, it can be converted into a glycolytic metabolite in one of two ways."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, let's begin by discussing the fructose one phosphate pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And this is the pathway that is found in the liver cells of our body because we find that the majority of these fructose molecules actually end up in these liver cells."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, fructose one phosphate, the fructose one phosphate pathway actually consists of three individual steps."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And ultimately what we want to do in this pathway is transform a fructose molecule into dihydroxy acetone phosphate and glycerol aldehyde three phosphate because these are the two molecules that are in fact glycolytic metabolites."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we can feed them directly into the glycolytic pathway and then we can use those molecules to form ATP molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So let's see what these three steps actually are."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So in step one of the fructose one phosphate pathway, we have an enzyme we call fructokinase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So what is fructokinase?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "What does it do?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, kinase means if it's four late."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we have to have an ATP molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And fructose means that the substrate molecule to this enzyme is a fructose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So we have our fructose carbon 12345 and six are fructose and fructose kinase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Fructoseinase basically uses the ATP suposphorylate carbon number one, and we form fructose one phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "We also form the ATP as well as the H. Now, what is the purpose of this step number one?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, the purpose is to basically destabilize this molecule once we add that phosphoral group that destabilizes our molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And now in the next step, we can basically cleave the molecule into two, three carbon molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So in the first step, fructose is the sporulated at carbon one."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "By fructokinase that destabilizes our fructose also traps that fructose in a cell."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And now we can basically cleave that fructose by the activity of an enzyme we call fructose one phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Aldolase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, what is an aldolase?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, an aldelase is an enzyme that catalyzes an aldol cleavage."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So essentially we have the fructose one phosphate that we form in step one."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "This interconverts into its open chain form."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this bond here in black essentially breaks."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we form this open chain form."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "This purple section is this region here, and the light purple is this section here, and the orange bond is the bond that is cleaved by this fructose one phosphate aldelase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And we form two, three carbon molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "One of these is dihydroxy acetone phosphate DHAP."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And this molecule is part of the glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so now we take this molecule and we place it into stage two of glycolysis."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And in stage two of glycolysis, this molecule is then transformed into glyceroaldehyde three phosphate gap."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now what about this?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, this is not actually part of that glycolytic pathway, but it's very close to glyceroaldehyde three phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "The only thing it's missing is of a sporal group on carbon number three."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so all we have to do in the third step is use a special enzyme and an ATP molecule to basically attach a phosphoryl onto carbon number three."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And that's exactly what trio's kinase actually does."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now trio simply means this substrate molecule is a three carbon sugar."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "One, two, three."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Trios is a three carbon sugar."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we have an attachment of the phosphoryl, we take it from the ATP and place it onto carbon number three."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we form our glycero aldehyde three phosphate, the gap molecule, which can be fed into stage two, actually stage three because in stage three, this molecule is eventually converted into Pyruvate molecules and ATP molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this is what our fructose one phosphate pathway is like and this is the pathway that is followed by liver cells."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So if fructose makes its way into the cells of our liver, this is how it's going to be basically transformed into molecules that can be fed into that glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, in other tissues, in other cells of our body, in non liver cells, there's a simpler pathway that is followed."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So if we recall stage one of glycolysis, in stage one we actually form fructose six phosphate in step number two."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And in step number three of stage one, we basically transform that fructose six phosphate into fructose one six bisphosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So the simplest step is to actually take that fructose, use an ATP molecule and a special enzyme we call Hexokinase, which was also actually used in stage one of glycolysis."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And we formed fructose six phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And fructose six phosphate can be fed directly into that glycolytic path into stage one."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And in stage one, step three involves transforming this into fructose 116 bisphosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And of course we form the ATP and the H because we have to use an ATP to actually transfer that phosphoryl group onto carbon number six, this carbon here."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So in non liver cells, other tissue cells, of our body, fructose can be converted into fructose six phosphate by the action of hexokinase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So these are the two pathways by which the cells of our body can basically incorporate fructose into the glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now let's move on to galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Unlike fructose, there's only one pathway that is followed by galactose molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So once galactose makes its way into the cells of our body, galactose is transformed into glucose six phosphate via the galactose fructose into a conversion pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And this pathway is made up of four steps."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And by the way, I have the green asterisk here, here, and here."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And that basically symbolizes the fact that these molecules are part of the glycolytic pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And once we form these molecules, they can be incorporated directly into that glycolytic pathway to form the Pyruvate and ATP molecules."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So let's take a look at the four steps of galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this pathway, once again is known as the galactose fructose into conversion pathway because ultimately our goal is to transform that galactose into glucose six phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And glucose six phosphate is basically in stage one."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So remember, in stage one of glycolysis, we transform glucose into glucose six phosphate via the action of hexokinase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So that's where we want to insert this molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "But let's see how we actually form this molecule in these four steps."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So we take our galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And by the way, what is the difference between galactose and glucose?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, galactose and glucose are epimers, and what that means is they only differ in the stereo chemistry at a single chiral carbon atom."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So which one?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, this carbon atom number four in galactose, it points up, in glucose, it points down."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So it might seem that the only thing we have to do is basically flip this down."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "But that's not actually what happens because our cells follow a slightly more complicated pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So we have an enzyme known as galactokinase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And what a galactokinase does, well, it's a kinase, so it has to use an ATP and it basically transfers a phosphoryl group from that ATP onto carbon number one of galactose, and we form galactose one phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So one phosphoryl from the ATP onto this oxygen here to form this galactose one phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "We form the ATP and the H plus."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, what this does is, again, it traps it inside the cell and destabilizes it in the next step."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Step number two, we have an enzyme known as galactose one phosphate because this is a substrate that it acts on and it's a urinal transferase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And what a transferase does is it basically transfers some type of group from one molecule onto a different molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, aside from having the galactose one phosphate, another molecule known as UDP glucose actually comes in."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this is a modified glucose molecule that contains a uridine diphosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So essentially attached onto carbon number one of glucose, we have the uradine diphosphate group."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And what this transferase enzyme does is it transfers up a sporal group from the urine diphosphate glucose onto this phosphate region here."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we go from galactose one phosphate to UDP galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this molecule is known as uridine diphosphate galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And notice we transferred the phosphoryl group as well as that uridine."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so this is the molecule that is formed."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "This is known as UDP galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "We also form glucose one phosphate because that uridine and a single phosphoryl group have been removed from the UDP glucose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we form the glucose one phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So these are the two products of step two."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, this product will go on to carry out step three, and this product will go on to carry out step four."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, step three is important because in step three, what we want to do is we want to reform the UDP glucose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And the way that we reform the UDP glucose is by taking this molecule, the UDP galactose, which looks like this."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So in step two, we form this molecule, right, this molecule here, which is the UDP galactose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And now what we do to this molecule is we use a special enzyme that flips this hydroxyl group from the up position to the down position."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And if we flip this hydroxyl from the up to this down, what we're going to form is a glucose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so we go from UDP galactose to UDP glucose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Because remember, as I mentioned a moment ago, the only difference between galactose and glucose is the orientation of this hydroxyl group."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So in a galactose, it points up, in glucose, it points downwards."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So this is in fact an example of a glucose."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So we go from UDP galactose to UDP glucose by the activity of UDP galactose for epimerase."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so epimerase, or epimerase, is basically an enzyme that transforms one epimer into a different epimer."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Now, the point of step three was to basically regenerate this molecule here."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so now if we sum up all these three steps, because this molecule, UDP glucose was regenerated here, these will simply cancel out."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so if we sum these up, this is the net equation after three steps."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So after three steps of this pathway, galactose plus ATP gives us glucose one phosphate plus ADP plus H. Now, what is the final step?"}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Because we still haven't formed a molecule that we wanted, so we wanted to form a glucose six phosphate."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Well, in the last step, we basically take this glucose, we take the glucose one phosphate in step two, and we use an enzyme known as phosphor glucom mutates."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "Remember, a mutase is an enzyme that moves a specific type of group on a molecule to a different location on that same molecule."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "So all we have to do is move that phosphoryl group from position one to position six."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And so in the final step, glucose one phosphate is transformed, or is glucose one phosphate is transformed into glucose six phosphate by the action of phosphor glucomutase in which it transfers."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "That the spoil group from carbon number one to carbon number six."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And this concludes the Galactose pathway, also known as Galactose fructose interconversion pathway."}, {"title": "Fructose and Galactose Breakdown Pathways .txt", "text": "And once we form, ah, the glucose six phosphate, it goes into stage one of glycolysis, and we can use that molecule to basically form Pyruvate molecules and ATP molecules."}, {"title": "Stage 2 of Glycolysis Part II .txt", "text": "Is in two steps."}, {"title": "Stage 2 of Glycolysis Part II .txt", "text": "First, this step takes place and only forms one of these two gap molecules."}, {"title": "Stage 2 of Glycolysis Part II .txt", "text": "In the other step, catalyzed by a different enzyme, this dihydroxy acetone phosphate is transformed into this molecule."}, {"title": "Stage 2 of Glycolysis Part II .txt", "text": "So at the end, we form these two identical glyceroaldehyde three phosphate molecules that can now move on into stage three, which we'll focus on in the next lecture."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Although enzymes are extremely useful and important biological catalysts that speed up the manual reactions that take place within living organisms, enzymes themselves must actually be regulated and their activity must be controlled."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And one way in which we can regulate the activity of enzymes is by using special molecules or ions known as inhale ##hibitors or enzyme inhibitors."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And the two processes of enzyme inhibition that can take place are Reversible inhibition and irreversible inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So we're going to discuss these two types of inhibition processes in this lecture."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So let's begin by defining and examining reversible inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, when our inhibitor molecule, or ion, binds to that enzyme via weak electric forces, via non covalent forces, and when that inhibitor can easily and effortlessly dissociate from that enzyme following the reaction, this inhibition process is known as reversible inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So basically, in reversible inhibition, our inhibitor binds to that enzyme via weak non covalent forces, and at the same time, it can easily dissociate from that enzyme at any given time."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, there are three different types of reversible inhibition processes."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "We have competitive inhibition, we have non competitive as well as non competitive."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And actually, there's a fourth type known as mixed inhibition, but we're not going to focus on that one in this lecture."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So let's begin by discussing each one of these processes, beginning with competitive inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, in competitive inhibition, our inhibitor molecule, or ion, actually binds to the active side of that enzyme because the structure of our inhibitor actually resembles the structure of our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, since the active side is occupied by that inhibitor, that means momentarily our enzyme will no longer be active and that substrate will no longer be able to bind into the active side of the enzyme because that inhibitor will be found inside that active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So this situation is described in this diagram."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So we have the enzyme, we have the substrate shown in green, we have the inhibitor shown in purple, and we have this whole is our active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So let's imagine we have a one to one ratio of substrate to inhibitor."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And so that inhibitor is just as likely to get into that active side as our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So for this particular case, because we're assuming the affinity of this enzyme to the inhibitor is the same as to our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So we see that once the inhibitor binds to the active side, this substrate cannot get inside, and so the enzyme is rendered inactive."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, the special thing about competitive inhibition is the following."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "For a given fixed concentration of inhibitor, if we begin to increase the concentration of that substrate, for example, we create a four to one ratio of green to purple molecules."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, what happens is these green substrate molecules are much more likely to actually bind into that active side than compared to our purple inhibitor molecule."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And that means by increasing the concentration of substrate, our substrate can basically compete and outcompete that inhibitor molecule and this is basically what defines competitive inhibition and what separates competitive inhibition from non competitive as well as non competitive."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So for any given inhibitor concentration, the competitive inhibition can be reversed by increasing the concentration of substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "That is, the substrate will begin to compete and eventually will out compete that inhibitor."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And once that substrate binds to the active side, that will activate our enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So this basically means that if we increase the concentration of substrate high enough, eventually all the active sites will be replaced by that substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And that means the overall maximum velocity V max or the maximum rate of activity of the enzyme does not actually change when we're dealing with competitive inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And because we have to increase the concentration of the substrate to reach that maximum velocity, the Km, the mechaless constant, has to basically increase."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And this means that our affinity for that substrate by that enzyme decreases."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, let's move on to our second type of reversible inhibition known as non competitive inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, in competitive inhibition, the inhibitor resembled our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "But in non competitive, the inhibitor does not actually resemble our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And that means it does not bind to the active site of the enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "It binds to completely different location, known as the allosteric site."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, since the two sites, the allosteric site and the active site, are different, the inhibitor can bind to the enzyme regardless of whether the substrate is actually bound to our enzyme or not."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So if we look at the following diagram, we have the enzyme shown by this brown region."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "We have this active side, we have the substrate shown in blue, and we have this inhibitor shown with our purple color."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So this here is the allosteric side to which our inhibitor will bind, and this is the active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So what this means here is the inhibitor can bind to the allosteric site regardless of whether this blue molecule, the substrate, is actually found inside that active site."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So once the inhibitor binds to our enzyme, it will slightly deform our enzyme, it will change the enzyme threedimensional structure and that will also slightly change the structure of our active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And even though the active side can still bind our substrate, the binding is no longer optimal and the enzyme activity will decrease."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So once the inhibitor binds to our allosteric side, that conforms or change our enzyme, changes the shape of the enzyme, change the shape of our active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, even though the substrate can still bind to that active side to form the enzyme substrate inhibitor complex, this is no longer an active enzyme because this shape is not perfect because this substrate does not fit perfectly into our enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So that means at any given time, because we're going to have the inhibitor bound to our enzyme, that means we'll have less active enzyme molecules and the VMAX will be reduced."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "However, the ratio basically stays the same."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So that basically means that the Km, our mechanics constant, remains constant, which means that the affinity of the enzyme to the substrate will not be decreased or increased as it was in this particular case."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And finally, let's move on to uncompetitive inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, the major difference between non competitive and uncompetitive is in non competitive, this inhibitor can bind to the allosteric site regardless of whether the enzyme is bound to the substrate or not."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "But in uncompetitive, the inhibitor can only bind to our site on that enzyme when the substrate actually binds to our active site."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "In fact, in uncompetitive inhibition, when the substrate, shown in blue binds to the active site of the enzyme here, when that binding takes place, only then do we create that site for this inhibitor."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So we can imagine this binds, then it creates that site for our inhibitor, shown in purple, that can then bind to that site to form this enzyme substrate inhibitor complex."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So that's the major difference between non competitive and non competitive."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So in this inhibitor process, the inhibitor only binds to the enzyme once the substrate is actually bound to that enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And once it binds, it basically deactivates that enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So in this case, the binding of the substrate to the active side creates a new side to which the inhibitor can bind."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And once it binds, it deactivates our enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And in this particular case, the VMAX, the maximum velocity, the maximum rate of activity will decrease because now we have less enzymes that are active and that will also decrease our mechaless constant."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, let's move on."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And one last thing I want to mention."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Basically, in our competitive inhibition, we saw that by increasing our concentration of the substrate, we can basically kick out our inhibitor from the active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, for this particular case, because the inhibitor does not actually bind to the active side, no matter how much we increase the substrate concentration by, that will basically not kick off our inhibitor."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So that's the major difference between competitive inhibition and these two types of inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, what exactly is Irreversible inhibition?"}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So remember, we have reversible and irreversible."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Now, Irreversible inhibition basically means that once the inhibitor binds to our enzyme, it will be extremely difficult to actually unbind that enzyme and inhibitor complex."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So in this inhibition, once the inhibitor binds to the enzyme, it is very difficult to actually unbind it from that enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And the binding can either be covalent or non covalent."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So all three types of these reversible inhibition processes are non covalent, but the Irreversible inhibition can be non covalent as well as covalent."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So whenever you hear covalent bonding, that usually means Irreversible inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So this diagram basically shows one form of Irreversible inhibition."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So basically, we have this purple inhibitor binds to some location on the enzyme that blocks this substrate from binding onto the active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And on top of that, this inhibitor, it will be very difficult to actually take that inhibitor off from our enzyme."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And this is the major difference between reversible and irreversible."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So Reversible basically means once we bind our enzyme or once we bind our inhibitor to the enzyme, we can easily dissociate it."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And the bonding is always non covalent, but in this case, it can be covalent or non covalent, and once we bonded, we cannot dissociate it very easily."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "For Reversible, we have three different cases."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "We have competitive, we have non competitive and non competitive incompetitive."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "Basically, the inhibitor resembles our substrate, and so it binds directly to the active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "And that means if we increase the concentration of our substrate while keeping the inhibitor concentration the same, we increase the ratio, and we increase the probability of this substrate binding to that active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "So we can basically displace that inhibitor from that active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "But in these two cases, our inhibitor does not actually bind to the active side because it doesn't actually resemble the structure of our substrate."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "In non competitive, we see that the inhibitor binds to an allosteric site regardless of whether or not the substrate is bound to that active side."}, {"title": "Reversible and Irreversible Enzyme Inhibition.txt", "text": "But in this case, the inhibitor can only bind to that special site when the substrate binds to the active side, which creates that pocket that side for our inhibitor."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "In the previous lecture, we focus on the first two steps of Gluconeogenesis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now we're going to basically discuss the remaining steps in Gluconeogenesis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "But before we actually look at that, let's remember what happened in steps one and two."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So in step number one, which takes place entirely in the mitochondrial matrix, we have Pyruvate being transformed into oxyloacetate by the activity of an enzyme line we call pyruvate carboxylate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So basically, this reaction involves the carboxylation of that Pyruvate into oxyloacetate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And in step number two, or actually before step number two takes place, the oxylo acetate is transformed into malade."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "That then moves into the cytoplasm and the malade is transformed back into the oxyloacetate within the cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And then step number two takes place and it is catalyzed by Pep carboxy kinase, where Pep stands for phosphorinl pyruvate carboxy kinase."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we form in step number two, phosphorinl Pyruvate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So step number one takes place in the mitochondrial matrix."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Step number two takes place in the cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And all these remaining steps except step number ten also take place in the cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And we'll see where step ten takes place in just a moment."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So let's essentially discuss this section here."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So once we form the phosphory Enlyruvate, we essentially follow step three, step four, step five, step six and step seven."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And all these steps basically are the reverse steps of the steps we saw in Glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And they even use the same exact types of enzymes."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we have phosphorino Pyruvate, it's transformed into two phosphorglycerate bioactivity of Enolase."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "We have two phosphorglycerate transformed into three phosphor glycerate bioactivity of phosphorlycerate kinase."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Then the one three bisphosoglycerate transformed into these two molecules."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So it's broken down into Glyceroaldehyde and DHAP, where DHAP stands for dihydroxy acetone phosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And in the 7th step, these two molecules are basically combined via the activity of aldease to form fructose 116 bisphosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So the question might be, why isn't these steps simply the reverse of the steps we saw in Glycolysis?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "But these steps are exactly the reverse steps that we saw in Glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Well, as I mentioned in the previous lecture, if we simply reversed the steps that we saw in Glycolysis, in this particular case, those steps would actually be very endergonic."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so we don't want to have the input energy."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And that's exactly why we change the reaction pathways for the conversion of Pyruvate into phosphorino Pyruvate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "But in these steps from three to seven, all these steps basically have a free energy value that is very close to zero."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And what that means is they're essentially at equilibrium."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And if our cellular conditions favor the formation of glucose, these reactions will readily take place in this direction."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And the phosphorino Pyruvate under those conditions that favor Gluconeogenesis will be transformed into fructose one six bisphosphate by the same enzymes that we discussed in the process of Glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So once again, once phosphate Enlyruvate is formed, once we form this molecule here, the reverse steps of Glycolysis are followed until fructose one SIG bisphosphate is formed, until we form this molecule here."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And these steps, steps three to seven, are equilibrium and will readily occur under the conditions that favor the formation of those glucose molecules."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "But why doesn't fructose one six bisphosphate simply follow the reverse step that we saw in Glycolysis to form the fructose six phosphate?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Well, because in Glycolysis, fructose six phosphate form fructose one six bits phosphate via an irreversible step."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And what that means is in Glycolysis, this step was basically a very exergonic step."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And in this case, we can't simply reverse the steps of Glycolysis because that would mean we would have to input a very large amount of energy."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so for the same exact reason that we have to follow a different pathway to get from Pyruvate to phosphorino Pyruvate, to get from fructose one six bits phosphosphate to fructose six phosphate, we also have to create a completely different reaction pathway and we have to use a completely different enzyme."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And that's exactly why the reaction pathways that we use is the hydrolysis of the Esther bond between carbon one and this oxygen in this fructose one six bisphosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So this is the reaction that allows us to basically convert the fructose one six bisphosphate into the fructose six phosphate via an exergonic reaction, an energy releasing step."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we have the fructose one six bisphosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So carbon number one contains the phosphate group as well as carbon number six."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And this is our fructose molecule."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, in the presence of water, which we have plenty in a cytoplasm, remember, all these steps basically take place in a cytoplasm except step number one and step number ten."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so the water is used to hydrolyze this ester bond via the activity of fructose one six bisphosphatase."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And remember, it's a phosphatase, because phosphatases take off phosphoryl groups while kinase is actually put on those phosphoryl groups."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And we basically break the bond and we form this fructose six phosphate and we release that inorganic phosphate, the orthophosphate as shown here."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, this enzyme is an allosteric enzyme."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And what that means is it contains allosteric regulatory sites."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And as we'll discuss in the next lecture, when we discuss how we regulate the process of Gluconeogenesis, this enzyme is actually used to regulate that process."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So fructose one six bisphosphate is an allosteric enzyme that is also used in Gluconeogenesis regulation."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And this enzyme catalyzes the exergonic hydrolysis of the established carbon one of fructose one six bisphosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we see that these two steps and this step are different than the steps in Glycolysis, but these steps are exactly the same."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, once we form the fructose six phosphate, then we follow the same exact step as in Glycolysis, except in reverse."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Why?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Well, for the same exact reason that we mentioned here."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Essentially these two molecules in Glycolysis are at equilibrium, and that means their free energy value is very, very close to zero."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so they're at equilibrium and we can basically use the same exact type of enzyme, phosphor, glucose isomerase, to transform the fructose six phosphate into the glucose six phosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So once fructose six phosphate is formed, it'll negotiate step nine, which is the reverse of step two that we saw in glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, once we form glucosex phosphate, what happens next basically depends on the type of cell that we're in."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "In the majority of the cells of our body, for instance, muscle cells, the glucose six phosphate basically stops here."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "It is not transformed for a further into glucose."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And that's because in muscle cells, for example, in skeleton muscle cells, once we form the glucose six phosphate, we can now take that glucose phosphate and either use it to form pyruvate molecules and then use that to form energy, or more importantly, we can probably store it as glycogen in case we have to use it later."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Because remember, what is the difference between glucose and glucose phosphate?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Well, glucose can easily leave that cell, but glucosex phosphate is trapped within the cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so glucosex phosphate cannot actually escape the cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And glucosex phosphate can then be easily transformed into glycogen."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so if the cell wants to form the glycogen, why would it want to basically go on to form the glucose and then because then it would have to go on to reform that glucose six phosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So in the majority of the cells of our muscle, like skeleton muscle cells, this step doesn't actually take place for two reasons."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Number one, we want to basically make sure that glucose doesn't leave the cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Number two, we want to have it in a form that can easily be transformed into glycogen."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Once the glucose six phosphate is formed, it is usually not transformed into glucose in the majority of our cells."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And this is because glucose six phosphate number one cannot escape out of that cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Number two can easily be transformed into glycogen."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now what about cells like liver cells or kidney cells?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Remember, the kidneys and the liver basically are responsible for regulating our blood glucose level."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So the liver predominantly regulates our blood glucose level, while the kidneys regulate to a much smaller extent."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "But the point is, because liver cells known as hepatocides and kidney cells basically regulate the blood glucose level, these cells have to be able to form the glucose because only the sugar in the glucose form can actually leave that cell, because glucose six phosphate is trapped inside that cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so hepatitis, liver cells and kidney cells have the ability to basically transform the glucose phosphate into the glucose, because then the glucose can exit that cell and enter that blood plasma where the glucose can basically be used to maintain that concentration, that regular normal concentration in the blood plasma."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Okay, so how exactly does step ten actually take place?"}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Well, first of all, as in this case, in this case, step ten in gluconeogenesis is not simply the reverse of step one in glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And that is because for the same reason that we discussed earlier in glycolysis, the transformation of glucose into glucose six phosphate is a very exergonic process."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "It releases lots of energy."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so if we simply reverse the step in glycolysis, that would make it a very endergonic process in glucanogenesis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so, once again, we see that this step actually follows a completely different pathway in glucanogenesis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And as we'll see, it actually involves five different proteins."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we know that step one takes place in the mitochondrial matrix, and these remaining steps up until step nine, all take place in a cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so let's begin in a cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Let's imagine this is a cytoplasm of our cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we have the glucose six phosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "What happens next is we use a special type of membrane protein found on the membrane of the endoplasm reticulum."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So this is the membrane of the er, and this is the lumen of the Er."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And so what happens is by using a special membrane protein known as T one, or glucose six phosphate transporter, the glucose six phosphate enters the lumen of the Er."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And once inside the lumen of the Er, the glucosex phosphate in the presence of water, because, again, we have plenty of water in the lumen of the Er, it's transformed into glucose and a single inorganic phosphate."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So orthophosphate is produced as well."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And the enzyme that catalyzes this is actually a membrane bound enzyme known as glucose phosphatase, which is found on the membrane of the Er."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "On top of that, we also have another protein that essentially assists with this process, known as the calcium binding stabilizing protein."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So this here is the calcium binding stabilizing protein that assists the glucose phosphatase to carry out its function of transforming the glucose phosphate into that glucose."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And once we form these two molecules, the orthophosphate inorganic phosphate basically uses its own type of transporter membrane to basically move into the cytoplasm in the cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So this is the phosphate transporter T two, while the glucose uses its own transporter, so known as T three, to move back into the cytoplasm of that cell."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And once inside the cytoplasm of that cell, if this is, for instance, a liver cell or a kidney cell, the glucose can be dumped into that blood plasma to basically regulate the levels of glucose in the blood plasma so that the rest of the cells can actually have enough glucose to carry out their cellular processes."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we see that in hepatocytes liver cells or kidney cells, glucose six phosphate is converted into glucose, and this takes place in the lumen of the endoplasm reticulum."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So let's summarize our results."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we basically have step one that takes place in the matrix of the mitochondria."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Step two takes place in a cytoplasm."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "And both of these steps are basically different steps than the steps that we saw in glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, steps three through seven are the same exact steps as we saw in glycolysis."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Step eight is not the same."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Step nine is the same, and step ten is not the same."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Step eight takes place in the cytoplasm, as does step nine, but ten takes place in the lumen of the Er."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "Now, the final thing that I'd like to mention is so remember, there are different types of non sugar precursor molecules that we can use to actually form glucose."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So we discussed pyrulate, but we also mentioned lactate, amino acids and glycerol."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So amino acids, depending on the type of amino acid, the amino acids can be either transformed into pyruvate or the DH 18 molecule, and they enter the process of gluconeogenesis to form the glucose as either this molecule or this molecule."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "So, for instance, if the amino acid is transformed into this, then it combines with the glycerol, the hyde, to go on to form that glucose."}, {"title": "Gluconeogenesis Steps 3-10.txt", "text": "In the case of lactate, it is transformed into pyruvate before it actually enters the Glucomune genesis cycle, and glycerol is transformed into the DHAP dihydroxy acid."}, {"title": "Introduction to Human Respiratory System.txt", "text": "The human respiratory system is a system of our body that is involved in the process of respiration."}, {"title": "Introduction to Human Respiratory System.txt", "text": "In the process of breathing, it exchanges oxygen for carbon dioxide."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the primary organ of the respiratory system are the lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And each person contains two different lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "We have a right lung and we have a left lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, these lungs are are found in the chest portion of our body, and that is called the thorax."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So within our thoracic cavity, we have our two lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So if this is the right side of the body and this is the left side of the body, then this is the left lung and this is our right lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, because of the position of the heart, it turns out that our left lung is slightly smaller than our right lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that's because our heart, which is found within this particular portion of the body, is actually accommodated inside the left lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So the left lung has to use some of its space to basically accommodate our heart."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that's exactly why our left lung is slightly smaller by volume and by mass than our right lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that's exactly why the left lung only consists of two lobes, while our right lung consists of three different lobes."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So let's begin with the left lung."}, {"title": "Introduction to Human Respiratory System.txt", "text": "We have this upper lobe, also known as our superior lobe, and we have the lower lobe of the left lung, also known as our inferior lobe."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the line, the fissure that separates these two lobes on the left lung is known as the left oblique fissure."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Oblique simply means it's at an angle, it's slanted."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, on the other hand, the right lung, which is slightly larger, consists of three different lobes."}, {"title": "Introduction to Human Respiratory System.txt", "text": "We have an upper or a superior lobe, and then we have a middle lobe."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the line separating these two lobes is straight, or relatively straight."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that's exactly why we call it the horizontal fissure."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, we also have a lower lobe, also known as our inferior lobe."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And this is separated by a line called the right oblique fissure because it's also slanted, just like this one."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So we have the upper, the middle and the lower lobe."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, superior simply means it's found above, and inferior means it's found below."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that's exactly why these two are referred to as a superior and these two lobes are referred to as our inferior lobes."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So we see that our two lungs are found within our thorax, within our thoracic cavity, and below our lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "As we'll see in just a moment, there's a special type of skeletal muscle known as our diaphragm."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the diaphragm separates our lungs from the stomach and the small intestine, and it also functions in the process of respiration."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, let's actually discuss the way that our air moves into our lungs via this passageway system that we have that connects between our nose and our lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So essentially, when we breathe in we can either breathe in through our mouth, or we normally breathe in through our nose."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, when we breathe in through our nose, the air, and this includes things like nitrogen oxygen that moves in to our nasal cavity, the nasal cavity, or the canals found within our nose."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the lining of the nasal cavity consists of a special type of slimy and sticky membrane known as the mucous membrane."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the mucus membrane is secreted and created by specialized cells known as goblet cells."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, as the air travels through our nasal cavity, the pollutants and bacterial cells and other harmful substances essentially get stuck within this mucus membrane."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So we see that the nasal cavity, because it contains these tiny extensions known as cilia, as well as a mucus membrane that helps trap this harmful substance, the nasal cavity actually functions in the process of filtering."}, {"title": "Introduction to Human Respiratory System.txt", "text": "It helps our immunity system."}, {"title": "Introduction to Human Respiratory System.txt", "text": "It helps protect our lungs from different types of harmful agents."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, once our air passes through the nasal cavity, it enters a region, a passageway known as our pharynx."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the pharynx is this connection between our esophagus and our larynx."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the larynx is essentially that section that connects to our passageway, the windpipe we call our trachea."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the larynx also contains our voice box that creates our voice."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, in order to prevent food from actually entering our trachea, the opening of our larynx actually contains a cartilage flap we call our epiglottis."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So the epiglottis is open when air passes in, but it closes when we swallow food into our esophagus, into our pharynx."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So air enters the body via the nose in the nasal cavity, a layer of mucous membrane acts as a filter and traps pollutants and other harmful substances that are found within the air that can ultimately end up in our lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Next, air moves into our pharynx."}, {"title": "Introduction to Human Respiratory System.txt", "text": "This is the tunnel that contains our intersection between the esophagus, the pipe that allows our food to move into our stomach, and our larynx, the connection between our pharynx and our trachea."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the opening of the larynx has a special flapper of cartilage we call our epiglottis, and this allows the movement of air, but does not allow the movement of food into our air passageway we call the trachea."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the trachea is also known as our windpipe, and a trachea contains these cartilage rings that essentially allow the trachea to remain open and not to constrict."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, the trachea eventually moves all the way down to this intersection and intersect."}, {"title": "Introduction to Human Respiratory System.txt", "text": "It basically bifurcates."}, {"title": "Introduction to Human Respiratory System.txt", "text": "It forms these two bronchi."}, {"title": "Introduction to Human Respiratory System.txt", "text": "We have the right bronchus and our left bronchus."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And each one of these bronchies essentially terminate within each one of our two lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, each of these bronchies subdivides into smaller structures called bronchioles."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And these bronchioles eventually terminate in a specialized sac structure known as our alveoli."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So if we zoom in on the smallest bronchio that terminates inside the lungs, we basically get the following diagram."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So this is a sac like structure that contains these tiny sacs known as alveoli."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And these alveoli are specialized structures where gas exchange actually takes place."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So the blood is oxygenated and it basically deposits our waste product, the carbon dioxide, back into the bronchioles."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And that eventually travels out of our system and to the outside environment."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And we'll discuss the structure and the function of the alveolis in much more detail in the next several electrodes."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So, as I mentioned earlier, our lungs are based inside the thoracic cavity."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So thorax is simply the term that refers to our chest portion of the body."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, at the bottom of the lungs, we have this sheet of skeletal muscle we call our diaphragm."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And the diaphragm not only separates the lungs from the stomach and our small intestine, large intestine, but it also actually moves up and down and that ultimately allows the process of breathing to actually take place."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, because the diaphragm is a skeletal muscle, that means we have voluntary control of our diaphragm."}, {"title": "Introduction to Human Respiratory System.txt", "text": "It is controlled by the somatic nervous system."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, our lungs are not actually by themselves, they are encased in this membrane we call the cirrus membrane and we call it a sears membrane because as we'll see in just a moment, it actually contains a fluid."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, this sears membrane consists of two individual membranes."}, {"title": "Introduction to Human Respiratory System.txt", "text": "We have an outer membrane and we have an inner membrane."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So this is a two layer protective barrier that encloses our lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So to see what we mean, let's take a look at the following simplified diagram of the lungs and our membrane."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, this entire membrane that encloses our lungs is known as aroplora."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So we have an outer membrane of the pleura, known as the parietal pleura."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And we have the inner membrane of our pleura known as the visceral pleura."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So the parietal pleura actually connects our lungs to outside organs of our body."}, {"title": "Introduction to Human Respiratory System.txt", "text": "For example, our ribcage and our visceral pleura actually connect to our two lungs."}, {"title": "Introduction to Human Respiratory System.txt", "text": "Now, in between the two pleura, we actually have a space."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And this space, this cavity, is known as the intraplural space, or the pleural cavity."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And this cavity contains a special liquid, a special fluid known as the pleura fluid."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And what this pleura of fluid actually does is it not only absorbs some of the shock that the lungs might experience as a result of some type of physical damage."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So it doesn't only protect our lungs, but more importantly, it actually decreases the amount of friction that the lungs experience every time they actually contract, they expand and contract."}, {"title": "Introduction to Human Respiratory System.txt", "text": "So inside this space separating our parietal and the visceral pleura, we have this parietal fluid that not only absorbs the shock and protects our lungs, but it also decreases the amount of friction that the lungs feel every time they contract and expand."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And below our lungs, we have this skeletal sheet of muscle known as our diaphragm."}, {"title": "Introduction to Human Respiratory System.txt", "text": "And as we'll see in the next several lectures, the diaphragm is a very important or a bit very important structure because it allows the lungs to basically carry out the process of respiration, carry out the process of breathing."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So to finish off our discussion on gluconegenesis and glycolysis, let's focus on lactate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Because as we discussed previously, lactate is one of the major types of nonsugar precursor molecules that our cells use to actually generate glucose in the process we call gluconeogenesis."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So why do cells produce lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "What types of cells produce lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And what happens to a lactate once the cells actually produces?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Let's begin by focusing on question number one."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Why do cells produce lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, remember that glycolysis, which is basically used to form ATP molecules and Pyruvate molecules from glucose, is not a perfect process."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And what that means is it actually uses up important molecules known as mad plus molecules, nicotine amide, adenine, dinucleotides."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And these molecules are needed by glycolysis to actually continue the process of glycolysis."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But glycolysis doesn't regenerate these molecules once it takes place."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that's precisely why under aerobic conditions, when we have plenty of oxygen inside the cell, that Pyruvate enters the mitochondria and we form more ATP molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And we also regenerate those NAD plus molecules from the breakdown of Pyruvate under aerobic conditions."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, sometimes in those cells that don't have mitochondria, or in those cells that are experiencing hypoxia, so a lack of oxygen, they cannot actually break down the Pyruvate in the citric acid cycle of the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So instead of using that, they switch to anaerobic respiration."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So in anaerobic respiration, which takes place entirely in the cytoplasm, we essentially undergo glycolysis to form the ATP molecules and the Pyruvate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But then to regenerate the much needed NAD plus coenzymes, the Pyruvate is transformed into lactic acid."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And under our conditions, under physiological conditions of the cells of our body, lactic acid associates into its conjugate based lactate and the h plus ions."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that's why our cells produce lactate."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So our cells undergo lactic acid fermentation to basically regenerate the NAD plus molecules needed for glycolys to actually continue."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So any type of cell that uses anaerobic respiration will generate these lactate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And two examples that we're going to focus on, the two dominant types of cells that actually use anaerobic respiration are red blood cells and skeleton muscle cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Let's focus on skeleton muscle cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So skeleton muscle cells are the cells that use ATP to basically contract the act of mice and filaments."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that allows voluntary motion."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So I can move my arm because of skeleton muscles or I can sprint across the room because of these skeletal muscle cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, skeleton muscle cells have the option of using aerobic or anaerobic respiration."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So if there is oxygen present, it will use aerobic, but if not, it will use anaerobic."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But red blood cells don't have organelles, they don't have any mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And what that means is they don't have the cell machinery needed for aerobic respiration."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So red blood cells only use anaerobic cellular respiration to produce ATP molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so red blood cells produce many of these lactate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So once again, lactate is the major precursor molecule that can be used to form glucose."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "In gluconeogenesis, skeleton muscle cells produce lactic acid which then dissociates into lactate and the H plus ions during exercise when the rate of glycolysis is greater than the rate of oxidative aspirulation that takes place in the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Other types of cells, like red blood cells, only produce lactic acid because they don't have the machinery the mitochondria needed to actually regenerate those NAD plus coenzymes that we must have if we want to actually use glycolysis to form those ATP molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, notice that if the cells continually use lactic acid fermentation, there's going to be a build up in the H plus concentration in the cell and the surrounding tissue and that will decrease the PH and increase the acidity."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that can be very dangerous."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Why?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, because all different types of structures, the proteins and Euclide acids and DNA molecules are held together by what types of bonds will electric bonds."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And these electric bonds can essentially be disrupted as a result of the increase in the ion concentration of the H plus ions."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so our cells actually have mechanisms that turn off glycolysis when there is too much build up of the H plus ions in our blood."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that's exactly why eventually as we're sprinting, we have to stop because of this idea, because glycolysis is shut down as a result of this molecule acting as an allosteric inhibitor to specific enzymes of glycolysis."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, we know what lactate is, we know why we produce lactate and we know what types of cells produce lactate."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But once the cells produce lactate, what is the ultimate fate of that lactate molecule?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "What happens to the lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So we see that metabolizing skeletal muscle cells or red blood cells cannot actually use the lactate molecule in any useful way."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "They can't actually do anything useful with the lactate."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But that doesn't mean that other cells, specialized cells of our body, cannot actually use the lactate for something special, for something useful."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "In fact, two specialized types of cells that can and do use lactate produced by red blood cell and skeleton muscle cells are cardiac muscle cells and liver cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So what is the ultimate fate of lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, once lactate moves across the membrane of these erythrocytes and skeletal muscle cells and enters the bloodstream of our cardiovascular system, the blood plasma, it generally ends up in one of two locations cardiac muscle cells and liver cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so let's focus on the following diagram as we go along this text."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And let's imagine that we're essentially sprinting."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So as we begin to sprint initially what happens in our skeleton muscle cells?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So in that skeleton muscle cell, we need to basically produce the ATP for the active mice and fibers to actually contract."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so the glycogen storages are essentially depleted."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "We break down glycogen into glucose six phosphate and that is then used to produce pyruvate molecules and ATP molecules and then to reform the NAD pluses."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Because initially, as we begin sprinting, we have plenty of oxygen, the Pyruvate will go into the mitochondria where we produce many more ATP molecules and regenerate those NAD plus coenzymes that are then reused by glycolysis."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "In addition, we also produce carbon dioxide and water molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, at the same exact time our glycogen storages are being depleted, what that means is the skeleton muscle cell will have to look elsewhere for the glucose supplied."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So because we have plenty of glucose in our bloodstream, that glucose is essentially uptaken by the skeleton muscle cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So we can get the glucose from the glycogen or we can get it from that circulating blood plasma."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, really quickly, if we're sprinting very rapidly, then what that means is the two will be depleted very quickly and we're going to enter anaerobic conditions in which we're going to use lactic acid fermentation to basically produce lactate molecules from Pyruvate, in the process regenerating those NAD plus coenzymes."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, what happens to the lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, once we produce the lactate, these cells have special type of membrane transporters that stimulate these lactate molecules to actually move into the bloodstream."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Why?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, because generally speaking, skeleton muscle cells don't actually do anything useful with the lactate molecules and so they deposited into the bloodstream with the hopes that other cells, specialized cells, will pick them up and essentially recycle them and use them for something useful."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And that's exactly what happens as we'll see in just a moment."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So at the same time we're running, we also have these red blood cells which are also carrying out many different types of processes."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so in these cells, the red blood cells also uptake these glucose molecules from the bloodstream because they need to use the glucose to form the ATP."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so glycolysis takes place in the urethra site."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And once we form the Pyruvate, because it doesn't have any mitochondria, it can't use aerobic respiration, so it depends strictly on fermentation."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so we transform the Pyruvate into lactate and just like in this case, it diffuses into the bloodstream."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so now we have a build up of lactate in our bloodstream."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "What happens next?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, let's focus on one."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "The first place it goes to are the cardiac muscle cells, because the cardiac muscle cells actually contain special membrane bound proteins that can transport these lactate into the cell."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, what happens to the lactate?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, inside cardiac muscle cells we have a special enzyme known as lactate dehydrogenase."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And what lactate dehydrogenase can do is it can basically transform the lactate molecules back into Pyruvate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "What for?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, when we're running women's sprinting, not only are the skeleton muscle cells working, but the cardiac muscle cells are continually pumping that blood through the cardiovascular system."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And as we begin running quicker, what that means is the heart has to pump quicker and more and with a more forceful contraction."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so what that happens is it also needs to actually create ATP molecules and the lactate molecules basically create this additional source of energy that can be used to basically form that glucose, to form the pyruvate that is actually then fed into the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So lactate goes into the cardiac muscle cell which is transformed by lactate dehydrogenase into Pyruvate and then the Pyruvate goes straight into the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Why?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, because cardiac muscle cells never undergo anaerobic respiration."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "There's always plenty of oxygen inside the cardiac muscle cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And so for that reason the Pyruvate is fed directly into the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So we see that these cardiac muscle cells really utilize these high energy molecules because not only do the glucose molecules inside the cardiac muscle cell actually transform into Pyruvate and then go into the mitochondria."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And not only are the glycogen storages used to produce the glucose six phosphate which ultimately form the ATP molecules, but in addition the lactate molecules produced by the other cells that undergo anaerobic respiration are also used to actually form these energy molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So we see that cardiac muscle cells can use lactate molecules to form the ATP energy molecules and so by doing that, they essentially create this additional source of energy and they also conserve the glucose molecules inside the bloodstream by conserving the glucose molecules by using less glucose molecules or more lactate molecules."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "That basically means other cells can basically use the glucose to carry out different types of different types of processes."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now that's basically the first place where the lactate ends up."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So cells such as cardiac muscle cells have special membrane proteins that can make the cell highly permeable to lactate."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And once inside the cardiac myosides, the lactate can be transformed back into Pyruvate by lactate dehydrogenase and then fed into the citric acid cycle to generate ATP."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Why?"}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Well, because in cardiac muscle cells we only use aerobic respiration, never anaerobic respiration."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "There's always plenty of oxygen inside these cells and this helps these cardiac muscle cells obtain an additional source of energy and also helps conserve the glucose in the blood so that other cells can actually use the glucose, for instance, brain cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now the second place where these lactate molecules end up is the liver cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And what happens to the liver cell or what happens to these lactate molecules in liver cells is known collectively as the chloride cycle and we'll focus on that in much more detail in a future lecture."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "So lactate essentially goes into these liver cells."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, once lactate goes into the liver cell, the lactate is transformed into Pyruvate and that can go in many different directions."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "The Pyruvate, if we're, for instance, exercising the Pyruvate can be used to actually form the glucose and then the glucose goes back into the bloodstream to actually maintain that level, the proper glucose level in our blood."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "But if we're not exercising, then the lactate is transformed into Pyruvate and then that is transformed into glucose phosphate which then goes and we store it as glycogen."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "Now, if we do need glucose molecules, or if we do need ATP molecules, the Pyruvate can actually go into the mitochondria as in this case in this case, and form those ATP molecules that are needed by the cell, the liver cells to actually carry out the many different types of processes."}, {"title": "Overview of Lactate Formation and Recycling .txt", "text": "And this is basically what happens to the lactate molecule once these skeleton muscle cells and red blood cells actually produce them inside our body."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "The pentose phosphate pathway is a very important biochemical process that takes place inside the cytoplasm of our cells."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, this process is important for two different reasons."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Number one is the penthouse phosphate pathway gives us a way to actually generate five carbon pencil sugar molecules."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we use these pento sugar molecules to basically generate generate biological molecules such as DNA molecules, RNA molecules, ATP molecules, NADH and Fad molecules."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "It also gives us a way to generate Co enzyme A on top of that."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "The second reason why the pentosphosphate pathway is important is because it gives us a way to generate reducing agent molecules, molecules we call NADPH, which stands for the reduced version of nicotine amide adenineucleotide phosphate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, this molecule is used in biosynthetic processes such as the building of fatty acids, the building of cholesterol molecules, the building of nucleotide molecules, and so forth."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We also use the NADPH molecules in different detoxification processes that take place inside our cells."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So in this lecture, I'd like to focus on the first phase of the pentose phosphate pathway and recall that the first phase of this pentose phosphate pathway is the oxidative phase."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "This is where we actually oxidize glucose."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We transform it into a pentose molecule, as we'll see in just a moment."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In the process, we release a carbon dioxide and we generate the much needed reducing agent molecules, the NADPH molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the first phase of the pencil phosphate pathway is the oxidative breakdown of glucose to release carbon dioxide and generate NADPH molecules."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So let's see exactly how this takes place."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So essentially, we can break down the first phase into four steps, and let's begin with reaction one."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Step one."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So in the first step, the enzyme that catalyzed the first step is known as glucosex phosphate dehydrogenase."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Why?"}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Well, because the substrate molecule is a glucose phosphate and this is actually a dehydrogenase reaction."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So what happens is we have this NADP plus molecule that will act as an electron acceptor."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we essentially extract two electrons from this particular glucose phosphate and those two electrons are picked up by this molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In addition, an H ion is picked up by this molecule as well."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we generate the reduced version of nicotine amide adenine Dinucleotide phosphate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We also release the H plus ion and we produce the six phosphoglucano delta lactone molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So this is essentially an Esther bond that we form."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so this is known as an intramolecular estermolecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And this bond here will be broken in step two, as we'll see in just a moment."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the important part of this step is we generate the much needed reducing agent molecule, this molecule here."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We also form the Esther bond here that will be broken down in step two."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the oxidative phase begins with the dehydrogenation of the glucose six phosphate at the first carbon."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So dehydrogenation simply means we're removing H ions."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So an enzyme called glucose six phosphate dehydrogenase catalyzes the transfer of a Hydride ion."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So that's an H plus ion and two electrons from the glucose and onto the NAD plus carrier molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So this is the electron acceptor that picks up two electrons and that H plus ion."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we also release a hydrogen ion."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we form this intramolecular ester molecule known as six phosphorluquino delta lactone."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now let's move on to step two."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So in step two, what we want to basically do is we want to prepare the molecule for a decorboxylation reaction."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And the way that we prepare the molecule is by opening up the ring structure."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We open up that ring structure via a hydrolysis reaction which is catalyzed by an enzyme known as Latinase."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So Latinase catalyzes the hydrolysis of this aster bond."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so we transform the six phosphorlucano delta lactone into a six phosphoglucanate molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "We also release the H plus ion as shown here."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So once we open up this molecule, it's now ready to undergo a decarboxylation reaction."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now along with releasing the carbon dioxide in step three, we also actually oxidize the six phosphaglucanate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And the molecule that picks up those electrons is once again the NAD plus molecule, NADP plus molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "This is the oxidized version of nicotine amide adenine dinucleotide phosphate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So essentially we remove carbon one along with these two oxygens."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we form the carbon dioxide."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In the process, we extract two electrons from the sugar molecule, place them onto this molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In addition, we take an H plus I and place it onto this."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we form the ribulose phosphate molecule as well as another NADPH molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the net amount of NADPH molecules that are formed when one glucose, six phosphate undergoes the first phase of the pentose phosphate pathway is two."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "One is formed in step one and the other one is formed in step three."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have an enzyme called six phosphoglucanate dehydrogenase."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Again, it's a dehydrogenase because we're essentially extracting the two H plus ions along with those two electrons which are picked up by this electron carrier molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So this enzyme catalyzes the oxidative decarboxylation."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So oxidative means we have an oxidation reduction reaction going on where this is oxidized and this is reduced."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we also have a decarboxylation reaction taking place where this carbon number one along with these two oxygen atoms are essentially removed."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so we form this ribulose five phosphate molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we kick off a carbon dioxide molecule, we form a pentosugar, a five carbon sugar."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have 123456 carbons here, while we have only 12345 carbons here."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we also form that reducing ancient molecule that can be used by the cell in a variety of different ways."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, once we form the ribulous phosphate, we have the final reaction taking place that is really an isomerization reaction in which we have the enzyme phosphatentose."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "Isomerase basically transforms this keto ribulase phosphate into an aldos, the derivose phyphosphate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the derivulose phosphate is transformed to the derivose phyphosphate via the activity of phosphorpentose isomerate."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we see that in the first phase of the pentose phosphate pathway, we basically have four steps."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In step one, we undergo an oxidative reaction, an oxidation reduction reaction, which we generate that first NADPH molecule."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "In the second step, we open up this molecule to basically prepare it for step three, because in step three, we want to generate yet another NADPH molecule as well as release that carbon dioxide to generate a pento sugar."}, {"title": "Oxidative Phase of Pentose Phosphate Pathway .txt", "text": "And the final step, we transform the ribulose phosphate into its isomer form, the ribose phyphosphate, which can then be used in the second phase of pentose phosphate pathway, the non oxidative phase that we're going to focus on in the next several lectures."}, {"title": "Introduction to Cardiovascular System .txt", "text": "The cardiovascular system, also known as the circulatory system consists of our heart, the blood vessels as well as the blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the heart is basically a pump."}, {"title": "Introduction to Cardiovascular System .txt", "text": "In fact it consists of two individual pumps that are connected in serious with respect to one another."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So next to one another we have a pump on the right side that consists of the right right atrium and the right ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And we have a pump on the left side that consists of the left atrium and the left ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, unlike skeletal muscle which is actually attached to our bone and contracts with the bone, the heart is not actually attached to any bone."}, {"title": "Introduction to Cardiovascular System .txt", "text": "The heart consists of cardiac muscle which forms a web like net that contracts upon itself."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, what exactly is the function of our heart?"}, {"title": "Introduction to Cardiovascular System .txt", "text": "Well, the heart essentially creates that hydrostatic pressure that is needed to move the blood through the blood vessels of our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, what exactly is a blood vessel?"}, {"title": "Introduction to Cardiovascular System .txt", "text": "Well, a blood vessel is a conduit."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It's a pipe that essentially allows the movement, the flow of blood through our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And the blood is this fluidlike substance that consists of many things."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It contains the blood plasma which has the ions, the electrolytes, water as well as proteins such as albumin."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We also have red blood cells inside our blood that carry the oxygen and we have different waste products such as urea ammonia as well as carbon dioxide."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, what exactly is the purpose, what exactly is the function of the cardiovascular system?"}, {"title": "Introduction to Cardiovascular System .txt", "text": "Well, the cardiovascular system is used to actually bring and deliver the nutrients and electrolytes to the cells, the tissues and organs found inside our body and the blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Our cardiovascular system also takes in the waste products produced by the cells and it brings those waste products to the proper organ of the body such as our skin and kidneys that are involved in excretion of those waste products."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now our cardiovascular system is said to be a closed cardiovascular system."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It's a closed circuit."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And what that basically means is all that blood travels throughout the blood vessels and it never actually leaves those blood vessels."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now that's not to say that the blood isn't actually filtered."}, {"title": "Introduction to Cardiovascular System .txt", "text": "In fact our kidneys are responsible for filtering our blood but our blood is reabsorbed back into the body in our kidneys and only our waste products are essentially excreted to the outside portion of the body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So the cardiovascular system forms a closed circuit which means that the blood remains inside the circuit, inside the blood vessels the entire time."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now if we take this entire loop, entire closed circuit we can divide the closed circuit into two systems."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have the systemic circulation and we have the pulmonary circulation."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Systemic circulation simply means we carry the oxygenated blood from the heart into the tissues and then we take the de oxygenated blood from the tissues and bring it back to our heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "But pulmonary circulation means we take that deoxian blood from the heart and we move it into the lungs and then we oxygenate our blood in the lungs and we bring the oxygen blood back into the heart and we'll discuss these two systems in more detail towards the end of the lecture."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now there are two types of blood vessels that are found inside our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have a blood vessel that carries blood away from the heart and this is known as an artery."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So by definition an artery is a blood vessel that always carries our blood away from the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And one easy way to remember this is by remembering that a wave starts with A and so does our artery."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the arteries most of the time carry oxygenated blood but there are times as we'll see in just a moment in which an artery can actually carry deoxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the arteries, these blood vessels come in many different sizes."}, {"title": "Introduction to Cardiovascular System .txt", "text": "The largest artery in the body is known as our aorter and then we have the arteries followed by smaller arteries known as arterios and finally our capillaries."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the second type of blood vessel is the vein and if the artery carries blood away from the heart and to the tissues then our veins bring our blood to the heart and away from our tissues and organs."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now most of the veins in the body actually carry deoxygenated blood but there are examples as we'll see in a moment in which veins actually carry oxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And just like arteries vary in size we also have a range of different size values for our veins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "The largest vein is known as our vena cava."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We also have the smaller veins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have the venuels very tiny veins and then we have the capillaries."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the capillaries are the blood vessels, very tiny blood vessels that connect the arteries to our veins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And in the capillaries this is where we have the exchange of nutrients for the waste products taking place within our organs and within our tissues."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now most of the time within our organs we have a single system of capillaries but sometimes in certain organs we have a portal system and that simply means we have two consecutive network of capillaries that are next to one another."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now we have several portal systems in our body as we'll discuss in the next several lectures."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have one in our brain, we also have one in the kidneys and our small intestine."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now the final thing that I'd like to mention is the pathway that the blood actually follows within our cardiovascular system."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So here we're going to show that the cardiovascular system of the human body is in fact a closed circuit."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So let's take a look at the following diagram which basically describes the simplified diagram for the cardiovascular system."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now if my body essentially points this way then this is the right side of my body, this is the left side of my body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And this is exactly what this diagram shows."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So we have the right lung, the left lung."}, {"title": "Introduction to Cardiovascular System .txt", "text": "This is the right portion of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And this is the left portion of our heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "These are the capillaries of the organs found in the upper portion of my body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And these are the capillaries of the organs found in the lower portion of our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So let's begin by taking a look at the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So we have the right side, the right pump that consists of the right atrium and our left right ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And this portion is the left side."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It's the left pump of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It contains our left atrium and the left ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, the atrium is the portion of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It's the compartment of the heart that accepts the blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "But it's the ventricle that contains the strong cardiac muscle that is responsible for creating that contraction and that hydrostatic pressure that moves the blood through the blood vessels of our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So let's begin at a certain portion of our cardiovascular system."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Let's suppose we begin in the right atrium of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So number one, so the deoxygenated blood returns to the right atrium of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So remember, the atrium always accepts the blood into our heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, the blue arrow basically designates the movement of deoxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "But the red arrow designates the movement of oxygenated blood blood that contains our red blood cells with the oxygen."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, from our right atrium, our blood flows through this valve system and into the right ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So number two, it then enters the right ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And this is essentially where the systemic circulation ends and the pulmonary circulation begins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So remember, pulmonary circulation means we take the deoxygenated blood, we bring it to our lungs where we oxygenate that blood and then we bring the oxygenated blood back to our heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So number two is where the pulmonary circulation begins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So the right ventricle basically pumps the de oxygenated blood into this artery that diverges into the left pulmonary artery."}, {"title": "Introduction to Cardiovascular System .txt", "text": "That brings the blood to the left lung and the right pulmonary artery, this artery here, that brings the blood to the right lung."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, notice that an artery always brings blood away from our heart and this is exactly what happens within the pulmonary arteries."}, {"title": "Introduction to Cardiovascular System .txt", "text": "But in both of these arteries, we have deoxygenated blood that is being carried."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So it's not always true that arteries carry oxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So let's go to number four."}, {"title": "Introduction to Cardiovascular System .txt", "text": "In number four, we have the blood moves from these pulmonary arteries into smaller arteries and arterioles and eventually they move into the capillary system that is found in the lung."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have the right lung and we have the left lung."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, within the lung, we have an exchange taking place."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We basically bring oxygen into the blood and we expel our carbon dioxide from our blood into the outside environment."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So when we inhale, we bring in that oxygen into our blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And when we exhale, we basically remove that carbon dioxide from our system, from our blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, in number five, once we actually oxygenate this blood within the lungs, we then take that oxygen blood and we move it through the venuels and through our pulmonary vein."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So we have the right pulmonary vein and the left pulmonary vein that both carry the oxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So once again, we see that veins always carry blood to the heart but they can carry both oxygenated as well as deoxygenated blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "In this case, they bring the oxygen blood into number six, which is basically our left atrium."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So once again, the atrium of the heart always receives that blood."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So in number six, it then moves into the left atrium of the heart."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, from six, once again, we have this valve system that moves our oxygenated blood into our left ventricle."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And it's the left ventricle that creates the hydrostatic pressure, the hydrostatic force that essentially propels and moves that oxygen blood filled with nutrients into the largest artery of the body known as our aorter."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And from the aorter, we basically diverge our aorter into the ascending and descending aorter."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So this is number nine."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And number nine, the ascending aorter moves the oxygen blood into the capillary system of the organs found in the upper body and this brings into the organs found in the lower portion of our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So the neck and our brain, while this is the leg portion of our body."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, in number ten, we basically have the oxygen blood is brought into the organs where we have an exchange taking place."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So the cells, tissues and organs pick up the nutrients and electrolytes that they actually need to survive."}, {"title": "Introduction to Cardiovascular System .txt", "text": "They also pick up our oxygen and they give off the carbon dioxide as well as our waste products."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And then our deoxy and blood travels into the tiny venues, then into the veins."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And all these veins basically converge into a single vein known as the vena cava."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Now, the superior vena cava is basically the upper vein that carries all that de oxygen blood away from the upper organs."}, {"title": "Introduction to Cardiovascular System .txt", "text": "This is a superior vena cava."}, {"title": "Introduction to Cardiovascular System .txt", "text": "Superior means above, while the inferior vena cava, where inferior means below, basically is our single blood vessel that carries our deoxy in blood from the organs in the lower portion of our body and to number one."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So notice that number one is simply our right atrium."}, {"title": "Introduction to Cardiovascular System .txt", "text": "It's where we began."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So notice that we began at zero one and we ended at zero one."}, {"title": "Introduction to Cardiovascular System .txt", "text": "And so this basically shows that the cardiovascular system is in fact a closed circuit."}, {"title": "Introduction to Cardiovascular System .txt", "text": "We have a closed cardiovascular system."}, {"title": "Introduction to Cardiovascular System .txt", "text": "So once again, our pulmonary circulation essentially begins in number two, our right ventricle, and it ends within number six, our left atrium, while our systemic circulation begins in seven, our left ventricle, and it ends at one, our right atriums."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Carbohydrate molecules vary in length."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So some carbohydrate molecules are very long and some are very short."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, long carbohydrate molecules are also known as polysaccharides, and that's because they consist of many individual monosaccharides."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the simplest sugars are called monosaccharides."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "They consist of a single sugar monomer."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, why do we call sugars carbohydrates?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Well, if we take a look at the empirical formula for carbohydrates, this is what we're going to find."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "We see that we have carbon, we have H and we have oxygen."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "In fact, we see that we have carbon and we have water."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And another name for water is hydrate."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so we have carbohydrates, these molecules that contain carbon as well as water molecules."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the empirical formula is ch 20 multiplied by N, where N is basically any positive integer, any positive N value that is equal to three or greater."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the simplest monosaccharide contains an nvalue that is equal to three."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And that means the simple monosaccharide consists of three carbon atoms, six H atoms and three oxygen atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, generally speaking, there are two types of categories of sugars."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "We have those sugars that contain aldehyde groups, and these are known as aldosis."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And we have those sugars that contain a ketone group, and these are known as ketosis."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And to demonstrate what the difference is, let's take a look at the simplest monosaccharide that contains and value that is equal to three."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So this is the ketos that consists of three carbons, six H atoms and three oxygens."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And notice it's a ketos because on both sides of this carbon ill group, we essentially have these carbon atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And the specific name for this is dihydroxy acetone."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, what about the aldos version of this same sugar molecule?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So this is what we basically have."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And the reason we have two of these aldoses is because we have a single stereogenic carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "We have a chiral carbon, and that means we're going to have two different isomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "These are known as enantomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Enantomers are mirror images of one another."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So we essentially, on this particular molecule, we don't have a mirror image because we don't actually have a stereogenic carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Remember, a stereogenic carbon is a carbon that is chiral, and that means it is attached to four different groups."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So in this particular molecule, we don't have that."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "But in this particular molecule, if we examine this carbon, we have four different groups attached to this carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So we have the hydroxyl, we have the H atom, we have this group here and this group here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so what that means is there will be an enantomer that will exist with respect to this carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And this is the Nantomer shown here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the D glycoaldehyde simply means that it's one of the Nantomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And the L simply means it's the other type of anantomer."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And we'll see exactly what the DNL represent in just a moment."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So, once again, the simplest sugars are a monosaccharides and we call them carbohydrates because the empirical formula tells us they consist of carbon as well as water molecules."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So monosaccharides can either be aldehydes or they can be ketones."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Aldehyde containing monosaccharides are known as aldosis, and ketone containing monosaccharides are known as ketosis."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the smallest functional monosaccharide, as we said, in just a moment, contains an N value of three."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So we have three carbon atoms, six H atoms and three oxygen atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So what exactly is the meaning of the D and the L?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And what does the D represent?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And what does the L represent?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Well, to demonstrate the meaning behind the D and the L letters, let's take a look at another type of carbohydrate molecule, namely erythros."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So let's compare D erythros and L erythros."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Notice what the D and the L mean is these will be mirror images with respect to one another."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "These are known as enantomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So sugars that are mirror images of one another are known as enantomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so if we draw a line, this will be a mirror image of this molecule."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so these oh groups, which point to this side, will point onto the opposite side on this molecule here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so in the deisomer, we see that this green hydroxyl group, which is the hydroxyl group that is found on the stereogenic carbon, that is far less away from this aldehyde group."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "This is the carbon that we have to worry about."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And if this hydroxyl group on the final stereogenic carbon points to the right side, then that is the deisomer, the Dnamer."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "But if it points to the left side, so that is called the L monosaccharide, in this case, the L erythros."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So the symbol D or L designates the absolute configuration of the stereogenic carbon, the chiral carbon, that is farthest away from the aldehyde or ketone group."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And in this particular case, it happens to be the aldehyde group."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, in deisomers, the oh points to the right side, and in L isomers, it points to the left side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So if this is the left side and this is the right side, then that means in this particular case, it points to the right side, and in this particular case, it points to the left side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So L, you could remember as left, and D is the opposite of left."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So that's right."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, the problem with the problem drawing aromatosaccharides in the following manner is the fact that the stereo chemistry is not actually seen, because all these bonds seem to lie along the same plane."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "But we know that sugar molecules are three dimensional molecules."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "They have stereo chemistry."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And to describe the stereo chemistry of sugar molecules correctly, the most common mechanism we use are the fissure projections."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So fissure projections are commonly used to describe the stereo chemistry, the three dimensional arrangement of the atoms and the bonds within the sugar molecule."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And to see what the fissure projection actually looks like, let's take a look at the following molecules."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So this is the same molecule that we essentially described here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "It's the de urethras."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So in this particular diagram, the problem with this diagram is all the atoms essentially lie along the same plane and all the bonds also lie along the same plane."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "But we know that is not true."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And to basically go from this diagram to a fissure projection, all we have to do is we take these horizontal lines and we bring them out of the board and we take the vertical lines and we place them into the board."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And this is basically what we get."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "This is our fissure projection."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And then if we take this and we actually try to draw a three dimensional diagram, this is what we're going to get."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So notice that this carbon and this carbon, they lie along the same plane."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "These two will point downward, as we see in this diagram."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "They go into the board or into the page, and these four groups are coming out of the board, as shown here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "They're going to come out of the page."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So horizontal lines are drawn in front of the plane coming out of the board, while vertical lines are drawn in the back of the plane going into the board."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So a fissure projection is nothing more than a way to basically describe the three dimensional stereo chemistry of the sugar molecule."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, the final thing I'd like to discuss are diary, isomers and ephemeris."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And as we'll see in just a moment, an epimer is basically a specific type of diaryoisomer."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So let's think back to organic chemistry for just a moment."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So what exactly is an isomer?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Well, from organic chemistry we know that isomers are basically those molecules that contain the same exact molecular formula."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So they have the same exact number of atoms and the same type of atoms, but they differ in their arrangement of atoms in the three dimensional space."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, we have two types of isomers when it comes to sugars."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "We have dirty isomers and we have enantomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So just a moment ago, we said enantomers are those isomers that are mirror images of one another."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, if it's not an enantomer, then it is a dioisomer."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So we have two categories of isomers, either enantomers or dioisomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So essentially, if two sugar molecules have the same exact molecular formula and they are not enantomers, then that means they must be diamers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And these are two examples of dioisomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So if we take a look at diurethrose, this is the same molecule that we basically have here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "This."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And this is an example of a diary isomer with respect to diurethrows."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Notice it contains the same exact molecular formula."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "It has the same exact number and type of atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So here we have 1234 carbon atoms, 1234 carbon atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "We have 1234-5678 H atoms and we have eight H atoms here."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And finally, we have 1234 oxygens."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "1234 oxygen."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So essentially they have the same number and type of atoms, but they differ in their arrangement of those atoms in the three dimensional space."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And notice that these are not examples of enantomers, because if we draw a line here, they will not be mirror images."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so what that means is, if they're not mere images, they're not an answers, they must be disregards."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And so these are two examples of diaryoisomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And notice that these are both the Dtype molecule, the deisomer, because this green hydroxyl group found on the final stereogenic carbon, the farthest away from this aldehyme group, points to the right side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Remember, in the deisomers, the hydroxyl group found on the last theogenic carbon points to the right side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "If this would have been the L, this would have pointed to the left side and we would have had this L erythro."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So these are two examples of dirtyisomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So, when two sugars have identical molecular formulas, have different arrangement of atoms and are not enantomers, they're not mere images, then they must be dieoisomers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, a specific subgroup, a specific subcategory of dialisomers, are epimers."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So what exactly is an epimer?"}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Well, two molecules are said to be epimers if or two sugars are set to be epimers if they differ in stereo chemistry only at a single chiral carbon atom."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And it doesn't matter which carbon atom it is, as long as it's a chiral carbon atom, it's stereogenic."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So, to see what we mean, let's compare D glucose and Dmannose."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Again, these are both D. And what that means is these two green hydroxyl groups found on a final stereogenic carbon will both point to the right side of the board."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, let's basically describe all the stereogenic carbons found on each one of these molecules."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Let's use a color that let's use orange."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So this is a stereogenic carbon, this is a stereogenic carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "This is a stereogenic carbon, and this is a stereogenic carbon."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Likewise, 1234."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So these are all stereogenic carbons."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, these are epimers, because they only differ in their stereo chemistry at a single one of these chiral carbon atoms."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And let's see which one that is."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So, if we begin at the first carbon, the first chiral carbon, notice that the hydroxyl group points to the right and the hydroxyl group here points to the right as well."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "Now, if we move on to the second stereogenic hydrocarbon, we'll see that the hydroxyl actually points to the left in D glucose, but it points to the right."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And D mannose."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "If we move on to the third stereogenic carbon, we'll see that once again, they point to the same side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "And the last one, they also point to the same side."}, {"title": "Aldoses, Ketoses Fischer Projections and Epimers .txt", "text": "So these are epimers, a specific type of dial isomers, because they essentially differ in their stereochemistry only at a single carbon atom."}, {"title": "Fatty Acids .txt", "text": "In nature, there are many different types of lipid molecules."}, {"title": "Fatty Acids .txt", "text": "And by definition, a lipid molecule is a biological molecule that is not soluble in water, so it does not dissolve in an aqueous environment."}, {"title": "Fatty Acids .txt", "text": "Now, that's because if we study the structure of a lipid molecule, the majority of that lipid molecule consists of a nonpolar hydrophobic section."}, {"title": "Fatty Acids .txt", "text": "Now, many of the lipids inside our body and inside other organisms as well, consist of a hydrophobic section known as the fatty acid."}, {"title": "Fatty Acids .txt", "text": "So whenever a lipid contains fatty acids, it's the fatty acid component of the lipid that makes it hydrophobic nonpolar."}, {"title": "Fatty Acids .txt", "text": "That basically gives it the ability to remain insoluble in an aqueous environment."}, {"title": "Fatty Acids .txt", "text": "So, because fatty acids are so dominant and so important, in this lecture, I'd like to focus on what fatty acids actually are, the systematic approach to naming fatty acids, and then discuss some properties of fatty acids and how going from one fatty acid to another fatty acid, the properties may actually change."}, {"title": "Fatty Acids .txt", "text": "So what exactly are fatty acids?"}, {"title": "Fatty Acids .txt", "text": "Well, fatty acids are molecules that contain a hydrocarbon chain, and at the end of that hydrocarbon chain, we have a carboxylic acid."}, {"title": "Fatty Acids .txt", "text": "So, two types of groups in a fatty acid, the hydrocarbon chain, which is nonpolar, and the carboxylic acid, which is actually polar."}, {"title": "Fatty Acids .txt", "text": "And so, because we have a polar and a non polar region, fatty acids are technically amphatic."}, {"title": "Fatty Acids .txt", "text": "But because the hydrocarbon section makes up a much larger portion of the fatty acid, fatty acids are non polar molecules, hydrophobic."}, {"title": "Fatty Acids .txt", "text": "They will not dissolve in aqueous environments."}, {"title": "Fatty Acids .txt", "text": "Now, to demonstrate what we mean by fatty acid, let's take a look at the most common type of fatty acid in humans and other animals, known as palmitic acid."}, {"title": "Fatty Acids .txt", "text": "Now, let's take a look at this molecule."}, {"title": "Fatty Acids .txt", "text": "So this entire section is the hydrocarbon chain, and this functional group is that carboxylic acid."}, {"title": "Fatty Acids .txt", "text": "So we have a tiny polar section and this dominant non polar section."}, {"title": "Fatty Acids .txt", "text": "So that's why fatty acids are predominantly non polar."}, {"title": "Fatty Acids .txt", "text": "Now, this is one of the many fatty acids that we can find in nature."}, {"title": "Fatty Acids .txt", "text": "So what differentiates one fatty acid from another fatty acid?"}, {"title": "Fatty Acids .txt", "text": "Well, basically, the length of that hydrocarbon chain."}, {"title": "Fatty Acids .txt", "text": "So the number of carbon atoms within that fatty acid."}, {"title": "Fatty Acids .txt", "text": "So, in humans and other animals, the dominant types of fatty acids are palmitic acid, which basically contains 16 carbons, as well as Olake acid, which contains 18 carbons."}, {"title": "Fatty Acids .txt", "text": "But in animals as well as humans, we can have fatty acids ranging anywhere from 14 to 24 carbon atoms."}, {"title": "Fatty Acids .txt", "text": "So, although the most common fatty acids in biological systems such as our cells are the 16 and 18 carbon fatty acids."}, {"title": "Fatty Acids .txt", "text": "So palmitic acid and oleic acid generally, they generally range from 14 to 24 carbons in length."}, {"title": "Fatty Acids .txt", "text": "Now, in all animals, including our own cells, these fatty acid hydrocarbon chains are not branched."}, {"title": "Fatty Acids .txt", "text": "They do not have any branching points, as shown in this particular diagram."}, {"title": "Fatty Acids .txt", "text": "So in animals, these hydrocarbon chains and fatty acids never actually branch."}, {"title": "Fatty Acids .txt", "text": "Now, the second point of difference between two or more fatty acids is the number of double bonds."}, {"title": "Fatty Acids .txt", "text": "And in this particular case, we have no double bonds."}, {"title": "Fatty Acids .txt", "text": "And what that means is this is a saturated fatty acid."}, {"title": "Fatty Acids .txt", "text": "Saturated basically means this hydrocarbon chain contains a maximum number of hydrogen atoms."}, {"title": "Fatty Acids .txt", "text": "Now, as we add double bonds, that decreases the hydrogen count along this backbone, and that makes the fatty acid unsaturated."}, {"title": "Fatty Acids .txt", "text": "So unsaturated means we have double bonds."}, {"title": "Fatty Acids .txt", "text": "Now, monounsaturated basically means we have one double bond in that hydrocarbon chain."}, {"title": "Fatty Acids .txt", "text": "If we're polyunsaturated, that means we have two or more of these double bonds."}, {"title": "Fatty Acids .txt", "text": "So two in this case and three in this particular case."}, {"title": "Fatty Acids .txt", "text": "Now, how do we describe the fact that we have 16 carbons and no double bonds?"}, {"title": "Fatty Acids .txt", "text": "Well, basically, after the name, we basically write 16 to 00:16 carbon atoms and zero double bonds."}, {"title": "Fatty Acids .txt", "text": "In this particular case, we have 16 of these atoms, one double bond."}, {"title": "Fatty Acids .txt", "text": "And so it's 16 to one in this case, it's 16 to two."}, {"title": "Fatty Acids .txt", "text": "We have two double bonds, and in this case, it's 16 to three because we have one, two, three of these double bonds."}, {"title": "Fatty Acids .txt", "text": "So we see that fatty acids basically vary in the number of carbons, their length, as well as degree of unsaturation."}, {"title": "Fatty Acids .txt", "text": "So if we have a high degree of unsaturation, that means we have many double bonds."}, {"title": "Fatty Acids .txt", "text": "If we have a low degree of unsaturation, that means we have few double bonds."}, {"title": "Fatty Acids .txt", "text": "And as we'll see in just a moment, it's the length and a degree of unsaturation that basically determines the properties of the fatty acid."}, {"title": "Fatty Acids .txt", "text": "So properties such as melting point, boiling point fluidity and so forth."}, {"title": "Fatty Acids .txt", "text": "But before we actually discuss the properties, let's discuss the systematic approach to actually naming these fatty acids."}, {"title": "Fatty Acids .txt", "text": "Because technically, palmitic acid is not the systematic name of this fatty acid."}, {"title": "Fatty Acids .txt", "text": "It's the more common name."}, {"title": "Fatty Acids .txt", "text": "So what exactly is the method that we use to find the systematic name of the fatty acid?"}, {"title": "Fatty Acids .txt", "text": "Well, basically, we begin by counting the number of carbons in the fatty acid."}, {"title": "Fatty Acids .txt", "text": "So we have one, two, three, all the way to 16."}, {"title": "Fatty Acids .txt", "text": "And we begin with the name for that 16 carbon hydrocarbon."}, {"title": "Fatty Acids .txt", "text": "And the name is Hexadecane."}, {"title": "Fatty Acids .txt", "text": "Where decane means ten, hexa means six."}, {"title": "Fatty Acids .txt", "text": "Six plus ten gives us 16."}, {"title": "Fatty Acids .txt", "text": "And the way that we basically go from this name to the name of this particular fatty acid is by removing the E at the end of the hydrocarbon name and replacing it with OIC and then adding acid afterwards."}, {"title": "Fatty Acids .txt", "text": "So in this particular case, we have hexadechanoic."}, {"title": "Fatty Acids .txt", "text": "Acid is the proper systematic name for the more common name of palmitic acid."}, {"title": "Fatty Acids .txt", "text": "So, generally speaking, the name of a fatty acid is derived from the hydrocarbon component."}, {"title": "Fatty Acids .txt", "text": "So we begin with the hydrocarbon name, remove the E at the end of the name and simply replace it with OIC and then add acid."}, {"title": "Fatty Acids .txt", "text": "The acid is there because we also have that carboxylic acid at the end of that hydrocarbon name."}, {"title": "Fatty Acids .txt", "text": "Now, in this particular case, things were pretty simple because we didn't have any double bonds."}, {"title": "Fatty Acids .txt", "text": "Now what happens if we have one double bond?"}, {"title": "Fatty Acids .txt", "text": "How can we incorporate the double bond into this name?"}, {"title": "Fatty Acids .txt", "text": "Well, in the case of one double bond, if we add a double bond anywhere into this hydrocarbon chain besides this location and this location, we basically all we have to do is replace the A with E and so the name becomes hexadecinoic acid."}, {"title": "Fatty Acids .txt", "text": "And of course, because we have one double bond, let's say you replace the double bond here."}, {"title": "Fatty Acids .txt", "text": "We replace the zero with the one because we have that additional double bond or we have that double bond."}, {"title": "Fatty Acids .txt", "text": "Now, let's say we go from a mono unsaturated to a polyunsaturated in which we have two of these double bonds."}, {"title": "Fatty Acids .txt", "text": "How do we incorporate that into our name?"}, {"title": "Fatty Acids .txt", "text": "Well, we basically keep the A."}, {"title": "Fatty Acids .txt", "text": "And after the A, we add the die component."}, {"title": "Fatty Acids .txt", "text": "So we have hexadeca dinoic acid, 16 to 216 carbons, and two double bonds."}, {"title": "Fatty Acids .txt", "text": "Now, if we increase the number of double bonds by one, so we have three double bonds, we have this polyunsaturated molecule."}, {"title": "Fatty Acids .txt", "text": "In that case, instead of the die, we have the tri."}, {"title": "Fatty Acids .txt", "text": "And so we have hexadeca trinoic acid, 16 to three."}, {"title": "Fatty Acids .txt", "text": "Now, this information is not actually complete because if I tell you that I'm dealing with a hexadecinoic acid, all you're going to know is we have 16 carbon atoms and somewhere in that molecule we have a double bond."}, {"title": "Fatty Acids .txt", "text": "What you won't know is where that double bond is actually found."}, {"title": "Fatty Acids .txt", "text": "So the question is how do we actually determine or how do we describe the location of that double bond?"}, {"title": "Fatty Acids .txt", "text": "Well, the way that we begin is we begin by numerically labeling, numbering these carbons."}, {"title": "Fatty Acids .txt", "text": "And typically we begin on the carboxylic acid side."}, {"title": "Fatty Acids .txt", "text": "So we have carbon one, carbon 2345, all the way to 16 in this particular case."}, {"title": "Fatty Acids .txt", "text": "But let's use another example."}, {"title": "Fatty Acids .txt", "text": "Let's use this molecule here."}, {"title": "Fatty Acids .txt", "text": "So carbon 12345 all the way to, let's say 13."}, {"title": "Fatty Acids .txt", "text": "Now, carbon number one is carbon number one."}, {"title": "Fatty Acids .txt", "text": "That is our reference point."}, {"title": "Fatty Acids .txt", "text": "Now, from organic chemistry we know the carbon next to a carbon nil is known as the alpha carbon."}, {"title": "Fatty Acids .txt", "text": "So this is the alpha carbon, this is the beta carbon and the carbon all the way at the end on the opposing side of the carboxylic acid."}, {"title": "Fatty Acids .txt", "text": "The last carbon is known as the omega carbon given by this Greek symbol omega."}, {"title": "Fatty Acids .txt", "text": "So we have alpha beta and then we have omega."}, {"title": "Fatty Acids .txt", "text": "We'll see why that's important in just a moment."}, {"title": "Fatty Acids .txt", "text": "Now, because to break this double bond, we actually have to input a certain amount of energy."}, {"title": "Fatty Acids .txt", "text": "And because the energy change symbol is given by the Greek symbol delta, this triangle, the double bond, is represented with the delta symbol."}, {"title": "Fatty Acids .txt", "text": "And to basically describe the position, the number of that double bond with respect to this reference point, carbon number one."}, {"title": "Fatty Acids .txt", "text": "All we have to do is we have to mark that triangle with a numerical SuperScript."}, {"title": "Fatty Acids .txt", "text": "So let's suppose we want to describe this particular bond here."}, {"title": "Fatty Acids .txt", "text": "So this atom is carbon four."}, {"title": "Fatty Acids .txt", "text": "And so it's delta four, where four means that's where the bond begins."}, {"title": "Fatty Acids .txt", "text": "So we have a bond between carbon four and five, and that's what we mean by delta four."}, {"title": "Fatty Acids .txt", "text": "Now in this particular case, what exactly is the configuration, what is the stereochemistry of this bond?"}, {"title": "Fatty Acids .txt", "text": "Well, it's a trans double bond because these two groups basically .2 opposites in the opposite side."}, {"title": "Fatty Acids .txt", "text": "And so what that means is it's a trans delta four."}, {"title": "Fatty Acids .txt", "text": "Basically to describe the stereo chemistry of the double bond, all we have to add is a CIS or trans to the beginning of that double bond."}, {"title": "Fatty Acids .txt", "text": "So in this case it's trans delta four, in this case it's trans delta ten."}, {"title": "Fatty Acids .txt", "text": "But we can also have CIS."}, {"title": "Fatty Acids .txt", "text": "In fact, the cysts are the more common ones inside our body."}, {"title": "Fatty Acids .txt", "text": "And so this is the CIS delta eight because this is carbon 1234-5678."}, {"title": "Fatty Acids .txt", "text": "And so that's the 8th carbon bond between eight and 9th carbon."}, {"title": "Fatty Acids .txt", "text": "And this is cysts because they point in the same exact size."}, {"title": "Fatty Acids .txt", "text": "So we can have cysts or trends."}, {"title": "Fatty Acids .txt", "text": "And actually cysts are the healthier ones as we'll see in just a moment."}, {"title": "Fatty Acids .txt", "text": "Now we can also describe the position of that bond in a slightly different way."}, {"title": "Fatty Acids .txt", "text": "So instead of beginning at this carbon, we can also begin at the Omega carbon."}, {"title": "Fatty Acids .txt", "text": "So let's suppose we have this fatty acid."}, {"title": "Fatty Acids .txt", "text": "Now we begin, we label that reference carbon as carbon number one."}, {"title": "Fatty Acids .txt", "text": "So the Omega carbon is the reference carbon and not this carbon."}, {"title": "Fatty Acids .txt", "text": "So 12345 all the way to carbon one two."}, {"title": "Fatty Acids .txt", "text": "And in this particular description."}, {"title": "Fatty Acids .txt", "text": "So when somebody says you're dealing with an omega three fatty acid, what that means is the double bond is on a third carbon from the Omega side of that fatty acid, where the Omega side is this carbon here."}, {"title": "Fatty Acids .txt", "text": "So."}, {"title": "Fatty Acids .txt", "text": "Remember Omega Carbon?"}, {"title": "Fatty Acids .txt", "text": "So one, two three, this is omega three, this would be omega six and this would be omega nine."}, {"title": "Fatty Acids .txt", "text": "In fact, the omega three six nine fatty acids that you commonly hear of are exactly these acids."}, {"title": "Fatty Acids .txt", "text": "Omega basically means that beginning carbon on the other side."}, {"title": "Fatty Acids .txt", "text": "And the number basically designates the position of that double bond with respect to that Omega reference atom."}, {"title": "Fatty Acids .txt", "text": "So two different ways to basically describe the position of that double bond within that particular fatty acid."}, {"title": "Fatty Acids .txt", "text": "Now the final thing I'd like to focus on is the properties of these fatty acids and what basically determines the properties of these fatty acids."}, {"title": "Fatty Acids .txt", "text": "Well, two things basically describe determine the properties."}, {"title": "Fatty Acids .txt", "text": "It's the length of that fatty acid and the number of double bonds within that fatty acid."}, {"title": "Fatty Acids .txt", "text": "So let's begin with the length."}, {"title": "Fatty Acids .txt", "text": "So let's suppose in one beaker we have this palmitic acid that contains 16 carbons."}, {"title": "Fatty Acids .txt", "text": "In the other beaker, we have an acid, a fatty acid that contains, let's say, 24 carbons, and it's also saturated."}, {"title": "Fatty Acids .txt", "text": "So neither of these molecules actually have double bonds."}, {"title": "Fatty Acids .txt", "text": "So we're essentially only comparing how the length actually describes the properties of the fatty acid."}, {"title": "Fatty Acids .txt", "text": "So it turns out that the melting point of the longer fatty acid will be higher than the melting point of that shorter fatty acid."}, {"title": "Fatty Acids .txt", "text": "The question is why?"}, {"title": "Fatty Acids .txt", "text": "Well, remember, to melt something, we actually have to input energy."}, {"title": "Fatty Acids .txt", "text": "And when we melt something by inputting energy, the energy is breaking the intermolecular bonds."}, {"title": "Fatty Acids .txt", "text": "And what that implies is the intermolecular bonds in the longer fatty acid are stronger than intermolecular bonds in that shorter fatty acid."}, {"title": "Fatty Acids .txt", "text": "The question is, why is that so?"}, {"title": "Fatty Acids .txt", "text": "Well, what types of bonds do we have between two non polar molecules?"}, {"title": "Fatty Acids .txt", "text": "Well, typically, the bonds are London dispersion forces."}, {"title": "Fatty Acids .txt", "text": "They're the attractions that exist as a result of the instantaneous dipole moments that exist along this entire hydrocarbon chain."}, {"title": "Fatty Acids .txt", "text": "And so, because longer fatty acids contain more of these carbon atoms and more h atoms, we have more lung and dispersion forces within the longer within the longer fatty acid solution."}, {"title": "Fatty Acids .txt", "text": "So as the length increases, the melting point increases as a result of more or Londondized version forces, a stronger intermolecular traction between those adjacent fatty acid molecules."}, {"title": "Fatty Acids .txt", "text": "Now, let's move on to degree of unsaturation."}, {"title": "Fatty Acids .txt", "text": "So how exactly does the number of."}, {"title": "Proteasome Complex.txt", "text": "So once we attach many ubiquitous molecules onto a given protein we ultimately target that protein for breakdown within the cell."}, {"title": "Proteasome Complex.txt", "text": "But what exactly is the structure inside the cell that allows us to break down these proteins?"}, {"title": "Proteasome Complex.txt", "text": "Well, it's a structure known as the proteasome."}, {"title": "Proteasome Complex.txt", "text": "And the proteasome is an ATP driven multisubune complex that actually consists of two Subun units or two units."}, {"title": "Proteasome Complex.txt", "text": "So one of these units we call the other unit we call the actually, as we see in this particular diagram we have two nineteen S units that flank the 20s subunit on both sides."}, {"title": "Proteasome Complex.txt", "text": "Now, the, as we'll see in just a moment are actually regulatory units and it's the that basically catalyzes the breakdown of the protein."}, {"title": "Proteasome Complex.txt", "text": "Now, if we zoom in on this twenty S unit we basically find this structure here."}, {"title": "Proteasome Complex.txt", "text": "So we have two types of subunits that make up this core structure."}, {"title": "Proteasome Complex.txt", "text": "We have the alpha subunit and we have the beta subunits."}, {"title": "Proteasome Complex.txt", "text": "So we have seven alpha subunits shown here and seven alpha subunits shown here."}, {"title": "Proteasome Complex.txt", "text": "And in the middle we have these two ring structures that each consist of seven beta subunits."}, {"title": "Proteasome Complex.txt", "text": "So we see that we form four of these rings that stack on top of one another and when they stack on top of one another they basically form this hollow cavity and within that hollow cavity is where we have the catalytic activity of this core structure."}, {"title": "Proteasome Complex.txt", "text": "So we form this barrel core and it's the barrel core that catalyzes the breakdown of protein."}, {"title": "Proteasome Complex.txt", "text": "Now, what exactly are the function of these 219s subunits?"}, {"title": "Proteasome Complex.txt", "text": "Well, it's the 19s subunits that essentially locates and binds to the polyubiquid native protein and once it locates it it has Atpa's activity that allows the 19s regulatory subunits to actually begin unfolding that protein."}, {"title": "Proteasome Complex.txt", "text": "Why do we need to unfold the protein?"}, {"title": "Proteasome Complex.txt", "text": "Well, because we need to fit the protein into the 20s core."}, {"title": "Proteasome Complex.txt", "text": "And so it's the 19s regulatory subunit that binds to the polyubiquitinated protein."}, {"title": "Proteasome Complex.txt", "text": "It begins using ATP molecules to basically unfold that protein and insert that protein into the 20s core."}, {"title": "Proteasome Complex.txt", "text": "And in the 20s core is where we begin to break down the protein into smaller peptides that consist of about seven to nine amino acids in length."}, {"title": "Proteasome Complex.txt", "text": "And also what happens inside a 20s protein is we have an enzyme known as Isappeptidase that begins to remove the ubiquitin molecules."}, {"title": "Proteasome Complex.txt", "text": "Because the ubiquitant molecules are not broken down our cells reuse the ubiquitan molecules over and over and over."}, {"title": "Proteasome Complex.txt", "text": "So we see that the proteosome consists of a core of 20s subunit and 219s subunits position at both ends of this core."}, {"title": "Proteasome Complex.txt", "text": "Now, the 19s subunits are the regulatory units and the 20s are the catalytic subunits."}, {"title": "Proteasome Complex.txt", "text": "So in a way you can imagine that the 20s subunit is like a garbage disposal."}, {"title": "Proteasome Complex.txt", "text": "It basically churns and breaks down that protein into smaller peptides while the 19s subunits basically bind to the poly ubiquitinated protein and they protect other proteins from actually entering the core and being broken down."}, {"title": "Proteasome Complex.txt", "text": "So if we look at the steps that involve this process, we can summarize the steps in this diagram."}, {"title": "Proteasome Complex.txt", "text": "So let's suppose we have some protein shown here."}, {"title": "Proteasome Complex.txt", "text": "And this protein has been ubiquitated with these ubiquitous molecules."}, {"title": "Proteasome Complex.txt", "text": "So we have five here, we have five here and we have five here."}, {"title": "Proteasome Complex.txt", "text": "So now that we marked this protein for degradation, the 19th as subunits not shown here for simplification purposes, these basically locate and bind to this polyubiquid protein."}, {"title": "Proteasome Complex.txt", "text": "And only then can the 19th subunit begin to use its Atpa's activity to basically unfold the protein and insert the protein into this core."}, {"title": "Proteasome Complex.txt", "text": "And inside this core, we'll find these catalytic units that basically have nuclear files."}, {"title": "Proteasome Complex.txt", "text": "And these nuclear files attack the peptide bonds and begin to break down the protein into smaller peptides."}, {"title": "Proteasome Complex.txt", "text": "Now, this process continues until we form peptides that are about seven to nine amino acids in length."}, {"title": "Proteasome Complex.txt", "text": "At that point we begin to remove those ubiquitous molecules."}, {"title": "Proteasome Complex.txt", "text": "And eventually, once all that takes place, those peptides shown here are released along with our ubiquitous molecules."}, {"title": "Proteasome Complex.txt", "text": "And these ubiquitous molecules, which are also proteins, are not actually broken down."}, {"title": "Proteasome Complex.txt", "text": "So in step one, we ultimately see the 19s subunit recognizes the target protein because of the polyubiquidination that happens on that target protein."}, {"title": "Proteasome Complex.txt", "text": "It binds to it and inserts it into the 20s core for degradation."}, {"title": "Proteasome Complex.txt", "text": "Now, in that barrel core, we basically cleave the protein into small peptides and then we remove the ubiquitin."}, {"title": "Proteasome Complex.txt", "text": "And that ubiquitin is recycled and reused by the cell."}, {"title": "Proteasome Complex.txt", "text": "Now, what is the fate of these peptides?"}, {"title": "Proteasome Complex.txt", "text": "Well, the peptides are basically broken down by cellular proteases into individual amino acid units."}, {"title": "Proteasome Complex.txt", "text": "And then those amino acids are basically used for various processes."}, {"title": "Proteasome Complex.txt", "text": "And their fate depends on what the cell actually needs."}, {"title": "Proteasome Complex.txt", "text": "If the cell needs to synthesize proteins or nucleotide bases, then we can use these amino acids for that."}, {"title": "Proteasome Complex.txt", "text": "But if the cell needs to use the amino acid for energy, what it can do is it can remove the carbon skeleton."}, {"title": "Proteasome Complex.txt", "text": "It could remove that urea via the urea cycle and we'll talk about that in more detail."}, {"title": "Proteasome Complex.txt", "text": "And then the carbon skeleton can basically be used to generate energy as we'll talk about in more detail in a lecture to come."}, {"title": "Proteasome Complex.txt", "text": "So we see that once we ubiquitate that particular protein, only then can the protein can actually bond to the special proteasome complex."}, {"title": "Proteasome Complex.txt", "text": "So the proteasome complex consists of the 19s regulatory submit that recognizes that target protein and prevents the other normal proteins that have not been ubiquitated from actually being broken down within this core."}, {"title": "Proteasome Complex.txt", "text": "And it's the core, the 20s catalytic core that actually catalyzed the breakdown of that protein into smaller peptides."}, {"title": "Proteasome Complex.txt", "text": "And remember that the ubiquitant molecules themselves are not actually degraded."}, {"title": "Proteasome Complex.txt", "text": "Our cells reuses and recycles these ubiquitous molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "One job of our liver cells, and to much smaller extent our kidney cells, is to actually regulate and maintain the proper glucose levels inside our blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, why is that actually important?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Why is it important to maintain the proper glucose levels?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Well, because the cells of our body actually use that glucose to form the energy ATP molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And the ATP molecules are then used to power many different types processes such as, for instance, gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So remember, gluconeogenesis actually uses up on that amount of ATP and GTP molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, liver cells and kidney cells can undergo gluconeogenesis and they do actually undergo gluconeogenesis to a very large extent compared to other cells because other cells such as brain cells and muscle cells don't actually use gluconyogenesis, they only use it to very small extent under very extreme conditions."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And in fact, we have cells of our bodies, such as red blood cells, that cannot use gluconyogenesis at all."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And that's because red blood cells actually don't have mitochondria."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so red blood cells actually depend entirely on the glucose found inside the blood plasma, as do the brain cells and muscle cells of our body."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So all these different types of cells actually get that glucose from the blood uptake that glucose and then use the glucose, break it down in glycolysis to form the ATP."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And that's why it's so important that our liver cells and kidney cells can actually properly regulate the levels of glucose in our blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, previously we saw how the energy charge value within the cell, the ratio of ATP to amp can actually be used to regulate the process of glycolysis and gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So we can use the energy charge of the cell to basically tell us if glycolysis or glucomaogenesis actually predominates."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, although that's true for liver cells and for kidney cells, because they regulate and maintain glucose levels, they also can use the glucose levels in the blood to basically determine whether glycolysis or gluconeogenesis actually predominate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So on top of using the energy charge value to help us determine which process predominates, the glucose levels in our blood can also be used to actually tell us which one of these two processes actually predominates glycolysis or gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, the key element in this regulatory pathway, which is once again a reciprocal regulatory pathway and we'll see what that means in just a moment."}, {"title": "Regulation of Glucose in Blood .txt", "text": "The key element in this pathway is a bifunctional allosteric enzyme that contains two different types of domains."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, Bifunctional simply means it has two different functions."}, {"title": "Regulation of Glucose in Blood .txt", "text": "In fact, the functions are essentially opposite functions and that's why we call it reciprocal."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, allosteric means it contains special sites that combine allosteric effect or molecules that can basically affect the activity of that protein."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So this is our bifunctional Alastairic enzyme and we have two different domains."}, {"title": "Regulation of Glucose in Blood .txt", "text": "This domain is known as the phosphorptokinase two domain, PFK two, and this domain is known as the fructose bisphosphatase II domain."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So FBPA two now, because this ends in a kinase, you might expect that its function is to basically attach a phosphoryl group onto some type of molecule."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And that's exactly right as we'll see in just a moment."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And likewise, because this molecule is known as a phosphatase, you might imagine that its function is to actually remove of a sporal group from a molecule."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And that is exactly right."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Their functionality is exactly opposite."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So this bifunctional enzyme can exist in two states."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So State A or State B?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "In state A the phosphorptokinase to this structure is active while this one is inactive."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And the reason it's active is because this serene residue found on this region here is not actually phosphorylated."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, if protein kinase A takes an ATP and phosphorylates that serine residue on this domain, we create state B and in state B this becomes inactive while the other one becomes active."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, we can go back to this state by the action of phosphor protein phosphatase which uses a water molecule to hydrolyze that ester bond and remove that inorganic phosphate reforming state A."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So we can basically cycle it between state A and state B."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So let's begin by looking at state A."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So in the unphosphorylated state, the PFK two domain, this one is active while this one is inactive."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And we said that when this one is active its function is to phosphorylate some type of molecule."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now what molecule will basically an intermediate in the process of glycolysis and also an intermediate in the process of gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So fructose six phosphates and this phosphorylates fructose six phosphate into fructose two six bisphosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And we actually spoke about fructose 26 bisphosphate in the previous lecture."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So we saw that fructose 26 bisphosphate is actually an allosteric effector molecule that affects the activity of enzymes in glycolysis as well as gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So if you don't remember what this does, go back to the previous lecture and check that out and notice this one is inactivated in state A."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, when we go to state B, when protein kinase A phosphorylates the serial residue to form this phosphorylated state, we see that that deactivates this molecule, the PFK two, while activating that fructose bisphosphatase two."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And what the fructose bisphosphatase two does is it basically reverses what this phosphorctocinase two actually does."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And that's why we say they have a reciprocal function, they're opposite in what they actually do."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So now what happens is the FDPH too, because it's active, it causes the defasphorylation, it removes that phosphoryl group from that fructose, fructose two six bisphosphate to form that fructose six phosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So now that we know what this key element is, the fact that we have this bifunctional allosteric enzyme found in the liver, in kidney cells that basically is used to regulate this process of glycolysis and gluconeogenesis, let's actually see how this all takes place."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And essentially we want to basically compare two different conditions."}, {"title": "Regulation of Glucose in Blood .txt", "text": "One condition is when we have high blood glucose levels."}, {"title": "Regulation of Glucose in Blood .txt", "text": "The other condition is when we have low blood glucose levels."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so let's begin with the high blood glucose levels."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So let's suppose we just ate a meal that is rich in carbohydrates and so we break down the carbohydrates into the individual glucose molecules and that means the concentration of glucose in the blood essentially rises."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And as it rises that signals the release of insulin hormone molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And insulin basically goes on and creates some type of signal cascade that essentially ultimately activates a molecule known as phosphoprotein, phosphatase."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And this is the same molecule that we basically discussed here."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Remember the phosphoprotein, phosphatase is the enzyme that catalyzes the transformation of the Bifunctional enzyme from B state to the A state."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so this basically stimulates this phosphor protein phosphatase to activate the PFK two domain."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And once the PFK two domain is activated, what it does is it goes on to activate the conversion of fructose six phosphate into fructose 26 bisphosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And again, remember, fructose six phosphate is the third intermediate or the second intermediate in the process of glycolysis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Remember in glycolysis we first take glucose and transform it into a glucose six phosphate and then we transform glucose phosphate into fructose six phosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And fructose six phosphate can either transform into fructose one six bits phosphate to contain the process of glycolysis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "But when this bifunctional enzyme is in this active state, it goes on to basically transform the fructose six phosphate into fructose 26 bisphosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And what this molecule does is it basically creates a positive feedback loop."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So this molecule, fructose 26 bisphosphate, acts as an allosteric effector, more specifically as a very potent allosteric activator of phosphorinase."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And phosphorctokinase is needed to actually transform the fructose six phosphate into the fructose one six bisphosphate."}, {"title": "Regulation of Glucose in Blood .txt", "text": "That basically commits that fructose molecule, the glucose to carrying out the process of glycolysis and that ultimately stimulates the process of glycolysis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "At the same time that fructose 206 bisphostate acts as an allosteric activator to phosphor fructoseinase, this same molecule will act as an allosteric inhibitor to molecule to an enzyme found in the process of gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So when this pathway is followed, when we have high blood glucose levels, we see that glycolysis is essentially activated, but gluconeogenesis is essentially inhibited."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now why does that actually make sense?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Well, if we have high levels of glucose in our blood, our kidney cells and liver cells want to actually remove the excess glucose from our blood because high levels of glucose can actually be very toxic."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so what that means is these liver cells want to pull in these glucose molecules and then break down the glucose molecules to ATP molecules because that will ultimately help us decrease the level of glucose in our blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now what about the other case?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "What about if we have low blood glucose level, for example?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Let's say we're fasting."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So if we fast, we essentially don't eat for an extended period of time."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And we actually all fast when we sleep."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So essentially, as we're sleeping, we essentially have a decrease in the glucose level in our blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So if we fast, the same exact thing actually happens."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And when we have a low blood glucose level, that stimulates a different type of hormone known as glucagon."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And glucagon also creates some type of signal transduction pathway."}, {"title": "Regulation of Glucose in Blood .txt", "text": "More specifically, it creates a cyclic Amp signal transduction pathway."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And this secondary messenger molecule goes on to activate PKA protein kinase A."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And as we know from this particular discussion, protein kinase A transforms this state into this state."}, {"title": "Regulation of Glucose in Blood .txt", "text": "It phosphorylates, that serene residue that inactivates the PFK two, and it activates that fructose bisphosphatase two."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so now what happens is in the presence of low blood glucose in our blood plasma, the fructose 26 bisphosphate molecule that we form here basically is transformed back into fructose six phosphate via the hydrolysis of that Esther Bond."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And when this process takes place, this potent activator of phosphor kinase can no longer activate that phosphorinase."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And because this concentration decreases, it can no longer inhibit the enzymes of gluconeogenesis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so this basically means gluconeogenesis will essentially be activated, while glycolysis will basically decrease in the rate at which it actually takes place."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, why does that actually make sense?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Well, if we have low blood glucose levels, what that means is we essentially want to create more glucose molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Why?"}, {"title": "Regulation of Glucose in Blood .txt", "text": "Well, because the cells of our body, such as red blood cells, our brain cells, our skeleton muscle cells, our cardiac muscle cells and so forth, all these different types of cells depend on glucose that is present in the blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And if the levels of the glucose drops, that can be very dangerous to those cells."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Because, for instance, if our red blood cells cannot actually get the glucose from the blood because of the low levels of glucose in the blood, that can essentially lead to many, many different types of problems."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so what happens is the liver cells essentially begin to produce these glucose molecules from non carbohydrate molecules such as pyruvate and lactate and amino acid and glycerol molecules."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And once we produce those glucose molecules, the cell's liver cells can release the glucose molecules into the blood and that will essentially maintain the proper glucose level in the blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So this is basically the pathway that the liver cells in the kidney cells actually use to regulate and maintain the glucose levels in our blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, one more thing I'd like to mention about insulin and glucagon is that these two different types of hormones also actually activate and inhibit certain types of gene expression."}, {"title": "Regulation of Glucose in Blood .txt", "text": "So insulin and glucagon also affect the rate at which our cells actually undergo gene expression and transcription."}, {"title": "Regulation of Glucose in Blood .txt", "text": "Now, in the case of insulin, because what insulin does is it ultimately wants to actually decrease the level of glucose in the blood."}, {"title": "Regulation of Glucose in Blood .txt", "text": "It essentially begins to or it helps express those enzymes involved in uptaking the glucose from the blood and actually using that glucose to break it down in glycolysis."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And so the enzymes of glycolysis basically will increase in the rate at which they're going to be produced."}, {"title": "Regulation of Glucose in Blood .txt", "text": "And also glucose transporters such as Glute Four will also express."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "If a cell is actually to exist and function effectively and efficiently it must be able to control and regulate the way that the cell expresses the genetic information that is found inside DNA molecules."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, what that basically means is the cell must be able to control the process of transcription."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It must be able to turn on transcripts prescription when we need to synthesize proteins and turn all transcriptions when we do not need to use those proteins."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And this process is known as gene expression and gene regulation."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, prokaryotic cells such as bacterial cells can regulate gene expression by using special types of molecules."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Special types of proteins known as DNA binding proteins and DNA binding proteins used by prokaryotes come in two categories."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "We have repressors and we have activators."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So during the process of transcription when we transcribe the DNA into RNA the activators can basically activate transcription while the repressors can block the process of transcription and ultimately block the synthesis of proteins that correspond to those genes."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, our activators at repressive protein molecules can themselves be controlled alisterally by other molecules as we'll see in just a moment."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So when we're discussing prokaryotic gene regulation and expression basically the model that describes the regulation of genes in prokaryotic organisms is known as the operon model."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And what the operon is?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It's basically a unit or a segment of DNA that contains two important sections."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It contains the regulatory section as well as the coding section."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, what exactly is the regulatory section and what is our coding section?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Well, to see what that is let's take a look at the following diagram."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So this is basically our opera."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So this operon consists of the regulatory section and the coding section."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now the regulatory section itself consists of two important control sites."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "We have the promoter side as well as the operator side and we'll see what the function of those sites is in just a moment."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And our coding section actually consists of sequence of DNA that code for certain types of polypeptides for certain types of proteins."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So this is our opera."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It consists of our control sites and also consists of the structural genes."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, any given unit, any given operon itself also is found next to a regulatory gene."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And the regulatory gene basically consists of the sequence of DNA that codes for the repressor or activator."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So every single opera next to the opera contains the regulatory gene that codes for either the repressor or the activator that is involved within that opera."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, to gain more intuition and understanding to what the opera is and how it actually works let's take a look at one particular example of the lack of an opera known as the Lac Operon which stands for the Lactose opera."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "This is the opera that is used by certain type of prokaryotic cell known as E. Coli."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So prokaryotic cells basically control the genes by using the change in concentration of certain types of biological molecules."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So prokaryotic cells have genes that respond to changes in concentration of certain types of biological molecules such as glucose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So basically when glucose concentration is high the glucose can basically or the cell can metabolize the glucose and use the ATP produced by the process of glycolysis to power the different types of processes that take place within our cell."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "However, what happens when the glucose concentration is low?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "When the glucose concentration is low the cell must actually metabolize some other type of biological molecule."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And one other common type of biological molecule that the cell metabolizes is lactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So lactose is a sugar molecule."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It's a disaccharide that consists of two individual sugar monomers."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So our lactose consists of a glucose as well as a galactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, the enzyme that actually catalyzes the breakdown of lactose into glucose is known as betagalactosidase and betagalactosidase is basically controlled."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So the synthesis of the protein, the enzyme beta Galacticidase is controlled by a special type of operon found on the DNA of the prokaryotic cell known as the lac operon."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So let's take a look at the lac opera."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "The lac opera is basically this section here."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So the lac operon consists of two sections."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "We have the regulatory section which is basically this section here and we have our coating section."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "The coating section basically consists of three genes that each code for a specific type of enzyme that is involved in the breakdown of lactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So this region, shown by region number six contains the gene for the base galacticidase while these other genes are genes that code for two other proteins two other enzymes involved in the breakdown of lactose into glucose and galactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, what about this section?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Basically this section is the regulatory section."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It consists of our control sites."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, the lac operon actually consists of three sites."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "We have our operator side, we have the promoter side and we also have another type of site known as the cap side."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And we'll discuss what that means in just a moment."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And to the left of our cap side of site number three we have the gene that codes for the repressor protein and we also have the promoter of our gene that codes for the repressive protein."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So let's discuss once again what happens when our cell contains a high concentration of glucose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So when glucose concentration is high RNA polymerase will bind to the promoter region so region number one and when RNA polymerase binds to our promoter region it will basically transcribe this DNA molecule into an mRNA molecule and then that mRNA molecule will be used by the ribosome to basically synthesize the repressor protein."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And once a repressive protein is formed it will go on and bind to site number five."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So site number five is one of the control sites."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "It's known as our operator region."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And once the repressive protein binds to the operator region by using electric forces once it binds it basically will block the process of transcription of these genes here."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So once formed, the repressive protein binds the operator region and blocks the RNA polymerase from transcribing, the mRNA molecule that codes for the beta Galacticase, as well as these other two types of genes."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, why exactly does the cell need to block the transcription of these mRNA molecules that code for the proteins that break down lactose?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So this is because inside the cell, we have a high concentration of glucose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So we do not actually have to break down lactose because we have the glucose that we can use as our energy source."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And so because the concentration of glucose is high, we do not need to synthesize the proteins, the enzymes that are involved in the breakdown of lactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So once again, this takes place because at high concentration of glucose, the cell does not need to use lactose as the energy source because it has the glucose in the first place."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And so the genes for our beta Galactosidase, as well as these other two genes, the proteins involved in the breakdown of lactose are essentially turned off."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "They are not expressed."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, what exactly happens when the glucose concentration drops?"}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So when the glucose concentration drops, our cyclic amp or cyclic adenosine monophosphate concentration will increase."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And our CA MP molecule will go on to bind to a special type of protein known as our cataboli activator protein or cap."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And what the cap eventually does is it will bind to site number three."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "But before that actually takes place, when we have a low concentration of glucose, we're going to have a high concentration of lactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And some of that lactose will transform into another molecule known as alo lactose."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And alo lactose is basically that allosteric molecule that will go on and bind to our repressor protein."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And once it binds to the repressive protein, shown in red, it will inactivate that repressive protein."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And that repressive protein that is bound to the operator will basically detach from the operator."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And once it detaches, then our cap can basically bind to the cap side and that will activate the promoter region, this region that basically promotes the transcription of these genes."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And so when our repressor is inactivated and our cap binds to our cap side, only then can the RNA polymerase actually bind to the promoter and begin the transcription of these genes."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So at a low concentration of our glucose, we want to be able to break down lactose to actually form the glucose that we can use to break down and form our ATP molecules."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And so at low concentration of glucose, we want to express the formation of our beta galacticidase so that we can use this betagalacticidase to actually break down our lactose molecule."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So once again, when the glucose concentration is low and lactose concentration is high, the lactose can transform into another disaccharide known as allo lactose, which binds to the repressor protein allosterically and inactivates that repressive protein which then detaches from the operator side on our apron on our lac operon."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "Now, at the same exact time, because we have a low concentration of glucose, we're going to have a high concentration of cyclic adenosine monophosphate or camp."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And then camp will go on and bind to a molecule known as the catabolite activated protein or cap."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And the cap goes on to special site that is shown by site number three that is known as the capsite."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "So the cap side is part of the regulatory section and once it binds to our cap side, that will activate our promoter and the RNA polymerase will bind to our promoter and will begin in the synthesis of the mRNA molecules that code for these proteins."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And then the proteins can synthesize."}, {"title": "Gene Regulation and the Lac Operon.txt", "text": "And once we synthesize our proteins, those proteins can be used to metabolize our lactose to form the glucose that can then be used to form ATP via the pathway of glycolysis."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "When scientists began studying the way that bacterial cells protect themselves from different types of viral agents from bacteriophages, they realized that inside bacterial cells are these special digestive proteins, these special digestive enzymes known as restriction enzymes or restriction endonucleases."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And what these restriction enzymes do is they are able to actually cut or cleave the viral DNA molecule into many different pieces, thereby destroying that viral DNA and deactivating that viral DNA."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So one way that bacterial cells protect themselves from bacteriophages is by using these special enzymes we call restriction enzymes."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now, because there are many different possibilities that a DNA sequence can consist of, we have many, many different types of restriction enzymes that exist in nature."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And each and every one of these restriction enzymes basically cleaves along a DNA molecule at a specific location on that double stranded DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now, many of these enzymes, in our study of these restriction enzymes, we realized that many of these restriction enzymes actually cut at palindromic sequences along that doublestrand the DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And to see what we mean by a palindromic sequence of DNA, let's take a look at the following diagram."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So, let's suppose we have a section, a palindromic section of our double stranded DNA."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So remember, in any double stranded DNA molecule we have two single strands that run antiparallel with respect to one another."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this blue strand begins at the five N and ends at the three end."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And this green strand begins at the three N and ends at the five N. That's what we mean by antiparallel."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now, we also have the base pairing between the two single strands and that's what holds the two strands together."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we have the adenine children red, we have the thymine shown in dark purple, we have the orange, that's the guanine, we have the cytosine, that's the light purple."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And so what we mean by palindromic sequences of DNA, if we read these bases going this way, we get the same exact reading if we go backwards."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So going this way along the blue single strand we have aagct."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And going this way in the opposite direction along the green strand, the other single strand we also get Aagct."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So that's exactly what we mean by a palindromic sequence."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And most of these restriction enzymes, restriction enzymes basically look for these types of Palindromic sequences on the DNA and that's where they cleave those DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So for this particular example, let's suppose we add some sort of restriction enzymes that looks for this specific Palindromic sequence."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "What the enzyme does is it finds that Palindromic sequence and it cuts at a specific location along that DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So for example, let's say this restriction enzyme that we add cuts between the A bases, between the adenine bases along this specific Palindromic sequence."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So that means because we have two A's here and two A's here, we have the restriction enzyme cuts not only here, but it also cuts here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And once we cut those single strand molecules, these hydrogen bonds basically dissociate and we form the following molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So now we basically have this asymmetric uneven cut."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And the reason we have an asymmetric cut is now we have these single strands of DNA molecule are exposed."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So they're no longer connected, but they are exposed."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So here we still have a double helix and here we still have a double helix."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "But within this section, and within this section we have single strands that are exposed."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And these single strands are commonly known as sticky ends."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Why do we call them sticky ends?"}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Well, because they're complementary with respect to one another."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And if we somehow allow them to reconnect and then we use a special type of enzyme to reform these bonds right over here, these sticky ends, because they're complementary, they're going to stick right back together."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now, when scientists discover this, they realize that one important application of restriction enzymes will be to form recombinant DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So remember, a recombinant DNA molecule is a DNA molecule that consists of two or more different DNA sequences, DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So to see what we mean by that, let's take a look at the following diagram."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So let's suppose we have two different DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So DNA molecule number one and DNA molecule number two that basically came from two different sources."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And what we want to do is we want to somehow combine these two DNA molecules and to form a single recombinant DNA molecule that consists of these two different DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So the way that we do it is we basically realize that let's say these two different DNA molecules both contain these Palindromic sequences that we discussed earlier."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So let's say this is the Palindromic sequence on this molecule that reflects this."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And this is the Palindromic sequence on the second DNA molecule that also reflects this sequence here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we have the red, the red, the orange, the light purple, dark purple, dark purple that reflects this."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And then along the green section we have the purple, the purple, the light purple, that orange, red and red."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And the same type of Palindromic sequence is found on this second DNA molecule as well."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we have red, red, orange, light purple, dark purple, dark purple on one strand and the lower strand has the dark purple, dark purple, light purple, orange, red and red."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So let's suppose we take these two DNA molecules and now we add the same restriction enzyme that we basically used in this particular case."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And what that means is this restriction enzyme will move along the DNA molecule until it locates this specific Palindromic sequence."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And once it locates that Palindromic sequence it will cleave between the A bases between those red bases."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we have two red bases here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So that means it will cut here and two red bases on the other one it cuts here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And so we form the following to an even sticky end."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this is how the cut basically takes place."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And now on the other one, the restriction enzyme also finds this palindromic sequence and cuts right over here and right over here, as shown by these two arrows."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And so we form the following two sticky ends."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now notice, because we use the same restriction enzyme to cut these two DNA molecules, these sticky ends will be complementary with respect to one another."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So what that means is this sticky end right over here will be complementary to this sticky end right over here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And likewise this sticky end right over here will be complementary to this sticky end right over there."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And so what happens is if we take a special enzyme known as DNA ligase that is able to reform these bonds between this section and this section and between this section and this section, then if we add this DNA lie gaze into the mixture."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "What happens is this entire section will be placed onto this complementary section."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And this entire section will be placed onto this complementary section."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And so at the end, we're going to form this single molecule, single DNA molecule, that is a recombinant DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "It will consist of these individual DNA molecules that ultimately came from two different sources."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So what scientists realized is once they actually discovered restriction enzymes, they then realized that they can use these restriction enzymes to basically form any recombinant DNA molecule that they actually want."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now the next question is, once they actually form that recombinant DNA molecule, how do you amplify your results?"}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "How do you produce many copies of that same recombinant DNA molecule?"}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Because if you want to conduct many different types of experiments, you need many different copies of that same recombinant DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Well, one way to do it is by using plasmids."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So remember, in any DNA molecule or in any bacterial cell, on top of having that DNA, of that bacterial cell, the bacterial cell also has these smaller DNA, smaller circular DNA known as plasmids."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So let's suppose we take a bacterial cell and we isolate, we take out that plasma."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this is our plasmid of some particular DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this is one DNA molecule."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And suppose that this is our target DNA, the recombinant DNA that we form, that we basically want to amplify."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So what we do now is we take these two different sources of DNA, we add a restriction enzyme, so we cut them at specific locations and then we add DNA ligase to basically produce this recombinant plasmid that contains this blue section that we basically want to amplify."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this is the same exact process that we followed right over here."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And now we take this recombinant plasmid and we insert it into bacterial cell."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And that bacterial cell will basically divide many, many times via binary fission and produce many identical copies of these recombinant plasmids."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And ultimately we can take these bacterial cells and we can once again isolate these recombinant DNA plasmids."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And now we can use the same restriction enzymes to basically cut at the same exact locations."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And we can isolate these blue sections, these recombinant DNA molecules."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And now we have many, many copies of these DNA molecules, recombinant DNA molecules that we can actually work with."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we see that to form recombinant DNA molecules, we actually mean restriction enzymes."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "And one way to amplify the recombinant DNA that we form is by using these plasmids."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "Now, another way we'll be focused in a different lecture."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So this method actually has one important limitation and that's the size of that recombinant DNA."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So we can't use recombinant DNA molecules that are too large because these plasmids have a limit to how large they can actually get."}, {"title": "Restriction Enzymes and Recombinant DNA.txt", "text": "So the problem with this method of amplifying the recombinant DNA is there is a limit to the size of that recombinant DNA that we can actually use to amplify via this particular method."}, {"title": "Structure of ATCase Part II.txt", "text": "Units."}, {"title": "Structure of ATCase Part II.txt", "text": "And what that means is, because we have more than one active site, those active sites will basically be able to interact with one another as a result of these structural changes that take place upon the binding of that substrate molecule to the active side of the enzyme."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Within our cells there's a coordinated and intricate interplay between the pentose phosphate pathway and the glycolytic pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so what I'd like to focus on in this lecture is the factors that actually influence how this coordinated interplay between these two processes actually plays out."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so what we're going to do is we're going to discuss four different cases that can exist within a given, given cell of our body."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So let's begin with case number one."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So in case number one, we're basically assuming that our cells need NADPH molecules as much as they actually need ribosphy phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now before we discuss this any further, let's actually remember what our cells use NADPH for and what our cells use the ribose phyphosphate molecule for."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, the NADPH molecule is a very important reducing agent that our cell uses for a variety of different types of bisynthetic processes and detoxification processes."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "For instance, our cells can use NADPH for processes such as fatty acid synthesis, cholesterol synthesis, neurotransmitter synthesis and nucleotide synthesis."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now what about ribose phyphosphate?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, ribose phyphosphate is a molecule that is basically needed to build nucleotide based molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So molecules such as DNA molecules and RNA molecules depend on the presence of ribose phyphosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So faracell needs to build, for instance, DNA molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "It needs to use, it needs to have a supply of ribose phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So once again in this particular case, when our cells need the NADPH as much as they actually need the ribose phyphosphate, this is what the cell will carry out."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So it will not carry out the glycolytic pathway and it will not carry out the non oxidative phase of the penzosphosphate pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Instead, it will only carry out the oxidative phase of the pathway, the pencil phosphate pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Why?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, because this is the phase that generates NADPH molecules as well as those ribose five phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So this is what the reaction looks like."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "We have an input of a single one glucose six phosphate molecule or a single glucose six phosphate molecule, a single water molecule and two NADP plus molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And what we form is the two NADPH molecules and one ribose phi phosphate molecule."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "In addition, we also produce a carbon dioxide and two H plus ions."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So basically this is what the cell will carry out and then it will use these molecules to help carry out other processes that we discussed just a moment ago."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now let's move on to case two."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now in case number two, we're assuming that our cell actually needs the ribose phyphosate molecule much more than it needs the NADPH molecule."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now what's an example of a cell that will experience this particular case?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, a cell that is about to divide, a cell that is about to divide needs to actually replicate and build nucleic acid DNA molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so in such a case, it actually needs the ribosugar molecule much more than it needs the NADPH molecule."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So what exactly will happen in such a case?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well in such a case the cell will not actually undergo oxidative phase of the pencils phosphate pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "What will happen is once again we begin with that glucose six phosphate molecule and now we undergo the glycolytic pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so what we form is fructose six phosphate molecules as well as glyceroaldehyde three phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Why?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, because now our cell can use the fructose six phosphate and the glyceroaldehyde three phosphate and it can undergo the reverse steps of non oxidative phase of the penthouse phosphate pathway because combining these two will allow the cell to actually build the much needed ribose biphosphate molecules which it can then use to build those DNA molecules nucleic acids."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So under such conditions when the cell needs the ribose phyphosphate much more than it needs the NADPH molecules, the glucose six phosphate metabolite is converted via the glycolytic pathway into gap glyceroaldehyde three phosphate and fructosex phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And then these molecules are converted via the reverse non oxidative steps of the pentose phosphate pathway into the ribose five phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now the correct stoichiometric net equation for this particular reaction is given to us here."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we input five glucose six phosphate molecules and we use up a single ATP molecule and we generate six ribose five phosphate molecules, a single ATP molecule and two H plus ions."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So let's discuss why we have a ratio of five to six molecules and where the ATP actually comes from."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have four glucose phosphate molecules that we convert into four fructose six phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "We take the fifth glucose phosphate and we convert it into a fructose six phosphate, but we don't stop there."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "We take that fructose six phosphate, we use an ATP molecule to transform it into the fructose one six bits phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So this ATP that we use here is the same ATP that is used to actually transform the fifth fructose six phosphate into this fructose one six bits phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And then we basically transform that into, or we break down this into these two intermediates thyroxy acetone phosphate and glycero aldehyde three phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now this is readily transformed into the glyceroaldehyde three phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so the SIF glucosex phosphate that goes into this glycolytic pathway is used to form two of these glyceroaldehyde three phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So four of these five glucose six phosphates are used to form four fructose six phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And the final glucose phosphate is used to form two of these glyceroaldehyde three phosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And that process actually needs an ATP."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so we form an ATP or we use an ATP and we form an ADP on the product side here."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now how do we form six ribose five phosphates from these five glucose six phosphates?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, remember the steps of the non oxidative phase of the penthouse phosphate pathway?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "In that particular phase we saw that we use three ribose phyphosphates to generate two fructose six phosphates and one glycero aldehyde three phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so what that means is because we have four fructose six phosphates and two glutaraldehyde three phosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "If we combine these two we're actually going to form six ribose phosphate molecules because we need two fructose and one gap to form three ribosphosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "But because we have double that amount, we form not three, but six ribose phyphosate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So this is what a dividing cell would actually follow because it actually needs the ribose five phosphate molecules much more than those NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now let's move on to case three."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So in case three, our cells need the NADPH much more than they actually need the ribose phyphosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So what type of cell would experience this type of scenario?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well, a cell that is continually undergoing fatty acid biosynthesis for instance, and this would mean a fast cell."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So fat cells basically follow this particular pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we actually have three individual steps."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have a glucose six phosphate, is transformed into ribose phosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Let's erase that for a moment."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have a single glucose phosphate, is transformed into ribosphy phosphate, and we generate the two NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And this is essentially the oxidative phase of the pentose phosphate pathway."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Next we undergo the non oxidative phase and we break down the ribosphy phosphate into fructose six phosphate and glyceroaldehyde three phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And actually the correct stoichiometric coefficient for this, we have two and we have one glyceroaldehyde for three of these molecules that are actually formed or that are actually used."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we need to actually use three ribose five phosphates to produce two fructose six phosphates and a single glyceroaldehyde three phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So that's the second step."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And in the third step, the fructose six phosphate molecules and the glyceroaldehyde three phosphate follow certain gluconeogenic steps."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we undergo gluconeogenesis and that allows us to reform that glucose six phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So this is basically what a fat cell follows, because a fat cell needs the NADPH molecules much more than it actually needs the ribose phyphosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And now that the cell was able to actually recycle these two intermediate molecules, fructose six phosphate and glucose aldehyde three phosphate back into the glucose phosphate, the cell can use that glucose phosphate via this step to produce even more NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So let's actually summarize these three steps."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So in step one we have six g six p, where g six P is the glucose phosphate molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have twelve NADP plus molecules and six water molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And that produces six r, five P where R stands for the ribose."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So our ribose phyphosphate, twelve NADPH molecules, six carbon dioxide molecules, and twelve H plus ions."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "This is basically this step."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we multiply all these coefficients by six, this becomes six, this becomes six, this becomes six, this becomes 1212, and twelve and six."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now in the second step is we're essentially going this way."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have six ribose five phosphates that we form, and that helps us generate four fructose six phosphates and two glutral aldehyde three phosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And then we take these two intermediates and we react them via the gluconeogenesis."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so we basically have these same two reactants here, a water molecule and that helps us generate five glucose phosphates and a single orthophosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so if we sum up all of these reactions, this is the net reaction that we're going to have."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so notice we have a single glucose phosphate and none of the glucose phosphates actually appear on the product side."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so ultimately what this basically tells us is in cells such as fat cells which need the NADPH much more than they actually need the ribose sugar molecule, these cells are able to actually metabolize and break down the g six P, the glucose six phosphate, and form the twelve NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And we also generate the carbon dioxide, the orthophosphate, as well as the twelve H plus ions."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so in these particular cells they don't actually need the Ribos, they only need the NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And so this is what they actually follow."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So we have this interplay, this coordinated interplay between the pencils phosphate pathway and the glycolytic pathway which allows the cell to actually maximize the production of these much needed NADPH molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And finally let's move on to case four, the final case."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So in case four, our cells basically need not only the NADPH molecules but also ATP molecules, energy molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So in this particular case this is what the cell actually follows."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So notice in this case we took these intermediates and we transformed them back into the glucose phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "But in this case these same intermediates will not follow gluconeogenesis, instead they will follow the glycolytic pathway to help us generate the ATP."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So let's see exactly what we mean."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So once again we begin with the glucose six phosphate metabolite."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "We have oxidative phosphorylation take place and we form the two NADPH molecules and the ribose six phosphate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So these molecules basically satisfy this requirement."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "But what about the ATP?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well the ribosix phosphate can undergo the non oxidative phase of the pentose phosphate pathway to generate the gap, the glyceroaldehyde three phosphates and the fructose six phosphates."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "And these intermediates can enter the glycolytic pathway and through the glycolytic pathway they can be used to actually form the Pyruvate molecules and the ATP molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So for the case of fructose six phosphate it goes on to form the fructose one six bisphosphate, then it goes on to break down to these two intermediates and that then goes on to form the Pyruvate."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "For the case of gap, the gap goes into these steps and then that forms the Pyruvate molecule."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Now the ATP form here satisfies this requirement."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "What about the Pyruvate?"}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "Well the Pyruvate can then enter oxidative phosphorylation, it can undergo oxidative phosphorylation, meaning the Pyruvate can go into the mitochondria on the cell, it can basically undergo the Krebs cycle and electron transport chain to basically form even more ATP molecules."}, {"title": "Interplay of Glycolysis and Pentose Phosphate Pathway .txt", "text": "So these are the four different cases that can exist inside our cells, which basically describe the coordinated interplay between the glycolytic pathway and the pentose phosphate pathway."}, {"title": "Primary Structure of Proteins .txt", "text": "Proteins usually have very complex structures, and that's exactly why we normally break down the complexity into different levels."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have the simplest level of complexity and we go all the way up to the highest level of complexity."}, {"title": "Primary Structure of Proteins .txt", "text": "So the simplest level of complexity that describes the structure of proteins is the primary structure."}, {"title": "Primary Structure of Proteins .txt", "text": "So the primary structure describes the specific sequence of amino acids within our protein, within our polypeptide."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, it turns out that every single protein inside our body has its own unique sequence of amino acids."}, {"title": "Primary Structure of Proteins .txt", "text": "And it's the primary structure, it's the sequence of amino acids that actually determines what the final structure of that protein is."}, {"title": "Primary Structure of Proteins .txt", "text": "And that's a very important point to remember."}, {"title": "Primary Structure of Proteins .txt", "text": "It's the primary structure, it's the specific sequence of amino acids in that polypeptide that determines the final three dimensional structure of that polypeptide."}, {"title": "Primary Structure of Proteins .txt", "text": "So let's suppose we have the following five amino acid polypeptide."}, {"title": "Primary Structure of Proteins .txt", "text": "So let's begin on the left side."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have amino acid number one."}, {"title": "Primary Structure of Proteins .txt", "text": "Then we have a peptide bond shown in green."}, {"title": "Primary Structure of Proteins .txt", "text": "We have amino acid number two, a second peptide bond, amino acid number three, a third peptide bond, amino acid number four, a fourth peptide bond, and amino acid number five."}, {"title": "Primary Structure of Proteins .txt", "text": "And these amino acids in a polypeptide are also known as residues."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have residue one, residue two, and so forth."}, {"title": "Primary Structure of Proteins .txt", "text": "So notice we have five amino acids, but only four peptide bonds."}, {"title": "Primary Structure of Proteins .txt", "text": "And normally, if we have, let's say, N number of amino acids, we always have N minus one number of peptide bonds."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, under normal physiological conditions, at a neutral PH, this polypeptide will always have polarity."}, {"title": "Primary Structure of Proteins .txt", "text": "And what that means is on one end of the polypeptide chain, the alpha amino group will contain a full positive charge, and at the other end, the alpha carboxyl group will contain a full negative charge."}, {"title": "Primary Structure of Proteins .txt", "text": "And so we have polarity as a result of these two different charges."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, by convention, the beginning of the polypeptide is always set to be at the positive end at the alpha amino group, and the end is always set to be at the negative side at the alpha carboxyl group."}, {"title": "Primary Structure of Proteins .txt", "text": "So we always read the amino acids beginning from the alpha amino side and ending at the alpha carboxyl side."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, notice if we go along the polypeptide chain, we will see a repeating unit of three atoms."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have nitrogen, carbon, carbon, nitrogen, carbon, carbon, nitrogen, carbon, carbon, nitrogen, carbon, carbon, nitrogen, carbon, carbon."}, {"title": "Primary Structure of Proteins .txt", "text": "And this can continue if we continually add amino acid."}, {"title": "Primary Structure of Proteins .txt", "text": "So this repeating section of the polypeptide is known as the backbone."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have NCC, NCC, NCC, NCC, and so forth."}, {"title": "Primary Structure of Proteins .txt", "text": "That is the backbone."}, {"title": "Primary Structure of Proteins .txt", "text": "It continues to repeat over and over."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, the variable section of our polypeptide are these groups, the side chain groups of our amino acid."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have sidechain R one, side chain R two, side chain R three, and so forth."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, if we study every single amino acid in our polypeptide."}, {"title": "Primary Structure of Proteins .txt", "text": "We'll see that the polypeptide as a whole has a great potential to form H bonds with other molecules as we'll see in the next lecture."}, {"title": "Primary Structure of Proteins .txt", "text": "Because these hydrogen bonds that are formed as a result of these atoms in the polypeptide basically creates the secondary structure of proteins as we'll see in the next lecture."}, {"title": "Primary Structure of Proteins .txt", "text": "So the polypeptide chain has the ability to form many hydrogen bonds and that's because each one of these amino acids basically contains two types of groups."}, {"title": "Primary Structure of Proteins .txt", "text": "It contains the NH group which acts as a hydrogen bond owner."}, {"title": "Primary Structure of Proteins .txt", "text": "And we have the Carbonal group Co that acts as the hydrogen bond acceptor."}, {"title": "Primary Structure of Proteins .txt", "text": "So what do we mean by that and why is that the case?"}, {"title": "Primary Structure of Proteins .txt", "text": "So let's take a look at one of these amino acids."}, {"title": "Primary Structure of Proteins .txt", "text": "Let's suppose this amino acid here, the fourth amino acid in our polypeptide chain."}, {"title": "Primary Structure of Proteins .txt", "text": "So the nitrogen is more electronegative than the H. And what that means is this H will have a partial positive charge, and this partially positive charge on the H will basically ensure that if we have some other atom that is electronegative in close proximity, then in that case, this will be donated to that electronegative atom."}, {"title": "Primary Structure of Proteins .txt", "text": "And we're going to form an H bond."}, {"title": "Primary Structure of Proteins .txt", "text": "So that is a hydrogen bond donor."}, {"title": "Primary Structure of Proteins .txt", "text": "Now let's take a look at this Carbonal group of this same amino acid."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have the oxygen that is more electronegative than the carbon and it develops a partial negative charge."}, {"title": "Primary Structure of Proteins .txt", "text": "And so if an H atom that has a partially positive charge is found in close proximity on the other side of this partially negative oxygen, then we have a bond that is formed and that bond is a hydrogen bond."}, {"title": "Primary Structure of Proteins .txt", "text": "And so this oxygen is said to be an acceptor of that partially positive H atom."}, {"title": "Primary Structure of Proteins .txt", "text": "So every single Carbonal group in our amino acid is a hydrogen bond acceptor."}, {"title": "Primary Structure of Proteins .txt", "text": "And every one of these and age groups is basically our hydrogen bond donor."}, {"title": "Primary Structure of Proteins .txt", "text": "And that will become important in our discussion of the secondary structure of proteins."}, {"title": "Primary Structure of Proteins .txt", "text": "Now previously we discussed how these peptide bonds, these green bonds are actually formed."}, {"title": "Primary Structure of Proteins .txt", "text": "Now let's discuss what the nature of these peptide bonds is."}, {"title": "Primary Structure of Proteins .txt", "text": "So in other words, are these peptide bonds single bonds as shown in the following diagram or are they something else?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well actually one thing that is not shown in a diagram is the fact that these peptide bonds actually are resonance stabilized."}, {"title": "Primary Structure of Proteins .txt", "text": "So what exactly do we mean by that?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, let's suppose we look at the following diagram and what this diagram basically describes is, well let's suppose that we take the following polypeptide."}, {"title": "Primary Structure of Proteins .txt", "text": "And let's suppose we cut the polypeptide right here."}, {"title": "Primary Structure of Proteins .txt", "text": "So we essentially cut it here."}, {"title": "Primary Structure of Proteins .txt", "text": "And then so this carbon is this carbon here."}, {"title": "Primary Structure of Proteins .txt", "text": "So let's say that this is our three, then this carbon."}, {"title": "Primary Structure of Proteins .txt", "text": "So this carbon is this carbon here, this nitrogen is this nitrogen here."}, {"title": "Primary Structure of Proteins .txt", "text": "This carbon is this carbon here."}, {"title": "Primary Structure of Proteins .txt", "text": "So let's change this to r four."}, {"title": "Primary Structure of Proteins .txt", "text": "And likewise this is r three and this is r four."}, {"title": "Primary Structure of Proteins .txt", "text": "So we essentially take a small section of the polypeptide and we redraw it in the following way."}, {"title": "Primary Structure of Proteins .txt", "text": "And what we want to show in this diagram is the fact that we have resonance stabilization in the following region."}, {"title": "Primary Structure of Proteins .txt", "text": "So this is not the only lewis dot structure that we can draw."}, {"title": "Primary Structure of Proteins .txt", "text": "We can also draw another lewis dot structure for this same structure."}, {"title": "Primary Structure of Proteins .txt", "text": "In particular, the following structure."}, {"title": "Primary Structure of Proteins .txt", "text": "And the way that we go from this truck to this structure is by moving these two electrons into the following pi bond."}, {"title": "Primary Structure of Proteins .txt", "text": "So these two lone pair of electrons can form a pi bond between the carbon and the nitrogen."}, {"title": "Primary Structure of Proteins .txt", "text": "And that kicks off this pi bond, these two electrons and places them onto that oxygen."}, {"title": "Primary Structure of Proteins .txt", "text": "And so we have a negative charge on the oxygen and a positive charge on this nitrogen."}, {"title": "Primary Structure of Proteins .txt", "text": "And the difference between this and this bond is in this case it's a single bond."}, {"title": "Primary Structure of Proteins .txt", "text": "And in this case it's a double bond."}, {"title": "Primary Structure of Proteins .txt", "text": "Now what do we know about resonance stabilized forms?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, the actual structure of this molecule is neither this nor this."}, {"title": "Primary Structure of Proteins .txt", "text": "It's somewhere in between."}, {"title": "Primary Structure of Proteins .txt", "text": "And what that means is this peptide bond will not be a single bond."}, {"title": "Primary Structure of Proteins .txt", "text": "It will have a double bond character."}, {"title": "Primary Structure of Proteins .txt", "text": "So peptide bonds are resonance stabilized, which means they have a double bond character."}, {"title": "Primary Structure of Proteins .txt", "text": "Now what do we mean by double bond character?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, basically the length between this carbon and this nitrogen will be somewhere in between a single bond and a double bond."}, {"title": "Primary Structure of Proteins .txt", "text": "Now remember from organic chemistry that single bonds can actually rotate, but double bonds cannot rotate."}, {"title": "Primary Structure of Proteins .txt", "text": "And because we have a double bond character between the carbon and the nitrogen, this peptide bond also will not be able to rotate in space."}, {"title": "Primary Structure of Proteins .txt", "text": "So this bond, this bond, this bond and this bond, the atoms that are connected by these bonds will not be able to rotate in space."}, {"title": "Primary Structure of Proteins .txt", "text": "And not only that, but because we have the double bond character, there will be six atoms arranged along the following diagram as we'll see in just a moment that will lie along the same plane."}, {"title": "Primary Structure of Proteins .txt", "text": "So the double bond nature of the peptide bond makes the peptide bond planar and prevents any rotation about the peptide bond."}, {"title": "Primary Structure of Proteins .txt", "text": "So basically this atom number one, this atom number two, this atom number three, this atom number four, this atom number five and this atom number six will all lie along the same plane."}, {"title": "Primary Structure of Proteins .txt", "text": "So if we place this molecule, let's say on the board and the board is our plane, then all these molecules will lie along the plane of that board."}, {"title": "Primary Structure of Proteins .txt", "text": "Now let's take a look at the following diagram."}, {"title": "Primary Structure of Proteins .txt", "text": "Something that we really haven't explained yet is the fact that we see predominantly the trans isomer configuration and not the CIS configuration."}, {"title": "Primary Structure of Proteins .txt", "text": "So in each one of these cases, the two alpha carbon groups pointed in opposite directions."}, {"title": "Primary Structure of Proteins .txt", "text": "They never pointed in the same directions."}, {"title": "Primary Structure of Proteins .txt", "text": "The question is why?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, to see what we mean by that, let's compare the following two diagrams."}, {"title": "Primary Structure of Proteins .txt", "text": "So, once again, we're basically taking the following diagrams."}, {"title": "Primary Structure of Proteins .txt", "text": "So we're only considering two amino acids."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have amino acid number one, amino acid number two that are connected by this peptide bond, which we're going to draw in the following manner to basically designate the fact that this is more of a double bond than it is a single bond."}, {"title": "Primary Structure of Proteins .txt", "text": "And what that means is now we have cyst, trans isomerism."}, {"title": "Primary Structure of Proteins .txt", "text": "So in this particular case, as the case is in all of these peptide bonds, we have a transconfiguration."}, {"title": "Primary Structure of Proteins .txt", "text": "And what that means is this alpha carbon points in the opposite direction with respect to this alpha carbon."}, {"title": "Primary Structure of Proteins .txt", "text": "So they point away."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, what this diagram tells us is if this is the Y axis, it describes the energy."}, {"title": "Primary Structure of Proteins .txt", "text": "What this tells us is this is thermodynamically more stable and lower in energy than the CIS configuration."}, {"title": "Primary Structure of Proteins .txt", "text": "The question is why?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, it's because in this case, all these atoms and this entire group, they point away."}, {"title": "Primary Structure of Proteins .txt", "text": "And so if they point away, there will be no steric hindrance, there will be no bumping of electrons or bumping of atoms, and there will be no electrostatic repulsion as a result of the bumping of atoms in this particular case."}, {"title": "Primary Structure of Proteins .txt", "text": "But if we flip it to basically form the CIS isomer, the CIS configuration, notice that now this alpha carbon and this alpha carbon, they point along the same direction."}, {"title": "Primary Structure of Proteins .txt", "text": "And now there will be stair kindle, there will be the bumping of electrons and atoms and that will increase the electrostatic repulsion due to the charges of these atoms."}, {"title": "Primary Structure of Proteins .txt", "text": "And that will drive the energy of the CIS configuration to be higher than that of the trans configuration."}, {"title": "Primary Structure of Proteins .txt", "text": "And so in the majority of cases, we only really see the trans peptide bonds and never the cyst configuration bonds because of this idea that this creates a more stable system that is lower in energy."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, I say in the majority of cases because actually in some cases we do see the CIS configuration, but we'll discuss that in much more detail in future electros."}, {"title": "Primary Structure of Proteins .txt", "text": "So from this discussion we saw that because we have these peptide bonds that have double bond character, there is no rotation about the atoms between our peptide bonds."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, the question is the following."}, {"title": "Primary Structure of Proteins .txt", "text": "Notice we have a linear polymer of amino acids, but the final three dimensional structure proteins is not a linear structure, it's a convoluted structure."}, {"title": "Primary Structure of Proteins .txt", "text": "So eventually, to go from our primary linear structure to the three dimensional convoluted structure of our protein, we have to actually rotate our bonds."}, {"title": "Primary Structure of Proteins .txt", "text": "But if these green bonds cannot rotate, which bonds could rotate?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, it turns out that in any one of these amino acids, these bonds cannot rotate, but these bonds can."}, {"title": "Primary Structure of Proteins .txt", "text": "So if we take a look at that diagram."}, {"title": "Primary Structure of Proteins .txt", "text": "This is what we get."}, {"title": "Primary Structure of Proteins .txt", "text": "So let's suppose that this nitrogen atom is this atom right over here."}, {"title": "Primary Structure of Proteins .txt", "text": "And this carbon atom is this carbon atom right here."}, {"title": "Primary Structure of Proteins .txt", "text": "So even though these cannot actually rotate, this carbon between the nitrogen and our alpha carbon and this bond between the alpha carbon and this carbon of the carbonyl, they can actually rotate."}, {"title": "Primary Structure of Proteins .txt", "text": "And these are known as torsion angles."}, {"title": "Primary Structure of Proteins .txt", "text": "So we have torsion angle Phi and torsion angle, Phi."}, {"title": "Primary Structure of Proteins .txt", "text": "The Phi angle is the angle of rotation about the single bond between the nitrogen and the alpha carbon, while the PSI angle is the angle of rotation about the single bond between the alpha carbon and the carbon of the carbon dill."}, {"title": "Primary Structure of Proteins .txt", "text": "Now, why is it that these can rotate and the peptide bond can?"}, {"title": "Primary Structure of Proteins .txt", "text": "Well, the peptide bond is rather than stabilized."}, {"title": "Primary Structure of Proteins .txt", "text": "It is not a single bond."}, {"title": "Primary Structure of Proteins .txt", "text": "It is more of a double bond."}, {"title": "Primary Structure of Proteins .txt", "text": "But these bonds are purely single bonds and signal bonds can actually rotate as opposed to double bonds, which cannot."}, {"title": "Primary Structure of Proteins .txt", "text": "And these bonds, once again, are known as torsion angle."}, {"title": "Primary Structure of Proteins .txt", "text": "These angles that can rotate are known as torsion angles."}, {"title": "Primary Structure of Proteins .txt", "text": "So it's actually the Phi and the PSI rotations that ultimately allows this linear sequence of amino acids to actually create that convoluted three dimensional structure of the protein, as we'll see in the next several electrodes."}, {"title": "Primary Structure of Proteins .txt", "text": "By the way, for the same exact reasoning that we discussed earlier, because of stereo hindrance, because of the collisions and the bumping of nearby atoms, not all of the PSI and Phi rotations are possible, once again, because some of."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "The most common bleeding disorder in humans is hemophilia A, also known as classic hemophilia."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, before we discuss this medical condition and before we actually discuss what causes it, let's remember the blood clot in cascade and what it actually is."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Well, whenever there is some type of trauma inside our blood vessel, so, for example, we have a cut or we have some type of rupture in the endothelium of a blood vessel in our cardiovascular system that basically initiates the blood clot and cascade."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And what the blood clot cascade is and what it does is so it basically consists of these many proteins and enzymes that work together to coordinate the formation of blood clots."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And these blood clots are basically mesh like networks of these individual fiber molecules that basically create the mesh like structure that ultimately forms the blood clots."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And these blood clots can basically coagulate and they can seal off that rupture, that cut, and that prevents the leakage of blood out of that blood vessel and into that surrounding tissue."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, if we actually examine the blood clot in cascade, we'll see that there are two important pathways."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "We have the extrinsic pathway and we have the intrinsic pathway."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So let's begin by focusing briefly on the extrinsic pathway."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So in the extrinsic pathway, what happens is, once we have the cut in the endothelium of the blood vessel, that exposes an important interior glycoprotein that wasn't there before."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And this is known as TF, which stands for tissue factor."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, everything shown in this diagram that is purple, that basically describes a protein that is not an enzyme."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so the tissue factor is not an actual enzyme."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "It's simply a glycoprotein that exists on the membrane of the of the endothelium."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, once this is exposed inside the blood plasma, we have this Zionogen we call factor seven."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And once this is exposed, factor seven is basically activated via proteolytic cleavage."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And once we activate factor seven, it goes on."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "It interacts and binds to the tissue factor to form a dimer complex."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And then the dimer complex, it interacts with a very important factor, factor X, factor X, to basically proteolytically cleave it and activate it into its active form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So the red one is the active form of factor ten."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So everything shown in blue is an enzyme, but it exists in a zymogen, inactive form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "The red molecules are those enzymes in their fully active form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So blue means inactive zymogen and red means fully active."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so once these two interact, they go on to activate this one into its fully functional and active factor ten."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, once we form factor X, factor ten basically combines and interacts with another protein called factor five."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And once they form that complex, that basically goes on and activates another important molecule we call prothrombin."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And this is what we spoke of earlier."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So basically, prothrombin is activated."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So thrombin."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And then it's this thrombin that basically goes on via the common pathway or the final common pathway to ultimately form this meshlike network of fibrin we call blood clots because thrombin activates fibrinogen into fibrin monomers and then these fibrin monomers basically aggregate."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "They form these clusters that form our blood clots."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now thrombin is also important because it actually goes back and creates many different positive feedback loops as we'll see in just a moment and that amplifies the effect."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now let's look at the intrinsic pathway because ultimately it's the intrinsic pathway that is affected by this medical condition we call Hemophilia A."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So in the intrinsic pathway following the exposure of the surrounding tissue, following that cut in the blood vessel that basically stimulates the proteolytic activation of factor twelve."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And then once factor twelve is activated it goes on to proteolytically activate factor eleven and that goes on to proteolytically activate factor nine."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now factor nine cannot by itself activate factor ten."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "What must happen is this protein that is not an enzyme."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So factor eight basically interacts and stimulates this factor nine to go on and activate factor ten."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so ultimately what we see is this is the converging point of these two pathways."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And these two pathways basically ultimately do the same exact thing."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "They basically activate factor ten which is needed to basically initiate the final common pathway that is needed to actually stimulate the activation of throbin which is then used to stimulate the activation of fibrin."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And these fibin molecules basically form this meshlike aggregate."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So these are the individual Fibon monomers and they basically aggregate spontaneously following activation to form our blood clot."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And the blood clot is used to basically coagulate the blood to form those clots on those cuts to basically prevent the leakage of blood out of that blood vessel."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now as I mentioned earlier, thrombin basically creates various different types of feedback loops and one of these positive feedback loops is shown on the board with the green arrow."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So what happens is once throbin is activated it not only activates fibrinogen to form fibrin, it also goes back and stimulates factor A to basically continue to interact with factor nine to basically stimulate or to basically convert even more of these factor x inactive zymogen, factor ten into the active form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so these two pathways along with all these different types of positive feedback loops basically greatly amplify the number of blood clots that we form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so what happens is because of the quickness and the efficiency of this blood clot and cascade as a result of the correct functioning of all these different proteins and enzymes and pathways we're actually able to actually quickly seal off that cut, that rupture in the blood vessel."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now what happens in hemophilia is as I mentioned earlier, it's the intrinsic pathway that is actually impeded, that is actually affected."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And to be more specific, it's factor eight that is affected as a result of hemophilia."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And that's exactly why factor eight is also commonly known as the antihmophilic factor."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And that's because if this antihemophilic factor is actually present and functions correctly inside our body, then that will prevent hemophilia A, also known as classic hemophilia."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So factor eight is a protein that plays a crucial role in the intrinsic pathway of the blood clot and cascade."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And there are two important roles, as we discussed just a moment ago."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So rule number one is it actually plays an important role in actually completing the intrinsic pathway."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So we see that at the final step of the intrinsic pathway, it's this antihmophilic factor, factor eight, that must stimulate, interact with this factor nine to basically go on and convert the Xymogen factor ten form into its active form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, if this molecule is destroyed, if there is some type of mutation or if it's missing altogether, then this will not be stimulated and will not be able to actually activate this factor ten."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so if that doesn't take place, then the entire intrinsic pathway basically slows down its impairment."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And what that means is we will not amplify the effects, the formation of the blood clots."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "We're not going to be able to form as many blood clots as we want."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "We're not going to be able to form them quickly enough."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so that will result in excessive bleeding."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Now, the other reason why the impairment of this factor aid is so negative is because thrombin actually uses this to create a very important positive feedback loop, as we discussed just a moment ago."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So thrombin essentially depends on factor eight, on the presence of factor eight to create the positive feedback loop that greatly amplifies the number of factor ten that we actually activate."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And that in turn amplifies how much of the blood clots we actually can form, how many of the blood clots we can form."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So two important functions of factba eight."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "Factba eight interacts with proteolytic enzyme factor nine and stimulates it to basically go on and activate factor X, which is needed to ultimately coagulate the blood and form the blood clots because it's this molecule, factor X, that initiates the final common pathway that is used to form those blood clots."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And the second important function of factor eight is thrombin creates a positive feedback loop, stimulating factor eight, swimming around in the blood to interact with factor nine, which causes an amplification effect."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And this is basically this positive feedback loop that I just discussed just a moment ago."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So we basically see that in individuals with classic hemophilia, there is some type of mutation."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "In fact, the eight, or in some cases, factor eight is missing entirely."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so what that means is the impairment of factor eight greatly impedes this process, the intrinsic pathway."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And if the intrinsic pathway does not function properly, we cannot amplify, we cannot create these blood clots quickly enough."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so what that means is once the blood vessel actually is cut, once the endothelium ruptures, the blood clots do not form at a high enough rate, and so excessive bleeding may occur."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And this is exactly why hemophilia A is a bleeding disorder."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "So in individuals with hemophilia A, when they essentially cut a blood vessel, this is basically what takes place."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And this is why it actually takes place."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And the final thing I'd like to mention is, as you might know from basic biology, hemophilia A is actually a sex linked recessive trait."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And that's exactly why male individuals basically are those that have an express the hemophilia a because it's a sex link recessive trait."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "If an individual that is a female contains one dominant trait and one recessive trait, that dominant trait will basically overpower that recessive trait."}, {"title": "Factor VIII and Hemophilia A .txt", "text": "And so a heterozygous female individual, even though she will be a carrier, she will not actually express this medical condition because she will have the gene to actually produce that fully functional ah, factor eight antihemophilic factor protein that is actually responsible for finishing off that intrinsic pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So along the electron transport chain, we have many complexes."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So as we discussed previously, in complex one of the electron transport chain, complex one essentially picks up the high energy electrons from NADH molecules and trams those electrons onto a special carrier molecule known as Ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And when Ubiquinone grabs those electrons, it is reduced into Ubiquinol form that is given by QH two."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this molecule is known as Ubiquinol."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Likewise, on complex two, the high energy electrons from Fadh two molecules are also transferred onto Ubiquinone to reduce Ubiquinone into Ubiquinol and the QH two, the Ubiquinone then travels onto complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And so in this lecture, I'd like to discuss the details of what happens when Ubiquinol, the reduced form of Ubiquinone, actually attaches onto complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, complex three goes by many names."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So complex three is also known as Q, cytochrome C, oxy reductase, where the Q stands for Ubiquinol."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Or we also have cytochrome reductase."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Both of these names refer to complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And complex three actually consists of many polypeptide chains."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "In fact, we have eleven polypeptide chains that make up complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, the entire function, the entire purpose of complex three is to actually transfer those high energy electrons from QH two from Ubiquinol onto another carrier molecule, another electron carrier used by the electron transport chain known as cytochrome C. And so in this lecture, we're going to discuss the details of how this transfer actually takes place."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So let's begin by focusing on the three major components that you should be familiar with that define on complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "The first one that you should know is cytochrome C one."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this is not the same thing as cytochrome C, even though they're both cytochrome molecules."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And cytochrome molecules are proteins that contain heme groups that combine and transfer electrons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Cytochrome C and cytochrome C one are not the same types of molecules."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, cytochrome C one actually contains a single hein group."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "But in the structure and complex three, we also have another cytochrome molecule known as cytochrome B."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this molecule actually contains two different heme groups that are capable of actually attaching electrons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And finally, we also have a structure known as the risky group."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this contains the two fe two sulfur group that can also bind electrons and transfer electrons onto different groups."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So the entire process by which electrons are transferred from the Ubiquinol onto the cytochrome C molecule is known as the Q cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And the Q cycle is actually composed of two major mini cycles."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So we have the first mini cycle shown here."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "We also call the half cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And the second half cycle, the second mini cycle is known as shown here."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And together these two half cycles, these two mini cycles make up a single Q cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So the process by which electrons travel from the QH to the Ubiquinol that is produced on either complex one or complex two of the electron transport chain onto another carrier molecule known as Cytochrome C is known as the Q cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And by the way, Cytochrome C is actually a water soluble protein, and it is attached onto the intermembrane space side of this complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this is the matrix side."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "This is the intermembrane of the mitochondria."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "We have complex three, and this is the intermembrane space."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this protein carrier molecule, Cytochrome C, when it actually attaches a single electron, when the oxidized version is reduced, the Cytochrome C will actually detach itself."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And because it's diffusible in water, it basically travels through the fluid and eventually attaches onto complex four found on the intramembrane side of complex four, as we'll see in the next lecture."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So let's begin by summarizing what takes place in the first mini cycle, the first half cycle of the Q cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So we have Ubiquinol attaches onto complex three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And when it attaches, the two protons, two H plus ions are basically pumped."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "They're transported to the intermembrane space of the mitochondria, and those two electrons follow two different pathways."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Remember, we not only have two H plus ions attached to our Ubiquinol, we also have two electrons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "These two H plus ions are pumped to this side, but the two electrons follow two different pathways."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "One of those electrons follows this pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "The other electron follows this pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So we have one electron being transferred onto the two Fe to sulfur group found on the risky center."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And then that same electron moves onto the Heme group of Cytochrome C one."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, by the way, inside the Heme group."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So in the oxidized version of Cytochrome C one, that Fe atom basically exists in this form."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "But when it gains a single electron, so we have an electron coming in."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "When it gains a single electron, it is reduced into the Fe two plus form."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So remember, in the Hen group, we have the iron atom that can actually gain that electron."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And when gains that electron, it is reduced."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And so as the electron travels from the risky sensor to the Cytochrome C one, it actually attaches onto the iron atom of the Heme group, and so it is reduced."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, the electron travels from the Hen group and ultimately ends up on the Heme group of Cytochrome C. And notice, only a single electron can actually bind onto Cytochrome C. So this is the major difference between Cytochrome C electron carrier and the Ubiquinone electron carrier."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Ubiquinone is able to actually bind two electrons, but Cytochrome C can only bind a single electron."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that's exactly why the second electron cannot follow this same pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "It has to follow a different pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And by following this different pathway, what we ultimately accomplish by the second electron pathway is we're able to actually recycle that electron and use that electron in a future process, as we'll see in more detail in just a moment."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So once this electron binds onto the oxidized Cytochrome C, it reduces that Cytochrome C the cytochrome C then detaches and diffuses within the fluid of the intermembrane space and travels and binds onto complex four."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "While the other electron, because it cannot go via this same pathway, it follows a different pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that's where Cytochrome B comes into play."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Cytochrome B actually contains two different heme groups."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And the electron first moves on to one heme group, then a second Hen group, and then it ultimately ends up on Ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this is basically the fully oxidized version of coal enzyme Q, also known as Ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And when it gains that electron, it is basically partially reduced into a molecule we call the semiquinone radical ion, which contains a negative charge."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And we'll see why we formed that in just a moment."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So let's summarize the first half cycle of the Q cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this Q cycle begins when the Ubiquinol QH two attaches onto complex three, as shown here."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And upon binding, the two electrons follow two different pathways, and the two protons are pumped into the intermembrane space of the mitochondria."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, one of these electrons moves onto the risky center, the two fe two sulfur group of the risky center, and then it is transferred onto the heme group of Cytochrome C one, reducing the three plus form into the two plus form."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "From there, it is then picked up by the final, except the Cytochrome C. And when Cytochrome C accents that electron, it itself is reduced."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that stimulates the detachment of the Cytochrome C is then is able to move along the fluid of the intermembrane space and attach onto complex four, as we'll see in the next lecture."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, what about that other electron?"}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Well, the second electron moves onto the heme groups of Cytochrome B before actually being picked up by Ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, this Ubiquinone is not the same one as this Ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So complex four, complex three actually contains an additional Ubiquinone that is attached onto a different site."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this Ubiquinone is actually used to recycle this electron so that once the Ubiquinone picks up that electron, it is partially reduced into semiquinone radical ion, which is given by this designation."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So Q a single electron and that negative sign."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, this is the first half cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Let's move on to the second half cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So next, this structure basically detaches and a second consecutive Ubiquinol actually binds onto this location."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And once this Ubiquinol, a second different Ubiquinol, binds onto this complex three, the same type of pathway is basically followed by those two electrons and by the protons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So once the binding takes place in the second half cycle, the two protons are essentially transported into the intermembrane fluid of the mitochondria and the two electrons follow this same pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this electron follows this pathway, binds into the Hein group, not the heme group, the two fe two sulfur group."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And then the electron moves on and binds until the heme group of Cytochrome C before actually being picked up by a second different cytochrome C molecule."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this cytochrome C molecule is different than this cytochrome C molecule."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this one basically detaches and an oxidized version."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Another one basically reattaches."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And so we see that in a single queue cycle, we actually generate two reduced cytochrome C molecules because of the fact that a single Ubiquinol can carry two electrons, but a single cytochrome C can only bind and carry a single electron."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now the other electron basically moves, attaches onto the heme groups of cytochrome B, and then that electron is picked up by the semiquinone radical ion and now gains two electrons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And then it takes two protons from the matrix of the mitochondria."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "It picks up those two protons to form Ubiquinol."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And the Ubiquinol detaches from complex three and enters the inner membrane of the mitochondria, where now we can use this Ubiquinol that is formed to attach it onto this complex and use that Ubiquinol to basically generate those reduced cytochrome scene molecules."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So the entire point of the second pathway here is to basically use or recycle those electrons so that we can actually use those electrons in a useful way so that we don't lose the electrons and we can recycle and reuse them in this pathway to actually generate that reduced cytochrome C. So in the second half cycle of the Q cycle, the second QH transfers a second pair of electrons through the same pathways as before, except now."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "At the end, we form a Ubiquinol because that semiquinol radical ion that is formed in the first half cycle picks up a second electron, is able to abstract two protons from the matrix of the mitochondria and form regenerate that Ubiquinol molecule."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that ubiquinol can then be used by this pathway here to basically generate the reduced cytochrome C. So we conclude the following four important points, and I've only listed three."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So the first important point is the following."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "The ubiquinone can actually carry two electrons, while the cytochromac can only carry a single electron."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that's exactly why we need this second pathway here to basically recycle the electron so that we can regenerate those Ubiquinol molecules and reuse the ubiquinol molecules in this above pathway."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So we need this bottom step."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So we see that in a single Q cycle, two Ubiquinol molecules are oxidized into ubiquinole, releasing four H plus ions to the inter membrane space."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Two are released in this first process, and two are released in the second process."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "At the same exact time, a single quinone, or ubiquinone, is reduced into ubiquinone."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And that allows us to recycle these electrons."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "So this is the recycling step of this process."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And we can imagine that this cytochrome B structure is actually a device that the complex uses to recycle those electrons so that we don't lose those electrons and we can reuse electrons to produce even more reduced cytochrome C molecules."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "Now, the two cytochrome C molecule or two cytochrome C molecules are actually reduced in a single queue cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "The first one is reduced as a result of the first half cycle and the second one is produced reduced as a result of that second half cycle."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And one thing I didn't mention here is the fact that in the second half cycle, because we want to produce that ubiquinol, two protons are actually uptaken from the matrix of the mitochondria area."}, {"title": "Q-Cycle and Complex III of Electron Transport Chain .txt", "text": "And this additional uptake of protons helps us generate that gradient, the proton electrochemical gradient that will be used by ATP synthase to generate those ATP molecules."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So far, in our study of biochemistry we focus primarily on proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "We focus on the structure of proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "We discussed how to purify proteins and also how to sequence proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "But where do proteins actually come from?"}, {"title": "Introduction to Nucleic Acids .txt", "text": "In the next 20 or so lectures, we're going to focus on nucleic acids because it's the nucleic acids that essentially are used to build these proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So what types of nucleic acids do we have inside our body?"}, {"title": "Introduction to Nucleic Acids .txt", "text": "So we have two types."}, {"title": "Introduction to Nucleic Acids .txt", "text": "We have deoxyribonucleic acids or DNA molecules and we have ribonucleic acids or RNA molecules."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And these two molecules essentially are linear polymers of these subunits we call nucleotides."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And a nucleotide consists of three components."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So we have a nitrogenous base, we have a sugar molecule and we have a phosphate group."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And just like in a protein, we have the linear polymer of amino acids."}, {"title": "Introduction to Nucleic Acids .txt", "text": "In nucleic acids, we have a linear polymer of nucleotides."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Now, in proteins, the bonds connecting the amino acids are peptide bonds."}, {"title": "Introduction to Nucleic Acids .txt", "text": "But in eucalyak acid, these bonds are phosphodia estate bonds and we'll see exactly what these bonds look like in a future lecture."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So if we examine, for example, a DNA molecule this is what the DNA molecule actually looks like for DNA."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Because of the structure of the sugar and DNA the DNA molecule is able to form a double helix formation."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And what the double helix means is we have two individual strands of DNA that run antiparallel with respect to one another."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Now, what allows them to actually form this antiparall arrangement is the fact that the bases are complementary with respect to one another."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So this here is our sugar."}, {"title": "Introduction to Nucleic Acids .txt", "text": "The blue section is the phosphate group and the green section is our nitrogenous base."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And this three molecule component is known as a monomer, a nucleotide."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And so on this strand, we have one nucleotide a second nucleotide, a third nucleotide."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And on the other strand, we also have this one nucleotide, second nucleotide, a third nucleotide."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And what it means for these to be complementary is that these bases here are complementary meaning that they can form an optimal arrangement of bonds."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So these bonds here are basically the hydrogen bonds that hold our bases together."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So what holds this entire double helix in DNA are the hydrogen bonds as well as Van der Vall forces and the hydrophobic effect."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So in the inside portion of our DNA we have these hydrophobic regions."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And on the outside portion, because these phosphate groups essentially point on the outside and they contain charge the exterior of the DNA of the double helix is negatively charged and it is hydrophilic while the interior is hydrophobic because it consists of these nonpolar nitrogenous bases."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So DNA exists predominantly as a double helix."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And what that means is we have these two strands of DNA that essentially run an antiparallel direction and they interact via different types of non covalent interactions."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So hydrogen bonds, London dispersion forces and so forth."}, {"title": "Introduction to Nucleic Acids .txt", "text": "The interior is hydrophobic, just like in proteins and the exterior is hydrophilic once again just like in proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And these two strands are complementary with respect to one another."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Now, what about RNA molecules?"}, {"title": "Introduction to Nucleic Acids .txt", "text": "Well, RNA molecules because they contain a slightly different sugar molecule they don't form the double helix."}, {"title": "Introduction to Nucleic Acids .txt", "text": "They exist predominantly as a single strand but they can also intertwine fold to form different types of tertiary and secondary structures."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So what about the function of DNA and RNA?"}, {"title": "Introduction to Nucleic Acids .txt", "text": "So the entire purpose of these nucleic acids is to basically store the genetic code, the genetic information in the cell and use it to build different types of proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And when the time comes when we reproduce to pass that genetic information down to the offspring."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So let's begin with the function of DNA."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So DNA molecules are these biological molecules that store that genetic information and the genetic information is stored in the sequence of these nitrogenous bases because the backbone of the DNA molecule that consists of the sugar molecule and the phosphate essentially repeats as we go from one nucleotide to another."}, {"title": "Introduction to Nucleic Acids .txt", "text": "That does not change."}, {"title": "Introduction to Nucleic Acids .txt", "text": "What does change is the sequence of nitrogenous bases and it's within the sequence of bases where the genetic information is actually stored as we'll see in much more detail in a future lecture."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So the first function of DNA molecule is to store that genetic information and keep it readily accessible to the cell."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And what that means is if the cell wants to synthesize some type of protein for example hemoglobin or my globin it has to go down to the DNA in the nucleus and get that genetic code that must be used to then create that protein."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Now the problem is ourselves don't actually use that code directly to form the protein."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So we don't simply form proteins from DNA."}, {"title": "Introduction to Nucleic Acids .txt", "text": "What must happen is we have to first translate or transcribe that genetic code into a code that is readable and can be understood by that cell and that is where RNA comes into play."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So RNA molecules are used to basically transcribe the information stored in DNA into a form that can be understood and read by that cell."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So to build the protein we take the DNA, we essentially transcribe that information from the DNA into the RNA and now the RNA is used directly to form the proteins in the ribosomes."}, {"title": "Introduction to Nucleic Acids .txt", "text": "Now the other function of DNA is to actually pass down the genetic information from one individual to the offspring."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So when we reproduce we replicate DNA molecules and pass those replicated identical DNA molecules or actually not identical, they are slightly different because of different types of variations but we pass them down into the offspring."}, {"title": "Introduction to Nucleic Acids .txt", "text": "And the second function of RNA is to actually assist in protein synthesis."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So we have different types of RNA molecules."}, {"title": "Introduction to Nucleic Acids .txt", "text": "For example, we have messenger RNA mRNA and that's the molecule that is actually used directly to build proteins."}, {"title": "Introduction to Nucleic Acids .txt", "text": "But we also have other RNA molecules that assist in the process."}, {"title": "Introduction to Nucleic Acids .txt", "text": "For example, we have tRNA and RNA molecules that essentially assist the ribosome in forming that protein."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So this is the introduction to Nucleic Acids and in the next several lectures we're going to begin our discussion on the structure."}, {"title": "Introduction to Nucleic Acids .txt", "text": "So we're going to look at a detailed discussion of the structure of DNA as well as RNA nucleic acids."}, {"title": "Melting and Annealing of DNA .txt", "text": "The double helix DNA structure consists of these two individual strands of DNA that run in an antiparallel direction and they are held together by different types of noncovalent bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And one of the more important noncovalent bonds are the hydrogen bonds that exist between those adjacent bases found on the two opposing nucleic acids."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, what happens once we break break those hydrogen bonds?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Well, if we break the hydrogen bonds and these hydrogen bonds hold the two nucleic acids together then that double helix structure will begin to break because as the H bonds break the two strands of DNA will begin to dissociate."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, in a laboratory setting we can cause the dissociation of these two strands by one of two ways."}, {"title": "Melting and Annealing of DNA .txt", "text": "Usually one of two ways."}, {"title": "Melting and Annealing of DNA .txt", "text": "We can either increase or decrease the PH of our solution that contains the DNA molecule."}, {"title": "Melting and Annealing of DNA .txt", "text": "And by changing our PH we essentially ionize the bases."}, {"title": "Melting and Annealing of DNA .txt", "text": "And by ionizing the basis we disrupt we break the hydrogen bonds holding our nucleic acids in that double helix structure."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, we can also heat our solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "So by heating the solution we're essentially bringing energy into the solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "So we're increasing the energy and we're increasing the energy of the bases and that will essentially disrupt the hydrogen bonds breaking and dissociating that double helix structure."}, {"title": "Melting and Annealing of DNA .txt", "text": "So in a lab, we can either heat our solution by increasing in temperature or we can change the PH."}, {"title": "Melting and Annealing of DNA .txt", "text": "And either one of these will basically break all these hydrogen bonds holding our two strands of DNA together."}, {"title": "Melting and Annealing of DNA .txt", "text": "Eventually we dissociate our DNA helix and we form these two individual strands of DNA."}, {"title": "Melting and Annealing of DNA .txt", "text": "So this is basically the backbone that consists of the phosphate and sugar groups and these color structures are our bases."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so in this structure, this is the double helix where these are the H bonds holding our double helix together."}, {"title": "Melting and Annealing of DNA .txt", "text": "And when we either increase the temperature or change the PH we essentially disrupt and break these hydrogen bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so we essentially dissociate our DNA molecule."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, the breaking of the hydrogen bonds and the subsequent dissociation of that DNA molecule is known as melting."}, {"title": "Melting and Annealing of DNA .txt", "text": "So DNA melting essentially refers to breaking these bonds and associating that DNA molecule."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, the process of melting takes place abruptly at a very specific temperature and this temperature is known as the melting temperature of the DNA."}, {"title": "Melting and Annealing of DNA .txt", "text": "In fact, the melting temperature of the DNA molecule is the temperature at which exactly half of that double helix structure has essentially dissociated."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, the next question is if we have a beaker and inside that beaker we have a solution of DNA molecules and we begin to increase the temperature, we begin to heat that solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "How can we measure in a laboratory how much of the DNA has actually dissociated?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Well, one way we can measure the dissociation of our DNA is by measuring how much UV light, how much UV radiation is actually absorbed by the DNA molecule."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, why is that important."}, {"title": "Melting and Annealing of DNA .txt", "text": "Why is UV radiation or absorbents of UV radiation relevant?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Well, because it turns out that if we have that double helix structure, because these bases are too busy forming those hydrogen bonds, they are not able to absorb as much light as the bases in the dissociated form can because these bases here are not forming any bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so they're free to absorb that UV radiation."}, {"title": "Melting and Annealing of DNA .txt", "text": "So if we shine light onto this structure here, these bases will be able to absorb much more UV radiation than in this particular case."}, {"title": "Melting and Annealing of DNA .txt", "text": "Because in this particular case, we have the stacking of these bases and we have vanderbal forces and hydrogen bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And those bonds will essentially decrease the amount of UV radiation that can be absorbed by those bases."}, {"title": "Melting and Annealing of DNA .txt", "text": "So how can we measure the dissociation of DNA molecules in solution?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Well, it turns out that the amount of UV radiation, UV light, where UV stands for ultraviolet absorbed by DNA molecules, increases as the DNA dissociates."}, {"title": "Melting and Annealing of DNA .txt", "text": "So as we shine light onto our solution, as we heat that solution, eventually that solution will begin to absorb more and more UV radiation."}, {"title": "Melting and Annealing of DNA .txt", "text": "And we can plot that on a graph."}, {"title": "Melting and Annealing of DNA .txt", "text": "So if the y axis is the relative absorbance of light, and because we're talking about UV radiation, that means the wavelength is about 260 nm, which falls exactly in the spectrum of UV radiation."}, {"title": "Melting and Annealing of DNA .txt", "text": "So we go from one to about 1.4."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so as we increase along the y axis, more and more light is actually absorbed by the molecules in our solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, the x axis is our temperature given in Celsius."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so as we go from left to right, we essentially heat our solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "We increase our temperature and notice what we get from our experimental data."}, {"title": "Melting and Annealing of DNA .txt", "text": "The experimental data basically gives us the following curve."}, {"title": "Melting and Annealing of DNA .txt", "text": "And what this curve tells us is there is an abrupt change in the relative absorbance at a specific temperature value."}, {"title": "Melting and Annealing of DNA .txt", "text": "And that's exactly why we call this dissociation process melting, because melting describes the process by which we essentially dissociate this DNA molecule very quickly at a specific temperature value."}, {"title": "Melting and Annealing of DNA .txt", "text": "And that temperature value is about 72 degrees Celsius."}, {"title": "Melting and Annealing of DNA .txt", "text": "That's the melting temperature of the DNA molecule, as shown in the following diagram."}, {"title": "Melting and Annealing of DNA .txt", "text": "So this temperature value describes this point on a curve."}, {"title": "Melting and Annealing of DNA .txt", "text": "And that's essentially the point where exactly half of those DNA molecules or exactly half of a DNA molecule, has associated its double helix structure."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, as I mentioned earlier, in the double helix, the bases are interacting via non Covalent bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And this interferes with the ability of those bases to actually absorb the light."}, {"title": "Melting and Annealing of DNA .txt", "text": "And as we increase the temperature, we essentially cause the bases to break those bonds."}, {"title": "Melting and Annealing of DNA .txt", "text": "And so once they're free, they can essentially absorb more light than before."}, {"title": "Melting and Annealing of DNA .txt", "text": "And that's exactly what we see in the following diagram."}, {"title": "Melting and Annealing of DNA .txt", "text": "So this area describes when our DNA molecule is essentially in this structure, in that form."}, {"title": "Melting and Annealing of DNA .txt", "text": "And this area describes where our DNA molecule has melted, has dissociated."}, {"title": "Melting and Annealing of DNA .txt", "text": "So let's suppose we have our solution of DNA."}, {"title": "Melting and Annealing of DNA .txt", "text": "We heat that solution to, let's say, 80 degrees Celsius."}, {"title": "Melting and Annealing of DNA .txt", "text": "And what we know is from this graph, all the DNA molecules in our solution will be dissociated."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, what happens if I bring that temperature back down to, let's say, 60 degrees Celsius?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Well, as I begin to bring the temperature down, those molecules, those individual strands of DNA, will begin to reassociate."}, {"title": "Melting and Annealing of DNA .txt", "text": "So they will begin to form that double helix structure."}, {"title": "Melting and Annealing of DNA .txt", "text": "And this process is known as annealing."}, {"title": "Melting and Annealing of DNA .txt", "text": "And it will become important when we'll discuss the hybridization process of DNA."}, {"title": "Melting and Annealing of DNA .txt", "text": "So in the laboratory setting, if we want to actually break that double helix structure, we can either change the PH of our solution or we can increase the temperature of that solution."}, {"title": "Melting and Annealing of DNA .txt", "text": "Now, we know that inside our body and inside our cells, we have this process of homeostasis that takes place."}, {"title": "Melting and Annealing of DNA .txt", "text": "And what that means is the temperature nor the PH actually changes."}, {"title": "Melting and Annealing of DNA .txt", "text": "So inside our cells, we don't change the temperature and we don't change our PH."}, {"title": "Melting and Annealing of DNA .txt", "text": "So how exactly do we separate the DNA strands inside our cells?"}, {"title": "Melting and Annealing of DNA .txt", "text": "Because, for example, in the process of DNA replication, we must be able to separate those DNA strands to actually replicate DNA molecules."}, {"title": "Melting and Annealing of DNA .txt", "text": "So inside ourselves, instead of changing the PH or the temperature, we use these enzymes, these molecules proteins known as helicases."}, {"title": "Melting and Annealing of DNA .txt", "text": "And what these helicases do is they essentially use energy molecules, ATP molecules, to break the bonds between our bases."}, {"title": "Melting and Annealing of DNA .txt", "text": "And that allows these enzymes to actually dissociate and melt our DNA structure."}, {"title": "Monoclonal Antibodies .txt", "text": "Previously we focused on polychlonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "Now let's discuss monoclonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "So what exactly is a monoclonal antibody?"}, {"title": "Monoclonal Antibodies .txt", "text": "So let's imagine a collection of plasma cells and all these plasma cells are identical."}, {"title": "Monoclonal Antibodies .txt", "text": "Now if we have some type of infectious agent, some type of antigen inside the body, then all these identical integral plasma cells will begin to produce identical antibodies for that specific antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "And all these identical antibodies will bind to a specific region, a specific epitope on that antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "And this collection of identical antibodies that bind to a single epitope on that antigen are known as monoclonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "And this is in contrast to polyclonal antibodies because as we said, polyclonal antibodies are produced by different types of plasma cells."}, {"title": "Monoclonal Antibodies .txt", "text": "So we produce a different collection of these different types of antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "And even though these different antibodies are for a specific antigen, they can bind to different epitopes on that antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "So this is the difference between monoclonal and polyclonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "So let's take a look at the following diagram that describes the binding process between monoclonal antibodies and antigens."}, {"title": "Monoclonal Antibodies .txt", "text": "So we have 123456 of these specific identical antigens and we have one, two, three different epitopes on each one of these antigens."}, {"title": "Monoclonal Antibodies .txt", "text": "We have the orange one, we have the brown one and we have the pink one."}, {"title": "Monoclonal Antibodies .txt", "text": "Now this is our collection of three identical monoclonal antibodies which were built by the same type of plasma cell."}, {"title": "Monoclonal Antibodies .txt", "text": "And so what that means is they will all bind to the same exact epitope on that antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "So let's suppose the orange epitope."}, {"title": "Monoclonal Antibodies .txt", "text": "So that means once they form that antibody antigen complex, all of these antigen binding sites on the three monoclonal antibodies will bind to these orange epitopes as shown in the following diagram."}, {"title": "Monoclonal Antibodies .txt", "text": "Now to summarize the difference between monoclonal and polyclonal antibodies, let's take a look at the following diagram."}, {"title": "Monoclonal Antibodies .txt", "text": "So we have monoclonal antibodies and polyclonal."}, {"title": "Monoclonal Antibodies .txt", "text": "Now mono simply means we have a collection of identical plasma cells, so a single type of plasma cell and they produce identical antibodies which bind to an identical epitope found on that specific antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "But when it comes to Polycal antibodies, polymers, we have a collection of different types of plasma cells and so they produce these different types of antibodies for that specific antigen and they combine to all different types of epitopes found on that specific antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "So this is the main difference between monoclonal and polyphonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "Now the question is how can we mass produce our monoclonal antibody?"}, {"title": "Monoclonal Antibodies .txt", "text": "So suppose we want to study a specific type of antibody that binds to a specific type of antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "To actually study that antibody, the monocle antibody, we have to mass produce that antibody."}, {"title": "Monoclonal Antibodies .txt", "text": "The question is how do we mass produce it to study it?"}, {"title": "Monoclonal Antibodies .txt", "text": "Well, inside our body and inside the bodies of different organisms, we have many different types of plasma cells and each one of the plasma cells produces a specific type of antibody that binds to a specific antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "Now, theoretically, to basically mass produce a specific type of antibody, what we would have to do is take out the different types of plasma cells from our body or from the body of some other organism, and then out."}, {"title": "Monoclonal Antibodies .txt", "text": "Of that collection of plasma cells."}, {"title": "Monoclonal Antibodies .txt", "text": "Isolate those plasma cells that we actually want to study because those plasma cells produce the antibody of interest."}, {"title": "Monoclonal Antibodies .txt", "text": "Now, once we isolate those specific plasma cells, we can then divide those plasma cells many times via mitosis."}, {"title": "Monoclonal Antibodies .txt", "text": "And those plasma cells, as they grow, they produce those antibodies that we want to study."}, {"title": "Monoclonal Antibodies .txt", "text": "So in this way, theoretically, we should be able to actually build as many specific antibodies as we'd like."}, {"title": "Monoclonal Antibodies .txt", "text": "Now, the problem with the method is, as soon as we take out that plasma cell from that organism, that plasma cell essentially dies."}, {"title": "Monoclonal Antibodies .txt", "text": "So the question is, how can we mass produce the monoclonal antibodies specific for some antigen?"}, {"title": "Monoclonal Antibodies .txt", "text": "If the antigen producing cells, our plasma cells quickly die as soon as we take them out of that organism."}, {"title": "Monoclonal Antibodies .txt", "text": "So the trick is to basically somehow take the plasma cell that we isolated for that specific antibody and turn it into a cancer cell."}, {"title": "Monoclonal Antibodies .txt", "text": "Because remember, cancer cells are immortal cells."}, {"title": "Monoclonal Antibodies .txt", "text": "They essentially divide outside that organism."}, {"title": "Monoclonal Antibodies .txt", "text": "They can divide on any medium that contains nutrients, and they divide indefinitely."}, {"title": "Monoclonal Antibodies .txt", "text": "And that can be a very, very useful technique if actually used correctly."}, {"title": "Monoclonal Antibodies .txt", "text": "So the solution lies in using immortal plasma cells derived from a type of cancer known as multiple myeloma."}, {"title": "Monoclonal Antibodies .txt", "text": "So multiple myeloma is a specific type of cancer cell of plasma cells."}, {"title": "Monoclonal Antibodies .txt", "text": "So let's take a look at the following three steps in our procedure to mass produce these specific monoclonal antibodies."}, {"title": "Monoclonal Antibodies .txt", "text": "So, in step one, what we basically want to do is we want to find an organism with a healthy and functional immune system."}, {"title": "Monoclonal Antibodies .txt", "text": "So, for example, let's take a mouse."}, {"title": "Monoclonal Antibodies .txt", "text": "And what we want to do is, since we want to produce a specific type of antibody, what we're going to do is we're going to inject that mouse with an antigen that binds to that antibody that we want to study."}, {"title": "Monoclonal Antibodies .txt", "text": "And so if we inject the antigen into the bloodstream of that mouse, the immune system of that mouse will begin to produce the plasma cells that produce the antibodies that bind to that antigen."}, {"title": "Monoclonal Antibodies .txt", "text": "So after time, when this mouse has those plasma cells, following injection, we can basically draw blood, let's say, from the spleen."}, {"title": "Monoclonal Antibodies .txt", "text": "And if we draw the spleen cells, because in the spleen cells, we have a high concentration of these plasma cells, some of these plasma cells in the spleen will basically contain the ability to produce that specific type of antibody."}, {"title": "Monoclonal Antibodies .txt", "text": "So we inject the antigen into our mouse, and we wait some time until that mouse produced our plasma cells that produce the antibody of choice."}, {"title": "Monoclonal Antibodies .txt", "text": "And so then we essentially draw some blood from our spleen, from the spleen of that mouse and we extract those spleen cells."}, {"title": "Monoclonal Antibodies .txt", "text": "Now, the majority of these spleen cells will not have the ability to actually build that antibody of choice, but some of these will be the plasma cells that produce the antibody of choice."}, {"title": "Monoclonal Antibodies .txt", "text": "And so, as we'll see in step three, we're going to want to screen these different types of plasma cells and we want to find those plasma cells that basically produce that particular antibody of interest."}, {"title": "Monoclonal Antibodies .txt", "text": "Now, in the second step, what we want to do is now we want to transform them into cancer cells."}, {"title": "Monoclonal Antibodies .txt", "text": "And the way that we transform these normal spleen cells, healthy spleen cells, into cancer cells is by mixing them with the multiple myeloma cancer cells."}, {"title": "Monoclonal Antibodies .txt", "text": "So if we mix these orange cancer cells with these normal purple cancer cells, the two types of plasma cells will essentially fuse in a solution of polyethylene glycol."}, {"title": "Monoclonal Antibodies .txt", "text": "And once they fuse, we essentially transform these healthy plasma cells in purple into these cancerous plasma cells known as hybridoma cells."}, {"title": "Monoclonal Antibodies .txt", "text": "So hybridoma cells are hybrid cells between these healthy plasma cells and these cancerous plasma cells."}, {"title": "Monoclonal Antibodies .txt", "text": "So now, in the beaker, some of these cells are basically cancer cells that are plasma cells that produce the antibody that we want to study."}, {"title": "Monoclonal Antibodies .txt", "text": "And so in the next step, in step three, we want to take these hyperdoma cells and we want to screen them many times with different types of essays to basically determine and isolate those plasma cells that produce that particular type of antibody that we want to study."}, {"title": "Monoclonal Antibodies .txt", "text": "So we remove all those cancer plasma cells that we don't want to study, and we only keep the plasma cells that produce that monoclonal antibody that we essentially want to study."}, {"title": "Monoclonal Antibodies .txt", "text": "And so now that we have these cancer cells that are plasma cells that produce the monoclonal antibodies, we can place him on the medium and we can basically grow them indefinitely."}, {"title": "Monoclonal Antibodies .txt", "text": "And as a result, we can mass produce that antibody of choice."}, {"title": "Monoclonal Antibodies .txt", "text": "So that means we can either mass produce and study those antibodies, or we can take them and inject them back into the mouth to basically study how the cancer actually progresses and how we can cure the cancer."}, {"title": "Monoclonal Antibodies .txt", "text": "And we can also actually freeze them, because by freezing the cancer cells, that doesn't actually kill the cancer cells."}, {"title": "Monoclonal Antibodies .txt", "text": "Once we unfreeze them, they will continue to divide indefinitely."}, {"title": "Monoclonal Antibodies .txt", "text": "So we see that these hybridoma cells are very convenient because they give us this procedure to basically create any type of monoclonal antibodies that we actually want."}, {"title": "Monoclonal Antibodies .txt", "text": "And this has many, many applications, especially in medicine."}, {"title": "Monoclonal Antibodies .txt", "text": "And as we study biochemistry, we're going to come back to this type of method because it actually is used in many different areas in biochemistry."}, {"title": "Lactose Intolerance .txt", "text": "Now, I'd like to briefly focus on a topic known as lactose intolerance."}, {"title": "Lactose Intolerance .txt", "text": "Now, lactose is a disaccharide sugar molecule and what that means is it actually consists of two individual monosaccharides."}, {"title": "Lactose Intolerance .txt", "text": "One of them is galactose and the other one is glucose."}, {"title": "Lactose Intolerance .txt", "text": "And these are connected by a special type of bond known as the beta one four glycocitic bond."}, {"title": "Lactose Intolerance .txt", "text": "Now, these lactose molecules are found in milk products and other dairy products."}, {"title": "Lactose Intolerance .txt", "text": "So if you ingest things like cheese or ice cream or milk itself, or let's say yogurt or sour cream, all of these dairy products basically contain lactose."}, {"title": "Lactose Intolerance .txt", "text": "Now, normally, if we ingest the lactose, eventually it makes its way into the small intestine of our body."}, {"title": "Lactose Intolerance .txt", "text": "And once inside our intestines, a special type of digestive enzyme is released, known as lactase."}, {"title": "Lactose Intolerance .txt", "text": "And what lactase does is it's able to actually use water molecules to catalytically cleave this glycocitic bond."}, {"title": "Lactose Intolerance .txt", "text": "And so he formed these two individual monosaccharides sugar molecules, so the glucose and the galactose."}, {"title": "Lactose Intolerance .txt", "text": "And once we form these monosaccharides in the lumen of our small intestine, only then can the cells actually uptake these individual monosaccharides into their cytoplasm."}, {"title": "Lactose Intolerance .txt", "text": "Before that, in this stage, they can't actually uptake this relatively large molecule due to its size."}, {"title": "Lactose Intolerance .txt", "text": "Now, some individuals are basically intolerant to lactose and this condition is commonly known as Hypo lactasia."}, {"title": "Lactose Intolerance .txt", "text": "So what happens is these individuals who have Hypo lactasia basically have some type of deficiency in the activity of this lactase enzyme."}, {"title": "Lactose Intolerance .txt", "text": "And so if the enzyme cannot actually carry out its function, that means it cannot break this bond, it cannot break the bond."}, {"title": "Lactose Intolerance .txt", "text": "And so if these two individual monosaccharides will not be formed, then this disaccharide will not be uptaken by the cells of our body."}, {"title": "Lactose Intolerance .txt", "text": "And so there will be a build up in the lactose, in the lumen of our colon and the small intestine."}, {"title": "Lactose Intolerance .txt", "text": "So colon is the large intestine and this causes symptoms such as gastrointestinal discomfort, so flatulate, this basically means the passing of gas digestive problems."}, {"title": "Lactose Intolerance .txt", "text": "So basically the inability to absorb fats, lipids and protein."}, {"title": "Lactose Intolerance .txt", "text": "So diarrhea, watery stool."}, {"title": "Lactose Intolerance .txt", "text": "The question is why?"}, {"title": "Lactose Intolerance .txt", "text": "Why is it that if an individual has this condition we call a Hypo lactasia, so basically they're intolerant to lactose, and if they actually ingest the lactose, there will be a build up of the lactose."}, {"title": "Lactose Intolerance .txt", "text": "But why is that build up?"}, {"title": "Lactose Intolerance .txt", "text": "Or why does the build up actually lead to these problems?"}, {"title": "Lactose Intolerance .txt", "text": "Well, in our gut we basically have many, many bacterial cells."}, {"title": "Lactose Intolerance .txt", "text": "In fact, we have ten times as many bacterial cells as the cells inside our body."}, {"title": "Lactose Intolerance .txt", "text": "We have over 100 trillion bacterial cells inside our body, inside our gut, and this is about \u00a33 of bacterial cells."}, {"title": "Lactose Intolerance .txt", "text": "Now, these cells, just like any other cells in nature, actually need ATP molecules to survive."}, {"title": "Lactose Intolerance .txt", "text": "And these cells use lactic acid fermentation, and when there is a build up of lactose inside our colon, these cells will use the lactose, the bacterial cells will use the lactose and break that lactose down to form ATP molecules in the process that will form lactate."}, {"title": "Lactose Intolerance .txt", "text": "So lactic acid, and if there's a build up of lactic acid lactate in our colon, that will cause the water to move out of the cell and into that lumen of the colon and that will lead to water restores."}, {"title": "Lactose Intolerance .txt", "text": "So diarrhea, in addition, these cells, when they break down the lactose, they also produce things like hydrogen gas and methane gas."}, {"title": "Lactose Intolerance .txt", "text": "And that will lead to build up in pressure, it will cause swelling and that will lead to flatulence as well as gastrointestinal discomfort."}, {"title": "Lactose Intolerance .txt", "text": "Now, these digestive problems can be a result of the combination of the gas build up as well as a diarrhea and it will basically cause the inability of our system, our GI tract, to basically absorb things like proteins and fats."}, {"title": "Lactose Intolerance .txt", "text": "Now lactose intolerant people can actually avoid these list of problems by doing one of two things."}, {"title": "Lactose Intolerance .txt", "text": "So by not eating these dairy products, because if you don't eat the lactose, then there will be no lactose build up in our GI tract or as they eat those dairy products that contain the lactose, they can also ingest enzymatically active enzymes, lactase enzymes."}, {"title": "Lactose Intolerance .txt", "text": "Now, a much more severe version of lactose intolerance is known as classic Galactosemia."}, {"title": "Lactose Intolerance .txt", "text": "And individuals who have classic galactosemia basically have an inability to actually digest the galactose molecule."}, {"title": "Lactose Intolerance .txt", "text": "So these individuals can actually break down that lactose into, these two individual monosaccharides and the cells can then uptake these two sugars."}, {"title": "Lactose Intolerance .txt", "text": "But then those individuals with classic galactic cannot actually break down this galactose molecule."}, {"title": "Lactose Intolerance .txt", "text": "And the build up of the galactose can lead to many different problems as we'll see in just a moment."}, {"title": "Lactose Intolerance .txt", "text": "Now, classic galactosemia is an autosomal recessive disease."}, {"title": "Lactose Intolerance .txt", "text": "And what that means is, so let's suppose we have some chromosomal pairs, that individual, what that basically means is these are two genes, two alleles for the same type of enzyme, for some specific type of enzyme."}, {"title": "Lactose Intolerance .txt", "text": "And in this particular case, this gene is for the enzyme we call galactose one phosphate urigal transphrase."}, {"title": "Lactose Intolerance .txt", "text": "And we'll see what it does in just a moment."}, {"title": "Lactose Intolerance .txt", "text": "And in individuals who have classic galactosemia, this gene or both of these genes are actually mutated."}, {"title": "Lactose Intolerance .txt", "text": "And what that means is these individuals cannot actually form a functional enzyme."}, {"title": "Lactose Intolerance .txt", "text": "And what that means is if this enzyme isn't actually formed or is dysfunctional, what that means is it can carry out a specific type of function."}, {"title": "Lactose Intolerance .txt", "text": "Now this enzyme is actually an important enzyme that is involved in the galactose glucose interconversion pathway that we focused on in detail in the previous lecture."}, {"title": "Lactose Intolerance .txt", "text": "So recall from the previous lecture that when galactose is uptaken by the cells, the galactose must be transformed into glucose six phosphate before it can actually begin to break down into ATP molecules."}, {"title": "Lactose Intolerance .txt", "text": "And the conversion of galactose into glucose phosphate is known as Galactose glucose interconversion pathway."}, {"title": "Lactose Intolerance .txt", "text": "And within this pathway."}, {"title": "Lactose Intolerance .txt", "text": "We have four different steps that are catalyzed by four different enzymes."}, {"title": "Lactose Intolerance .txt", "text": "And one of these steps, step number two, is catalyzed by galactose one phosphate, urinal transferase."}, {"title": "Lactose Intolerance .txt", "text": "So what this enzyme does on the normal conditions is it takes galactose one phosphate in the presence of UDP glucose."}, {"title": "Lactose Intolerance .txt", "text": "This enzyme catalyzed the transformation into UDP galactose."}, {"title": "Lactose Intolerance .txt", "text": "So this becomes UDP galactose, and the UDP glucose becomes glucose one phosphate."}, {"title": "Lactose Intolerance .txt", "text": "And then the glucose one phosphate can basically go on to form glucose six phosphate, which can be fed, incorporated into the glycolytic pathway, and the UDP galactose can be transformed into the UDP glucose."}, {"title": "Lactose Intolerance .txt", "text": "That's what happens on the normal condition."}, {"title": "Lactose Intolerance .txt", "text": "So normally, the galactose is transformed into galactose one phosphate."}, {"title": "Lactose Intolerance .txt", "text": "Then this one is transformed into this molecule and a glucose one phosphate."}, {"title": "Lactose Intolerance .txt", "text": "And then two more steps take place and ultimately we're able to break down the galactose into ATP molecules."}, {"title": "Lactose Intolerance .txt", "text": "But if both of these alleles, both of these genes are impaired in some way, that means we cannot actually create that functional galactose one phosphate urilotransphrase."}, {"title": "Lactose Intolerance .txt", "text": "And so what happens is our cells will be able to break down the lactose into these two molecules, then the galactose will be broken down or will be essentially modified to form the galactose one phosphate."}, {"title": "Lactose Intolerance .txt", "text": "But the galactose one phosphate will not be able to form these molecules here."}, {"title": "Lactose Intolerance .txt", "text": "And so what that means is, as we ingest the lactose, if we have classic galactosemia, there will be a build up of this galactose as well as the galactose one phosphate."}, {"title": "Lactose Intolerance .txt", "text": "And that can be very toxic to our body."}, {"title": "Lactose Intolerance .txt", "text": "Why?"}, {"title": "Lactose Intolerance .txt", "text": "Well, let's take a look at the following conversion."}, {"title": "Lactose Intolerance .txt", "text": "So, if there's a build up of galactose inside our body well, first of all, this is a cyclical galactose and this is its open chain confirmation."}, {"title": "Lactose Intolerance .txt", "text": "And so if there's a build up of the galactose, an enzyme known as Aldos reductase will use this molecule and the H plus ion to transform this sugar molecule into an alcohol known as galactitol."}, {"title": "Lactose Intolerance .txt", "text": "Now, galactitol, if there's a build up of galactitol in certain areas of our body, that can cause very, very dangerous conditions."}, {"title": "Lactose Intolerance .txt", "text": "So the high concentration of galactose and subsequent high concentrations of the alcohol, galactitol is toxic to the body and it can actually cause damage to many areas of our body."}, {"title": "Lactose Intolerance .txt", "text": "For instance, it can cause liver enlargement, it can cause damage to our liver, and that eventually might actually progress to cirrhosis."}, {"title": "Lactose Intolerance .txt", "text": "And cirrhosis is basically a very advanced form of liver damage."}, {"title": "Lactose Intolerance .txt", "text": "It can also cause, cause cataract formation, delayed mental development, ovarian failure, and a feeling of laziness or lack of enthusiasm and so forth."}, {"title": "Lactose Intolerance .txt", "text": "So what I'd like to focus on in this lecture is cataract formation."}, {"title": "Lactose Intolerance .txt", "text": "So how does the build up of the galactos actually lead to cataract formation?"}, {"title": "Lactose Intolerance .txt", "text": "Well, what exactly is a cataract?"}, {"title": "Lactose Intolerance .txt", "text": "Well, cataract quite literally means there's a wall of water that exists in the length of our eye and that basically decreases the transparency of the lens and so we essentially become blind so we can't see very well."}, {"title": "Lactose Intolerance .txt", "text": "Now how does an increase in galactose actually lead to the building of a cataract?"}, {"title": "Lactose Intolerance .txt", "text": "Well, inside the lens we essentially have cells and when the cells when there's an increase in the galactose concentration inside the cell the galactose begins to slowly convert into the galactitol as a result of the activity of the Aldos reductase."}, {"title": "Lactose Intolerance .txt", "text": "And so there's a build up in the concentration of this alcohol inside the cells of the lens and inside the lens itself."}, {"title": "Lactose Intolerance .txt", "text": "Now if there's a build up of this metabolite inside the cell that will create a hypertonic environment, an environment in which will essentially have a high concentration of solute molecules and that will cause the flow of water into the lens of the eye."}, {"title": "Lactose Intolerance .txt", "text": "And if water flows into the lens of the eye that is precisely what will cause a cataract to form because a cataract bites."}, {"title": "Lactose Intolerance .txt", "text": "Very different definition is essentially a wall of water that forms inside that eye decreasing the transparency of that eye."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So far in our discussion on the breakdown of fatty acids, we only really discussed the breakdown of saturated fatty acids."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So these are fatty acids that do not contain any double bonds."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "But our diet consists of many different types of fatty acids that do contain double bonds."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So the next logical question is how exactly can the cells of our body actually break down fatty acid acids that do contain one or more double bonds?"}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So this will be the focus of this lecture."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, fatty acids with double bonds can be broken down into one of two categories."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "They can either contain an odd number of double bonds, so 13579 and so forth, or they can contain an even number of double bonds, so 2468 and so forth."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So in this lecture, we're going to look at two different cases."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "We're going to begin by focusing on the odd case and then we're going to focus on the even case."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, in the odd case, we're going to use palmatoliate as our example."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And palmatoliate is a common 16 carbon fatty acid that contains a single double bond between the 9th and 10th position."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, when we ingest the palmatoliate into our body, the palmatoliate ultimately ends up in our liver cell in our paticide."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And once the pepticide absorbs the palmatoliate into the cytoplasm, in the cytoplasm, that cell activates that palmatoliate into palmatolial coenzyme A."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And once we have the active form of the palmatoliate, it then could be transported into the matrix of the mitochondrion."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, once the palmitolial coenzyme A is in the matrix of the mitochondria, it then undergoes three cycles of beta oxidation, the same beta oxidation pathway that we discussed in the previous lecture."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So once this undergoes three cycles of beta oxidation, it produces two acetoco enzyme A molecules and it shortens this 16 carbon molecule into a ten carbon molecule."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "This CIS delta three in oil coenzyme A molecule."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, the problem with this molecule is the following."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "The first enzyme that catalyzes step one of beta oxidation, the acyl coenzyme adhdrogenase, cannot actually act on this molecule."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Why?"}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Well, recall that acyl coenzyme adhdrogenase basically generates a double bond between carbon two and carbon three."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And the problem with this molecule is we already have a double bond between carbon three and carbon four."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And so this enzyme cannot generate a double bond between carbon two and carbon three because of the presence of another double bond between carbon three and carbon four."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So this molecule is not a substrate for acyl coenzyme adhdrogenase."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So how exactly the cells of our body actually prevent this problem, fix this problem?"}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Well, one thing that our cells do is they take this molecule and transform it into an intermediate that can be fed into the beta oxidation pathway."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And this enzyme that carries out this process is an isomerase."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So it's called CIS delta three enol coenzyme Aisomerase."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And what this does is this enzyme changes the location and the configuration of this double bond."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So it takes a double bond and places it onto this position."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And that also changes the configuration from CIS to trans."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we transform the CIS delta three enol coenzyme A into a trans delta two enol coenzyme A."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now this is an important step because now the second enzyme, namely the enolco enzyme A hydratase e, and the beta oxidation pathway can now act on this molecule and then transform it into ultimately acetylco enzyme A."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And then we can have three more cycles of beta oxidation to basically release and produce all those acetylco enzyme A molecules."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we see that anytime we ingest a fatty acid that contains an odd number of double bonds, this is basically what we're going to find taking place."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we're going to have this isomerase that will transform the CIS delta three null coenzyme A molecules into the trans delta two nullenzine coenzyme A molecule so that they can be fed into the beta oxidation pathway."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, what about the case when we have an even number of double bonds in that fatty acid?"}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So to demonstrate what our cells actually do, let's discuss linoleate."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Linoleate is an 18 carbon fatty acid that contains two double bonds."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "One double bond is between carbon nine and ten, and the other double bond is between carbon twelve and carbon 13."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, in the same exact way that we discussed in this particular case, where we take the palmatoliate, we activate it in a cytoplasm and then move it into the mitochondria, the matrix of the mitochondria."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "The same thing happens here."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "We take the linoleate, we activate it, we move it into the matrix of the mitochondria of that hepatitis."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And then just like in this case, we basically undergo three cycles of beta oxidation to release three acetyl coenzyme A molecule."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we essentially shorten this 18 carbon molecule to a twelve carbon molecule to form a CIS delta three enol coenzyme A."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now notice we basically come to the same exact position as we were in this particular case."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So here this acyl coenzyme A dehydrogenase cannot act on this molecule because of the presence of a double bond between carbon three and carbon four, as we saw in this case."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And so once again, this same isomerase has to act on this molecule to basically change the position and the location."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So the position and the configuration of this double bond."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we go from a sith double bond between carbon three and carbon four to a trans double bond between carbon two and carbon three."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And so once we form this intermediate, this is a trans delta two enol coenzyme A, as we saw in this particular case."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now this can basically complete that beta oxidation pathway to basically form a CIS delta four enol coenzyme A molecule that now contains only one double bond, as can be seen between the carbon four and carbon five."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, this molecule is a substrate to two acyl coenzyme a dehydrogenase."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And once the ACL coenzyme a dehydrogenase acts acts on this molecule, it forms a double bond between carbon two and carbon three."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And so he formed this molecule, which we call the 24 dienol coenzyme a intermediate."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, the problem with this molecule is this molecule is not a substrate molecule to enol coenzyme a hydrate."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So enol coenzyme a hydrates, the second enzyme in the beta oxygen pathway, cannot actually act on this molecule."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And so, once again, we have to use some type of enzyme to basically transform this molecule into a molecule that can ultimately be fed, can be incorporated into the beta oxidation pathway."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And the enzyme that carries out this process is known as two four dienol coenzyme a reductase."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "It basically uses an NADP plus molecule to basically oxidize this intermediate into this molecule, at the same time reducing and forming the NADPH."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now, once we form this molecule, a trans delta three enoll coenzyme a."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "Now an isomerase, this isomerase here can act on this molecule, basically moves that double bond onto this location here."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So if the isomerase acts on this molecule, it will form an intermediate that is not shown here, but that intermediate will basically have a double bond between carbon two and carbon three."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And then that can be fed into the beta oxidation pathway."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "And ultimately, this entire fatty acid can be broken down into acetyl coenzyme a molecules."}, {"title": "Oxidation of Unsaturated fatty acids .txt", "text": "So we see that no matter what type type of unsaturated fatty acid that we actually ingest, if it contains either an odd number of double bonds or an even number of double bonds, we see that our cells can use an isomerase, or in this case, the combination of an isomerase and a reductase, to basically transform and break down those fatty acids into acetyl coenzyme a molecules."}, {"title": "Electrical Conduction in the heart .txt", "text": "Our heart is a very important organ."}, {"title": "Electrical Conduction in the heart .txt", "text": "And that's because it contracts and generates the hydrostatic pressure that is needed to move all that blood through the blood vessels of our cardiovascular system."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, the question is, what exactly causes the muscle, the heart, to actually contract in the first place?"}, {"title": "Electrical Conduction in the heart .txt", "text": "This is what we're going to focus on in this lecture."}, {"title": "Electrical Conduction in the heart .txt", "text": "So it turns out that the heart itself is actually capable of generating an electrical signal."}, {"title": "Electrical Conduction in the heart .txt", "text": "And as this electrical signal moves within the chambers of the heart, it causes those chambers to actually contract."}, {"title": "Electrical Conduction in the heart .txt", "text": "So it's the electrical signal that moves to the heart that causes the heart to contract as a whole and pump all that blood through the blood vessels of our body."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, recall that the autonomic nervous system is capable of regulating the rate at which the heart contracts."}, {"title": "Electrical Conduction in the heart .txt", "text": "But, and this is an important but even though the autonomic nervous system regulates the beat of the heart, it doesn't initiate that beat."}, {"title": "Electrical Conduction in the heart .txt", "text": "So recall that cardiac muscle cells exhibit myogenic activity."}, {"title": "Electrical Conduction in the heart .txt", "text": "And what myogenic activity means is our cardiac muscle cells are actually capable of generating their own electrical signal on their own accord without the input of our nervous system."}, {"title": "Electrical Conduction in the heart .txt", "text": "So let's begin by taking a look at a cross section of the heart, as shown in this diagram."}, {"title": "Electrical Conduction in the heart .txt", "text": "So we have the right side of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "We have the left side of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "This is our superior and inferior vena cava, the right atrium, the right ventricle, the left atrium, the left ventricle."}, {"title": "Electrical Conduction in the heart .txt", "text": "We have the pulmonary arteries that extend into the lungs."}, {"title": "Electrical Conduction in the heart .txt", "text": "And we have our order that splits into the ascending and descending a order."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now let's zoom in."}, {"title": "Electrical Conduction in the heart .txt", "text": "Let's take a look at the right atrium of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "So this is the right atrium and the upper wall of the right atrium of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "This section here contains a collection, a bundle of specialized cells that together are known as the sinoatrial note, or simply the SA node."}, {"title": "Electrical Conduction in the heart .txt", "text": "And it's the ACA node."}, {"title": "Electrical Conduction in the heart .txt", "text": "It's the cells within the essay node that are responsible for initiating an action potential by depolarizing."}, {"title": "Electrical Conduction in the heart .txt", "text": "So, as the cells depolarize within the essay node, they generate an impulse, an action potential that moves within the atria of our heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "And as it moves within the two atrium of the heart, it causes those atria to actually contract."}, {"title": "Electrical Conduction in the heart .txt", "text": "So the essay node basically initiates its own action potential without the input of our autonomic nervous system."}, {"title": "Electrical Conduction in the heart .txt", "text": "And that's exactly why the essay node is commonly referred to as the natural pacemaker of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "It generates an action potential in the right atrium, which then moves into the left atrium and eventually into our two ventricles."}, {"title": "Electrical Conduction in the heart .txt", "text": "So it triggers a set of electrical events within the heart that causes the heart to actually contract and pump all that blood through the blood vessels of our body."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, the rate at which the SA node actually contracts varies from about 60 to 100 beats every single minute."}, {"title": "Electrical Conduction in the heart .txt", "text": "And this is actually pretty high."}, {"title": "Electrical Conduction in the heart .txt", "text": "So what the parasympathetic nervous system does is it uses the vagus nerve to actually decrease the rate at which the heart actually contracts."}, {"title": "Electrical Conduction in the heart .txt", "text": "And we'll see what that means and how that works in just a moment."}, {"title": "Electrical Conduction in the heart .txt", "text": "So, once again, the essay node is the sino atrial node."}, {"title": "Electrical Conduction in the heart .txt", "text": "It's a collection of specialized cardiac muscle cells found in the upper portion of the right atrium that generates an action potential and impulse."}, {"title": "Electrical Conduction in the heart .txt", "text": "And then that impulse moves within special conduction channels through the right atrium and the left atrium."}, {"title": "Electrical Conduction in the heart .txt", "text": "And at the same time it causes these two atrium to actually contract."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, what exactly happens next?"}, {"title": "Electrical Conduction in the heart .txt", "text": "Well, if we notice, if we take a look at the following diagram, we have the SA node and we have another type of node known as the AV node, which stands for the atrioventricular node."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now the atrio ventricular node is also a collection of specialized cardiac muscle cells that is located inside the interatrial septum of our heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "That's basically the wall that separates the two atrium of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "So this is found between the atria and between the ventricles of our heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now what this AV node does is it does two things."}, {"title": "Electrical Conduction in the heart .txt", "text": "Firstly, once it actually receives that action potential from the essay node, it delays that action potential by about zero point twelve of a second."}, {"title": "Electrical Conduction in the heart .txt", "text": "And the reason it creates this delay in electrical signal is because it wants to make sure that the two atria finish contracting and finish moving all that blood into our ventricles of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "So once the AV node receives that electrical signal, that AV node delays that signal before actually depolarizing."}, {"title": "Electrical Conduction in the heart .txt", "text": "And once it depolarizes, it also creates its own action potential that then moves via specialized cardiac fibers called the bundle of his."}, {"title": "Electrical Conduction in the heart .txt", "text": "And these bundles of his are found within the wall that separates the right ventricle from the left ventricle."}, {"title": "Electrical Conduction in the heart .txt", "text": "So let's move on to the following diagram."}, {"title": "Electrical Conduction in the heart .txt", "text": "So in this diagram, this is our right ventricle, this is the left ventricle."}, {"title": "Electrical Conduction in the heart .txt", "text": "And this wall that separates these two ventricles is known as our interventricular septum, which is the wall between the right and the left ventricle."}, {"title": "Electrical Conduction in the heart .txt", "text": "So within this wall we have this bundle of his, which is basically a conduction channel that begins at the AV node and it travels through this wall separating our two ventricles."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now as it travels, as it moves, the bundle of his then splits into two different branches."}, {"title": "Electrical Conduction in the heart .txt", "text": "We have the left bundle and the right bundle."}, {"title": "Electrical Conduction in the heart .txt", "text": "And these continue moving within the interventricular septum and eventually also begin to split into very tiny extensions, very tiny fibers we call the perkinji fibers."}, {"title": "Electrical Conduction in the heart .txt", "text": "And these PerkinsI fibers are found between the endocardium and the myocardium of our heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now together the bundle of his and these perkinji fibers basically distribute that electrical signal through the bowl, through the two ventricles of the heart and it causes these two ventricles to actually contract at the same time, simultaneously."}, {"title": "Electrical Conduction in the heart .txt", "text": "So, once again, the electrical signal is generated within the SA node, which is found in the upper right atrium of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "And as this electrical signal is generated, it moves not only through these conduction fibers found within the right atrium, but it also moves through specialized conduction fibers known as the back men's bundle, which travels through the left atrium of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "And so what that causes is it causes the right atrium and left atrium to contract at the same exact time."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, as they begin to contract, they begin to move that blood into these ventricles of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, as these electrical signals come to the AV node, the atrial ventricular node found in the interatrial septum in this section right here, that AV node delays that signal ever so slightly."}, {"title": "Electrical Conduction in the heart .txt", "text": "And that is to make sure that all that blood efficiently flows into the ventricles of the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "Once our delay takes place, the depolarization within the AV bundle takes place and that generates an action potential that moves via the bundle of his."}, {"title": "Electrical Conduction in the heart .txt", "text": "And then it splits into the left and right bundle and then even more splitting takes place until we get to our perkinji fibers."}, {"title": "Electrical Conduction in the heart .txt", "text": "And these PerkinsI fibers, what they basically do is they allow these ventricles to contract in a forceful manner at the same exact time."}, {"title": "Electrical Conduction in the heart .txt", "text": "So these atria contract first, then they relax, and then the ventricles contract while the atria relax."}, {"title": "Electrical Conduction in the heart .txt", "text": "And that creates a single forceful motion of the heart and that pumps all that blood through the rest of our body."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, it's the heart that actually generates the electrical signal itself, but the autonomic nervous system is capable of regulating the rate of that heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "So, although the base heart rate is set by the essay note, and that's why we call it the natural pacemaker of the heart, our autonomic nervous system can regulate the heart rate as needed."}, {"title": "Electrical Conduction in the heart .txt", "text": "For example, if we need the heart to actually pump quicker, the sympathetic nervous system can actually cause the heart to basically pump quicker."}, {"title": "Electrical Conduction in the heart .txt", "text": "But if we need to rest the heart, if the pace needs to be lowered, the parasympathetic nervous system, via the vagus nerve that innovates the cardiac muscle cells can basically extend into the heart and cause that rate to lower."}, {"title": "Electrical Conduction in the heart .txt", "text": "In fact, because the essay node generates a rather quick pace, what the parasympathetic system does is actually lowers that base pace that is created by the heart itself."}, {"title": "Electrical Conduction in the heart .txt", "text": "Now, medically, the electrical conduction of the heart can be monitored and this is known as the electrocardiogram."}, {"title": "Electrical Conduction in the heart .txt", "text": "So if you're ever been into the doctor's office when they conducted an electrocardiogram, what they basically do is they put these six electrodes around the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "And what those electrodes do is they basically monitor the voltage that is created by the heart."}, {"title": "Electrical Conduction in the heart .txt", "text": "They monitor the electrical signal that is is generated by the heart and by studying your electrical signal that is generated by the heart, they can determine whether or not some type of condition exists within the heart."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "In biology, and more specifically in the field of genetics, there are three terms that are constantly being used by scientists, and sometimes these words are used interchangeably."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And that's exactly why they create a sense of confusion, especially to those who are beginning their study of genetics."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So what exactly are these three words?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we have something called the locus, we have something called a gene and something called an allele."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And before we discuss what the difference is between these three different words and how they're related to one another, let's recall what a chromosome is."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So, inside the nuclei of cells of different types of organisms, we have DNA molecules."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, the problem is, if we take any single DNA molecule and we stretch it out like so, it will actually be quite long."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So let's suppose that this is the nucleus of our cell and this is the actual DNA molecule."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So notice it's much longer than the size of the nucleus itself."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we can't actually fit the DNA in the way that we have it now into the nucleus of cells."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "For example, in humans, if we take a human DNA and we stretch it out, it's going to be somewhere between five and 6ft in length, and that's clearly too large to fit it into a tiny, tiny microscopic nucleus of any of our somatic cells."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So the way that organisms solve this problem is by creating something called the chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So they take these special proteins and they take the DNA and they wrap the DNA around the proteins many, many times."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So they create coils, and then super coils, and then solenoids and more coils, and eventually they form this extremely condensed and dense version of the DNA we call a chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So, if this is our protein and this is our DNA, we basically take the DNA and we wrap the DNA around the protein many, many, many times."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Of course, it's more complicated than this, but you get the point."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And once we wrap it around, it's now much smaller than before, and now we can fit it easily into the nucleus of our cell."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So that is what a chromosome is."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "It's this entire structure that contains the DNA, as well as the proteins that hold that dense structure together."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So the chromosomes are basically the DNA, along with the proteins that are found within the nucleus of our cells and the cells of other organisms."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, what's the special feature?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "What's the special thing about DNA?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Well, DNA basically contains the code that the cells use to create proteins."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And proteins are important in forming different organelles within the cell, as well as helping the cell carry out different types of cellular processes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, what about on the macroscopic level?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Why are proteins important?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Well, because proteins are used to express the different types of traits and characteristics that are found within that given organism."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So if we're talking about humans, the height of humans is one trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "The eye color is another trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "The hair color is a third trait, and so forth."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So in this lecture, we're going to focus on Pea plants and we can talk about many different types of traits."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "For pea plants, we have basically a trait for height."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have a trait for a seed color, for the pond color."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So the ponds are basically the structures in which the seeds are found in."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have seed shape."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have pod shape."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We also have the seed coat color."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, within the DNA, the DNA actually consists of these sequences of nucleotides."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, some of these sequences do not actually code for any protein, but those sequences of nucleotides that do contain the information that do code for a special type of protein that, once built, is used to help us express the traits."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Those special segments of DNA are known as genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So a gene is a special segment of the DNA, the sequence of nucleotides that codes for a protein that is used to help us express those traits and those characteristics that are found on that individual, on that organism."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, along the chromosome, so this is a single chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Along the chromosome, we can have thousands of different types of genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And in this particular diagram, we have only six genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we have a red gene, we have a green gene, we have our blue gene, the light green gene, the dark purple and the light purple gene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And each one of these genes basically codes for its own protein that is used to express some type of trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So, for example, this gene can code for a tall plant."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And so this is the hygiene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "It codes for a protein that is used to express the height of that particular plant."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, in the same exact way that when I tell somebody my dress, they know exactly where to live and where to find me when I tell somebody the locus of any given gene, the locus basically refers to where that gene is found along that DNA, along that chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So a locus refers to the location on that chromosome for that specific gene that codes for some specific trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So a locus is not the same thing as a gene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So a locus basically tells us the dress of that given gene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So on the following chromosome, we have many different loci."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And each one of these loci basically tells us where that gene is actually found."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we have locust number one that contains a gene that codes for a protein that expresses the height of that plant."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "The second locus is basically the locus that contains the gene that codes for a different trait, for example, the seed color."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Then we have the pot color and so forth."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And along the chromosome, we have many, many of these genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Here we have six genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "But normally we have thousands of these different types of genes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, let's recall an important piece of information about diploid organisms."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So in any diploid organism, in any to end organism we have, every single chromosome comes in a pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So basically, in deployed organisms, chromosomes always come in pairs."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And that's exactly why you have a second chromosome on the board."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So in humans, even though we have 46 individual chromosomes, we actually have 23 pairs of chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And each pair of chromosomes is called a homologous pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And we'll see what that means in just a moment."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So in any homologous pair, one chromosome came from the female gamete, and the other chromosome came from the male gamete."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So if we look at the following diagram, let's suppose we have a male gamete, the sperm cell."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have one chromosome, we have a female gamete."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Let's say that's the egg, and they combine."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And once they combine, they form the zygote."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And now we have N number of chromosomes, n number of chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And once we form the Zygote, we have two N number of chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we have a homologous pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, in humans, this would be 23 individual chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Plus 23 individual chromosomes, they combine to form 23 homologous pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Or 46 individual chromosomes would be found in a single human zygote."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, because we're talking about pea plants, this would be seven chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And seven chromosomes would give us 14 total chromosomes or seven homologous pairs."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, what's the big deal about a homologous pair?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Why do we have this pairing of our chromosomes in the first place?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So what are the criteria for homologous chromosomes?"}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So, homologous chromosomes satisfy two things."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "First of all, they have similar size, they have similar structure and similar shape."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And second of all, they have genes that code for similar proteins that express the same exact trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So number two is the important criterion for homologous chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So they carry genetic information, so they carry the genes that have the same type of information, that code for those same types of proteins that help us express some given trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So if we, for example, take one chromosome and that chromosome contains, let's say, the seed color, then it's homologous chromosome will also contain a corresponding gene that creates proteins that expresses the seed color."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So if we take a look at the following diagram, if this is, let's say, chromosome number one, and this is its homologous chromosome, what that means is this will contain a gene in this locus that will code for height."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And this homologous chromosome will also contain a similar gene that will also code for a protein that will help us express our height."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And these two genes, with respect to one another, these two homologous genes are known as alleles or alleles."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So basically, such a pair of genes, such a pair of genes found on homologous chromosomes that code for polypeptides, that express the same physical trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "In this case, it's the height."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "In this case, it's the seed color, the pod color, the seed shape and so forth."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "These are known as alleles."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So alleles are basically two genes that are located on homologous chromosomes that code for a similar polypeptide, a similar protein that gives us or helps us express that same type of trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So in this particular homologous pair, we have 1234 genes on this chromosome, 1234 genes on this chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So we have a total of eight genes, but we have a total of four alleles."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "This is one allele pair, a second allele pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have a third allele pair and a fourth allele pair."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So let's say that this codes for some type of trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Let's suppose it's the height, and this also must code for that same type of trait for the height."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "But that doesn't mean that these must code for the same exact type of protein."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "The proteins can actually differ."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "In fact, this gene can code for a toll plant, but this gene can code for a short plant."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And in that particular case, because the toll trade is dominant over the short trade, this will actually express the trade."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "But this will not be expressed because by the law of dominance we have a dominant trait will basically inhibit the expression of that recessive trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So also notice that because homologous chromosomes have similar size, shape and structure, each allel pair are found at similar locations along the chromosome that is at a similar locus."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So if g number one for height is found on the top at this locus, then on the homologous chromosome, the locus will also be found in that location on the top of that chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "That's exactly what we have here."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have essentially a perfect pairing of these alleles."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "Now, as I mentioned earlier, and this is an important point, even though each allele pair contains similar genes, the genes that code for similar traits, the genes do not have to code for identical traits."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So, for example, if we're talking about humans, and let's say this allele or this gene codes for the color blue of our eyes, and this codes for some other color, then they will not be the same exact gene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "This could be blue, this could be green, or this could be blue, this could be brown, and so forth."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So what that means is these allele pairs do not have to code for that same identical type of protein."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "The proteins can be different, but those two proteins will be involved with expressing that same type of trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So this is the difference between a locus, a gene and an allele."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So a locus is basically the address point of that gene."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "It tells us where that gene is located along that particular chromosome."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "And an allele basically comes in pairs because in diploid organisms, we have these homologous chromosomes."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "We have two genes that each come from both parents that code for some given trait."}, {"title": "Genes, Alleles and Loci on Chromosomes.txt", "text": "So this gene might have come from, let's say, the male parent, but this gene came from the female parent when we underwent the process of fertilization, when we actually produced that zygote."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "Following distribution."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "So one to one to one to one ratio, then we know then we know that the two genes, the color gene and the hygiene, are not linked."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "Now, in the next lecture, we're going to see that as a result of these two genes being linked, if they are linked, because they are linked, and crossing over takes place randomly, will see that the distribution will be slightly different."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "And that's exactly how we differentiate, how we tell if the two genes are actually linked or not linked."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "If they are not linked, we have a one to one to one to one ratio being produced when we make these two individuals."}, {"title": "Non-linked Genes and Offspring Distribution Part II.txt", "text": "But if they are linked, the ratio will be something else, as we'll see in the next lecture."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "Here we get a girl and a boy."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "Here we get a boy and a girl."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And here we get a girl and a girl."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "Now, the probabilities of these individual events taking place because they're independent, we have to use the product pool, as we use is here and here."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And so we have one fourth here, one fourth here, one fourth here, and one fourth here."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "This is exactly the same as in this case."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So first we applied the product rule and now we have to apply the sum rule."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So what we want is one girl and one boy."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And we don't care about the order."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So let's take a look at all the four potential outcomes."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "We can either get a boy and a boy, which is not what we want."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "We can either get a girl and a girl, which is also not what we want, but the other two outcomes are boy and a girl and girl and a boy."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And in both of these cases, we basically get one girl and one boy."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "Now, these two events are mutually exclusive."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And what that means is if this event took place, this event cannot possibly take place."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And likewise, if this event took place, this event could not have possibly taken place."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And so because they're mutually exclusive, we apply the sum rule and we have one fourth plus one fourth."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "And that gives us one half."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So one four plus one four gives us two eight or two four, which is equal to one half or 50%."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So this is the probability of basically getting one girl on one boy."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "This is the probability of getting two girls, and this is the probability of example number one, getting two consecutive heads on two consecutive coin flips."}, {"title": "Sum and Product Rule in Genetics Part II.txt", "text": "So these are the two common rules that we use in genetics."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "In our discussion on the gas exchange process that takes place inside the alveoli of our lungs, we said that the partial pressure inside the alveolar space is much greater than the partial pressure inside the capillaries of our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that's precisely why oxygen will move down its pressure gradient from the alveoli of the lungs and it into the capillaries of our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, the next question is what exactly happens to our oxygen as soon as the oxygen arrives in the blood plasma of the capillaries?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Recall that blood plasma consists predominantly of water."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that makes our blood plasma a polar substance."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, diatomic oxygen, as it exists in our blood in the atmosphere, is a nonpolar substance."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "It's a nonpolar molecule."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that means it's hydrophobic."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "It will not easily dissolve in our blood plasma."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So how exactly do we solve this problem?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, basically, our red blood cells carry a special type of transporter protein of carrier protein known as hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And what hemoglobin does is it picks up these oxygen molecules and it carries and it protects those oxygen molecules from the hydrophilic environment."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So basically, hemoglobin consists of four polypeptide subunits."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So this is what the hemoglobin, the hemoglobin protein, actually looks like."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "We have subunit one shown in green, subunit two shown in purple, subunit three shown in brown and subunit four shown in orange."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, notice that within each one of these subunits, we have a hydrophobic section right inside."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So these red sections basically are the heme groups."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "They're a percent of groups that are found within each subunit and each one of these heme groups, so we have 1234."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Each one of these contains a single iron atom."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And this iron atom can bind oxygen via an oxidation reduction process."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So the iron is capable of changing its oxidation state via a redux reaction and that can bind our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, one heme group can bind a single diatomic oxygen molecule."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So that means because we have four heme groups, in a single hemoglobin, a maximum of four diatomic oxygen molecules can be carried by our hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So we see that as oxygen diffuses across our respiratory membrane from the alveoli and into the capillaries in the lungs, our red blood cells pick up our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And inside the red blood cells, the hemoglobin then picks up the oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And a single hemoglobin can carry a maximum of four oxygen molecules one in each one of these four hein groups."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, when our hemoglobin is fully saturated with oxygen, we call it oxymoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "But when the hemoglobin isn't actually carrying any oxygen, in that case, we call it deoxyhemogglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, one important property of hemoglobin, one important property that hemoglobin actually exhibits is something known as positive cooperativity."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, what exactly is positive cooperativity?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, when one oxygen molecule is taken up by the hemoglobin, it causes a conformational change."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "It causes a change in the three dimensional structure of the entire hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And as the structure changes, it makes it much more likely to actually pick up other oxygen molecules."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So as soon as our deoxy hemoglobin picks up a single oxygen, it changes its shape ever so slightly, and it changes the shape in such a way that it makes it much more likely to pick up other oxygen molecules."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Likewise, when our hemoglobin is fully saturated with oxygen and one of those oxygen molecules actually dissociates, that dissociation process creates a conformational change in the hemoglobin that causes it to be more likely to dissociate the other three oxygen molecules."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And this process, this type of behavior of hemoglobin, is referred to as positive."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Cooperativity so the question is, what will make our hemoglobin actually release an oxygen?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, recall that oxygen always spontaneously and naturally travels from a high concentration of oxygen to a low concentration of oxygen, from a high partial pressure of oxygen to a low partial pressure of oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And we'll see that's exactly what happens when the hemoglobin actually reaches the tissues and organs of our body."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, by the way, the way that we designate partial pressure of oxygen is p two, where P is the partial pressure and two is our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So we know what happens to our oxygen when the alveoli basically released that oxygen into the capillaries."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "But what happens to our oxygen as the hemoglobin and the red blood cells carry that oxygen along our blood vessel system, to our tissues and organs of the body?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So as hemoglobin carries oxygen in the red blood cells and within our blood plasma of the blood vessels, it protects the non polar water molecule from the polar cytoplasm of the red blood cell and the polar plasma of our blood."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And what that means is our hemoglobin keeps the oxygen protected and it keeps the oxygen comfortable within that hydrophobic section of the inside of our hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So, remember, the outside of the protein is polar, but the inside of the protein where we have the oxygen is a hydrophobic portion."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So it's non polar."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that's why oxygen can reside comfortably within these four sections of our hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, let's suppose we take a small cross section of our capillary."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Let's suppose this is some capillary inside our blood system."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And this outside portion is basically the area where we have cells of some particular tissue."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, these are the red blood cells."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And inside these red blood cells, we have a bunch of these hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And these hemoglobin carry the oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, as the red blood cells travel, let's say, from this side to this side, inside the blood plasma, we have a relatively high concentration of oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And so the partial pressure of oxygen inside our capillary will be relatively high compared to the partial pressure of oxygen inside the cells of our tissue."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, why would the partial pressure inside the tissue be low?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, that's because the cells inside the tissue continually use, let's say, glucose in the process of cellular respiration to actually break down glucose and form ATP molecules."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And in the process, they use up oxygen in the electron transport chain and they produce carbon dioxide."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, as they use up oxygen, that decreases the concentration of oxygen in the cells of the tissue, and that therefore decreases the partial pressure of oxygen in our tissue."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that's exactly why we have this difference in pressure now, because oxygen will always move naturally from a higher partial pressure to a lower partial pressure."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "As our red blood cells move along our capillary, our hemoglobin will unload our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "The oxygen will dissociate."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And as one oxygen dissociates, it makes the other oxygens more likely to dissociate."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And this is positive."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Cooperativity and we can plot something called the oxygen hemoglobin dissociation curve on the following x Y axis, where the X axis is the partial pressure of the oxygen within our tissue, and our Y axis is the percent saturation of hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So we have from zero to 100 and from zero to 100."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And the units of our x axis are millimeters per mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So as the red blood cells travel along our capillary, the hemoglobin unloads that oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "The oxygen moves through our cell membrane into the blood plasma and then travels into the tissues and to the cells in the tissue, where it is picked up by other molecules, other proteins within those tissue cells."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So the tissue and organs of our body have a low partial pressure of oxygen, about 40 mercury of mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Because there is a higher concentration of oxygen, a higher partial pressure of oxygen in the capillaries, hemoglobin will dissociate oxygen and it will move the oxygen into the tissues of our body."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And if we plot the percent of hemoglobin saturated with oxygen versus the partial pressure of oxygen, we get the oxygen hemoglobin dissociation curve, which is shown by the following blue curve."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, notice the blue curve has an S shape."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "This is known as a Sigmoidal shape."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And the reason it is a Sigmoidal shape is because of this positive cooperative behavior of hemoglobin."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And we'll see why that's the case in just a moment."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So let's examine and let's try to describe and understand what this curve actually tells us."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So let's begin with the alveoli of our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "We know that in the alveoli of our lungs, in the Alveolar space, the partial pressure of oxygen is about 105 mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that means inside the Alveoli, we're going to be at about this position along our X."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And if we find the corresponding value along the Y, this graph tells us that about 98% of all the hemoglobin in the capillaries of our lungs will be fully saturated with our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that makes sense because the entire point of hemoglobin is to pick up our oxygen within the capillaries of our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So because of the high partial pressure of oxygen within the Alveoli, our hemoglobin in the red blood cells will easily pick up our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And so that 98%, or about 98% of hemoglobin will be fully saturated with oxygen within the alveoli of our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So in the alveoli of the lungs, the partial pressure of oxygen in the alveolar space is about one to 5 mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Therefore, most of the hemoglobin is saturated."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, notice if we examine this curve, within this region of the curve, we have a relatively flat slope."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, what exactly does that mean?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, this flat slow basically means that even if our partial pressure inside the Alveoli dropped to below 105 mercury, most of that hemorglobin will still be fully saturated."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So even if we go from, let's say, 105 to about 80 mercury inside the alveoli of the lungs, most of that hemoglobin will still be able to pick up our oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that is an important point, because in the lungs, our hemoglobin must be able to pick up that oxygen to carry it to the tissues of our body that require the oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So the flat curve tells us that even if the partial pressure in the Alveoloi drops, hemoglobin will still be pretty much saturated."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, let's move on to point number two."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, within our tissues, if our tissues aren't active, if we're not actively exercising, then our partial pressure of oxygen inside the tissues, on average, is about 40 mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So we're about somewhere right here."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, if we check out the corresponding Y value, we'll see that the percent saturation of hemoglobin at that partial pressure drops."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, what does that mean?"}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Well, that basically means when our red blood cells carrying the hemoglobin arrive at the tissues that hemoglobin, some of that hemoglobin will unload that oxygen and the oxygen will readily transfer to the tissues as a result of that difference in partial pressure."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And so what this graph tells us is our percent saturation will be somewhere in the 70s, which is lower than what it is within our lungs."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Within the lungs, it's about 98% because most of that oxygen is picked up."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "But within the tissue, we begin the process of unloading."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So the hemoglobin, some of it dissociates the oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And so now not all of it is fully saturated."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So in the tissues of our body, the partial pressure of oxygen is about 40 mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "This means that hemoglobin will unload some of that oxygen and it will move from the blood and into the tissue cells down its partial pressure concentration gradient."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Partial pressure gradient."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, if we begin to exercise, if our tissues are exercising, then what happens is the pressure, the partial pressure inside the tissue, drops even more."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So let's say now it drops to 20 mercury."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "Now, because of this sigmoidal curve, we have a very steep slope."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And what that means is a very small change in partial pressure will cause almost all of that hemoglobin to fully unload its oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that will ensure that all the oxygen is readily delivered to the exercising and active tissue."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So on this side of the curve we see that a small drop in pressure will basically unload most of that oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "But on this side of the curve we see that we can basically experience a relatively large change in pressure, but our oxygen will still take up our hemoglobin will still take up the oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And this is important because on this side we are within our lungs and on this side we are within our tissues."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "So when we're in the lungs, we want to make sure that even if we have a drop in pressure, the hemoglobin can still actually bind that oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "But within the tissues we want to make sure that even if there's a slight drop in the partial pressure of oxygen inside our tissue, we want to make sure that tissue receives that oxygen."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And so we have a drop in our slow."}, {"title": "Hemoglobin Cooperativity and Oxygen Dissociation Curve .txt", "text": "And that basically means that the hemoglobin will unload all of that oxygen and give the oxygen to the tissues of our body."}, {"title": "Polysaccharides .txt", "text": "So far we discussed monosaccharides and disaccharides."}, {"title": "Polysaccharides .txt", "text": "Now let's move on and talk about polysaccharides."}, {"title": "Polysaccharides .txt", "text": "So what exactly is a polysaccharide and what's the purpose of polysaccharides in nature?"}, {"title": "Polysaccharides .txt", "text": "Well, a polysaccharide is basically a very large carbohydrate that consists of many, many individual monosaccharides which are connected by Oglycoacetic bonds and the ore. Organisms in nature, including our own cells, use polysaccharides for one of two purposes."}, {"title": "Polysaccharides .txt", "text": "They either use polysaccharides as a form of storing energy."}, {"title": "Polysaccharides .txt", "text": "So we basically store glucose, as we'll see in just a moment, in the form we call glycogen, which is a polysaccharide."}, {"title": "Polysaccharides .txt", "text": "And whenever we want to form ATP molecules, we can break down glycogen into the individual glucose constituents and then we can feed those glucose molecules into the metabolism cycle glycolysis to basically form ATP molecules."}, {"title": "Polysaccharides .txt", "text": "Now, certain organisms, such as plants, as we'll see in just a moment, also use polysaccharides to basically form structure, give the cell structure and protection."}, {"title": "Polysaccharides .txt", "text": "Now, those polysaccharides that consist entirely of the same identical type of monosaccharide, these polysaccharides are known as homopolymers."}, {"title": "Polysaccharides .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Polysaccharides .txt", "text": "We're going to begin by discussing glycogen, which is the major type of polysaccharide that exists in our own cells and other animal cells."}, {"title": "Polysaccharides .txt", "text": "And then we're going to move on and discuss starch as well as cellulose."}, {"title": "Polysaccharides .txt", "text": "So let's begin with glycogen."}, {"title": "Polysaccharides .txt", "text": "So inside our cells, we store glucose in the glycogen form."}, {"title": "Polysaccharides .txt", "text": "And glycogen is essentially a homopolymer."}, {"title": "Polysaccharides .txt", "text": "It's a polysaccharide that consists of glucose molecules."}, {"title": "Polysaccharides .txt", "text": "Now, there are two types of bonds."}, {"title": "Polysaccharides .txt", "text": "Within glycogen."}, {"title": "Polysaccharides .txt", "text": "We have the more common alpha 114 glycocitic bond and the less common alpha 116 glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "Now, we call this an alpha one four glycocitic bond because it's a bond that exists between carbon number one on one glucose molecule and carbon number four on the adjacent glucose molecule."}, {"title": "Polysaccharides .txt", "text": "Now, if we examine the stereo chemistry of carbon number one, this will have an alpha arrangement of atoms."}, {"title": "Polysaccharides .txt", "text": "And what that means is we'll have an alpha one four glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "So remember, the alpha atomer means that this bond points in the opposite direction downward with respect to this bond here, which points upward."}, {"title": "Polysaccharides .txt", "text": "So this group points up and this bond here points downward."}, {"title": "Polysaccharides .txt", "text": "So just erase the oxygen."}, {"title": "Polysaccharides .txt", "text": "So let's redraw that oxygen here."}, {"title": "Polysaccharides .txt", "text": "Okay?"}, {"title": "Polysaccharides .txt", "text": "Now, as a result of the alpha one four glycositic bonds, these alpha one four glycocitic bonds basically give the glycogen a helical structure."}, {"title": "Polysaccharides .txt", "text": "So as a result of the alpha one four glycocitic bonds, even though this looks like a linear molecule, glycogen is not actually a linear molecule."}, {"title": "Polysaccharides .txt", "text": "It looks like a helical structure."}, {"title": "Polysaccharides .txt", "text": "Now, notice we also have the alpha 116 glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "So about every ten or so sugars, we're going to have this alpha one six glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "And these will be the branching points."}, {"title": "Polysaccharides .txt", "text": "These will cause branching along that helical structure."}, {"title": "Polysaccharides .txt", "text": "Now, we call this an alpha 116 glycocitic bond because it's between this first carbon."}, {"title": "Polysaccharides .txt", "text": "And this carbon number six on the adjacent sugar molecule."}, {"title": "Polysaccharides .txt", "text": "And this, just like that one, is an alpha anomer."}, {"title": "Polysaccharides .txt", "text": "And so that means we have the alpha 116 glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "So glycogen consists of glucose monomers linked via alpha one four glycocitic bonds in a helical fashion."}, {"title": "Polysaccharides .txt", "text": "So these alpha one four glycocitic bonds, this one, this one, this one, this one, this one, this one and so forth, they basically create this helical structure."}, {"title": "Polysaccharides .txt", "text": "And the helical chain has these branching points every ten or so units as a result of these alpha one six glycocitic bonds."}, {"title": "Polysaccharides .txt", "text": "And together, this basically gives glycogen a very branched structure."}, {"title": "Polysaccharides .txt", "text": "Now, when we want to break down glycogen, we can easily break down glycogen because we have the proteins, the enzymes that are able to break down glycogen into the individual constituents, the glucose molecules."}, {"title": "Polysaccharides .txt", "text": "And then we can use the glucose molecules in the process of glycolysis and the crept cycle to basically form the ATP molecules, the energy molecules which are used by our cells."}, {"title": "Polysaccharides .txt", "text": "So even though glycogen is not directly used as the energy source, we transform glycogen into something that we can use as an energy source, namely the high energy adenosine triphosphate molecules."}, {"title": "Polysaccharides .txt", "text": "Now, let's move on to starch."}, {"title": "Polysaccharides .txt", "text": "So if glycogen is the energy storage in animals and humans, starch is the energy storage in plant."}, {"title": "Polysaccharides .txt", "text": "So the most common polysaccharide in plants used for energy storage is starch."}, {"title": "Polysaccharides .txt", "text": "And unlike glycogen, which comes in one form, starch actually comes in two forms."}, {"title": "Polysaccharides .txt", "text": "We have a starch known as amylose and a starch known as amylopectin."}, {"title": "Polysaccharides .txt", "text": "Now, Amylose essentially consists of only one type of bond, the alpha one four glycositic bond."}, {"title": "Polysaccharides .txt", "text": "So Amylose is an unbranched polysaccharide that consists of glucose monosaccharides connected via alpha one four glycocitic bond."}, {"title": "Polysaccharides .txt", "text": "So the only difference between amylose and glycogen is in amylose, we don't have these alpha one six glycocitic bonds, we only have these alpha one four glycocitic bonds."}, {"title": "Polysaccharides .txt", "text": "So this is our example of amylose."}, {"title": "Polysaccharides .txt", "text": "Now, again, because of the presence of these alpha one four glycocity bonds, the actual structure of starch will essentially be like a helical structure as a result of these alpha one four glycosytic bonds."}, {"title": "Polysaccharides .txt", "text": "So even though in this diagram it looks like it's a linear molecule, it's not actually a linear molecule, because if we redraw these molecules in their chair conformations, we're going to see this helical structure that is formed."}, {"title": "Polysaccharides .txt", "text": "Now, the other type of starch molecule is amylopectin."}, {"title": "Polysaccharides .txt", "text": "And amylopectin is essentially almost the same as glycogen, because Amylopectin, just like glycogen, contains the alpha one four glycocytic bonds and the alpha one six glycocytic bonds."}, {"title": "Polysaccharides .txt", "text": "The only difference between amylopectin and glycogen is that in Amylopectin, these alpha one six glycocitic bonds are less common."}, {"title": "Polysaccharides .txt", "text": "In glycogen, these appear every ten or so units, but in starch, in amylopectum, they appear every 30 or so units."}, {"title": "Polysaccharides .txt", "text": "So amylopectum is a branched polysaccharide that consists of glucose monomers linked via alpha 114 linkages and branches connected via alpha one six glycocytic bonds."}, {"title": "Polysaccharides .txt", "text": "And the branches occur every 30 or so units."}, {"title": "Polysaccharides .txt", "text": "So amylopectin is just like glycogen, except it contains less of these branching points that we find in glycogen."}, {"title": "Polysaccharides .txt", "text": "Now, inside our mouth, we have the salivary glands, and inside our small intestine, at least inside our body, we have the pancreas that basically release the alpha amylase."}, {"title": "Polysaccharides .txt", "text": "So both of these glands release alpha amylase."}, {"title": "Polysaccharides .txt", "text": "So salivary glands in our mouth and our pancreas produce the alpha amylase, which are responsible for basically breaking down these bonds."}, {"title": "Polysaccharides .txt", "text": "And when we ingest the starch, the amylose, and the amylopectin, this is the enzyme that is responsible for breaking down these bonds and forming those individual glucose molecules."}, {"title": "Polysaccharides .txt", "text": "Actually, we form Maltose, and then maltose is broken down by Maltase at the brush border of our small intestine, as we discussed in the previous lecture."}, {"title": "Polysaccharides .txt", "text": "So glycogen is the polysaccharide that is used to store energy in animals, while starch is the polysaccharide that is used to store energy in plants."}, {"title": "Polysaccharides .txt", "text": "Now, let's move on to cellulose."}, {"title": "Polysaccharides .txt", "text": "Cellulose is actually one of the most common types of organic compounds on Earth, and cellulose is basically another very common type of polysaccharide that we'll find in plants."}, {"title": "Polysaccharides .txt", "text": "So cellulose, unlike starch and glycogen, plays a role in structure, and we'll see why that's the case."}, {"title": "Polysaccharides .txt", "text": "It has to do with the type of bonds that exist in cellulose."}, {"title": "Polysaccharides .txt", "text": "So we saw that in glycogen, as well as starch, we have these bonds we call the alpha one four glycocitic bonds."}, {"title": "Polysaccharides .txt", "text": "And we said that these alpha one four glycocitic bonds create a helical structure, and the helical structure is perfect to store it as energy."}, {"title": "Polysaccharides .txt", "text": "On the other hand, in Cellulose, we have individual monosaccharides of glucose that are connected via beta one four glycocytic bonds."}, {"title": "Polysaccharides .txt", "text": "And as a result of these beta one four glycocitic bonds, cellulose doesn't have a helicopter structure."}, {"title": "Polysaccharides .txt", "text": "Instead, it has a linear structure."}, {"title": "Polysaccharides .txt", "text": "So the beta one four linkages allow cellulose to form very long, straight chain linear fibers, as shown in the following diagram."}, {"title": "Polysaccharides .txt", "text": "So, unlike in this case and in this case, where the structure actually looks like a helical structure, here, it actually looks like a long, linear straight chain fiber as a result of the confirmation of the beta one four glycosytic bond."}, {"title": "Polysaccharides .txt", "text": "So why is this one four glycocitic bond?"}, {"title": "Polysaccharides .txt", "text": "Well, because the bond is once again between carbon number one of one glucose and the fourth carbon of the adjacent glucose."}, {"title": "Polysaccharides .txt", "text": "But the arrangement, the orientation of this first carbon, the Animeric carbon, is the beta arrangement."}, {"title": "Polysaccharides .txt", "text": "That means this bond points in the same direction up with respect to this bond."}, {"title": "Polysaccharides .txt", "text": "And so this is precisely what gives it that long linear structure."}, {"title": "Polysaccharides .txt", "text": "Now, as a result of the long linear structure, many of these fibers can basically stack on top of one another, and they can interact via hydrogen bonds."}, {"title": "Polysaccharides .txt", "text": "And that will give cellulose a very, very strong nature."}, {"title": "Polysaccharides .txt", "text": "So essentially many of these individual fibers of cellulose can stack on top of one another via hydrogen bonds and that gives it a very high tensile strength."}, {"title": "Polysaccharides .txt", "text": "And that's exactly why cellulose is optimal."}, {"title": "Polysaccharides .txt", "text": "It's used for providing structure protection as well as support to plant cells."}, {"title": "Polysaccharides .txt", "text": "And we'll talk much more about cellulose in future lecture."}, {"title": "Polysaccharides .txt", "text": "So we see that polysaccharides are used either to store energy and then convert that into ATP molecules as it happens inside our cells or they can be used in the form or they can be used to give the cell structure and protection as the case is."}, {"title": "Polysaccharides .txt", "text": "With cellulose in plant cells now inside our body we do not have enzymes that can break down these beta one four Glycosytic bonds in cellulose."}, {"title": "Polysaccharides .txt", "text": "But even though we can break down cellulose these types of polysaccharides are very important constituents of our diet because this is what we call dietary fiber."}, {"title": "Polysaccharides .txt", "text": "Cellulose is an insoluble fiber that we can ingest into our body."}, {"title": "Polysaccharides .txt", "text": "And what it does is it AIDS in the process of digestion."}, {"title": "Polysaccharides .txt", "text": "It speeds up the rate at which the food products basically move along our small and large intestine."}, {"title": "Polysaccharides .txt", "text": "And what that means is it decreases the likelihood that we're going to actually ingest toxins into our body."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "The next series of organelles that exist inside eukaryotic cells that we're going to discuss in detail include the vacuole Lysosomes, as well as the two types of microbodies, paroxysomes and glioxosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So let's begin by discussing what the vacuole is, where the vacuums are found, and what the function of the vacuums is."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So vacuum are membrane in closed organelles, so they contain a phospholipid bilayer."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And vacuoles are predominantly found in plant cells as well as fungal cells, but they can also be found in animal cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, vaccines are found inside the cytoplasm of our cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And the functionality, the shape and size of vaccines depends on the type of cell that we are examining."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So let's begin by examining plant cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So, in plant cells, the vacuums serves three important purposes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "One, it basically stores the water that is used by the cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Two, it creates and maintains the hydrostatic pressure, the turtle pressure that gives the plant cell its ability to resist forces as well as pressure."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And three, our vacuum basically creates an acidic environment that allows hydrolytic enzymes to break down macromolecules as well as waste products."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So generally in plants, vacuums function to store harmful materials and waste products, store water and maintain hydrostatic pressure, also known as turkey pressure."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And our acidic environment inside plant cells is basically a result of the integral proteins that are found inside the phospholipid layer of our plant vacuums."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Basically, those proteins inside the phospholipid bilayer pump H ions into our vacuole and that increases the acidity and lowers our PH."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And that gives these enzymes, the hydrolytic enzymes, the ability to break down the waste products stored inside vacuoles."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, in animal cells, vacuoles are much smaller, they do not store as much water, and they basically function in aiding endocytotic and endo and exocytotic processes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Remember, endocytosis is the process by which the cell engulfs extracellular material and exocytosis is the process by which the animal cell spits out wasteful types of products."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, let's move on to our Lysosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So what exactly is a Lysosome?"}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Well, a Lysosome is a spherically shaped, membrane enclosed organelle that are found in animal cells, although recent evidence shows that they can also be found in plant cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So basically, Lysosomes, just like vacuums, contain an acidic environment that is created as a result of the integral proteins found inside the phospholipid bilayer of the Lysosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So the H ions are pumped from the cytosol into the Lysosome and that creates that low PH, about 4.8 to five PH."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, this low PH allows our hydrolytic enzymes, also known as acid hydrolase enzymes, to basically break down the four different types of macromolecules."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And this includes lipids proteins, nucleic acids, as well as carbohydrates."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So all these different types of macromolecules, as well as other type of waste products and materials are broken down inside our Lysosomes as a result of these different types of enzymes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, because the Lysosome contains these hydrolytic enzymes and also contains a low PH."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "The Lysosome also has the ability to basically destroy that cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So if the Lysosome decides to basically rupture, it releases all these harmful types of things inside the cytosol and that can kill the cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, why exactly would a cell want to kill itself?"}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Well, imagine that the DNA of the cell is somehow damaged and that could cause serious problems."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So to basically kill off the cell, the Lysosome can rupture and that destroys the cell, as well as killing off that type of DNA that was basically damaged."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And this process is known as autolysis."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, where exactly are Lysosomes produced and where are the proteins inside the Lysosomes produced?"}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So basically, the proteins, the enzymatic proteins inside the Lysosomes are produced in the rough endoplasmic reticulum."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And once they are produced, they travel through the smooth endoplasmic material and eventually end up in the Golgi apparatus."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And the Golgi apparatus basically modifies those hydrolytic enzymes and then releases them inside secretory vesicles, which then fuse with endosomes, such as, for example, phangosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And that creates our Lysosome."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So basically, Lysosomes can also be used inside cells to destroy things like bacteria."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So inside our immune system, we have cell known as phagocytes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And those phagocytes undergo a process known as phagocytosis."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So engulfing things like bacteria, and the Lysosomes confuse with the phagosome that contains our bacterial cell and that can destroy our bacterial cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So we can see how Lysosomes can be very important inside animal cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, let's move on to a type of organelle known as the microbody."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So microbodies are generally small, spherical membrane enclosed organelles that contain a single phospholipid bilayer."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And there are two types of micro bodies."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "We have Paroxysomes as well as glyoxosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And let's begin by defining what a peroxoposome is."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So Paroxysomes are microbodies that carry out the different types of oxidation reduction reactions found inside the cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And it also produces a harmful byproduct known as hydrogen peroxide, which is then further broken down by using different types of enzymes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So there are many different types of protein enzymes found inside the Paroxysome."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And one of the major function, one of the major roles of the Paroxysome is to basically break down fatty acids into a type of energy source."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So it basically creates ATP."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So the mitochondria is not the only place in the animal cell where we create ATP."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Paroxysomes can also create ATP by breaking down the fatty acids."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, not only can we break down fatty acids inside Paroxysomes, we can also synthesize lipids, for example, cholesterol, inside our Paroxysomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And another important function of the Paroxysome is to basically detoxify our cell from different types of toxins as well as drugs."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So we have different types of protein enzymes found inside the Paroxosome that basically function to break down fatty acids to create lipids such as cholesterol, as well as detoxify our cell break down toxin as well as drugs such as, for example, alcohol so Paroxosomes are especially important in the cells found in the liver inside our bodies."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, what exactly is the major difference between a Lysosome and our Paroxysome?"}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So the hydrolytic enzymes found inside Lysosomes are generated in the rough endoplasmic reticulum, but unlike Lymphosomes, the enzymatic proteins inside Paroxosomes are not formed inside the rough endoplasmic reticulum, they are formed inside the free ribosomes, inside the cytosol of the cell."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So basically, once we form those proteins inside the free ribosomes, the proteins will basically go inside our Paroxysome."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And this is the major difference between Lysosomes and our peroxosomes."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, Paroxysomes can be found in both animals as well as plants."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "In animals, the peroxosome is called a Paroxysome, but in plants the Paroxysome is known as a Glioxosome."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So the Glioxosome is simply a specialized type of Paroxysome that is found in plant cells, especially in germinating plant cell, and it's also found in fungal cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So Glioxosomes are responsible for oxidizing fatty acids into intermediates that eventually become sugar."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So basically, before our plant cell matures into the mature plant cell, our Glyoxosome is the major source of the production of sugars."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And until the chloroplast of the plant cells mature, the Glyoxosome is the organelle that is responsible for producing sugar from fatty acids."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "So we see that Paroxysomes and Glyoxosomes are basically microbodies whose major function is to break down fatty acids into a usable source of energy."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, Paroxysome can also break down different types of toxins as well as drugs, and it can also synthesize lipids such as cholesterol."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, Lysosomes are spherically shaped membrane enclosed organelles that contain hydrolytic enzymes which are formed inside the rough endoplasmic reticulum."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And this organelle basically acts to break down the different types of macromolecules as well as break down harmful materials as well as bacterial cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And our vacuole is predominantly found in plant cells, so it stores water, it maintains hydrostatic pressure, turbulent pressure, and it also contains a low PH just like the Lysosol."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "And so it acts to kill off different types of toxic things and waste products."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Now, vacuums are predominantly found in plant cells, can also be found in animal cells, but the functionality differs."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "Lysosomes are predominantly believed to be found in animal cells, although recent evidence does show that Lysosomes might also be found in animal cells and microbodies are found in both animal cells and plant cells."}, {"title": "Vacuoles, Lysosomes, and Microbodies .txt", "text": "In animal cells, our microbody is called the Paroxysome, while in plant cells the Paroxysome is called agly oxosome."}, {"title": "Structure of ATP Synthase.txt", "text": "Complex one all the way through complex four."}, {"title": "Structure of ATP Synthase.txt", "text": "These complexes of the electron transport chain basically function to allow the movement of electrons across the inner membrane of the mitochondria and that ultimately allows us to establish a proton electrochemical gradient along the inner membrane of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "Now, following the establishment of this proton gradient, the final complex known as ATP synthase or sometimes known as complex five of the electron transport chain basically uses that proton motive force, that proton electrochemical gradient that was established to actually synthesize and release ATP molecules into the matrix of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "And in this lecture I'd like to focus on the structure of ATP synthase complex five of the electron transport chain."}, {"title": "Structure of ATP Synthase.txt", "text": "So just like the previous complexes, complex five is also found in the inner membrane of the mitochondria and it has the following elaborate structure."}, {"title": "Structure of ATP Synthase.txt", "text": "So the structure of ATP synthase is quite complex and we can break down the structure into two general regions."}, {"title": "Structure of ATP Synthase.txt", "text": "We have the f zero region and the f one region."}, {"title": "Structure of ATP Synthase.txt", "text": "Now the f zero region is this section here and the f one region is this section here."}, {"title": "Structure of ATP Synthase.txt", "text": "Let's begin by describing the f one region."}, {"title": "Structure of ATP Synthase.txt", "text": "Now the f one region basically consists of those polypeptide chains which are responsible for actually binding the ADP molecules and the orthophosphate molecules and forming those ATP and releasing the ATP into the matrix of that mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "So the f one region is the catalytic unit of this complex."}, {"title": "Structure of ATP Synthase.txt", "text": "So this region basically lies in the matrix of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "And we find five different types of polypeptide chains."}, {"title": "Structure of ATP Synthase.txt", "text": "Within the f one region we have the alpha shown in dark green."}, {"title": "Structure of ATP Synthase.txt", "text": "We have the beta shown in light green."}, {"title": "Structure of ATP Synthase.txt", "text": "We have the gamma shown in red."}, {"title": "Structure of ATP Synthase.txt", "text": "We have the epsilon shown in blue and we have the delta shown in purple here."}, {"title": "Structure of ATP Synthase.txt", "text": "Now let's discuss this alpha and the beta."}, {"title": "Structure of ATP Synthase.txt", "text": "We actually have three individual alpha units and three individual beta units."}, {"title": "Structure of ATP Synthase.txt", "text": "And these three alpha and three beta units basically create this hexameric alpha three beta three ring structure as shown in the following diagram."}, {"title": "Structure of ATP Synthase.txt", "text": "So these alpha and beta units basically alternate to form this ring structure that consists of these six individual polypeptide chains."}, {"title": "Structure of ATP Synthase.txt", "text": "Now, the function of this hexameric structure, as we'll see in the future lecture, is to actually bind the ADP and the orthophosphate molecules to synthesize the ATP molecules and then release the ATP molecules into the matrix of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "Now, although the alpha units can in fact bind the ATP molecules, only the beta units of this hexamer have the capability of actually synthesizing and releasing those ATP molecules."}, {"title": "Structure of ATP Synthase.txt", "text": "So once again, the three alpha and the three beta chains combine to form a hexameric alpha three beta three ring structure that will be responsible for catalyzing the synthesis of ATP molecules."}, {"title": "Structure of ATP Synthase.txt", "text": "And once again, although both of these chains, alpha and beta, have the ability to bind ATP, only the beta has the ability to actually synthesize and release those ATP molecules into the matrix of the mitochondria and we'll discuss how that mechanism actually takes place in a future lecture."}, {"title": "Structure of ATP Synthase.txt", "text": "Now so we discussed the alpha and the beta units."}, {"title": "Structure of ATP Synthase.txt", "text": "Now let's move on to the gamma and the epsilon unit."}, {"title": "Structure of ATP Synthase.txt", "text": "So we have a single gamma and a single epsilon unit that actually organized."}, {"title": "Structure of ATP Synthase.txt", "text": "They combine to form something called essential stock."}, {"title": "Structure of ATP Synthase.txt", "text": "And this central stock is this elongated structure that runs through the inner cavity of that hexameric ring and it also connects to this structure that is found within the S not region as we'll see in just a moment."}, {"title": "Structure of ATP Synthase.txt", "text": "So the gamma and the epsilon polypeptide so the red and the blue structures organize themselves to form something called essential stalk and this runs through the inner cavity of the hexameric ring."}, {"title": "Structure of ATP Synthase.txt", "text": "So if we take a cross section of this structure here this is basically what we're going to see."}, {"title": "Structure of ATP Synthase.txt", "text": "So we have these six chains, the alpha and the beta."}, {"title": "Structure of ATP Synthase.txt", "text": "And through the inner cavity we have that stock that is made up of this red structure as well as this blue structure as we see in this particular diagram."}, {"title": "Structure of ATP Synthase.txt", "text": "Now, what's the function of this gamma epsilon central stock?"}, {"title": "Structure of ATP Synthase.txt", "text": "Well, the GAM epsilon central stock will essentially connect this structure shown in orange to this structure here."}, {"title": "Structure of ATP Synthase.txt", "text": "And as that stalk basically rotates it will cause the catalysis of the ADP and the orthophosphate to form the ATP molecules and the subsequent release of those ATP molecules into the matrix of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "So once again the GAM epsilon central stalk will interact with the hexamer ring."}, {"title": "Structure of ATP Synthase.txt", "text": "As the stalk rotates it stimulates the synthesis and the release of ATP molecules and we'll discuss the details of that in a future lecture."}, {"title": "Structure of ATP Synthase.txt", "text": "And finally we have this delta chain as shown right over here."}, {"title": "Structure of ATP Synthase.txt", "text": "Now the delta subunit basically helps hold this entire hexameric structure in place so that it doesn't actually rotate."}, {"title": "Structure of ATP Synthase.txt", "text": "It is also actually used to connect this hexameric structure to this structure here that is part of the F not unit."}, {"title": "Structure of ATP Synthase.txt", "text": "So now let's move on and discuss the F zero unit."}, {"title": "Structure of ATP Synthase.txt", "text": "Now the F one region basically contains the catalytic unit while the F zero region as we'll see in just a moment actually contains that structure that allows the movement of the protons, the hydrogen ions down their electrochemical gradient from the intermembrane side to the matrix side of our ATP synthase."}, {"title": "Structure of ATP Synthase.txt", "text": "So the F knot region is mostly hydrophobic and lies within the inner membrane of the mitochondria and basically consists of two types of units."}, {"title": "Structure of ATP Synthase.txt", "text": "We have the C unit, the C subunit as well as the A subunits."}, {"title": "Structure of ATP Synthase.txt", "text": "And together the C and the A subunit basically interact to form this proton channel that allows the movement of those protons across the membrane of the of the mitochondria, the inner membrane of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "So the F knot region consists of ten to 14 C subunits."}, {"title": "Structure of ATP Synthase.txt", "text": "So in this particular case I've drawn ten."}, {"title": "Structure of ATP Synthase.txt", "text": "So we have 1234-5678, 910 of these orange structures and these ten C units basically organize themselves to form this ring structure which acts as a channel to allow the movement of those protons."}, {"title": "Structure of ATP Synthase.txt", "text": "So the ten to 14 C subunits organized into a ring structure that act as a proton channel."}, {"title": "Structure of ATP Synthase.txt", "text": "It ultimately allows the hydrogen ions to flow from the intermembrane space and into the matrix down their electrochemical gradients."}, {"title": "Structure of ATP Synthase.txt", "text": "Now we also have this A subunit that is shown here and the A subunit basically lies on the outer portion of this C ring structure."}, {"title": "Structure of ATP Synthase.txt", "text": "And the A subune also plays a role in helping move those protons along the membrane, across the membrane, the inner membrane of the mitochondria."}, {"title": "Structure of ATP Synthase.txt", "text": "Now on top of that the A subunit actually also holds this."}, {"title": "Structure of ATP Synthase.txt", "text": "The asymmet also actually connects this C structure to this structure that is part of the F one unit."}, {"title": "Structure of ATP Synthase.txt", "text": "So as shown in the following diagram we have a single A sub unit that is attached onto this arm which consists of two B change and that in turn is attached onto that delta subunit."}, {"title": "Structure of ATP Synthase.txt", "text": "And together this entire structure connects the F not to the F one section."}, {"title": "Structure of ATP Synthase.txt", "text": "So a single A subunit that binds to the outside of the C ring structure and the A subunit helps connect the F knot to the F one unit and also plays a role in proton transport."}, {"title": "Structure of ATP Synthase.txt", "text": "Now up to this point we basically see that the F zero region and the F one region are bound to one another at two locations by two structures."}, {"title": "Structure of ATP Synthase.txt", "text": "The first structure that holds the F zero to the F one is that central stock that consists of the gamma and the epsilon."}, {"title": "Structure of ATP Synthase.txt", "text": "So the gamma epsilon central stock connects the F zero region to the F one region."}, {"title": "Structure of ATP Synthase.txt", "text": "On top of that, we also have this arm on the outside composed of the single A, the two B structures and the single delta structure that hold these two units together."}, {"title": "Structure of ATP Synthase.txt", "text": "So the F one and the F zero are connected at two points."}, {"title": "Structure of ATP Synthase.txt", "text": "Firstly, they're connected through the gamma epsilon central stock and then they're also connected through the arm formed by the A subunit, the two B subunits and the delta subunits."}, {"title": "Structure of ATP Synthase.txt", "text": "Now some of these polypeptide chains actually rotate and some of them are stationary."}, {"title": "Structure of ATP Synthase.txt", "text": "So we can generalize and break down the ATP synthase into two regions the rotating region and the stationary region."}, {"title": "Structure of ATP Synthase.txt", "text": "Now the rotating region basically consists of the sea ring."}, {"title": "Structure of ATP Synthase.txt", "text": "So this entire orange structure as well as that central stalk that consists of this red gamma structure and this blue epsilon structure."}, {"title": "Structure of ATP Synthase.txt", "text": "So the rotating region, the structure that actually rotates as those protons actually move through this ATP synthase is composed of the Cring and the gamma epsilon stock and everything else is basically the stationary region."}, {"title": "Structure of ATP Synthase.txt", "text": "So we see that this A unit, the two B units, this delta unit as well as the alpha and the beta units are all stationary, they do not actually move."}, {"title": "Structure of ATP Synthase.txt", "text": "In fact, this section here, this A, B and the delta units, this structure together holds this hexameric structure in place and prevents it from actually moving."}, {"title": "Structure of ATP Synthase.txt", "text": "So in the next several lectures, we're actually going to discuss how or we're going to discuss what the mechanism of this ATP synthase actually is and how the movement of the protons along this region actually allows the structure to synthesize those high energy ATP molecules."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "The next topic that we're going to focus on will be the metabolism of amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So we're going to look at the synthesis of amino acids, the breakdown of amino acids, and we'll also actually go into study other biosynthetic processes that utilize amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So what exactly are amino acids and what are amino acids actually used for?"}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Well, amino acids are these nitrogencontaining molecules, molecules that, as you may know, are the building blocks of protein."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "But we also use amino acids to actually synthesize other important molecules, such as nucleotide bases."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And nucleotide bases are used to form DNA molecules, RNA molecules that are used to form ACP, the energy currency of the cell."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So amino acids are very important molecules, and we also actually utilize amino acids for energy, as we'll see in electra to come."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, what exactly are the sources of amino acids?"}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Well, ten out of the 20 amino acids used by the cells of our body are actually synthesized inside our cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So we can synthesize amino acids, ten amino acids from scratch, but the other ten amino acids are called essential amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And that's because we cannot actually synthesize those ten amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "These ten essential amino acids are obtained from two sources."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Source number one are dietary sources."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So we can ingest protein, break down the protein into amino acids, and then use the amino acids for some type of process."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And the other source of amino acids are the breakdown of preexisting proteins found inside our body, inside our cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So recall that we ingest food, and then that food, if it contains protein, it makes its way into the lumen of the stomach."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, in the lumen of the stomach, we have a low PH, a high acidity, an acidity of about two."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So the PH is about two."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And that low PH essentially stimulates it, activates an enzyme, a proteolytic enzyme known as pepsin."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So the protein inside the stomach is essentially denatured."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "It essentially goes from being a very structured protein to a randomly coiled protein, and that increases the surface area of that particular protein."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And now the pepsin can act on that increased surface area and cleave break down that protein into smaller protein molecules."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, those smaller protein molecules move from this lumen of the stomach is the lumen of the small intestine."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And once inside the lumen of the small intestine, we have other proteolytic enzymes produced by the pancreas are secreted into the lumen of the small intestine."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And these proteolytic digestive enzymes essentially begin to cleave the smaller proteins into oligopeptides and free amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, these amino acids are essentially absorbed into the cytoplasm of the small intestinal cells via special type of transport proteins."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, what about these allegateptides?"}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Well, oligopeptides are further digested to form dye and tripepptides by the enzymes found on the brush border of the small intestinal cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And these dying tripepptides can be absorbed via specific types of transport protein molecules."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Found within the cell membrane of these small intestinal cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, these dying trippeptides inside the cytoplasm, they're further cleaved into amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And then those amino acids, in combination of these amino acids, are transported into the bloodstream, in the bloodstream."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Then they move to their target location, their target cell."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, the other pathway by which we attain these 20 amino acids is by breaking down the existing proteins that are found inside our body."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So we have proteins found inside the cells as well as outside the cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And these proteins can be broken down and recycled into amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So we have many different types of proteins that exist as enzymes, and these enzymes must be inactivated."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And sometimes, to inactivate an enzyme, we proteolytically cleavage, we destroy it, and then we recycle those amino acids."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, some proteins can be damaged, for example, the oxidation processes."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And when proteins are damaged, we have special types of complexes that exist inside our cells, as we'll talk about in the next lecture, that utilize a protein known as Ubiquitin and a complex known as the proteosome complex that essentially breaks down and degrades damage or misfolded proteins into their amino acid constituents."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And then those amino acid constituents can be utilized by the cell to carry out some type of process, to build some type of important molecule."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Now, unlike fatty acid molecules or glucose molecules, amino acids are not actually stored inside our body."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So if we have excess amino acids, we cannot actually store that excess amino acids in the same way that we can store glucose as glycogen or fatty acids in our fat cells."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So what exactly happens to these excess amino acids?"}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "Well, as we'll discuss in the future lecture, these amino acids are actually broken down into carbon skeletons, as well as is into nitrogen containing molecules, ammonia, in the process known as urea."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "And we'll talk about this in much more detail in Electra to Come."}, {"title": "Introduction to Amino Acid Metabolism .txt", "text": "So in the next lecture, we're going to focus on the breakdown of proteins into amino acids by complex, known as the proteasome complex."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "In the next several lectures we're going to begin our discussion on the process of protein synthesis also known as translation."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now recall that DNA molecules although they do carry and store the genetic information that is needed for protein synthesis the DNA molecules themselves are not actually directly involved in protein synthesis."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So what happens is the genetic information that is stored in DNA is transferred, is passed down to RNA molecules and it's the RNA molecules that are directly involved in protein synthesis that takes place in the cytoplasm of the cell."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now remember, there are three different types of RNA molecules that we should be aware of and each one of these RNA molecules serves its own specific function."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now let's recall what these RNA molecules are and what their function is and let's begin with the messenger RNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So the messenger RNA, also known as the mRNA is basically the molecule that carries the genetic information from the nucleus into the cytoplasm of the cell and it's the mRNA molecule that is used as a template by the ribosomes to synthesize our polypeptide chain, our protein."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now the second type of RNA molecule that we should be aware of is the ribosomal RNA or rRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now rRNA is synthesized in the nucleolus of the nucleus of the cell and once synthesized it travels into the cytoplasm through the nuclear pores of the nuclear membrane of the cell."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now basically the rRNA is itself a constituent of the ribosomes."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So ribosomes are composed of proteins as well as rRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And the final type of RNA molecule that we should be aware of is transfer RNA or tRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So tRNA is also synthesized in the nucleus and the function of tRNA is to basically collect and bring the proper amino acids from the cytoplasm and into the ribosomes."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So the ribosomes can use those amino acids to synthesize the polypeptide chain."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, before we actually examine the process of translation let's discuss what ribosomes actually are and what they consist of."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So translation or the process of protein synthesis basically involves these special cell machineries known as ribosomes."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And any given ribosome itself consists of a small unit and a large unit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So we have the small subunit and a large subunit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So together a ribosome consists of two subunits."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, these subunits are basically composed of proteins as well as rRNA molecules."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So the r RNA molecules are created within the nucleolus and then they are brought into the cytoplasm and in the cytoplasm, as we'll see in just a moment the two subunits the large and the small subunits combined with our mRNA to form our ribosome."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now both prokaryotic and eukaryotic organism contain ribosomes but in eukaryotic and prokaryotic organisms our ribosomes are slightly different so they consist of slightly different small and large subunits."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So let's take a look at the differences between our subunits."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So let's begin with eukaryotic organisms."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So in eukaryotes our small subunit is the 40s while the large subunit is the."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "They combine to form a unit known as the."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now in prokaryotic organism, the small subunit is the, large subunit is the they combine to form the."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, the question that you might be asking is what exactly is the s?"}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "What does the s actually stand for?"}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Well, S basically stands for the Svetberg unit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And this is basically a unit that measures the rate at which the given particle or molecule in this case are a subunit sediments."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So the Svetberg unit usually refers to how quickly something sediments or travels along or down a test tube that is basically rotating with some angular velocity."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And the Svedberg unit is directly related to the mass of our particle and it also depends on the size and the shape of the molecule."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So heavier molecules will be found farther down the test tube than lighter molecules."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So we see that the larger subunits the will be found farther down our test tube than the because the are basically heavier molecules."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, what exactly is the purpose of these small and large subunits?"}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Well, basically before our translation actually takes place, the small and large subunits are separated."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "They only come together during the process of translation as we'll see in just a moment and the purpose of our ribosome."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So basically the large and the small subunit combined to form the ribosome."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And the purpose of the ribosome is to basically translate the sequence of nucleotides into the proper sequence of amino acids."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And this is exactly what we mean by translation."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So the ribosome is basically translate the language of the mRNA into the language of our protein and thereby synthesize our proteins by using our genetic code."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, our process of translation can be broken down into three stages."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "We have the initiation stage, we have the elongation stage and the termination stage."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "In this lecture, we're only going to focus on our initiation stage."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So once our precursor mRNA or pre RNA actually undergoes the proper post transcriptional modifications in the nucleus, it basically becomes the mRNA and it leaves the nucleus via the nuclear pores."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Now, once it enters a cytoplasm, special types of proteins that are known as initiation factors basically help the mRNA find the small subunit and the small subunit binds to the five end of our mRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And once the small subiant binds to our five end, it begins to travel along our mRNA until it finds, until it locates a specific sequence of amino of nucleotides that is known as the start codon."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And this sequence is beginning with the five naug and ending with our three n. So basically this is described in the following diagram."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So once our mRNA is inside the nucleus, a set of proteins known as initiation factors helps our small subians locate the five end of our mRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And once it binds, it travels along our mRNA until it locates our star codon."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "The sequence aug. And once it locates the aug sequence."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "Our small subunit basically tells its signals a tRNA molecule to go out and find a methionine molecule and it brings our tRNA brings that methionine molecule to our aug."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So this is our tRNA molecule."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "It contains the complementary sequence to our aug."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So if this is the five end and this is the three end we have aug, then this is the three end UAC and this is the five end."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And so once our small subune locates the start codon, this basically goes out and this goes out and finds our methionine which is shown in orange and then it brings our methionine to this location."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And once our tRNA combines with this region, our large subunit also combines with a small subunit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And so we form our ribosome molecule."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And this concludes the process of initiation and the site the location of our tRNA molecule inside the ribosome is known as the psych."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "In the next lecture, we're going to discuss the next stage known as elongation and the final stage known as termination."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And we'll see that there are two other important sites that exist inside our ribosome known as the a side as well as our e site."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So we see that the process of translation involves three types of RNA molecules."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "We have mRNA, tRNA and rRNA."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And basically what happens during the first stage of translation is our mRNA locates our small subunit which then basically finds our aug star codon sequence."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And once it finds, it signals Atrna to pick up the methionine amino acid and bring it into our small subunit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And once that bi takes place, it signals the large subunits shown here."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "So this is a small this is the large unit."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "It tells the large subunit to basically attach to the small subunit and that forms the ribosome."}, {"title": "Translation: Ribosomes and Initiation.txt", "text": "And that concludes the process of initiation."}, {"title": "Sickle-Cell Anemia .txt", "text": "In humans, a condition we call sickle cell anemia afflicts red blood cells and more specifically, the hemoglobin molecules found inside red blood cells."}, {"title": "Sickle-Cell Anemia .txt", "text": "So in individuals who have sickle cell anemia the hemoglobin molecules are slightly abnormal and we'll see exactly what that abnormality is in just a moment."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, as a result of this abnormality in the hemoglobin globin molecule, when the hemoglobin molecule is in its deoxygenated state the hemoglobin molecules will begin to bind to one another and aggregate and eventually they'll form these long fibers in the shape of a sickle."}, {"title": "Sickle-Cell Anemia .txt", "text": "And as a result of the formation of these fibers inside red blood cells the healthy biconcave shape of the red blood cells will transform into this abnormal sickle shape."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, what exactly will that do?"}, {"title": "Sickle-Cell Anemia .txt", "text": "Well, let's take a look at the following diagram."}, {"title": "Sickle-Cell Anemia .txt", "text": "So we have this blood capillary and we have the deviation in the blood capillary as shown."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, these are the normal healthy biconcave red blood cells and because of their bi concave nature they will easily and effectively be able to squeeze through the tiny capillaries of our cardiovascular system and they will not bind, they will not aggregate to one another."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, when the red blood cells transform their biconcave shape into the sickle shape, these sickle shaped red blood cells will begin to aggregate and that can lead to clogging of these capillaries."}, {"title": "Sickle-Cell Anemia .txt", "text": "So for example, if we clog this region of the capillary, what that does is it increases the pressure on this side and that can push against the walls of the capillaries and that can lead to very painful swelling."}, {"title": "Sickle-Cell Anemia .txt", "text": "On top of that, if we clogged this section then there will be poor blood flow in this region of our capillary and that can lead to poor circulation of the blood in the cardiovascular system."}, {"title": "Sickle-Cell Anemia .txt", "text": "And this in turn can lead to an increased risk of stroke because stroke, remember, is the process by which we don't get enough blood and don't get enough oxygen to the brain."}, {"title": "Sickle-Cell Anemia .txt", "text": "It also will increase the risk of bacterial and pathogenic infection because remember, the immune system of our body uses the cardiovascular system to transport the different types of antibodies and immune cells throughout our system."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so if our blood flow is poor, what that means is there is a decrease in the ability of that immune system to actually carry out its response."}, {"title": "Sickle-Cell Anemia .txt", "text": "So once again, individuals with sickle cell anemia have abnormal hemoglobin molecules."}, {"title": "Sickle-Cell Anemia .txt", "text": "The hemoglobin molecules are the hemoglobin molecules in their deoxygenated state and we'll discuss why that."}, {"title": "Sickle-Cell Anemia .txt", "text": "So in just a moment begin to aggregate with one another to form long sickle shape fibers."}, {"title": "Sickle-Cell Anemia .txt", "text": "And this in turn transforms the health feed normal by concave shape of the red blood cells into the sickle shape as shown in this diagram."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, these sickle shaped red blood cells can aggregate and clog the tiny capillaries found in our cardiovascular system and this can result in painful swelling, impaired blood flow, increased risk of stroke as a result of poor blood flow to the brain, as well as increased risk of pathogenic infection as a result of the impaired blood flow."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, in addition to these different results, these abnormal shaped red blood cells, the sequel shaped red blood cells, have a shorter lifespan."}, {"title": "Sickle-Cell Anemia .txt", "text": "And what that means is that will cause these red blood cells to die quicker."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so there will be a decrease in the number of red blood cells found inside our body."}, {"title": "Sickle-Cell Anemia .txt", "text": "And this is known as anemia."}, {"title": "Sickle-Cell Anemia .txt", "text": "And that's exactly why we call this condition sickle cell anemia."}, {"title": "Sickle-Cell Anemia .txt", "text": "The sickle cells simply don't live as long as the normal cells, and so they eventually die at a quicker rate."}, {"title": "Sickle-Cell Anemia .txt", "text": "And that leads to anemia, a lower blood count, a lower red blood cell count."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, the question is, what exactly is the abnormality in the hemoglobin molecule?"}, {"title": "Sickle-Cell Anemia .txt", "text": "Well, it turns out it's a genetic abnormality."}, {"title": "Sickle-Cell Anemia .txt", "text": "So instead of sequencing a specific polypeptide chain, we sequence a slightly different polypeptide chain."}, {"title": "Sickle-Cell Anemia .txt", "text": "And in the case of sickle cell anemia, there's a single substitution of a single amino acid in the beta subunit of the hemoglobin molecule."}, {"title": "Sickle-Cell Anemia .txt", "text": "So instead of synthesizing glutamate at the 6th position, we synthesize valine at that 6th position."}, {"title": "Sickle-Cell Anemia .txt", "text": "And the problem is the properties of these two amino acids is different."}, {"title": "Sickle-Cell Anemia .txt", "text": "The properties of this one is that of a polar molecule."}, {"title": "Sickle-Cell Anemia .txt", "text": "But valine is a non polar molecule, and that will create the difference, as we'll see in just a moment."}, {"title": "Sickle-Cell Anemia .txt", "text": "So what causes that normal shape of hemoglobin?"}, {"title": "Sickle-Cell Anemia .txt", "text": "Well, it turns out that there is a genetic error that leads to a single amino acid substitution in the beta chains of the hemoglobin molecules."}, {"title": "Sickle-Cell Anemia .txt", "text": "Remember, we have two beta chains in a single hemoglobin molecules, and both of those chains will have that abnormality."}, {"title": "Sickle-Cell Anemia .txt", "text": "So glutamate at the 6th position is substituted to the valley in that same position."}, {"title": "Sickle-Cell Anemia .txt", "text": "So in normal hemoglobin, glutamate six is a polar molecule, and normally it points to the surface, to the outside of the blood plasma."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, blood plasma consists predominantly of water molecules, and water is polar."}, {"title": "Sickle-Cell Anemia .txt", "text": "And because glutamate is polar, glutamate has no problem interacting with the water molecules."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so that creates no problem because that glutamate would much rather interact with the polar molecules than any other nonpolar molecule."}, {"title": "Sickle-Cell Anemia .txt", "text": "So the beta subunits of the normal hemoglobin, as shown in the following diagram, have a polar residue at a six position."}, {"title": "Sickle-Cell Anemia .txt", "text": "And that means the glutamate has no problem interacting with the polar water molecules found in close proximity."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, let's take a look at this diagram."}, {"title": "Sickle-Cell Anemia .txt", "text": "In this diagram, this is the abnormal beta subunit of the hemoglobin molecule."}, {"title": "Sickle-Cell Anemia .txt", "text": "And instead of having glutamate, we now have Valene."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, the problem with this is valine is nonpolar, and it doesn't want to interact with the polar water molecules."}, {"title": "Sickle-Cell Anemia .txt", "text": "So what that means is if it comes in close proximity to some type of nonpolar molecule, it will react with that molecule and interact with that molecule via electrostatic interactions."}, {"title": "Sickle-Cell Anemia .txt", "text": "And what happens is if this abnormal beta subunit of one hemoglobin molecule comes in close proximity with the beta subunit of an adjacent deoxy hemoglobin molecule, there are two amino acids, nonpolar amino acids that the valine can interact with."}, {"title": "Sickle-Cell Anemia .txt", "text": "We have valine 88 or a phenylalanine 85."}, {"title": "Sickle-Cell Anemia .txt", "text": "Either one of these non polar amino acids on this beta subunit will interact with this valine and that will form the aggregate."}, {"title": "Sickle-Cell Anemia .txt", "text": "And this will continue its aggregation process and eventually form that long fiber that has a sickle shape and that will distort the biconcape shape and form that sickle shape for those red blood cells."}, {"title": "Sickle-Cell Anemia .txt", "text": "Now, the reason we require a deoxy hemoglobin is because when the hemoglobin molecule is oxygenated, these two amino acids, valine and phenylalamine, disappear into inside that structure of the beta submune."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so in that case, when we're dealing with the oxygenated form of hemoglobin, these two amino acids are found inside."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so since they cannot interact with the valley, they will not aggregate."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so that's why the aggregation only takes place in the deoxygenated state of hemoglobin."}, {"title": "Sickle-Cell Anemia .txt", "text": "So this is what sickle cell anemia is."}, {"title": "Sickle-Cell Anemia .txt", "text": "Sickle cell anemia is basically the condition in which the genes that code for the beta subunits are basically they have some type of genetic mistake."}, {"title": "Sickle-Cell Anemia .txt", "text": "And so when those genes are read and we express the proteins, there's a single substitution."}, {"title": "Sickle-Cell Anemia .txt", "text": "Instead of forming the glutamate at the 6th position on the beta subunit, we form the valley."}, {"title": "Sickle-Cell Anemia .txt", "text": "And that creates all the difference that's leads to the aggregation of those deoxygenated hemoglobin molecules and that forms the sickle shape of these red blood cells."}, {"title": "Resting Membrane Potential .txt", "text": "If we measure the voltage difference, the electric potential difference between the two sides of the membrane of a resting neuron, we'll see the value is equal to about negative 70 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "And this is what we call the resting membrane potential of that cell."}, {"title": "Resting Membrane Potential .txt", "text": "The resting membrane voltage."}, {"title": "Resting Membrane Potential .txt", "text": "Now the question is, what exactly establishes the resting membrane potential?"}, {"title": "Resting Membrane Potential .txt", "text": "Where does it actually come?"}, {"title": "Resting Membrane Potential .txt", "text": "And more precisely, how can we actually measure the resting potential the resting memory potential of a cell?"}, {"title": "Resting Membrane Potential .txt", "text": "So how can we calculate the value of negative 70 millivolts?"}, {"title": "Resting Membrane Potential .txt", "text": "Well, let's begin by taking a look at the following diagram."}, {"title": "Resting Membrane Potential .txt", "text": "So this is our phospholipid bilayer membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And in that membrane, we have some type of ion channel."}, {"title": "Resting Membrane Potential .txt", "text": "Now, this ion channel in this diagram is closed, and it will not allow the movement of any one of these ions."}, {"title": "Resting Membrane Potential .txt", "text": "And let's suppose we're only focusing on two different types of ions."}, {"title": "Resting Membrane Potential .txt", "text": "So we have these positively charged orange ions and these negatively charged green ions."}, {"title": "Resting Membrane Potential .txt", "text": "Now, because this is closed and because the membrane is predominantly hydrophobic nonpolar, none of these ions will begin to pass across."}, {"title": "Resting Membrane Potential .txt", "text": "Even though we have a concentration gradient that exists between the two sides."}, {"title": "Resting Membrane Potential .txt", "text": "So we have a higher concentration here."}, {"title": "Resting Membrane Potential .txt", "text": "So this is the higher concentration potential."}, {"title": "Resting Membrane Potential .txt", "text": "A lower concentration here for both of these ions."}, {"title": "Resting Membrane Potential .txt", "text": "So this is the lower potential and that creates this concentration gradient."}, {"title": "Resting Membrane Potential .txt", "text": "And so if we somehow create a pathway, these ions will want to move spontaneously."}, {"title": "Resting Membrane Potential .txt", "text": "This way."}, {"title": "Resting Membrane Potential .txt", "text": "So when we open up these channel, this channel what begins to happen?"}, {"title": "Resting Membrane Potential .txt", "text": "Well, let's suppose the channel is a specific ion channel, and it only allows the movement of these cat ions."}, {"title": "Resting Membrane Potential .txt", "text": "It doesn't allow the movement of the Anion."}, {"title": "Resting Membrane Potential .txt", "text": "So as we open it up, what happens is because of this concentration difference that exists between the two sides, these positively charged ions will begin to move spontaneously from this side to this side."}, {"title": "Resting Membrane Potential .txt", "text": "But what happens?"}, {"title": "Resting Membrane Potential .txt", "text": "Over time, the rate of movement begins to decrease until the rate of movement is equal to zero."}, {"title": "Resting Membrane Potential .txt", "text": "The question is, why does that actually take place?"}, {"title": "Resting Membrane Potential .txt", "text": "Why does the rate of movement of these cations from this side to this side ultimately decrease to zero?"}, {"title": "Resting Membrane Potential .txt", "text": "Well as these cations are brought to this side, as they move to this side, that increases the total amount of positive charge on this side of the membrane, because as each one of these cations move this way, it brings with it a full positive charge."}, {"title": "Resting Membrane Potential .txt", "text": "And so, as each one of these cations moves this way, as a result of that positive charge build up, they begin to feel an electrostatic repulsive force."}, {"title": "Resting Membrane Potential .txt", "text": "Due to that positive charge build up, and so that's why the rate begins to decrease."}, {"title": "Resting Membrane Potential .txt", "text": "And eventually, when the force due to that concentration gradient is equal to the force due to that electric repulsion, when these two forces are equal because they point in opposite directions, if we sum them up, the net force will be equal to zero."}, {"title": "Resting Membrane Potential .txt", "text": "And we know by Newton's second law of motion, if the net force is zero, they will not actually move across that cell membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And this moment in time is known as the equilibrium point."}, {"title": "Resting Membrane Potential .txt", "text": "So when these cations reach their equilibrium points, there will still be an unequal distribution of these molecules, these ions."}, {"title": "Resting Membrane Potential .txt", "text": "And at that moment in time, we can calculate exactly what that voltage potential difference is."}, {"title": "Resting Membrane Potential .txt", "text": "What that voltage difference is between the two sides of the membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And if we carry the same exact procedure as with the other ions, and then we take the average of those values, that will give us the resting membrane potential, So the electric potential difference across the membrane at the equilibrium point is what we call the resting membrane potential."}, {"title": "Resting Membrane Potential .txt", "text": "So the resting potential is a result of the existence of the unequal distribution of these charged ions across that cell membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And the next question is, how can we actually calculate what the resting membrane potential is?"}, {"title": "Resting Membrane Potential .txt", "text": "And to demonstrate this, let's use two types of ions."}, {"title": "Resting Membrane Potential .txt", "text": "So we're going to look at sodium as well as potassium."}, {"title": "Resting Membrane Potential .txt", "text": "So this is our membrane."}, {"title": "Resting Membrane Potential .txt", "text": "Now for a resting cell."}, {"title": "Resting Membrane Potential .txt", "text": "For a resting neuron."}, {"title": "Resting Membrane Potential .txt", "text": "The inside concentration of sodium is about 14 millimeter."}, {"title": "Resting Membrane Potential .txt", "text": "Millimolar?"}, {"title": "Resting Membrane Potential .txt", "text": "The outside concentration is about 143 millimolar."}, {"title": "Resting Membrane Potential .txt", "text": "The inner concentration of potassium is about 157."}, {"title": "Resting Membrane Potential .txt", "text": "And the average concentration is about four millimolar."}, {"title": "Resting Membrane Potential .txt", "text": "Now, from basic chemistry, we know that to calculate the voltage difference between these two points as a result of the unequal distribution of these two charged species, all we have to do is use the nurse equation."}, {"title": "Resting Membrane Potential .txt", "text": "So the voltage due To The concentration difference between Some ion x is Equal To The negative of RT divided by ZF, where R is the gas constant, t is the temperature in Kelvin, z is the charge on that ion, and F is Sarah d's constant."}, {"title": "Resting Membrane Potential .txt", "text": "We multiply this ratio by the natural log of the ratio of the concentration of the inside to the concentration of the outside."}, {"title": "Resting Membrane Potential .txt", "text": "So this is the equation that we can use to actually calculate what the voltage difference is at the equilibrium point for each one of these two ions."}, {"title": "Resting Membrane Potential .txt", "text": "So let's begin with sodium."}, {"title": "Resting Membrane Potential .txt", "text": "So for sodium."}, {"title": "Resting Membrane Potential .txt", "text": "So the gas constant."}, {"title": "Resting Membrane Potential .txt", "text": "And it is 8.3 114 joules divided by moles times Kelvin."}, {"title": "Resting Membrane Potential .txt", "text": "The pharisees constant is 96,500 couloms per mole."}, {"title": "Resting Membrane Potential .txt", "text": "D for sodium is."}, {"title": "Resting Membrane Potential .txt", "text": "Well, we have a charge of positive one."}, {"title": "Resting Membrane Potential .txt", "text": "And the T. Well, let's assume where at our cellular temperature, that's about 37 degrees Celsius."}, {"title": "Resting Membrane Potential .txt", "text": "So 37 plus 273, that gives us 310 Kelvin."}, {"title": "Resting Membrane Potential .txt", "text": "And so t is 310 Kelvin."}, {"title": "Resting Membrane Potential .txt", "text": "So we plug these values in."}, {"title": "Resting Membrane Potential .txt", "text": "Then we plug in 14 millimolar for this X in."}, {"title": "Resting Membrane Potential .txt", "text": "And then we plug in 143 millimolar for the X out."}, {"title": "Resting Membrane Potential .txt", "text": "And so because the natural log of a ratio that is less than one is negative, this negative value becomes a positive."}, {"title": "Resting Membrane Potential .txt", "text": "And So We get a value about positive zero point 62 volts."}, {"title": "Resting Membrane Potential .txt", "text": "And if we multiply this by 1000, that gives us the value in millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "So, 62 millivolts is the electric potential difference between the two sides due to these sodium ions."}, {"title": "Resting Membrane Potential .txt", "text": "So, if we omit all the other ions that are present across the two sides, then what that means is in such a case, the resting memory potential of that cell would simply be equal to positive 62 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "But we know we have other ions present across the cell membrane."}, {"title": "Resting Membrane Potential .txt", "text": "For instance, we have this potassium."}, {"title": "Resting Membrane Potential .txt", "text": "So let's carry out that same procedure with potassium."}, {"title": "Resting Membrane Potential .txt", "text": "So we plug in our constants."}, {"title": "Resting Membrane Potential .txt", "text": "So notice that the charge is also positive one."}, {"title": "Resting Membrane Potential .txt", "text": "And now we plug in our concentrations, and now this higher concentration is at the top."}, {"title": "Resting Membrane Potential .txt", "text": "And so natural log of a ratio that is greater than one will be a positive number."}, {"title": "Resting Membrane Potential .txt", "text": "And so this will remain negative."}, {"title": "Resting Membrane Potential .txt", "text": "And if we plug this into our calculator, we get about negative zero point 98 volts, or equivalent to negative 98 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "So what that means is, if we are only considering these two ions, and if we assume that the membrane is impermeable to either one of these ions, that means all these ion channels are actually closed."}, {"title": "Resting Membrane Potential .txt", "text": "And if we omit, if we neglect all the other ions to calculate the actual resting memory potential, all we have to do is find the average of these two values."}, {"title": "Resting Membrane Potential .txt", "text": "And so the average of these two values is about negative 18 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "So we can basically approximate this to around negative 20 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "Now, the question is, why then is the resting memory potential of our resting neuron negative 70 millivolts?"}, {"title": "Resting Membrane Potential .txt", "text": "Why isn't it this quantity?"}, {"title": "Resting Membrane Potential .txt", "text": "Well, first of all, because we also have other ions across that cell membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And so we have to also consider the voltages of those other ions."}, {"title": "Resting Membrane Potential .txt", "text": "And that's why this value will actually change."}, {"title": "Resting Membrane Potential .txt", "text": "But that's not the most important factor that actually determines this quantity."}, {"title": "Resting Membrane Potential .txt", "text": "The more important factor is the following."}, {"title": "Resting Membrane Potential .txt", "text": "It turns out that the potassium ion channels are actually more permeable to potassium than the sodium ion channels are permeable to sodium."}, {"title": "Resting Membrane Potential .txt", "text": "In fact, we actually have these potassium ion channels that are open within that membrane."}, {"title": "Resting Membrane Potential .txt", "text": "And if we have some of these potassium ion channels open along that resting membrane, what that means is we'll have a movement, a leakage of these K plus ions out of that cell."}, {"title": "Resting Membrane Potential .txt", "text": "And that leakage will basically drive this value to a more negative value."}, {"title": "Resting Membrane Potential .txt", "text": "It will basically decrease it."}, {"title": "Resting Membrane Potential .txt", "text": "And that's exactly why the actual resting membrane potential is actually way closer to this value than to this value because of those K plus ion channels."}, {"title": "Resting Membrane Potential .txt", "text": "So because the potassium ion channels are actually open, some of them are open."}, {"title": "Resting Membrane Potential .txt", "text": "What that means is this will be closer to this value than to this value."}, {"title": "Resting Membrane Potential .txt", "text": "And that's exactly why it's around negative 70 millivolts, which is closer to this than to this value."}, {"title": "Resting Membrane Potential .txt", "text": "So we see that in the absence of other ions, and assuming all ion channels are closed and the membrane is impermeable to either one of these ions, in such a case, the resting memory potential would simply be the average of these two values, which is around negative 20 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "But that is not the case."}, {"title": "Resting Membrane Potential .txt", "text": "Why?"}, {"title": "Resting Membrane Potential .txt", "text": "Well, it turns out that some of the K plus ion channels are actually open, so they're more permeable to the K plus then the sodium channels are permeable to the N A plus."}, {"title": "Resting Membrane Potential .txt", "text": "And so this causes the leaking of the positive charge out of that cell because some of these K plus odds can actually leak out through those open channels."}, {"title": "Resting Membrane Potential .txt", "text": "And that basically makes this value more negative."}, {"title": "Resting Membrane Potential .txt", "text": "It decreases it to a value of around negative 70 millivolts."}, {"title": "Resting Membrane Potential .txt", "text": "So we see that the resting membrane potential is basically the average of all these different voltages that exist due to the unequal distribution of all these different ions."}, {"title": "Resting Membrane Potential .txt", "text": "So we conclude that the resting potential is a result of the unequal distribution of these ions that exist along or across that resting membrane."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Previously, we discussed the concept of enzyme inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And we said there are two categories of enzyme inhibitors."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "We have irreversible enzyme inhibitors that bind onto the enzymes and don't let go, don't dissociate very easily."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And we also have the reversible enzyme inhibitors that bind onto the enzymes, but they can dissociate quite easily under specific conditions."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, we also said we can subdivide reversible inhibitors into three types."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "We have competitive inhibitors, we have uncompetitive, and we have non competitive reversible inhibitors."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what I want to focus in this lecture is how exactly do these three types of reversible inhibitors actually affect the kinetics of enzymes?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "How do they affect things like the turnover number, the Macalus constant, and VMAX, the maximum velocity of that enzyme?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So let's begin by focusing on competitive inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So this is the equation that describes competitive inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So in the absence of an inhibitor, that substrate is going to collide into and bind to the active site of the enzyme, forming the functional enzyme substrate complex."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And then that complex will catalyze and transform the substrate into the product, which will then dissociate and be released from that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, in the absence of an inhibitor, the curve that describes the substrate concentration to the velocity is this black curve here."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And notice the black curve eventually reaches a maximum velocity."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "That's the point when all the active sites of all the enzymes are filled by that substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, in the presence of an inhibitor, what happens is because the inhibitor resembles that substrate, it's going to bind to that same active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And once it binds, it forms this enzyme inhibitor complex."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And because that inhibitor is found in that active side, the substrate is not found in that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so that enzyme is inhibited."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, the thing about competitive inhibition is because the substrate binds the same exact region as the inhibitor, if we increase the concentration of that substrate, there is a greater likelihood that the substrate is going to collide into that active site, and that can displace and replace that inhibitor in the active side to form back this enzyme substrate complex."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so all we have to do to basically overcome competitive inhibitors is to increase the concentration of the substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that ultimately means is if we examine the red curve, which ascribes the presence of the inhibitor, if we increase the concentration of S, if we move along to the right side along the X axis, eventually the red curve is going to reach the same VMAX value as the black curve."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that means is in the presence of a competitive inhibitor, that VMAX does not actually change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And once again, this is because that inhibitor binds to the same exact section as that substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so that inhibitor can be overcome by increasing the concentration of that substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So even though we have to increase the concentration of that substrate, eventually all those inhibitors in the active sites will be replaced with that substrate, and all the same active sites are going to be filled by that substrate in the inhibition case, as in the absence of the inhibitor."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so the same Dmax will actually be reached."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, let's move on to fact number two about competitive inhibition and enzyme kinetics."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "The turnover number, KCAD does not actually change is not affected by a competitive inhibitor."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that can be seen from the following equation."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So in our lecture, in our discussion on the turnover number, we said that the turnover number basically describes the efficiency of that active site."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So it's basically the number of substrate molecules that can be transformed into the product molecules over some amount of time per single active site, so per enzyme."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And because the turnover number is not changed, what that means is the efficiency of that active site in the presence of the inhibitor does not actually change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And this can be seen from this equation."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "If VMAX does not actually change and the total concentration of that enzyme that is functional does not change, then Kcat also does not change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "It remains constant."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so because these two don't change, the turnover number also does not change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So VMAX doesn't change, Kcat doesn't change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "But what does change is the Km."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "The Km value essentially increases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And all that means is to reach the same rates in the inhibition case as in the absence of the inhibitor, to reach the same rate of activity."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "All we have to do is increase the substrate concentration to basically reach that same velocity of that enzyme."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that means our Km value will increase."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Because remember, the Km value basically describes the VMAX divided by two."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So when our mixture reaches a concentration of substrate that is equal to Km, the velocity of that enzyme will be exactly midway between the VMAX and the zero point."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So v max divided by two, because v max doesn't change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "V max divided by two doesn't change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so if we look at the corresponding Y coordinate point, at the corresponding x coordinate point for this Y coordinate, in the case of no inhibitor, present it's here."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "In the case of the inhibitor, present it's farther along that x axis, and so the Km is greater."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So competitive inhibitors increase the parent Km value."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So since most of the active sites are occupied by the inhibitor, a larger amount of substrate needs to be present to actually overcome and displace that inhibitor to reach that same enzyme rate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And this means a higher amount of substrate is actually needed to reach that rate of VMAX divided by two."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, what this also means is, because the Km increases, the finity of that substrate for the active side decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that's because now we have an inhibitor that has a higher affinity for that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so we have to increase the number of substrate molecules to increase the likelihood of collision with that active side to actually displace and replace that inhibitor in the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, let's move on to uncompetitive inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "In this type of inhibition, the only time the inhibitor can bind onto that enzyme is when the substrate is bound to that enzyme."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So we have the substrate collides and binds into the active site of the enzyme."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And once we form the enzyme substrate complex, that creates a conformational change that creates this brand new pocket, the allosteric site that the inhibitor can now bind to."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, in the absence of the inhibitor, the enzyme substrate complex will simply form the product, and then the product will dissociate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "But in the presence of the inhibitor, that inhibitor will bind onto that brand new allosteric site found on the enzyme substrate complex, and that will form the enzyme substrate inhibitor complex."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And once this complex is formed, no reaction will take place."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that's because once the inhibitor binds onto the enzyme substrate complex, it will keep that substrate inside that active side, and that active side will not be able to catalyze the transformation of that substrate into that particular product."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, this leads us directly into point number one."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Uncompetitive inhibitors actually decrease the VMAX value, and that's because they decrease the number of enzyme substrate complexes that are efficient, that are functional, that can actually convert the substrate into that particular product."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So uncompetitive inhibitors bind to the enzyme substrate complex and decrease the total number of functional enzymes."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And we can see how that affects VMAX by looking at this particular equation."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So if we rearrange this equation, we get this equation here, and what it basically tells us is the V max is reached when all the active sides are filled with that particular substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And in this particular case, because we decrease the total number of functional enzymes, we decrease this quantity."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Because some of them are transformed into this quantity, we decrease the V max value."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "What about the Kcat?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "What about the turnover number?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Well, the turnover number basically describes the ability of that active side to actually transform the substrate molecules into the product molecules per unit time."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, because when the inhibitor is not bound to that particular enzyme substrate complex, that active site's ability or efficiency to change that substrate to the product doesn't actually change, we see that the Kcat value in uncompetitive inhibition also doesn't actually change."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "It remains the same."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So the Kcat value in this equation remains unchanged."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "But because this changes decreases, the V max also decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And finally, what about that Km value?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "What happens to the Michaela's constant?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Well, to answer that question, let's take a look at the following equation."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Remember Km, the Mikaelas constant describes the affinity of that particular substrate to the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "If Km increases, the Finity decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "If Km decreases, the Finity increases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So what happens in the presence of the inhibitor?"}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Well, when the inhibitor binds onto the enzyme substrate complex, what happens is once we form the enzyme substrate inhibitor complex, that inhibitor, by binding onto that complex, it prevents that substrate from actually leaving that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that means is, because that active side does not release that substrate, the affinity of that substrate for the enzyme increases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And if the affinity of that enzyme and if the affinity of the substrate for the active side of the enzyme increases, when the inhibitor binds into the complex, the Km value decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that's one way that we can explain how the Km actually decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Another way of explaining it is in the following manner."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So since the total number of functional enzymes decreases and the VMAX decreases, that means we need to add a lower concentration of that substrate to actually reach V max divided by two."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that's why the Km decreases."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So if we compare no inhibitor to inhibitor present, we see that the V max is lower in the presence of the inhibitor and the Km value is closer."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "It's more to the left side along the X axis."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So the parent Km decreases compared to this Km."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So let's move on to the final one, non competitive inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So in non competitive inhibition on that enzyme, there is a permanent allosteric site that is present."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that means is that inhibitor can bind onto that enzyme regardless of whether or not that substrate is actually bound onto that active site."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so this is the equation that describes this process."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So in the absence of the inhibitor, the substrate is going to bind to the active site of the enzyme, forming the enzyme substrate complex, and that will transform the substrate of the product, and then the product will be released."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, in the presence of the inhibitor, that inhibitor can either bind onto that individual enzyme forming that enzyme inhibitor complex, or it can bind onto the enzyme substrate complex to form that particular enzyme substrate inhibitor complex."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And notice that if we form the enzyme inhibitor complex, that doesn't change the likelihood that the substrate is going to bind to that enzyme."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And that is important in part three, as we'll see in just a moment."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So let's begin with one."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "The VMAX is lowered and the VMAX is lowered for the same reason that the VMAX is lowered in this uncompetitive inhibition case."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So we simply decrease the number of active size, number of enzymes that are functional."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And if we decrease that value, we essentially decrease the VMAX."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "So since some number of inhibitors are balanced on the enzyme at any given moment in time and that inhibits the functionality of the enzyme, less functional enzymes will be present, and so VMAX will decrease."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "Now, let's move on to two."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "The Kcat is lowered."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "The Kcat, the turnover number is lowered."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that basically means is the efficiency of that active side in transforming the substrate into that particular product is decreased."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And this makes sense why well, because as it turns out, when that enzyme binds onto that inhibitor, that inhibitor changes the shape of the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And so the active side is essentially no longer complementary to that particular substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And although the substrate can bind to that active side just as likely as in the case of the absence of the inhibitor, once the substrate binds onto this enzyme inhibitor complex, that fit Will not be perfect."}, {"title": "Enzyme Kinetics of Reversible Inhibition.txt", "text": "And what that means is the active side's ability to actually trust."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So enzymes inside our cells and inside our body catalyze many different types of biological processes and reactions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "But how exactly do we actually measure how good of an enzyme we have?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "How do we measure the catalytic efficiency of enzymes found inside our cells and inside our body?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This will be the focus of this lecture."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So let's begin by taking a look at the following graph."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This is the same graph we focused on many times in previous lectures."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so on this graph, the x axis is a substrate concentration and the y axis is the velocity, is the rate at which the enzyme actually operates on that specific substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And what the blue curve describes is how the rate, the velocity of that enzyme changes as we increase the substrate concentration in the environment."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So as we increase at the beginning we see that there is a linear increase."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So that means the velocity is directly proportional to the concentration of S. But then the rate slowly begins to decrease, the slope decreases and it levels off and eventually it reaches a maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And that is given by this horizontal green line."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So that horizontal green line describes the maximum possible rate at which the enzyme can operate on that particular substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And in the previous lecture, when we discussed the turnover number Kcat, we basically gave an equation that describes how to actually obtain the maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we said that v max of an enzyme is equal to the product of the turnover number KCAD and the concentration, the total concentration of the enzyme."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And this basically describes that situation when all the active sites in our enzyme mixture are filled with the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This is when the velocity, the rate of the enzyme mixture will be at a maximum."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So the enzyme operates at a maximum rate when all the active sites are filled."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And this is given by this equation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, if we take a look at the following curve when exactly under what conditions will the blue curve actually reach the maximum velocity?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Well, notice as we increase the concentration, this blue curve essentially reaches or approaches that maximum velocity asymptotically."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And what that means is if we continually increase the concentration of S, the substrate, it will eventually approach and reach very closely the maximum velocity of that enzyme mixture."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so what we see happen is when the concentration of the substrate is very high, that is when the value of S, the concentration of substrate is much greater than the Km value for that enzyme mixture, we see that our blue curve will essentially reach that maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now remember, Km is basically the concentration of the substrate at which the enzyme operates at exactly half of the maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So if Km is this x value, the concentration of the s, then if we check out the Y coordinate, that will be exactly midway between the zero velocity value and the VMAX value as shown in the following diagram on the following curve."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we see that when Km is much, much smaller than the concentration of the substrate in that environment, we see that our enzyme mixture is operating at a maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And this is equivalent to saying that all the active sites in the enzyme mixture are filled and so the enzyme's velocity is at a maximum."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, what exactly happens under normal physiological conditions inside our body and inside our cells?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Well, typical physiological conditions basically involve a relatively low concentration of substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So under typical physiological conditions inside our cells, the substrate concentration is usually very low and the substrate concentration is usually between zero and the Km value."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so what that means is the concentration of that substrate under normal conditions is usually much smaller than the Km value."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So if we are to pinpoint where the concentration of that substrate in our cells usually is, it's somewhere around, let's say, this quantity here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So it ranges between this X value range here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so what that basically means is inside our cells, the efficiency, or I should say not the efficiency, but the rate, the velocity of that enzyme is usually much lower than its maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So for example, if the concentration is somewhere here, then the corresponding rate will be somewhere here, much smaller than that maximum velocity."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, what we want to basically explore in this lecture is how to actually measure the catalytic efficiency of the enzyme inside our cell."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we want to come up with an equation, a rate law that describes how the rate of a particular enzyme catalyzed reaction is affected by different types of variables."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This is what we basically want to explore."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So as always, let's begin with the same equation that we use to derive the Maclus methane equation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So this is the equation that describes a general enzyme catalyze reaction at its beginning stages."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So at the beginning, this is the chemical equation that describes any enzyme catalyzed reaction."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we have an enzyme and we have a substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And when they combine, when the substrate combines into the active side of the enzyme, we form the enzyme substrate complex Es and K. One is the rate constant of this reaction."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, once we form this complex, there are two ways that this complex can basically dissociate the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "If it is not bound very strongly to that active side, it can simply dissociate and leave the active side without actually being transformed into the product."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And this simply means it goes back to reform these two reactants in a rate constant."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "That case is K minus one."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "But if the substrate is bound strongly to the active side, that active side will be able to catalyze and transform that substrate into the product."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And this is the reaction shown here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And K cat is the turnover number we spoke of previously."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This is the rate constant of this reaction."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, let's begin by describing the rate law of this reaction going this way."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So if we're going this way, then the rate law is given by V knot."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "The rate of this reaction is equal to Kcat."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "This rate constant multiplied by the concentration of the reactant, in this case, that enzyme substrate complex."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And let's call this equation number one."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, if you recall our discussion, our derivation of the of the Michaelis methane equation, we basically used the steady state conditions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we assumed that the reaction was under steady state conditions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So this reaction was under steady state conditions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And what that basically means is the intermediate concentration, the intermediate being the enzyme substrate complex."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "The intermediate concentration is not changing over time."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So this concentration remains exactly the same even though the concentration of reactants and products over time is changing."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "That's what we mean by a steady state condition."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And the only way that the concentration of the intermediate is not changing is if the rate of formation of this intermediate is equal to the rate of dissociation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "If these two rates are equal, only then will the concentration of the intermediate be actually the same."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So under steady state conditions, we see that the rate of formation of the enzyme substrate complex is equal to the rate of dissociation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now how many reactions actually describe the rate of formation?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Well, we only have one reaction that forms this enzyme substrate complex."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And it's this reaction here that contains the rate constant of K one."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So the rate of formation of Es is given by this rate law, k one multiplied by the concentration of the enzyme multiplied by the concentration of the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, what about the rate of dissociation?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Well, here we have two equations that describe the dissociation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "One dissociates into the product and the other one dissociates back into the enzyme and the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So on the left side of the equation, we have one term."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "On the right side, we have two terms because we have these two reactions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So one of them basically describes let's begin with this one."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we have the concentration of the reactor."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "The enzyme substrate complex basically dissociates into this."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we say the concentration of enzyme substrate complex multiplied by K minus one and we add it to this reaction."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So the concentration of the enzyme substrate complex multiplied by K cat this quantity here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now notice on the right side this, and this appears in these two terms."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so we can bring that out of our equation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And then we get K minus one plus K cat multiplied by the concentration of Es."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so now if we solve for K minus one plus Kcat divided by K one, we get the following result."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we simply rearrange this equation and we get this."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now this is the quantity that we defined previously as the K and the Mcales constant."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So we said that the Michael is constant is equal to this ratio here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so now we replace this with the Maclus constant and that is equal to this entire quantity here."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And finally, if we take this and we rearrange it and solve for the Es concentration, we bring this here and Km to the bottom, we get the following equation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Let's call this equation two."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So the concentration of the enzyme substrate complex is equal to the product of these two concentrations divided by the Mikaela's constant."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, what was the entire point of getting equation two?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Well, the point was to take equation one and replace the enzyme substrate concentration in terms of these quantities, where now we have the Km term and we'll see why the Km term will become important in just a moment."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So now we substitute two into one."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "We replace the concentration of Es with this entire ratio and this is basically what we are left with."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So V Naught, the velocity of that enzyme, the rate at which the enzyme catalyzes is equal to K capped, divided by Km multiplied by the concentration of the enzyme multiplied by the concentration of the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, we are not yet done."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, what we basically want to do is we want to assume this same condition that we assumed previously."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So I said that under normal physiological conditions, when the reactions take place inside our cells, the concentration of the substrate is much smaller than the concentration than the Km value."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So this is around where the concentration inside our cells is usually at."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So basically, equation three, this equation here, as we'll see in just a moment, can be used to give us insight into how enzymes operate under typical physiological conditions."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "That is, when the concentration of the substrate is much, much smaller than our Km value."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So when we're right around here along that x axis, now, what can we assume when we basically state the following statement?"}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So when the concentration of our substrate is much smaller than Km, this is the assumption that we can make."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So let's take a look at the following equation."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "So this equation is telling us that the total amount of enzyme inside our cell, inside that environment is equal to the sum of the free enzyme that is not bound to any substrate plus the enzyme that is bound to that substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, we know that when the concentration of the substrate is very low, when we're right here, the rate of the enzyme will be low because not much of the substrate will actually be bound to the enzyme."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so that means our E total is equal to approximately the concentration of the free enzyme."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Because by making this assumption here, we're saying that inside our cells we have a very low concentration of S. And because we have a low amount of S substrate, not too much substrate will be bound to the enzyme."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so the majority of the enzyme will exist in its free state, not bound to the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And that means the total enzyme is equal to approximately the free enzyme."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Because this quantity here can be assumed to be very, very small when the concentration of S is low."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And so this is equation four, e total is equal to the free enzyme concentration."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "And now we take equation three and we replace the free enzyme E with our total enzyme E. And so once we replace this with this, this is the equation that we can now ultimately use to basically study how the enzymes catalyze reactions inside our body."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Under normal physiological conditions when the concentration of S is very small, is much smaller than the Macaelis constant M. So V Naught is equal to KCAD divided by Km multiplied by the concentration of the enzyme the total concentration of the enzyme multiplied by the concentration of the substrate."}, {"title": "Catalytic Efficiency of Enzymes .txt", "text": "Now, notice one important."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "DNA molecules are important biological molecules whose function is to store the genetic information that is found within our biological cells."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, whenever a given organism actually wants to reproduce, one important thing that must take place is the DNA must be replicated within our cells."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So in the next several lectures, we're going to discuss the process of DNA replication and how it actually proceeds."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And let's begin with the process of unwinding."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So recall that any given DNA molecule actually consists of two individual and complementary single stranded DNA molecules."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And these two single stranded molecules basically combine via an antiparallel fashion to form our double helix."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And the bonds that hold our two individual complementary single stranded DNA molecules are hydrogen bonds between our adjacent nitrogenous basis."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, the question is, what exactly is the first process that takes place when our DNA replicates?"}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Well, before our DNA is replicated, what must happen is our double stranded DNA molecule must actually unwind."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So we see that in order for replication to actually occur, the two strands of DNA must first unwind."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, the problem is a double stranded DNA molecule wants to naturally exist as a double strand because that is a stabilizing form."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So to actually unwind our molecule, our cell must use special types of proteins, special types of enzymes known as the helicase enzyme."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So our helicase binds to a location on our double stranded DNA known as the origin of replication."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And it basically acts to unwind our double stranded DNA."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And since the two strands of DNA naturally want to reform those hydrogen bonds because that forms a stabilizing effect, we have a different set of proteins of enzymes known as single stranded binding proteins or simply SSB proteins that also have to bind to the individual unwound single stranded DNA molecules."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And once they bind, they stabilize those molecules and keep those DNA molecules apart."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So to see what we mean, let's take a look at the following picture."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So, in diagram one, we basically have our two single stranded DNAs."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So DNA one and DNA two and we form this double helix structure."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, when our helicase or helicase actually binds to the origin of replication, it unwinds that double stranded DNA."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And once our two single stranded DNAs are exposed and once we unwind it, we have the single stranded binding proteins bind to each of these two single strands and that keeps those two strands apart."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, as hellicase unwinds our double helix, that unwinding process actually introduces positive super coils."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And positive super coils basically destabilize our molecule by increasing its energy."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So to stabilize the unwound DNA molecule, a protein known as DNA gyrates has to bind to our molecule and introduces negative super coils which decreases the number of positive super coils and therefore stabilizes by decreasing the amount of stress that our molecule experiences."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, once the helicase unwinds our DNA from this picture, we see that we expose these individual complementary single stranded DNA molecules."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And once we expose these two molecules another type of enzyme known as primates which is basically an RNA polymerase binds to each one of these two individual and exposed single stranded DNA molecules and it adds a set or a series of nucleotides that together are known as RNA primer."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So primase adds a series of nucleotides onto these two exposed single stranded DNA molecules and these are known as RNA primer."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "An RNA primer basically acts as a signal and signals for another protein known as DNA polymerase to actually bind to that primer region and initiate DNA replication."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So basically the DNA polymerase bind to the primer region and adds individual nucleotides one by one extending our synthesized strand known as the daughter strand."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So basically the single stranded DNA molecule that is being synthesized is known as the daughter strand."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "But the actual original DNA single stranded molecule that is used as a template to synthesize the new molecule is known as the parent strand."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So let's take a look at the following diagram."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So we have our double helix DNA that basically unwinds in this location as soon as the helicase protein as well as the other proteins bind to the origin of replication."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So we can imagine the group of proteins that includes our helicase binds to our origin replication that unzips or unwinds our DNA double strands to expose these two single stranded molecules that are known as the parent strands."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So we have our primates that creates the RNA primer that is shown in green."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And the RNA primer is basically a series of nucleotides that signal the beginning of our replication."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "It signals for our DNA polymerase shown in red to bind to that primer region and initiate our replication process."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "We also have the SSB proteins that bind to the individual strands thereby stabilizing them which keeps them apart and keeps them from reforming that double helix."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And as time progresses our DNA polymerase shown in red basically moves along our parent strand and synthesizes our daughter strand one nucleotide at a time."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, two important things that we have to remember about DNA replication is the following two concepts."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So firstly DNA replication is a semiconservative process which means that once we form our new DNA one of the single stranded DNA molecules is the new synthesized one and the other one comes from our original DNA molecule that we used as a template."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So for example, if we have a single DNA molecule and it undergoes DNA replication we essentially form two DNA molecules and each one of those two DNA molecules contains one new synthesized strand and one original parent strand that came from the original DNA molecule."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And this is what we mean by a semiconservative process."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now once the proteins, once the group of proteins binds to the DNA molecule at the point of origin replication proceeds on both strands but it takes place in opposite direction."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So to see what we mean let's take a look at the following diagram."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So let's suppose we have the original DNA molecule shown."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "We have one of the strands shown in blue and the second parent strand is shown with this brown color."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Now, what basically happens is our groups of proteins including our helicase, binds to the point of origin."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "Let's suppose in this location and one of the newly synthesized single stranded DNA molecules is synthesized in this direction and the other DNA molecule, the other single stranded DNA molecule, the daughter strand is synthesized in the opposite direction."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And the fact that DNA replication takes place on both strands and in opposite directions is known as a bidirectional process."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So this makes it a bidirectional process."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "So DNA replication is both semiconservative and it's a bidirectional process."}, {"title": "DNA Replication: Helices and Unwinding.txt", "text": "And as we'll discuss in the next lecture one of these strands is known as the leaving strand because our nucleotides are added continuously one by one along single direction and the other strand is known as the lagging strand because it is synthesized in a discontinuous fashion as we'll discuss in the next lecture."}, {"title": "Introduction to Proteins .txt", "text": "Proteins are extremely important macromolecules that are used by the cells of our body in many, many different ways."}, {"title": "Introduction to Proteins .txt", "text": "So proteins have an extremely wide range of different functions."}, {"title": "Introduction to Proteins .txt", "text": "For example, some proteins act as biological catalysts, speeding up different types of biochemical reactions that are used that are carried out by our cells."}, {"title": "Introduction to Proteins .txt", "text": "For example, the production of ATP involves many different types of enzymes, many different types of biological catalysts."}, {"title": "Introduction to Proteins .txt", "text": "Now, proteins also function in transport."}, {"title": "Introduction to Proteins .txt", "text": "For example, we know that hemoglobin is a type of protein that transports oxygen from the lungs and to the tissues and cells of our body."}, {"title": "Introduction to Proteins .txt", "text": "And oxygen is necessary to basically produce ATP."}, {"title": "Introduction to Proteins .txt", "text": "Now, proteins can also be embedded inside cell membranes."}, {"title": "Introduction to Proteins .txt", "text": "And when proteins are embedded inside cell membranes, usually they act as transport proteins, and they allow the movement of different types of molecules and ions across the cell membrane of cells."}, {"title": "Introduction to Proteins .txt", "text": "Now, proteins are also involved in giving our cells structure."}, {"title": "Introduction to Proteins .txt", "text": "For example, the entire cytoskeleton structure consists of different types of proteins."}, {"title": "Introduction to Proteins .txt", "text": "Proteins also are involved in giving certain cells mobility."}, {"title": "Introduction to Proteins .txt", "text": "For example, sperm cells have a structure known as a Flagellum."}, {"title": "Introduction to Proteins .txt", "text": "And that flagellum is necessary to allow the sperm cell to actually move and navigate through the vaginal cavity and through the oviduct, the fallopian tube, in the female reproductive system."}, {"title": "Introduction to Proteins .txt", "text": "And this Flagellum is composed predominantly of different types of proteins."}, {"title": "Introduction to Proteins .txt", "text": "Now, proteins are also involved in protecting our cells in our body from different types of pathogenic agents."}, {"title": "Introduction to Proteins .txt", "text": "So antibodies and antigens consist of proteins."}, {"title": "Introduction to Proteins .txt", "text": "Proteins are also involved in communication."}, {"title": "Introduction to Proteins .txt", "text": "For instance, we have these molecules known as hormones, peptide hormones that are involved in intracellular and cell to cell communication."}, {"title": "Introduction to Proteins .txt", "text": "And we'll discuss that much more in future lectures."}, {"title": "Introduction to Proteins .txt", "text": "So, as we can see, proteins have many different types of functions."}, {"title": "Introduction to Proteins .txt", "text": "So let's discuss a bit more about proteins."}, {"title": "Introduction to Proteins .txt", "text": "So what are proteins on the molecular level?"}, {"title": "Introduction to Proteins .txt", "text": "So proteins basically consist of these subunits, these building blocks we call amino acids."}, {"title": "Introduction to Proteins .txt", "text": "And there are 20 types of amino acids that exist inside our body."}, {"title": "Introduction to Proteins .txt", "text": "So proteins are built from the selection of 20 different amino acids."}, {"title": "Introduction to Proteins .txt", "text": "And the fact that we have 20 different amino acids means we have a great variety of possible sequences for any given protein."}, {"title": "Introduction to Proteins .txt", "text": "And to demonstrate what we mean by that, let's consider a protein that contains only ten amino acids."}, {"title": "Introduction to Proteins .txt", "text": "So we have amino acid one, amino acid two, amino acid three, all the way to amino acid number ten."}, {"title": "Introduction to Proteins .txt", "text": "Now, notice these amino acids are held together by covalent bonds known as peptide bonds."}, {"title": "Introduction to Proteins .txt", "text": "And we'll talk about what those are in much more detail in a future lecture."}, {"title": "Introduction to Proteins .txt", "text": "Now, the question we want to answer is how many possible sequences are there if we have these ten amino acids?"}, {"title": "Introduction to Proteins .txt", "text": "And each one of these amino acids can basically be any one of those 20 amino acids."}, {"title": "Introduction to Proteins .txt", "text": "So, to carry this out, we have to use a bit of mathematics and probability."}, {"title": "Introduction to Proteins .txt", "text": "So let's begin with amino acid number one."}, {"title": "Introduction to Proteins .txt", "text": "So we have 20 different possibilities for amino acid number one."}, {"title": "Introduction to Proteins .txt", "text": "And so we have 20 possibilities."}, {"title": "Introduction to Proteins .txt", "text": "The same thing is true for amino acid number two, for amino acid number three, for amino acid number four, number five, number six, number seven, number eight, number nine, and number ten."}, {"title": "Introduction to Proteins .txt", "text": "Now, we have to multiply these out to basically find the total possibility, the total number of possibilities that we can have."}, {"title": "Introduction to Proteins .txt", "text": "And if we multiply these out, we get 20 to the 10th power, and that's about 1.0 24 times ten to 13 possibilities."}, {"title": "Introduction to Proteins .txt", "text": "So 10 trillion possibilities exist for an amino for a protein that consists of only ten amino acids."}, {"title": "Introduction to Proteins .txt", "text": "And usually proteins consist of hundreds and sometimes thousands of amino acids."}, {"title": "Introduction to Proteins .txt", "text": "And that means there is a great number of different types of sequences that are possible inside the proteins found inside our body."}, {"title": "Introduction to Proteins .txt", "text": "Now, what's so special about this sequence of amino acids?"}, {"title": "Introduction to Proteins .txt", "text": "Well, as we'll see in a future lecture, it turns out that the sequence of amino acids in a protein actually determines its three dimensional structure."}, {"title": "Introduction to Proteins .txt", "text": "So under the proper cellular conditions, this linear sequence of amino acids can actually fold into its three dimensional structure spontaneously."}, {"title": "Introduction to Proteins .txt", "text": "And once these proteins form their three dimensional conformation, their function is basically determined."}, {"title": "Introduction to Proteins .txt", "text": "So it turns out, as we'll see in a future lecture, that the three dimensional structure of the protein determines its actual function."}, {"title": "Introduction to Proteins .txt", "text": "Now, the next question is, what exactly is the difference between one amino acid and another amino acid?"}, {"title": "Introduction to Proteins .txt", "text": "Well, basically, amino acids differ from one another based on the side chain group, the functional group that exists on that amino acid."}, {"title": "Introduction to Proteins .txt", "text": "For example, we have one type of amino acid known as glycine, and this contains an age group, while another amino acid contains this side chain group that is known as cysteine."}, {"title": "Introduction to Proteins .txt", "text": "And these two amino acids have different functionalities."}, {"title": "Introduction to Proteins .txt", "text": "For example, cysteine is important in forming these linkages known as disulfide bridges."}, {"title": "Introduction to Proteins .txt", "text": "And we'll talk much more about what these are in a future electra."}, {"title": "Introduction to Proteins .txt", "text": "So basically, different functional groups have different capabilities and different reactivities."}, {"title": "Introduction to Proteins .txt", "text": "And the arrangement and sequence of these amino acids and their functional groups helps determine the ways in which the proteins are actually involved in helping the different types of reactions that exist inside our body."}, {"title": "Introduction to Proteins .txt", "text": "And this is particularly important when we'll talk about enzymes, those biological catalysts, because these biological catalysts essentially use these functional groups to carry out different types of reactions in which they speed up the biochemical processes inside our body."}, {"title": "Introduction to Proteins .txt", "text": "Now, different proteins have different characteristics."}, {"title": "Introduction to Proteins .txt", "text": "Some proteins are very, very rigid, while other proteins are not so rigid."}, {"title": "Introduction to Proteins .txt", "text": "So, for example, the rigid proteins might be involved in giving ourselves its structure, so they might be involved in creating the cyoskeleton, while the not so rigid proteins basically are involved in those processes that require a bit more flexibility."}, {"title": "Introduction to Proteins .txt", "text": "Now, proteins do not act by themselves or usually they don't act by themselves."}, {"title": "Introduction to Proteins .txt", "text": "Proteins usually interact with other proteins or other macromolecules to form these fully functional complexes."}, {"title": "Introduction to Proteins .txt", "text": "And these protein complexes are responsible for creating those different types of processes and reactions."}, {"title": "Introduction to Proteins .txt", "text": "So, for instance, when we study DNA replication, we'll see that a single protein is not actually involved in DNA replication."}, {"title": "Introduction to Proteins .txt", "text": "We have many, many different types of proteins that have to work together and form these protein complexes to actually carry out the process of synthesizing, replicating DNA molecules and DNA strands."}, {"title": "Introduction to Proteins .txt", "text": "So another example is the transport proteins found inside our cell membrane."}, {"title": "Introduction to Proteins .txt", "text": "So cell membranes consist of phospholipids."}, {"title": "Introduction to Proteins .txt", "text": "And so these transport proteins have to actually interact with these phospholipids to be able to actually transport those molecules and ions across the cell membrane."}, {"title": "Introduction to Proteins .txt", "text": "So we have many different types of examples, as we'll see in our study of biochemistry, in which proteins have to either interact with other proteins or with other macromolecules to actually carry out a specific type of function."}, {"title": "Introduction to Proteins .txt", "text": "Now, the final thing that we have to know about proteins is where they actually come from."}, {"title": "Introduction to Proteins .txt", "text": "So proteins are encoded by the DNA found inside our body."}, {"title": "Introduction to Proteins .txt", "text": "So remember, our cells use DNA to actually create RNA, and then the RNA basically combines with ribosomes, and those ribosomes translate the RNA into proteins."}, {"title": "Introduction to Proteins .txt", "text": "So essentially, our DNA molecules contain specific genes, specific segments of nucleotide that ultimately code for the many different types of proteins that are found and used by the cells of our body."}, {"title": "Introduction to Proteins .txt", "text": "So in the next lecture, we're going to begin our discussion on the amino acids, the different types of amino acids that exist inside Arabia."}, {"title": "Michaelis Constant .txt", "text": "Previously we focused on understanding the meaning behind the Michaela's methyl equation."}, {"title": "Michaelis Constant .txt", "text": "And what we said was that the rate or the velocity at which the enzyme operates V naught is equal to the product of the maximum velocity, the maximum rate of the enzyme V max."}, {"title": "Michaelis Constant .txt", "text": "And this ratio, so the numerator, is the substrate concentration and the denominator is M plus the substrate concentration."}, {"title": "Michaelis Constant .txt", "text": "Now, previously we said that Km is known as the Michaelis constant."}, {"title": "Michaelis Constant .txt", "text": "And we also said that the Michaelus constant has units of molarity."}, {"title": "Michaelis Constant .txt", "text": "So the units of Km is the same as the units of the substrate concentration."}, {"title": "Michaelis Constant .txt", "text": "In fact, inside our body, all the different enzymes have a Km value that range from about 0.1 molar to about tenths to negative seven molar."}, {"title": "Michaelis Constant .txt", "text": "So we see that the Km value, the magnitude of the Km value, depends not only on the type of enzyme and the type of substrate, but it also depends on the conditions in the environment."}, {"title": "Michaelis Constant .txt", "text": "So by changing, for example, the PH or the temperature of the environment, we can affect the value of Km."}, {"title": "Michaelis Constant .txt", "text": "Now, what exactly is the meaning behind Km?"}, {"title": "Michaelis Constant .txt", "text": "What is the physiological importance of the Michelis constant?"}, {"title": "Michaelis Constant .txt", "text": "This is what we want to focus on in this lecture."}, {"title": "Michaelis Constant .txt", "text": "And actually, previously we discussed one meaning of the Michaela's constant."}, {"title": "Michaelis Constant .txt", "text": "But as we'll see in this lecture, there are two ways that we can actually interpret the meaning of the Michael's constant value."}, {"title": "Michaelis Constant .txt", "text": "So let's begin with what we said in the previous lecture."}, {"title": "Michaelis Constant .txt", "text": "So previously in our discussion of the Michaelis constant, we said that the Michaelis constant represents the concentration of the substrate at which the enzymes activity."}, {"title": "Michaelis Constant .txt", "text": "The enzymes rate is exactly half of its maximum rate."}, {"title": "Michaelis Constant .txt", "text": "So the Km describes the substrate concentration that is needed to reach exactly half of that maximum velocity of that particular enzyme."}, {"title": "Michaelis Constant .txt", "text": "And what that basically means is when our substrate concentration is equal to Km, exactly half of all the active sites in the enzyme mixture are filled with the substrate."}, {"title": "Michaelis Constant .txt", "text": "And this can be seen in the following diagram."}, {"title": "Michaelis Constant .txt", "text": "So initially we begin with, let's say, an enzyme mixture that consists of four identical enzymes."}, {"title": "Michaelis Constant .txt", "text": "And these are shown in red."}, {"title": "Michaelis Constant .txt", "text": "And notice that each one of these enzymes contains this Crevice and that's the active site to which a substrate can actually bind."}, {"title": "Michaelis Constant .txt", "text": "Now, if we take this enzyme mixture and we add a concentration of substrate that is equal to Km, the Macalus constant, exactly half of these active sites will be filled."}, {"title": "Michaelis Constant .txt", "text": "So in this case, if we add two of these blue molecules, then that means two of these enzymes will form the enzyme substrate complex, as shown in this diagram."}, {"title": "Michaelis Constant .txt", "text": "And so this means that exactly half of the active sites will be filled."}, {"title": "Michaelis Constant .txt", "text": "And another way of saying this is in the following manner."}, {"title": "Michaelis Constant .txt", "text": "So when the concentration of substrate is equal to Km, the concentration of the enzyme substrate complex."}, {"title": "Michaelis Constant .txt", "text": "So Es is equal to exactly half of the total initial concentration of that enzyme."}, {"title": "Michaelis Constant .txt", "text": "So what that means is initially we begin with four enzyme molecules."}, {"title": "Michaelis Constant .txt", "text": "And when we add Km, namely the two blue molecules, then the concentration of the enzyme substrate complex will be equal to exactly half of that initial."}, {"title": "Michaelis Constant .txt", "text": "So four divided by two."}, {"title": "Michaelis Constant .txt", "text": "And that gives us two."}, {"title": "Michaelis Constant .txt", "text": "And that's what we mean by this equation here."}, {"title": "Michaelis Constant .txt", "text": "Now, not only that, but what that also means is the rate of activity, the velocity of that enzyme will be exactly half of the maximum."}, {"title": "Michaelis Constant .txt", "text": "And that makes sense because if half the enzymes have activides which are occupied, that means the rate will be exactly half of its maximum."}, {"title": "Michaelis Constant .txt", "text": "So this is the first and perhaps the more important meaning of the Michael's constant value."}, {"title": "Michaelis Constant .txt", "text": "Now, what about the second meaning of the Michael's constant?"}, {"title": "Michaelis Constant .txt", "text": "Well, this is where we have to actually recall some information that we discussed when we derived the Michaelis Methan equation."}, {"title": "Michaelis Constant .txt", "text": "So in our derivation on the Mechaless Methane equation, we basically use the following chemical equation."}, {"title": "Michaelis Constant .txt", "text": "And this chemical equation describes when that reaction, the enzyme catalyze reaction, is in its beginning stages."}, {"title": "Michaelis Constant .txt", "text": "So when the time is approximately equal to zero."}, {"title": "Michaelis Constant .txt", "text": "And what this equation basically tells us is if we take the enzyme so this is the red enzyme and we add the substrate so given in blue, then what will begin to happen is some the substrate will begin to bind onto the active side to form the enzyme substrate complex."}, {"title": "Michaelis Constant .txt", "text": "And this is our intermediate."}, {"title": "Michaelis Constant .txt", "text": "Now, what we also said was we assumed the steady state condition and the steady state condition means that the concentration of this intermediate, the enzyme substrate complex, is not changing over time."}, {"title": "Michaelis Constant .txt", "text": "So the concentration of this remains the same even though this concentration and this can actually change over time."}, {"title": "Michaelis Constant .txt", "text": "And by making that steady state assumption, we were able to basically create the following Michael's constant."}, {"title": "Michaelis Constant .txt", "text": "So Km, we said, was equal to K minus one plus K two divided by K one, where K minus one is simply the rate constant for this reaction, the dissociation of the enzyme substrate complex back into the enzyme and the substrate."}, {"title": "Michaelis Constant .txt", "text": "So when the substrate essentially dissociates from the active site we produce back this enzyme and a substrate that K minus one."}, {"title": "Michaelis Constant .txt", "text": "K one is basically the association, the formation of this enzyme substrate complex."}, {"title": "Michaelis Constant .txt", "text": "And K two is the rate constant for this reaction, the dissociation of the enzyme substrate complex into the product molecule and that enzyme."}, {"title": "Michaelis Constant .txt", "text": "So we were able to basically derive this equation in that lecture and we're going to use this equation in just a moment to basically give the Michelin constant a second physiological meaning."}, {"title": "Michaelis Constant .txt", "text": "This is the important assumption we want to make."}, {"title": "Michaelis Constant .txt", "text": "Let's suppose that the dissociation of the enzyme substrate complex is much more rapid."}, {"title": "Michaelis Constant .txt", "text": "So the dissociation of the enzyme substrate complex into the enzyme and the substrate."}, {"title": "Michaelis Constant .txt", "text": "So the reaction going this way takes place much more quickly than the reaction going this way."}, {"title": "Michaelis Constant .txt", "text": "So the dissociation going this way takes place much more readily than our dissociation into the enzyme and this product."}, {"title": "Michaelis Constant .txt", "text": "So we suppose that the enzyme substrate complex dissociates into E and S much more rapidly and much more readily than E into P. And what this basically implies is the value of K two is much smaller than the value of K minus one."}, {"title": "Michaelis Constant .txt", "text": "Because if this rate is much greater, that implies that K minus one must be much greater than K two."}, {"title": "Michaelis Constant .txt", "text": "And if K minus one is assumed to be much larger than K two we can simplify this equation in the following way."}, {"title": "Michaelis Constant .txt", "text": "So the MCA les constant Km is equal to so K minus one plus K two divided by K one."}, {"title": "Michaelis Constant .txt", "text": "And because K minus one this quantity is much greater than K two."}, {"title": "Michaelis Constant .txt", "text": "For example, let's say if this is 1 million and this is one, then 1 million plus one doesn't really change the value of K minus one by too much."}, {"title": "Michaelis Constant .txt", "text": "And so what that means is we can approximate this to equal to this."}, {"title": "Michaelis Constant .txt", "text": "So because this is much smaller than this, this sum is approximately equal to simply K minus one."}, {"title": "Michaelis Constant .txt", "text": "So our numerator is replaced by K minus one."}, {"title": "Michaelis Constant .txt", "text": "And so we see that the Michael is constant is approximately equal to K minus one divided by K, assuming that K two is much smaller than K minus one."}, {"title": "Michaelis Constant .txt", "text": "And this is where we give meaning to the Michael's constant."}, {"title": "Michaelis Constant .txt", "text": "What this basically means is the Km value."}, {"title": "Michaelis Constant .txt", "text": "The Michaelis constant describes the equilibrium dissociation constant of the dissociation of the enzyme substrate complex back into the enzyme and the substrate."}, {"title": "Michaelis Constant .txt", "text": "So in such a case, Km describes the equilibrium constant of the enzyme substrate complex dissociation."}, {"title": "Michaelis Constant .txt", "text": "And to see why that's so, let's take a look at this equation."}, {"title": "Michaelis Constant .txt", "text": "So we basically take this equation and we flip it going this way."}, {"title": "Michaelis Constant .txt", "text": "And we obtain this."}, {"title": "Michaelis Constant .txt", "text": "So the enzyme substrate complex dissociates back into the enzyme and a substrate and the rate constant going this way is given to decay minus one."}, {"title": "Michaelis Constant .txt", "text": "Now, going backwards, the enzyme and the substrate reassociate to form back the complex."}, {"title": "Michaelis Constant .txt", "text": "So this is the rate constant going this way."}, {"title": "Michaelis Constant .txt", "text": "This is the rate constant going in reverse."}, {"title": "Michaelis Constant .txt", "text": "Now, if we assume this takes place very quickly, then equilibrium is established very quickly."}, {"title": "Michaelis Constant .txt", "text": "And if equilibrium is established, what that means is the rate of the four reaction is equal to the rate of the reverse reaction."}, {"title": "Michaelis Constant .txt", "text": "And so we can basically determine what the rate law is of this reaction and the reverse reaction and we set them equal."}, {"title": "Michaelis Constant .txt", "text": "So the rate law going this way is given to us by K minus one multiplied by the concentration of this should be the enzyme substrate complex."}, {"title": "Michaelis Constant .txt", "text": "And that is equal to going this way."}, {"title": "Michaelis Constant .txt", "text": "So K one multiplied by the concentration of the enzyme and the concentration of the substrate."}, {"title": "Michaelis Constant .txt", "text": "So this we obtained by assuming that this was at equilibrium."}, {"title": "Michaelis Constant .txt", "text": "And that's a good assumption because this reaction takes place very quickly."}, {"title": "Michaelis Constant .txt", "text": "Now, we could basically solve for K minus one divided by K. So we basically take this, we bring it to this side, take this, bring it to this side, and we get this proportion."}, {"title": "Michaelis Constant .txt", "text": "So K minus one divided by K is equal to the product of these two concentrations divided by the enzyme substrate concentration."}, {"title": "Michaelis Constant .txt", "text": "And this, from general chemistry, we define to be the equilibrium constant of the dissociation of the enzyme substrate complex."}, {"title": "Michaelis Constant .txt", "text": "And because Km is equal to K minus one divided by K, which is the same thing as here, the equilibrium constant is equal to Km."}, {"title": "Michaelis Constant .txt", "text": "So we conclude that the second meaning of the Michelis constant, as long as we make the assumption that K minus one is much greater than K two, so this reaction is much quicker than this reaction."}, {"title": "Michaelis Constant .txt", "text": "We basically see that the Michaelis constant describes the likelihood of the dissociation of the substrate from the active side of that enzyme."}, {"title": "Michaelis Constant .txt", "text": "So we see that if the Km value is very large, then that means our numerator term in the ratio is much greater than our denominated term."}, {"title": "Michaelis Constant .txt", "text": "And if the numerator term is large compared to our denominator, that means we have a high concentration of the enzyme and the substrate in its dissociated form."}, {"title": "Michaelis Constant .txt", "text": "And that implies that the substrate does not bind very strongly to the active side of that enzyme."}, {"title": "Michaelis Constant .txt", "text": "So we see that if Km is large, the enzyme binds weakly to the substrate and there is a high probability that the substrate will dissociate from the active site of the enzyme because Km describes the equilibrium constant."}, {"title": "Michaelis Constant .txt", "text": "On the other hand, if Km is actually small, then that means we have a small concentration of the enzyme and the substrate in its individual form compared to the complex form."}, {"title": "Michaelis Constant .txt", "text": "And so if the Km is small, equilibrium will lie to the left side."}, {"title": "Michaelis Constant .txt", "text": "So we have a lot of the enzyme substrate complex and that means the substrate will bind strongly and tightly to the active side of the enzyme."}, {"title": "Michaelis Constant .txt", "text": "So if Km is small, the enzyme binds tightly to the substrate and the substrate will tend to remain bound to the active side."}, {"title": "Michaelis Constant .txt", "text": "So we see that we can actually give two different meanings to the Mikalus constant."}, {"title": "Michaelis Constant .txt", "text": "So physiological meaning number one is the Km describes the concentration of that substrate."}, {"title": "Michaelis Constant .txt", "text": "When the enzymes activity, the velocity of the enzyme is exactly half of the maximum velocity and at this point, exactly half of the active sites on the enzyme mixture in the enzyme mixture are actually filled with the substrate."}, {"title": "Michaelis Constant .txt", "text": "Now, and this must be emphasized, we can only use this second meaning as long as we remember that we made this assumption because this entire work is only meaningful if this is actually used."}, {"title": "Michaelis Constant .txt", "text": "So if this is true, if K one is much greater than K two."}, {"title": "Michaelis Constant .txt", "text": "And what that means is if a dissociation of the enzyme complex going this way takes place at a much higher rate than the enzyme substrate complex dissociation going this way, then in that particular case the mechanics constant also describes the likelihood that the substrate will dissociate from the enzyme."}, {"title": "Michaelis Constant .txt", "text": "If Km is high, that means our dissociation constant is high."}, {"title": "Michaelis Constant .txt", "text": "And so our equation will shift towards the right side."}, {"title": "Michaelis Constant .txt", "text": "And that means our complex will not likely will be very likely to actually dissociate into these products."}, {"title": "Michaelis Constant .txt", "text": "But if the Km is very small, then that means it binds very tightly, the substrate binds tightly into the active side of that enzyme and so the equilibrium will shift this way."}, {"title": "Michaelis Constant .txt", "text": "So once again, Km describes the likelihood that the substrate will dissociate from the enzyme."}, {"title": "Michaelis Constant .txt", "text": "If Km is high, it will be likely to dissociate."}, {"title": "Michaelis Constant .txt", "text": "If the Km is low, it will not be very likely to actually dissociate into that enzyme and that individual substrate."}, {"title": "Cell Cycle and Interphase .txt", "text": "The cell cycle of an animal cell refers to the different stages of the life cycle of that cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now for an animal cell there are two main stages."}, {"title": "Cell Cycle and Interphase .txt", "text": "We have the interface and the M stage also known as mitosis."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now mitosis is the process by which the cell actually divides into two identical cells and we're going to focus, focus on that stage in the next lecture."}, {"title": "Cell Cycle and Interphase .txt", "text": "In this lecture we're going to discuss the process of the interface or the stage known as interface."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now interface is the stage of the life cycle of the animal cell that prepares the cell for the process of cell division."}, {"title": "Cell Cycle and Interphase .txt", "text": "Interface is the longest stage of the life cycle of that cell and it takes up about 90% of the time."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now the reason it's so long is because interphase actually consists of three individual phases."}, {"title": "Cell Cycle and Interphase .txt", "text": "We have the G One phase, the S phase as well as the G Two phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now each one of these phases basically serves its own unique function."}, {"title": "Cell Cycle and Interphase .txt", "text": "So let's actually discuss each one of these individual phases that together make up our interface."}, {"title": "Cell Cycle and Interphase .txt", "text": "So let's begin with the G One phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "So as soon as the cell divides the cell enters the G One phase and the G One phase is known as the growth phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "So basically in this phase our chromosome unwinds and uncoils into Uchromatin and the Uchromatin is used to produce RNA that is used to synthesize the proteins that are needed by the cell and those proteins are used to synthesize the many organelles and the different types of cell machinery that are needed for the cell survival."}, {"title": "Cell Cycle and Interphase .txt", "text": "So the G One phase is the phase where we produce the majority of the organelles and the proteins that are used by the cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "And as a result the cell basically increases in size."}, {"title": "Cell Cycle and Interphase .txt", "text": "In fact the cell doubles in size during the phase known as the G One phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now towards the end of the G One phase is a checkpoint known as the restriction point."}, {"title": "Cell Cycle and Interphase .txt", "text": "And if the conditions are favorable and if the requirements have been met by the cell, the cell can basically commit itself to the process of cell division by exiting the G One phase and entering the next phase of interface known as the F phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "However, what happens if the cell doesn't actually want to divide?"}, {"title": "Cell Cycle and Interphase .txt", "text": "What happens if the conditions are not favorable or if the requirements have not been met?"}, {"title": "Cell Cycle and Interphase .txt", "text": "In this case the cell exits the G One phase and it exits Interphase entirely and it enters a completely different phase known as the G Not phase which is the resting phase of the cell cycle."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now some cells spend very little time in the resting phase, in the genot phase because they need to continually divide and some examples include skin cells, intestinal cells as well as stomach cells."}, {"title": "Cell Cycle and Interphase .txt", "text": "On the other hand, other cells that spend their entire lifetime in the genot phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "Basically that means that our cells do not actually divide."}, {"title": "Cell Cycle and Interphase .txt", "text": "And one example of a cell cell that doesn't actually divide and spends the majority of its time and the G Not phase in the resting phase is the nerve cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, if the cell actually wants to divide, if the conditions have been met, and if the requirements have been met, if the conditions are favorable, then the G One phase goes into the S phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "So if the G One phase is the growth phase of our cell cycle, then the S phase is basically the replication phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "In this phase, the cell also produces a small amount of proteins and organelles."}, {"title": "Cell Cycle and Interphase .txt", "text": "But the majority of the resources of the cell basically focus on DNA replication."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, in human cells, all 46 individual chromosomes are actually replicated."}, {"title": "Cell Cycle and Interphase .txt", "text": "And the original chromosome and the replicated chromosome are joined together in a region known as the centromere, which involves different types of proteins that assist in the joining process."}, {"title": "Cell Cycle and Interphase .txt", "text": "So let's take a look at the following diagram."}, {"title": "Cell Cycle and Interphase .txt", "text": "So, at the beginning of S phase, we have individual original chromosomes."}, {"title": "Cell Cycle and Interphase .txt", "text": "But as the S phase proceeds, we basically use the cell machinery to replicate our DNA molecule, the chromosomes."}, {"title": "Cell Cycle and Interphase .txt", "text": "So each one of the 46 individual chromosomes in human cells are replicated."}, {"title": "Cell Cycle and Interphase .txt", "text": "And we produce the following two chromosomes, the original as well as the replicated."}, {"title": "Cell Cycle and Interphase .txt", "text": "And we join these two chromosomes by using special proteins at a region known as the centromere found in this center location."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, once we actually replicate the individual chromosomes, these individual chromosomes are now known as chromatids."}, {"title": "Cell Cycle and Interphase .txt", "text": "So at this point, the cell basically contains 46 original chromatids and 46 replicative chromatids to make a combined total of 92 chromatids."}, {"title": "Cell Cycle and Interphase .txt", "text": "So at the end of S phase, our cell contains 92 chromatids in human cells."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, once the S phase is completed, it goes on into the G Two phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "So the G Two phase is basically the phase of interface that makes sure that the cell is fully prepared for the process of mitosis, for the process of cell division."}, {"title": "Cell Cycle and Interphase .txt", "text": "So in this phase, our cell basically continues producing the proteins and the organelles that are needed by that cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "So once the chromosomes are replicated and the chromosome number is doubled, the cell enters the G Two phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "During this phase, the cell prepares for cell division by making sure it contains enough proteins and organelles."}, {"title": "Cell Cycle and Interphase .txt", "text": "That means protein synthesis and organelle production continues in the G Two phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, at the end of the G Two phase, just like the G One phase contains a checkpoint, the G Two phase also contains a checkpoint at the end."}, {"title": "Cell Cycle and Interphase .txt", "text": "At the checkpoint, the cell basically checks for the level or the concentration of a certain type of protein known as the mitosis promoting factor or MPF."}, {"title": "Cell Cycle and Interphase .txt", "text": "MPF sometimes also stands for the maturation promoting factor."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, if the concentration levels are high enough, the cell will basically exit the G Two phase and exits the interface and enters the second stage known as the M stage."}, {"title": "Cell Cycle and Interphase .txt", "text": "So as we'll see in the next lecture this is the stage that consists of the process of mitosis which is the process by which the cell basically divides and produces an identical daughter cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now, mitosis can be broken down into ProPhase, metaphase, anaphase and telephase."}, {"title": "Cell Cycle and Interphase .txt", "text": "And the process by which the cell actually divides is known as cytokinesis."}, {"title": "Cell Cycle and Interphase .txt", "text": "And we'll discuss that in the next lecture."}, {"title": "Cell Cycle and Interphase .txt", "text": "So basically the process of interface is the first stage of the life cycle of an animal cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "Interface consists of the G one phase, the S phase and the G two phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "In the G one phase the cell basically grows in size because the majority of the proteins and organelles are synthesized within our cell."}, {"title": "Cell Cycle and Interphase .txt", "text": "The S phase is based basically the replication phase."}, {"title": "Cell Cycle and Interphase .txt", "text": "This is when the cell actually replicates the DNA."}, {"title": "Cell Cycle and Interphase .txt", "text": "Now the last phase, the G two phase this is the phase in which the cell basically makes sure that the cell is prepared for the process of cell division."}, {"title": "Cell Cycle and Interphase .txt", "text": "So the cell continues to synthesize the proteins as well as our organelles."}, {"title": "Incomplete Dominance.txt", "text": "So far in our discussion on genetic inheritance, we focused on a specific type of mode of inheritance known as complete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Now, in complete dominance, we have the existence of a dominant gene and the existence of a recessive gene."}, {"title": "Incomplete Dominance.txt", "text": "And when we mix a dominant gene with a recessive gene to produce a heterozygous individual, that dominant gene gene basically hides it, inhibits the effect of that recessive gene."}, {"title": "Incomplete Dominance.txt", "text": "So that's what we mean by complete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Now, we're going to focus on a different type of mode of inheritance known as Incomplete Dominance, which is different than complete dominance."}, {"title": "Incomplete Dominance.txt", "text": "So to demonstrate what Incomplete dominance is, let's suppose we have the following two parental phenotypes."}, {"title": "Incomplete Dominance.txt", "text": "So we have the following two parents."}, {"title": "Incomplete Dominance.txt", "text": "So we have a true breeding red plant that we cross with the true breeding white plant."}, {"title": "Incomplete Dominance.txt", "text": "Now, a true breeding red plant means both of those alleles code for that red color, while a true breeding white plant means both of those alleles found on the pair of homologous chromosomes code for that white color."}, {"title": "Incomplete Dominance.txt", "text": "Now, when we actually cross these two individuals, all the offsprings that are produced will be heterozygous."}, {"title": "Incomplete Dominance.txt", "text": "And we can see that based on the Punnett square here."}, {"title": "Incomplete Dominance.txt", "text": "So this true breeding red plant will produce only one type of sex cell, only one type of gamete, namely the Cr, where the C stands for color and R stands for the red color."}, {"title": "Incomplete Dominance.txt", "text": "So we have two of these slots which basically describe the same type of gamete that is produced by this particular true breeding red plan."}, {"title": "Incomplete Dominance.txt", "text": "And likewise, these are the two gametes that are produced by the true breeding white plan."}, {"title": "Incomplete Dominance.txt", "text": "So we have CW and CW where W stands for the color white."}, {"title": "Incomplete Dominance.txt", "text": "Now, when let's say this is the female, this is the male."}, {"title": "Incomplete Dominance.txt", "text": "When this excel combines with this sperm cell, we produce this heterozygous individual."}, {"title": "Incomplete Dominance.txt", "text": "Unlikewise when each one of these XLS and sperm cells combines, all of these individuals will be heterozygous."}, {"title": "Incomplete Dominance.txt", "text": "Now, in this particular case, what is the phenotype of the offspring that is produced?"}, {"title": "Incomplete Dominance.txt", "text": "Is it white or is it red?"}, {"title": "Incomplete Dominance.txt", "text": "Now, if we had complete dominance, what that would mean is this would either be red or it would be white, depending on which one of these color traits, red or white is dominant with respect to the other."}, {"title": "Incomplete Dominance.txt", "text": "But what we actually obtain are pink flowers."}, {"title": "Incomplete Dominance.txt", "text": "So all of these individuals, all of these heterozygous individuals will have a phenotype that is somewhere in between is intermediate of these two different types of phenotypes."}, {"title": "Incomplete Dominance.txt", "text": "So all the offspring in this particular case are heterozygous for that color trait."}, {"title": "Incomplete Dominance.txt", "text": "So that means we have one red allele and one white allele."}, {"title": "Incomplete Dominance.txt", "text": "Now, notice that neither of the trade is dominant with respect to the other and that's because these offspring that are produced are neither red nor white, they're somewhere in between."}, {"title": "Incomplete Dominance.txt", "text": "And so what that means is the expression of one allele will not actually be inhibited by the other allele."}, {"title": "Incomplete Dominance.txt", "text": "And in such a case, the phenotype of that offspring will be somewhere in between, somewhere intermediate between the two true breeding parents."}, {"title": "Incomplete Dominance.txt", "text": "And this type of mode of inheritance is known as incomplete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Now, it's important to emphasize the following important point."}, {"title": "Incomplete Dominance.txt", "text": "Incomplete dominance is not the same thing as blending inheritance."}, {"title": "Incomplete Dominance.txt", "text": "And that's because when this process, when this mode of inheritance takes place that offspring will still have a pair it will still have a pair of chromosomes in which one of the chromosomes will have a distinctly different allele than the other chromosome."}, {"title": "Incomplete Dominance.txt", "text": "In this case will have the rec allele in this case will have the white allele."}, {"title": "Incomplete Dominance.txt", "text": "So incomplete dominance is not an example of blending inheritance because the heterozygous individual that is produced still has two distinct alleles."}, {"title": "Incomplete Dominance.txt", "text": "We have that red allele, and we have the white allele."}, {"title": "Incomplete Dominance.txt", "text": "Now, the question is, why exactly is this pink?"}, {"title": "Incomplete Dominance.txt", "text": "Why is it in between these two phenotypes?"}, {"title": "Incomplete Dominance.txt", "text": "Well, because this offspring has twice as less of the red pigment as this individual."}, {"title": "Incomplete Dominance.txt", "text": "And because it has twice as less of the red pigment, it will be less red than this individual."}, {"title": "Incomplete Dominance.txt", "text": "And so it will be somewhere in between these two different flowers, the red and the white flower."}, {"title": "Incomplete Dominance.txt", "text": "Now, another question that we can ask is what exactly will the genotype and the phenotype distribution be when we'll take a pink flower and cross it with itself?"}, {"title": "Incomplete Dominance.txt", "text": "So let's suppose we take two of these offspring pink flowers that are heterozygous for that color trait, and we cross them."}, {"title": "Incomplete Dominance.txt", "text": "What will be the distribution of the offspring?"}, {"title": "Incomplete Dominance.txt", "text": "So, once again, let's apply our opponent square."}, {"title": "Incomplete Dominance.txt", "text": "Now, this produces two types of gametes, and this also produces two types of gametes."}, {"title": "Incomplete Dominance.txt", "text": "So let's suppose that this individual is the male individual and this individual is the female individual."}, {"title": "Incomplete Dominance.txt", "text": "So let's say that this is basically our sperm cells and these are our excel."}, {"title": "Incomplete Dominance.txt", "text": "So when this sperm cell combines with this excel, we produce a true breeding red color."}, {"title": "Incomplete Dominance.txt", "text": "When this mates with this, we produce a heterozygous individual."}, {"title": "Incomplete Dominance.txt", "text": "When this mates with this, we once again produce a heterozygous individual."}, {"title": "Incomplete Dominance.txt", "text": "And when this sperm cell combines with this Xcel, we produce a homozygous white individual."}, {"title": "Incomplete Dominance.txt", "text": "So we see that 25% are homozygous red."}, {"title": "Incomplete Dominance.txt", "text": "50% are heterozygous pink because two fourths so one two out of four are heterozygous pink, and one fourth so 25% are homozygous white."}, {"title": "Incomplete Dominance.txt", "text": "So we see a 25 to 50 to 25 or one to two to one ratio of phenotypes."}, {"title": "Incomplete Dominance.txt", "text": "But not only that, if we examine the genotypes, we're also going to see a one to two to one ratio of genotypes."}, {"title": "Incomplete Dominance.txt", "text": "So we conclude that whenever we're dealing with incomplete dominance, the genotype ratio of the offspring is exactly the same as the phenotype ratio."}, {"title": "Incomplete Dominance.txt", "text": "And this is not the same thing that we see when we're dealing with complete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Incomplete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Usually the genotype ratio is not the same thing as the phenotype ratio."}, {"title": "Incomplete Dominance.txt", "text": "So one thing to remember about incomplete dominance is you can actually tell exactly what the genotype is directly from the phenotype."}, {"title": "Incomplete Dominance.txt", "text": "So if we know that the phenotype of this color, of this flower is pink, then we know that this individual has two alleles."}, {"title": "Incomplete Dominance.txt", "text": "One allele is the red allele."}, {"title": "Incomplete Dominance.txt", "text": "The other one is the white allele."}, {"title": "Incomplete Dominance.txt", "text": "So this will be the genotype of this particular individual."}, {"title": "Incomplete Dominance.txt", "text": "So three important things to remember about incomplete dominance."}, {"title": "Incomplete Dominance.txt", "text": "Number one, in incomplete dominance, if we cross these true breeding plants for two different types of alleles, the product will be intermediate between these two phenotypes."}, {"title": "Incomplete Dominance.txt", "text": "Important point number two the genotype and the phenotype ratio is exactly the same as we saw in this particular case."}, {"title": "Incomplete Dominance.txt", "text": "So we have a one to two to one ratio of phenotype and a one to two to one ratio of genotype."}, {"title": "Incomplete Dominance.txt", "text": "And finally, just by knowing what the phenotype is, we can determine exactly what the genotype is whenever we're dealing with incomplete dominance."}, {"title": "Linked Genes Part II.txt", "text": "100 of these and about 100 of these."}, {"title": "Linked Genes Part II.txt", "text": "And this is basically how you tell whether or not a gene is or two genes are actually linked with respect to one another."}, {"title": "Linked Genes Part II.txt", "text": "If they are linked, then when we make these two individuals, we get this ratio."}, {"title": "Linked Genes Part II.txt", "text": "But if they are not linked, then the ratio will we get is basically four to four to one, one to one."}, {"title": "Linked Genes Part II.txt", "text": "So we have 400 to 400 to 100 to 100."}, {"title": "Linked Genes Part II.txt", "text": "Basically reduces to this ratio right here."}, {"title": "Linked Genes Part II.txt", "text": "And this is because of the process of crossing over that actually takes place randomly."}, {"title": "Linked Genes Part II.txt", "text": "And so it forms this distribution of our gametes for this particular individual."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "In the presence of oxygen."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "The way that a cell produces ATP molecules that are used as the energy source in that cell is via certain types of processes that together are known as aerobic cellular respiration."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And this includes glycolysis, pyruvate decarboxylation, the citric acid cycle, as well as the electron transport chain."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, glycolysis breaks down our glucose into two pyruvate molecules as well as a net of two ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And in the presence of oxygen, those two pyruvate molecules will then go into the mitochondrial matrix where they will undergo a series of processes that eventually produce NADH molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And those NADH molecules then go onto the electron transport chain, give off their electrons onto the enzymes of the electron transport chain, and the NADH molecules are oxidized back into the NAD plus molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And these NAD plus molecules can then be reused in the process of glycolysis, pyruvate decarboxylation and the citric acid cycle."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So we see that under aerobic conditions, basically the electron transport chain is where we synthesize the majority of the ATP molecules and it's also the location where we oxidize the NADH back into the NAD plus."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, the question is, why do we have to actually regenerate these NAD plus molecules?"}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Well, basically because without NAD plus molecules, glycolysis will not take place."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So things are pretty simple during the presence of oxygen, when we have enough oxygen present in the cell."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "But what happens if we do not have any oxygen present in the cell?"}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "What happens if we do not have enough oxygen present in the cell?"}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So these types of conditions when we do not have oxygen are known as anaerobic conditions."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And under anaerobic conditions, glycolysis is the only method by which we actually produce ATP."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Remember, glycolysis can take place regardless of whether or not we actually have oxygen present in the cell."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So glycolysis is the process, the first process of aerobic respiration, and it's the first process of anaerobic respiration as well."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "However, under anaerobic conditions, glycolysis is the only method by which we produce ATP molecules in the cell."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, the problem with this is glycolysis uses up NAD plus molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "But in order for glycolysis to continually take place, we have to somehow continually regenerate the NAD plus molecules from the NADH molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And the way that we regenerate these NAD plus molecules that are needed by glycolysis is by the process of fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So once again, under anaerobic conditions, glycolysis still occurs, which means that we break down glucose into two pyruvate molecules and produce a net of two ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "In the process, we also deplete our pool, our concentration of NAD plus molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "But we need these NAD plus molecules for glycolysis to continually take place."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So that implies that we must have some way to regenerate the NAD plus molecules by oxidizing NADH back to NAD plus."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And since under anaerobic conditions, the NADH molecules do not actually go onto the electron transport chain, another method of regenerating the NAD plus molecules is via the process of fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And there are two types of fermentation processes."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So we have alcohol fermentation and lactic acid fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So let's begin with alcohol fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So certain types of bacterial cells as well as these cells basically undergo this process of alcohol fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So glycolysis is the method by which they create ATP molecules and in order to continually create those ATP molecules our yeast cells as well as bacterial cells have to actually regenerate the NAD plus molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So in this type of fermentation basically Pyruvate is first or Pyruvate first undergoes the process of decarboxylation to produce acetyl aldehyde as well as the carbon dioxide."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And then our acetyl aldehyde reacts with our NADH and an extra H ion to form our ethanol alcohol as well as our oxidized NAD plus."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So this is exactly why we call it alcohol fermentation because we form ethanol."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "In fact, this is the method by which we actually synthesize alcohol that is then sold in bars and so forth."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So we see that alcohol fermentation involves the process of glycolysis as well as this process here."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So in yeast cells, for example, they produce ATP and to continually produce the ATP the Pyruvate basically undergoes these two steps to produce ethanol as well as regenerate the NAD plus that can then go into our glycolysis cycle to produce even more ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So this is how we actually regenerate and we reuse our NAD plus molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, let's move on to a more common cycle that takes place in human cells known as the lactic acid fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So in certain cells, including human cells, bacterial cells as well as fungi cells when oxygen supply runs low, for example during some type of vigorous exercise too many Pyruvate molecules and too many NADH molecules are produced."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And because not all pyruvates and NADH molecules can be placed through the citric acid cycle and the electron transport chain at the same exact time we have a build up of NADH molecules that takes place."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And so we have a very little amount of NAD plus present in the cell and we need NAD plus for glycolysis to take place."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So what the cell actually does is it undergoes this lactic acid fermentation process in which a special enzyme known as lactate dehydrogenase transforms our Pyrulbate."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "It reduces the Pyrulbate into lactic acid as well as forming our oxidized version of NADH, our NAD plus."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And this NAD plus can then be placed into the glycolysis cycle to produce our continual source of ATP."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, lactic acid can basically break down into its conjugate base, lactate and this releases H plus ions into the cell and that means it decreases the PH of the cell by increasing the concentration of H plus ions."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So the build up of lactic acid in the cell decreases its PH and it's the decrease in PH that basically causes the feeling of fatigue following our vigorous exercise."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, the lactic acid must eventually be transformed back into Pyruvate and this takes place in the liver."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So once we form our lactic acid, the lactic acid travels back into the liver."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And inside the liver, the lactic acid undergoes a process known as the core cycle."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "In the core cycle, we basically use oxygen to transform our lactic acid back into Pyruvate."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And the quantity of oxygen that we have to use to transform the lactic acid back into Pyruvate is known as the oxygen debt."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So we see that the process of fermentation is the method by which we basically regenerate our NAD plus molecules from the NADH molecules, because we need our NAD plus molecules to basically undergo the process of glycolysis and produce our continual source of ATP."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And our fermentation only takes place under anaerobic conditions."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Remember, under aerobic conditions, we have our citric acid cycle and we have the electron transport chain that actually produces the majority of the ATP molecules, as well as oxidizes the NADH back into the NAD plus."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "But under anaerobic conditions, we have glycolysis being the only method by which we produce our ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And to regenerate those NAD plus, we have to undergo the process of fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "Now, whenever somebody says fermentation, that basically incorporates glycolysis."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So glycolysis followed by this process or this process together is known as fermentation."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "So fermentation produces a net of two ATP molecules when we take one glucose and break it down, so we see that these processes do not actually themselves produce any ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "It's only glycolysis that produces those ATP molecules."}, {"title": "Alcohol and Lactic Acid Fermentation .txt", "text": "And when we break down one glucose molecule, we always produce a net of two ATP molecules."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "The chloride shift refers to the exchange in the bicarbonate ion for the chloride ion that takes place inside the red blood cells of our body."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And the chloride shift takes place not only in the tissues but also in the lungs."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "But the process is reversed, as we'll see in just a moment."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So let's begin by focusing on the chloride shift as it takes place inside our tissues."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So, inside the cells of exercising tissues, these cells are continually undergoing different types of metabolic processes such as cellular respiration."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And so the major waste byproduct that is produced in the process is carbon dioxide."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, of course, carbon dioxide is a nonpolar molecule and so it will not readily diffuse in our blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Only about 5% of the carbon dioxide will exist in the blood plasma in its CO2 form."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "About 90% of the carbon dioxide, as we'll see in just a moment, actually exist in its bicarbonate ion form."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, how exactly do we transform the carbon dioxide into its soluble bicarbonate ion form?"}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So basically, inside the cells of our tissue, different types of processes produce a bunch of carbon dioxide molecules."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And because these molecules are non polar, they can easily diffuse across the membrane of the cells of the tissue and enter the extracellular matrix."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And then they diffuse across the capillary walls found nearby our tissue cells."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, once inside the blood plasma, the CO2, about 5% of that CO2 remains inside the blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "But the rest essentially enters or diffuses across the membrane of the red blood cells."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, once inside the red blood cells, what happens is a catalytic enzyme known as carbonic anhydrates, catalyzes the combination of gaseous, CO2 and liquid water to basically form an acid known as carbonic acid."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, carbonic acid, H two CO2, is a weak acid and that means it will dissociate into bicarbonate, the conjugate base to this acid, as well as a hydrogen ion."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, this hydrogen ion ultimately leads to the bore effect."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "It binds onto a special allosteric site on our hemoglobin and that causes the hemoglobin to decrease its affinity for oxygen."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And that leads to more oxygen diffusing out of the red blood cell and into the cells of our tissue."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, what happens to our bicarbonate ion?"}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Well, the bicarbonate ion ultimately leaves the red blood cells found next to our tissues."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And the way that this takes place is we have a special ion exchange protein found within our membrane of the red blood cells."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And what happens is a single bicarbonate ion leaves the cell and enters the blood plasma because it can easily dissolve inside the blood plasma because unlike CO2, bicarbonate has a full negative charge, it is polar."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "But at the same time that our bicarbonate ion leaves the cell, in order to maintain an electrically neutral state, in order to not build any charge, we need to transport another particle, another atom that contains a negative charge into the cell."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Because if one negative charge exits the cell, we have to basically take a negatively charged atom and make it go into the cell to maintain an electrically neutral state, because we do not actually want to affect the electrochemical gradient that exists between the inside of the red blood cell and the outside the blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So we essentially exchange a single bicarbonate ion for a single chloride ion."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And this is what we call the chloride shift."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So the chloride shift takes place to maintain a balance of electrical charge between the inside of the red blood cell, the cytoplasm portion, and the outside environment, the blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So about 90% of the carbon dioxide exists in its bicarbonate ion state inside the blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "About 5% exist dissolved inside our blood plasma at CO2."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And the rest of it is actually bound to hemoglobin."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So hemoglobin doesn't only bind oxygen."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "It can also bind a tiny bit of carbon dioxide."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, let's move on to our lungs."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "What exactly takes place inside our lungs?"}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So, basically, inside the lungs, we also have the chloride shift that exists, but it takes place in the opposite direction."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And that's because the entire purpose of the tissue is to take the CO2 and bring it into the red blood cells."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "But the entire purpose of the lungs is to take the CO2 from the red blood cell and bring into the space of our alveoli, which ultimately expels that CO2 during the process of exhalation."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So let's see what takes place."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So, the bicarbonate ion enters the blood plasma, and then it travels with the blood plasma all the way to the pulmonary capillaries."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And once we find it in the pulmonary capillaries, what happens is the opposite process takes place."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, in order to maintain electrical neutrality, when a single bicarbonate ion enters our red blood cell, a single chloride ion must leave that red blood cell so that we have a net charge of zero that essentially travels across the red blood cells."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So one negative charge enters, and one negative charge leaves."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, once our bicarbonate is inside our red blood cell, only then can it basically interact with the H ion and form our carbonic acid."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And only then can our carbonic anhydrase catalyze the formation of CO2 and water by breaking this carbonic acid down."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So remember, the carbonic anhydrase enzyme is only found within our red blood cell."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "It is not found inside the blood plasma."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And that's why this anion must first cross the membrane and enter the red blood cell before we can actually form our carbon dioxide."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Now, once we form the carbon dioxide, because it is nonpolar, it can easily diffuse across the membrane of the red blood cell, then across our wall of the capillary, and finally enter the alveolar space, where we exhale."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And we basically expel that carbon dioxide to the outside environment."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "So we see that the chloride shift takes place inside the red blood cells and it takes place not only in the tissues but also in the lungs."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "But the process is reversed in these two cases here to maintain an electrically neutral passageway of ions so that we don't have any build up of negative charge."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "What happens is, within the red blood cells of the tissues, the car, the bicarbonate exits, but the cloride interest."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "In this case, the opposite is true because we want to take in bicarbonate to transform it into carbon dioxide inside the lungs."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "Basically, a single chloride ion exits when a single bicarbonate enters our red blood cell."}, {"title": "Chloride Shift in Red Blood Cells .txt", "text": "And this is what we call the chloride shift."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So, to begin our discussion on glucose metabolism, let's take a look at glycolysis."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, glycolysis is also known as the glycolytic pathway, and glycolysis actually involves many individual steps and many individual processes."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so we typically divide glycolysis into three different stages, stage one, stage two and stage three."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, in this lecture, we're going to focus us on stage one."}, {"title": "Stage 1 of Glycolysis .txt", "text": "But before we take a look at the details of stage one, let's actually discuss what each stage actually does."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So what's the point of stage one, stage two and stage three?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Well, stage one basically aims to trap that glucose molecule inside the cytoplas on the cell so that the glucose cannot actually leave that cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And it also destabilizes that glucose molecule, increases its overall energy and that makes it more reactive, and that prepares the glucose for stage two."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, in stage two, we break down that destabilized glucose molecule into two components."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And then in stage three, we essentially take those two components, we oxidize those two components and that allows us to actually harvest the energy in those molecules and form ATP molecules, as well as pyruvate molecules and NADH molecules."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So let's focus on stage one."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So in stage one, we basically want to take that glucose molecule and transform it into fructose one six bisphosphate, and we'll see exactly why that is in just a moment."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So actually, if we look at stage one, we can break down stage one into three different steps."}, {"title": "Stage 1 of Glycolysis .txt", "text": "We have step one, we have step two and we have step three."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So let's quickly go over what each step does and why."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So in step one, we basically first formulate one of the carbons on glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "In step two, we transform that glucose into an isomer called fructose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And in step three, we essentially take that fructose and we add another phosphate group onto that fructose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So let's focus on step one."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So what exactly are the details of step one and why does it actually take place?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "So let's suppose we have a glucose on the outside of the cell, and in the membrane of that cell, there's a special type of membrane protein that we're going to focus on in a future lecture that actually transports that glucose into the cytoplasm of that cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, once that glucose is inside the cytoplasm of that cell, a special type of enzyme, a protein kinase we call hexokinase, actually catalyzes the addition of a phosphoryl group from an ATP molecule onto the carbon number six of this glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So this carbon number six basically gains a phosphoryl group as a result of the catalyzation of this hexokinase."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now we'll take a look at the details of hexokinase in just a moment."}, {"title": "Stage 1 of Glycolysis .txt", "text": "First, I'd like to answer the following question."}, {"title": "Stage 1 of Glycolysis .txt", "text": "What is the entire point of step one?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Why do we have to actually add a phosphoryl group onto the glucose molecule?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Well, two important reasons."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Number one is we want to trap that glucose in the cytoplasm of that cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So by adding that phosphoryl group onto carbon number six, we change the structure of this glucose molecule, we transform it into glucose six phosphates."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So what we do is we basically make it much more polar because now it contains a full negative charge, in fact a negative charge of two, whereas in this case it wasn't as polar because it didn't contain a full charge."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so what that means is those membrane transport proteins that were able to actually move the glucose into the cell or out of that cell cannot bind the glucosex phosphate because of this charged component."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so these glucose molecules cannot leave the cytoplasm, cannot exit the cell and that means they are trapped inside the cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now the second reason for step one is to basically begin destabilizing that glucose molecule."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So remember, whenever we have charge that destabilize the structure and in this particular case we have no charge, in this case we have a charge of negative two."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So that means this molecule is higher in energy, less stable and more reactive than this glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that's important in basically destabilizing that structure so that in step two it is able to actually react and break down into smaller components."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Remember, the entire point of stage one is to trap the molecule and make it less stable."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So once again, glucose moves into the cell with the help of a membrane transporter."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Once inside the cytoplasm, it undergoes a phosphorylation process in which hexokinase adds a phosphate group, phosphoryl group onto the 6th carbon by taking it away from ATP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And we also form the ADP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So actually this step requires energy, requires an ATP molecule."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So this step is significant for two reasons."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Number one is it makes the glucose more polar by adding that negative charge and this traps the glucose inside the cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So the negatively charged phosphate group prevents the glucose from moving across the cell membrane because that membrane transport protein cannot actually attach to the glucose six phosphate because of this altered structure."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now the second reason is to begin destabilizing this molecule that increases its energy, makes it more reactive."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So the addition of a charged moiety onto the glucose destabilize the structure of that glucose and increases its energy."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And this makes it more reactive and more likely to actually undergo and continue glycolysis."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now let's focus in on the hexokinase."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So what is a hexokinase?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Well, a hexokinase is a protein kinase that basically catalyzes the addition of asphalt groups onto hexosugars."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And glucose is an example of a HEXO sugar."}, {"title": "Stage 1 of Glycolysis .txt", "text": "It contains these six carbon atoms."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, like all protein kinases, hexokinase requires a diveant metal atom to actually function effectively."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that's because the divalent metal atom such as magnesium two plus or magnesium two plus, interacts with the ATP molecules."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So when the diveant ion interacts with that ATP molecule, it changes the confirmation of that ATP molecules and makes it perfect to undergo this reaction in the active side of the hexokinase."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So this is hexokinase before the binding of the glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "This is our glucose, and this is hexokinase after that glucose has balanced the active side."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So before the binding actually took place, we see that we have two domains and these two domains are found relatively far apart."}, {"title": "Stage 1 of Glycolysis .txt", "text": "But when that glucose moves into this pocket, the active side of the hexokinase, these two lobes, these two domains basically rotate about twelve degrees inward."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And as they rotate, they essentially create this induced fit for the glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that means the glucose will fit snugly inside this region."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So as it essentially closes in, it basically squeezes all the water molecules out of this region."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so once we form this structure, we have this induced fit, this perfect fit, and all the water molecules have been removed from the active side."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So it creates a perfect environment for this reaction to actually take place."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So on top of actually creating this close proximity, it also creates an environment in which we don't have any water molecules."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, why is that important?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Well, whenever we have an ATP molecule and we have a water molecule in close proximity, remember the ATP is not very stable."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so the water molecule will generally want to hydrolyze and break down that ATP into ADP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so by creating this environment in which we don't have any water molecules, what that does is it prevents any unwanted reactions, that is, it prevents the water from hydrolyzing the ATP into ADP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And what that means is the ATP can go ahead and transfer the enzyme can go ahead and transfer that phosphoryl group from the ATP onto this glucose molecule into producing that ADP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So the movement of the glucose into the active side of hexokinase causes the two domains, these two domains to basically rotate about twelve degrees."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So they actually move about ten angstroms and that rotates these sections and closes that glucose molecule inside this active site, creating an induced fist and this seals off the glucose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So removes all the water molecules and positions the fixed carbon right next to that ATP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that also prevents the ATP from actually being hydrolyzed prematurely by that water molecule."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Because if the ATP is hydrolyzed by water before that phosphoryl group is actually transferred onto the glucose, then we form the ADP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And the ADP will not be able to transfer that phosphoral group."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so that's why this is a very important step."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now let's move on to step number two."}, {"title": "Stage 1 of Glycolysis .txt", "text": "We call the isomerization step."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So once we actually form that glucose, a glucose six phosphate, so glucose that contains a phosphoryl group on carbon number six, the next step is to actually transform that glucose into a fructose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And to transform it into a fructose, what must happen first is it actually has to open up into its open chain."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Confirmation."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Why?"}, {"title": "Stage 1 of Glycolysis .txt", "text": "Well, remember in our discussion of glucose molecules and sugar molecules."}, {"title": "Stage 1 of Glycolysis .txt", "text": "We said that when the sugar molecules exist in their cyclic form, they do not typically undergo any reactions because that aldehyde group or the ketone group is not actually exposed."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so what happens is a special enzyme known as phosphorglucose isomerase opens up this structure to form the open chain, confirmation now that exposes this reactive aldehyde group."}, {"title": "Stage 1 of Glycolysis .txt", "text": "In the next step, we basically catalyze the transformation of this glucose in its open chain into a fructose in the open chain."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And next we transform the open chain into its closed cyclic chain."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so this is the final product in step number two."}, {"title": "Stage 1 of Glycolysis .txt", "text": "This is what we call fructose six phosphate."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So in the second step, the enzyme phosphoglucose isomerase transforms the glucose which is an aldos, it contains an aldehyde group into a fructose, which is a keto that contains this ketone group."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So this is a ketone and this is an aldehyde."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So we see that in step two of stage one, the entire point is to transform an aldos into a keto."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now let's move on to step three of stage one."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So it's basically not enough to add that phosphoryl group, we have to add a second phosphoryl group because remember, the entire point of step or stage one is to destabilize that glucose as much as we can."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so to further destabilize the structure of glucose to increase its energy and make it much more reactive, in step three of stage one, we have an enzyme known as phosphor fructosekinase PFK that catalyzes the addition of yet another phosphoryl group onto a carbon of that fructose."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so this we begin with fructose six phosphate and then we form fructose one six bisphosphate."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so now, instead of having one, we actually have two of these phosphate groups."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so just like this step actually requires ATP, this step also requires ATP."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so we see that stage one actually uses up two ATP molecules and no ATP molecules have been actually formed so far."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, another important thing about this step, step three of stage one is once the step actually takes place, that commits that sugar molecule to undergoing the glycolysis process."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Because before this step actually took place, that sugar molecule can be stored in the form we call glycogen."}, {"title": "Stage 1 of Glycolysis .txt", "text": "But once this step takes place, we call it the committed step because it commits that sugar to undergo that process of glycolysis."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So in step three of stage one, phosphor fructokinase PFK adds a second phosphoryl group onto that sugar to make it much less stable, higher in energy and therefore much more reactive."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that will allow it to actually break down in stage two into smaller components as we'll see in the next lecture."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And so we transform the fructose six phosphate into fructose one six bisphosphate."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And this is what we call the commitment step."}, {"title": "Stage 1 of Glycolysis .txt", "text": "It commits it to the process of glycolysis."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So once again, the point of stage one is to trap that molecule inside the cell."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And that's exactly what we do in step one."}, {"title": "Stage 1 of Glycolysis .txt", "text": "So we add the phosphoryl group to basically trap it inside the cytoplasm."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And by adding that phosphoryl group, we also destabilize stabilize that molecule."}, {"title": "Stage 1 of Glycolysis .txt", "text": "Now, in step two, we transform it into from an aldos into a keto."}, {"title": "Stage 1 of Glycolysis .txt", "text": "And then in step three, we continue the process of destabilization by basically adding a second phosphoro group onto that sugar molecule."}, {"title": "Structure of the Kidney.txt", "text": "The kidneys are very important organs found not only in humans, but also many other animals."}, {"title": "Structure of the Kidney.txt", "text": "And each person contains two identical and symmetrical kidneys."}, {"title": "Structure of the Kidney.txt", "text": "So the function of the kidney we're going to focus on in the next several lectures."}, {"title": "Structure of the Kidney.txt", "text": "The kidneys basically function in not only in excretion, but also in controlling and regulating the osmolarity of our blood plasma."}, {"title": "Structure of the Kidney.txt", "text": "Now, in this lecture, we're going to focus on the basic anatomy and structure of the kidney."}, {"title": "Structure of the Kidney.txt", "text": "So let's begin by taking a cross section of any one of our kidneys."}, {"title": "Structure of the Kidney.txt", "text": "We basically obtained the following diagram."}, {"title": "Structure of the Kidney.txt", "text": "So we sliced our kidney and this is what it looks like."}, {"title": "Structure of the Kidney.txt", "text": "So notice that we have many of these individual sections and structures found inside our kidney and this is what we're going to focus on in this lecture."}, {"title": "Structure of the Kidney.txt", "text": "So on this side of the kidney, we have the renal vein shown in blue."}, {"title": "Structure of the Kidney.txt", "text": "We have the renal arteries shown in red."}, {"title": "Structure of the Kidney.txt", "text": "And we have the ureter shown in green."}, {"title": "Structure of the Kidney.txt", "text": "On the other side we have the renal capsule, the renal cortex, the renal medulla, our renal pelvis, the renal pyramids, which are these brown sections here."}, {"title": "Structure of the Kidney.txt", "text": "And we have the nephron shown in purple."}, {"title": "Structure of the Kidney.txt", "text": "Now, this diagram only shows a single nephron, but actually we have over a million nephrons within this single kidney."}, {"title": "Structure of the Kidney.txt", "text": "And the nephron is the basic unit of structure of the kidney."}, {"title": "Structure of the Kidney.txt", "text": "And we'll discuss what the structure of the nephron is in just a moment."}, {"title": "Structure of the Kidney.txt", "text": "First, let's discuss the renal capsule, the renal cortex and the renal medulla."}, {"title": "Structure of the Kidney.txt", "text": "Now, the renal capsule is a very thin membrane."}, {"title": "Structure of the Kidney.txt", "text": "It's essentially a transparent fibrous membrane that encloses and surrounds the entire kidney."}, {"title": "Structure of the Kidney.txt", "text": "It's found on this outermost portion here."}, {"title": "Structure of the Kidney.txt", "text": "Now, the purpose of the renal capsule is twofold."}, {"title": "Structure of the Kidney.txt", "text": "It basically serves as a protective layer."}, {"title": "Structure of the Kidney.txt", "text": "It protects the kidney from being damaged and also gives our kidney its bean like shape."}, {"title": "Structure of the Kidney.txt", "text": "Now the structure, the section of the kidney right below the renal capsule is known as the renal cortex."}, {"title": "Structure of the Kidney.txt", "text": "It basically begins right below the capsule and ends right about here."}, {"title": "Structure of the Kidney.txt", "text": "So this entire section here is our renal cortex."}, {"title": "Structure of the Kidney.txt", "text": "Now, the renal cortex is the uppermost section if we don't consider the capsule."}, {"title": "Structure of the Kidney.txt", "text": "And it also contains several important structures of the nephron."}, {"title": "Structure of the Kidney.txt", "text": "So it basically contains something called the Bowman's capsule and the glomerolus."}, {"title": "Structure of the Kidney.txt", "text": "It also contains the proximal and the distal convoluted tubules."}, {"title": "Structure of the Kidney.txt", "text": "And we'll see what that is in just a moment."}, {"title": "Structure of the Kidney.txt", "text": "Now, if we move to right below the renal cortex, we have a section known as the renal medulla."}, {"title": "Structure of the Kidney.txt", "text": "The renal medulla is basically this entire section here that consists of these renal pyramids."}, {"title": "Structure of the Kidney.txt", "text": "And the renal pyramids exist as a result of the stacking of these nephrons."}, {"title": "Structure of the Kidney.txt", "text": "They basically are stacked adjacent to one another along the entire section of the medulla as well as the cortex, and they form these renal pyramids."}, {"title": "Structure of the Kidney.txt", "text": "So the real medulla is the inner portion of the kidney and it basically contains several important structures of the nephron, just like the cortex does."}, {"title": "Structure of the Kidney.txt", "text": "The medulla contains a structure known as the Loop of Henley."}, {"title": "Structure of the Kidney.txt", "text": "It also contains the vase orcta, which is a bed of capillaries, as we'll see in just a moment."}, {"title": "Structure of the Kidney.txt", "text": "And it contains our collecting ducts."}, {"title": "Structure of the Kidney.txt", "text": "So now that we discussed these three structures, we are ready to define what a nephron actually looks like."}, {"title": "Structure of the Kidney.txt", "text": "So the nephron, if we take the nephron shown in purple, we zoom in on the nephron and we place it right side up."}, {"title": "Structure of the Kidney.txt", "text": "So we flip it this way, we basically get the following diagram."}, {"title": "Structure of the Kidney.txt", "text": "So let's begin with this section here, found in the cortex known as the Bowman's capsule."}, {"title": "Structure of the Kidney.txt", "text": "So this entire section here is the Bowman's capsule."}, {"title": "Structure of the Kidney.txt", "text": "It kind of looks like a claw."}, {"title": "Structure of the Kidney.txt", "text": "Now the Bowman's capsule, inside this Bowman's capsule, enclosed inside is a capillary, is a bed of capillaries."}, {"title": "Structure of the Kidney.txt", "text": "And this bed of capillaries is known as araglomerilus."}, {"title": "Structure of the Kidney.txt", "text": "So as we'll see in just a moment, the renal artery divides and subdivides into many tiny blood vessels known as the Afarin arteriols, and they bring the blood, the blood plasma into this bed of capillaries known as araglomerolus."}, {"title": "Structure of the Kidney.txt", "text": "Now, connected to the Bowman's capsule is a section of the tube known as the proximal convoluteu two."}, {"title": "Structure of the Kidney.txt", "text": "Next is our descending and ascending loop of Henley, followed by the distal convoluted tubule and finally our collecting duct."}, {"title": "Structure of the Kidney.txt", "text": "Now notice that this dashed line separates the renal cortex, this section here, from the real medulla, which is this section here."}, {"title": "Structure of the Kidney.txt", "text": "Now so this is the cortex, this is our medulla."}, {"title": "Structure of the Kidney.txt", "text": "So inside the cortex, we have the Bowman's capsule as well as araglomerolus."}, {"title": "Structure of the Kidney.txt", "text": "We also have the proximal convolute, as well as the distal convolute."}, {"title": "Structure of the Kidney.txt", "text": "Now, inside the medulla, we have the D standing and the ascending loop of Henley."}, {"title": "Structure of the Kidney.txt", "text": "We also have the collecting duct and we have a second capillary bed system known as the vasa rectan."}, {"title": "Structure of the Kidney.txt", "text": "So the vasaecta is basically this entire bed of capillaries."}, {"title": "Structure of the Kidney.txt", "text": "And we'll discuss what the function of that is in just a moment."}, {"title": "Structure of the Kidney.txt", "text": "So let's discuss what the renal pelvis is."}, {"title": "Structure of the Kidney.txt", "text": "The renal pelvis is this entire section here."}, {"title": "Structure of the Kidney.txt", "text": "It's basically a funnel shaped cavity that collects the urine that is produced by the individual nephrons."}, {"title": "Structure of the Kidney.txt", "text": "And it directs that urine into a structure known as our ureter."}, {"title": "Structure of the Kidney.txt", "text": "The ureter is a structure that moves urine from the kidney and into the urinary bladder where it is stored before we secrete that to outside of our body."}, {"title": "Structure of the Kidney.txt", "text": "Now let's move on to our renal artery."}, {"title": "Structure of the Kidney.txt", "text": "So basically, the renal artery is the blood vessel system that brings the oxygenated blood, the blood filled with nutrients and also filled with the waste products that must be secreted by that kidney."}, {"title": "Structure of the Kidney.txt", "text": "So the renal artery delivers oxygenated blood to the kidneys and it splits and it subdivides into these very tiny blood vessels known as APA arterios."}, {"title": "Structure of the Kidney.txt", "text": "And these are the blood vessels that bring the blood, the oxygenated blood to each one of these nephrons found along the entire medulla and cortex of the kidney."}, {"title": "Structure of the Kidney.txt", "text": "So if this is our nephron, this is our a ferrint arterial that ultimately comes from the renal arteries."}, {"title": "Structure of the Kidney.txt", "text": "So it brings that blood plasma hydrostatic pressure pushes some of that blood plasma, including our excretory waste products, from this glomerulus into the Bowman's capsule and eventually through this entire system into the collecting duct and then into the ureter, into the bladder and eventually outside of our body."}, {"title": "Structure of the Kidney.txt", "text": "Now, this blood vessel is also an oxygenated blood vessel, but it is known as the etherrin arterio."}, {"title": "Structure of the Kidney.txt", "text": "So we have the Afarin and the efharin arterio and this brings our oxygenated blood to a second system of capillaries known as the vasa recta."}, {"title": "Structure of the Kidney.txt", "text": "So basically, this set of capillaries brings the oxygenated blood, the nutrients to the cells found in this section and then it empties out that deoxygenated blood to this entire vein system that basically connects and eventually enters and becomes the renal vein."}, {"title": "Structure of the Kidney.txt", "text": "So the renal vein receives the deoxygenated blood from the kidney, specifically from the vasa rectan of our nephron of each one of these nephrons found inside the kidneys."}, {"title": "Structure of the Kidney.txt", "text": "So it returns that deoxy in the blood back to the systemic blood circulation system and will define what systemic blood circulation system is when we'll discuss the cardiovascular system and the heart."}, {"title": "Structure of the Kidney.txt", "text": "So basically, this is the basic structure of our kidney."}, {"title": "Structure of the Kidney.txt", "text": "The kidney consists of these basic units known as nephrons that are found throughout the cortex and throughout our medulla."}, {"title": "Structure of the Kidney.txt", "text": "Now, in the next lecture, we're going to focus on the structure and the function of the nephron in much more detail and we'll see what the function of each one of these sections of the nephron is."}, {"title": "Structure of the Kidney.txt", "text": "We'll discuss how the blood plasma actually gets through the Bowman's capsule and what happens to it as it travels through this nephron."}, {"title": "Acid-Base Reactions and pH .txt", "text": "One particularly important type of chemical reaction that takes place inside our body and inside our cells is the acidbased reaction."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now remember, acidbased reactions determine what the PH of the solution is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And the PH is a factor that can influence the many different types of biological processes that take place inside our body."}, {"title": "Acid-Base Reactions and pH .txt", "text": "As we'll see the next lecture, for example, the PH can determine what the final structure is of biological molecules such as proteins and DNA."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, in this lecture, we're going to focus simply on what an acidbased reaction is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "We're going to remember what PH is and we're going to remember what acidic and basic solutions are."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So let's begin by recalling what an acid based reaction is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So an acidbase reaction is a reaction in which we exchange an H plus ion between two different molecules."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we have the acid molecule that donates an H plus ion and a bond is broken while the other molecule, the base, accepts that H plus ion because it has a lone pair of electrons and it forms a Covalent bond."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So in an aft base reaction, we have an exchange of a proton."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And the reason we say a proton is because a hydrogen ion lacks an electron and it only has a proton in the nucleus."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So in any acid base reaction we have a hydrogen atom that is exchanged between our two molecules, the acid in the base."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And at the same time, one Covalent bond is broken and another Covalent bond is actually formed."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So let's suppose we have some hypothetical acid ha where A is simply an atom or a group of atoms that are attached to our H atom and this is a Covalent bond."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, when this acid dissociates, this Covalent bond is broken and the two electrons in that Covalent bond end up on the A atom."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so this gains an additional electron and so it becomes an anion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "It gains a negative charge while this one loses an electron."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so it only consists of a proton in a nucleus."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so this is the hydrogen ion, aka."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Also known as a proton."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, usually these acid reactions, acidbased reactions take place in water because our body consists predominantly of water."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so we have a water molecule that will grab the H ion using one of its lone pair of electrons on the oxygen to form the following hydronium ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, the next question is what exactly is the method by which we calculate we measure the hydrogen ion concentration inside solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we use something called the PH."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And the PH is nothing more than a fancy way of determining what the concentration is of our solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So the PH is equal to negative log of the hydrogen ion concentration in that solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So if we know what the PH is, then we can easily calculate what the concentration of the hydrogen ion in solution is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "For example, if you know that the PH is equal to seven at room temperature."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Then you can use this and a bit of algebra to calculate what the concentration is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So if the PH is equal to seven, we set the left side of the equation equal to seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And then we solve for the hydrogen ion concentration."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we essentially take the negative side."}, {"title": "Acid-Base Reactions and pH .txt", "text": "We negate both sides."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So this becomes negative, this becomes positive."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Then we raise both of these to the power of ten so that the law cancels out."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And we get that the concentration of the hydrogen ion in solution is equal to one times ten to negative ten when our PH is equal to 7.0."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, by knowing what the hydrogen ion concentration is, we can also determine what the hydroxide concentration in solution is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And that's because of the following equation."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So if we have a beaker of pure water, even in that beaker of pure water, water molecules will also dissociate by this same equation."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So even though water is a weak acid, water molecules will still dissociate into these two ions, an H plus ion and a hydroxide ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, by using basic chemistry, we can set up the equation for the equilibrium constant K. So the equilibrium constant K for this reaction is equal to the product of the concentration or the product of the concentrations of these two molecules divided by the concentration of the reactant, in this case, pure water."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, at room temperature, this cave value is measured to be 1.8 times ten to negative 16."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And the concentration of water in pure water is always a constant value."}, {"title": "Acid-Base Reactions and pH .txt", "text": "It's always equal to 55.5."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so because this is a constant and this is a constant, we can plug those values into this equation and we get 1.8 times ten to negative 16 is equal to this multiplied by this, our two unknowns divided by a constant."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So 55.5."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so if we bring this to the left side, we multiply them out, we get 1.0 times ten to negative 14 is equal to the product of the concentration of the hydrogen ion and the concentration of that hydroxide ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And this is always true at room temperature."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So basically what this equation is, and let's call this equation A."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And by the way, this is equation B, and this is equation A from equation B."}, {"title": "Acid-Base Reactions and pH .txt", "text": "If we know what the concentration of the hydrogen ion is, and we can calculate that by using this equation A, then we can easily calculate what the concentration of the hydroxide ion is by using equation B."}, {"title": "Acid-Base Reactions and pH .txt", "text": "For example, let's use this case once again."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Let's suppose our PH is seven, where at room temperature."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And what that means is, based by this calculation, the concentration of the hydrogen ion at a PH of seven is equal to one times ten to negative seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So now that we know equation B and we know what this value is, we can plug that into this equation and solve for the concentration of the hydroxide ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so if we plug that in we get 1.0 times ten to negative 14 is equal to."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So now we know what this value is."}, {"title": "Acid-Base Reactions and pH .txt", "text": "It's 1.0 times ten to negative seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And we're looking for this concentration."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we solve for that and we see that this is also equal to 1.0 times ten to negative seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we see that if the PH is equal to seven and we're at room temperature, then the concentration of the hydroxide ion is equal to the concentration of the hydrogen ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And at this particular moment in time the solution is said to be neutral because the two concentrations are equal."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And by the way, this 1.10 times ten to negative 14 value is equal to K with the W subscript."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So this is equal to K with the W subscript where the W stands for water."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And this particular value works at room temperature."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, what exactly do we mean by an acidic solution?"}, {"title": "Acid-Base Reactions and pH .txt", "text": "And what exactly do we mean by a basic solution?"}, {"title": "Acid-Base Reactions and pH .txt", "text": "So an acidic solution is a solution in which the concentration of the hydrogen ion in solution is greater than the concentration of the hydroxide ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we know if this is equal to this, then this is a neutral solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "But an acidic solution is a solution in which this concentration is greater than this concentration."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now for example, let's suppose we know that the concentration of the H plus ion of our solution is equal to 1.0 times ten to negative six."}, {"title": "Acid-Base Reactions and pH .txt", "text": "The question is what exactly is the PH of this solution?"}, {"title": "Acid-Base Reactions and pH .txt", "text": "Well, to find the PH, we use equation A."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So the PH is equal to the negative log of the concentration of that hydrogen ion which is ten to negative six."}, {"title": "Acid-Base Reactions and pH .txt", "text": "We plug that in and we get a PH of six."}, {"title": "Acid-Base Reactions and pH .txt", "text": "In fact, we see that anytime this is greater than this the PH of that solution will be below seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so if the PH of our solution is below seven at room temperature, that solution is said to be acidic."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, what about basic solutions?"}, {"title": "Acid-Base Reactions and pH .txt", "text": "Well, a solution is said to be basic if the concentration of the hydrogen ion is less than the concentration of the hydro hydroxide ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And so in this case, the solution is said to be basic."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Now, by the same exact reasoning, let's suppose that our hydrogen concentration is 1.0 times ten to negative eight."}, {"title": "Acid-Base Reactions and pH .txt", "text": "Let's find what the PH is of this particular solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So once again we apply the same exact equation, equation A."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So the PH is equal to negative log of the hydrogen I concentration and is equal to."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So you plug that into the calculator and we get a value of eight."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we see that anytime this condition is true, the PH will always be above seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "In fact, anytime we have a solution with a PH of above seven and we are at room temperature, that means our solution will be a basic solution."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So at room temperature, a PH of above seven means the solution is basic."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So we have an acidic solution, is a solution in which the PH is below seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "A basic solution is a solution in which the PH is above seven, and a neutral solution solution where the PH is equal to seven."}, {"title": "Acid-Base Reactions and pH .txt", "text": "And at that particular moment in time, the concentration of our base, the hydroxide, is equal to the concentration of our acid, our hydrogen ion."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So these are the basics you're going to need to use in the next lecture."}, {"title": "Acid-Base Reactions and pH .txt", "text": "So in the next lecture, we're basically going to discuss how the PH of a solution inside our body can actually influence what the reaction is, what the biochemical reaction pathway is, and what the final structure is of that biological molecule that is produced in that particular biochemical reaction."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "The process of glycolysis allows cells to actually generate ATP molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "In the process, it also generates NADH molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, for glycolysis to actually continue taking place, the NAD plus molecules that are used up in glycolysis must be regenerated."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And that's because NAD plus concentration is limited inside our cells and under aerobic conditions, when we have oxygen present side ourselves, these NAD plus molecules are regenerated on the electron transport chain."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So the NADH molecules that we form in glycolysis must somehow move onto the electron transport chain found on the inner membrane of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And there the electrons are extracted from the NADH to form the NAD plus."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And electrons are also used to actually generate ATP molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So the question that I'd like to focus on in this lecture is how exactly do the NADH molecules produced in the process of glycolysis actually get to the electron transport chain?"}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So once again, under aerobic conditions, NADH molecules produced in glycolysis must be transported into the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Why?"}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Well, because the cell must use the NADH molecules to not only produce ATP molecules, but to also regenerate the NAD plus Co enzyme that is needed for glycolysis to actually continue taking place."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, there are actually different ways by which the NADH molecules can actually get into the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And in this lecture, I'd like to focus on a specific type of membrane transport system known as the glycerol three phosphate shuttle."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And this is the shuttle that is used predominantly by skeletal muscle cells of our body."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So the inner mitochondrial membrane is actually impermeable to NAD plus or NADH molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And that means these NADH molecules, once formed in glycolysis, cannot simply move across the membranes of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And their movement basically depends on a specialized membrane transport system that we call glycerol three phosphate shuttle."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So let's begin in glycolysis."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So in glycolysis, we oxidize glucose into pyruvate molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "In the process, we also generate these NADH molecules."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, once the NADH molecule is formed in the process of glycolysis, it remains in the cytoplasm."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And what happens to it is a special enzyme known as cytoplasmic."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Glycerol three phosphate dehydrogenase actually oxidizes the NADH back into NAD plus."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "That regenerates the NAD plus coenzymeter for glycolysis."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And what this process also does is it passes those high energy electrons from the NADH onto a molecule known as DHAP, dihydroxy acetone phosphate."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And this is the same molecule that we find as an intermediate in the glycolytic pathway."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So in process one, NADH plus a proton reacts with the DHAP and intermediate of glycolysis."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So we essentially reduce this molecule into g three P, where g three P stands for glycerol three phosphate."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And that's why this is known as the glycerol three phosphate shuttle, because once we form the g three P, the g three P can now move across the outer membrane of the mitochondria and enter the intermembrane space."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So in step one in the cytoplasm, NADH produced in glycolysis is oxidized back into NAD."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Plus, by reducing dihydroxy acetone phosphate DHAP into glycerol three phosphate g three P. And this reaction allows us to regenerate the energy plus."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Needed for the glycolytic pathway and also allows us to actually pass down the electrons onto a molecule that can now move into the intermembrane space of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And this is catalyzed by the cytoplasmic glycerol three phosphate dehydrogenase enzyme."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, once the g three P actually moves into the intermembrane space of the mitochondria, it is now oxidized back into DHAP by an enzyme that is found on the outer portion of the inner membrane of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And this enzyme, shown here in orange, is actually an isozyme version of this cytoplasmic glycerol three phosphate dehydrogenous enzyme."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so we call this enzyme the mitochondrial version glycerol three phosphate dehydrogenase, or simply the mitochondrial glycerol three phosphate dehydrogenase."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, what this enzyme actually does is it oxidizes the g three P into DHAP by taking off those two electrons and two protons and placing them onto an Fad molecule that is bound to that enzyme."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So Fad is flavin adenine dinucleotide, and it can accept two protons and two electrons."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So in step number two, we see that the enzyme transfers the two electrons and two protons from the g three P onto Fad to form the Fadh two."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And in the final step of the glycerol 35 state shuttle, the Fadh two is actually oxidized back into Fad."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "In the process, those two electrons and the two protons that ultimately came from these two reactants here are basically transferred onto a Ubiquinone that is found within the hydrophobic core of the inner membrane of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And we reduced that ubiquinone into ubiquinol."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, remember, back in our discussion on electron transport chain, we said that Ubiquinol basically carries the high energy electrons and the protons onto complex three of the electron transport chain."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So if this is our electron transport chain, we have complex one, complex two, complex three, four, and complex five."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "This molecule here is this mitochondrial glycerol three phosphate dehydrogenase that we discussed in this diagram."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so, ultimately, the two electrons are passed onto this molecule and then the Ubiquinol takes those two electrons and becomes Ubiquinol and passes those two electrons directly onto complex three."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And what that means is we essentially bypass complex one because when the NADH molecules are produced in a citric acid cycle, because the citric acid cycle takes place in the matrix of the mitochondria, these NADH molecules actually pass down their electrons onto complex one of the electron transport chain."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "But the NADH molecules produced in the cytoplasm via glycolysis, they actually pass down their electrons onto complex three via this enzyme known as glycerol three phosphate dehydrogenase."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So because of that, what actually happens is the net number of ATP molecules produced by the NADH, which is formed glycolysis, is only 1.5 compared to a value of 2.5 that is produced by NADH molecules formed in the citric acid cycle."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And to see what we mean, let's take a look at the following calculations."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So, let's get a red marker and a black marker."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Okay, so for those NADH molecules produced in the matrix of the mitochondria V, the citric acid cycle, these NADH molecules are oxidized back into NAD plus along complex one of the electron transport chain."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And when these two electrons travel through complex one and ultimately end up on Ubiquinone, a net result of four protons are pumped into the intermembrane space of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So when these electrons travel through complex one, this pumps four protons."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, these two electrons are collected by Ubiquinol."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "That becomes ubiquinol."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Ubiquinol then travels through the core of the membrane and attaches onto complex three."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And complex three then moves those electrons ultimately onto cytochrome C. In the process, a total of two, a net result of two protons, are actually pumped across the membrane from the matrix and into the intermembrane space."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And finally, cytochrome C carries those electrons onto complex four."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And in complex four, as those electrons travel through the complex and ultimately are used to reduce oxygen into water, we pump a net result of four ATP molecules from the matrix of the mitochondria into the intermembrane space."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so when a single NADH molecule produced in the citric acid cycle found in the matrix is oxidized into NAD plus by the electron transport chain, we transport a net result of four, two and two so ten protons into the intermembrane space."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, these ten protons then move via complex five, also known as ATP synthase."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "To actually generate those ATP molecules, and recall from the previous discussion, four protons are needed to actually generate a single ATP molecule."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so we see that we have a total of ten H plus ions pumped into the intermembrane space by this NADH produced in a citric acid cycle."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "We need four H plus ions to generate a single ATP molecule."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so we divide these numbers."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "We get a value of 2.5 of ATP molecules are generated when a single NADH produced by the citric acid cycle is oxidized into NAD plus by the electron transport chain."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now let's carry out the same calculation, except now we do it for the NADH produced by glycolytic pathway, which takes place in a cytoplasm, because NADH actually passes down the electrons to the DHAP to form the g three P. And then the g three p goes into the inner membrane of the mitochondria, binds up to this enzyme here."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so ultimately, those two electrons on the NADH produced in the glycolytic pathway actually end up on this protein, and then they're picked up by Ubiquinone to form Ubiquinol."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so NADH bypasses complex one."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And that means as the electrons pass down to Ubiquinol, the Ubiquinol travels and attaches onto complex three."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so now two protons are pumped here, four protons are pumped here."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So we form a net result of six protons in this case as compared to the ten protons in the previous case."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And so now six H plus ions divided by we still need four H plus to generate a single ATP."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "We form 1.5 ATP per single NADH that is, oxidized that is produced in the glycolytic pathway."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So from this result, we can conclude the following."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Since the mitochondrial membrane is impermeable to NADH, the solution to actually transporting the NADH is not actually moving the NADH, but rather transporting those electrons onto a different molecule, then moving that molecule across the outer membrane and using that molecule to move the electrons onto this enzyme, which then moves those electrons onto Ubiquinone."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "So, since the mitochondrial membrane is a permeable to NADH molecules, the solution is to extract electrons from NADH produced in a glycolytic pathway and ultimately pass them down to Ubiquinol to form Ubiquinone and then Ubiquinone."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Ubiquinol essentially completely bypasses complex one because it gives the two electrons onto complex three."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And since NADH from glycolysis bypasses complex one, it only produces a net result of 1.5 ATP molecules rather than the 2.5 which are produced from the NADH that is formed in the citric acid cycle that takes place in the matrix of the mitochondria."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, this process, called a glycerol three phosphate shuttle, is used predominantly by skeleton muscle cells."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And this process allows the skeleton muscle cells not only to use the high energy electrons to generate the much needed ATP molecules, but it also allows the skeleton muscle cells to actually regenerate the entity plus molecules needed to continue glycolysis."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "Now, this actually is not the only type of shuttle that our cells can use."}, {"title": "Glycerol 3-Phosphate Shuttle .txt", "text": "And as we'll see in the next lecture, liver cells and cardiac muscle cells actually use a slightly different shuttle system."}, {"title": "Triglyceride Metabolism .txt", "text": "So one way by which we obtain energy from the surroundings is by ingesting food products."}, {"title": "Triglyceride Metabolism .txt", "text": "And one of the type of food products that we ingest, our carbohydrates."}, {"title": "Triglyceride Metabolism .txt", "text": "So the simplest and the most common monomer of sugar of our carbohydrate is a glucose."}, {"title": "Triglyceride Metabolism .txt", "text": "And we can store glucose in our body in the form of glycogen."}, {"title": "Triglyceride Metabolism .txt", "text": "And when we need to, we break down glucose glycogen into our individual glucose molecules which can be used via the process of aerobic cellular respiration to basically break down the glucose into ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "So we have the glycolysis process that breaks down glucose into two pyruvate molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "Those eventually go into the mitochondrial matrix where they undergo a decarboxylation reaction to form a Ctilt coenzyme a, which is fed into the citric acid cycle."}, {"title": "Triglyceride Metabolism .txt", "text": "And the citric acid cycle ultimately produces NADH molecules and fadh two molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "And then all the NADH and fadh two molecules produced in aerobic cellular respiration go onto the electron transport chain to basically form ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, we know in aerobic cellular respiration one glucose molecule produces a net of 36 ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, the problem is, glucose is not the only type of molecule from which we can actually obtain our energy."}, {"title": "Triglyceride Metabolism .txt", "text": "Another very common type of molecule from which we can obtain energy are fats or is fat."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, in fact, the majority of the energy that is stored in the human body is stored in fat, in special type of fat molecules known as triglycerides."}, {"title": "Triglyceride Metabolism .txt", "text": "So triglycerides are basically three fatty acids attached to a single glycerol backbone."}, {"title": "Triglyceride Metabolism .txt", "text": "So a triglyceride is composed of three fatty acids and one glycerol."}, {"title": "Triglyceride Metabolism .txt", "text": "And in the same analogous way that we store our glucose in the form of glycologen, we store our fatty acids in the form of our triglyceride."}, {"title": "Triglyceride Metabolism .txt", "text": "So fats ingested into the body are stored in a specialized type of tissue known as adipose tissue and it is stored in the form of triglycerides."}, {"title": "Triglyceride Metabolism .txt", "text": "Now the question is, how exactly do we actually harvest the energy that is stored in triglycerides?"}, {"title": "Triglyceride Metabolism .txt", "text": "In fact, how can we use that energy and transform that energy to form our ATP molecules that are used by our body?"}, {"title": "Triglyceride Metabolism .txt", "text": "Now, basically, triglycerides have to undergo three important stages before we can actually obtain those ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "So we have stage one, stage two and stage number three."}, {"title": "Triglyceride Metabolism .txt", "text": "Now let's take a look at each one of these stages briefly."}, {"title": "Triglyceride Metabolism .txt", "text": "So we have the triglycerides actually must be released and mobilized from within our adipose tissue."}, {"title": "Triglyceride Metabolism .txt", "text": "So a special type of enzyme known as lipase basically breaks down our triglycerides into the three fatty acids and a single glycerol and they go into the bloodstream of our body."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, the bloodstream is composed predominantly of water."}, {"title": "Triglyceride Metabolism .txt", "text": "Glycerol is actually water soluble and it ends up traveling to the cytoplasm of liver cells."}, {"title": "Triglyceride Metabolism .txt", "text": "However, fatty acids are hydrophobic and they have to attach to special type of globular protein or carrier protein known as serum albumin."}, {"title": "Triglyceride Metabolism .txt", "text": "And what our albumin basically does is it attaches our fatty acids and transports them to the location, to the cell that requires energy."}, {"title": "Triglyceride Metabolism .txt", "text": "So once our products of this breakdown of triglyceride ends up in the cytoplasm of the cell, they follow different pathways."}, {"title": "Triglyceride Metabolism .txt", "text": "So let's examine what happens to our glycerol."}, {"title": "Triglyceride Metabolism .txt", "text": "The glycerol is basically broken down into a molecule known as PGAL or glyceroaldehyde three phosphate, which is basically an intermediate within our glycolysis cycle."}, {"title": "Triglyceride Metabolism .txt", "text": "So our glycerol ultimately ends up in glycolysis."}, {"title": "Triglyceride Metabolism .txt", "text": "So our glycerol goes into glycolysis and we use glycerol to form pyruvate molecules, which then end up in the mitochondrial matrix where they are fed into our decarboxylation reaction, producing acetyl coenzyme A, which goes into the crept cycle and eventually on the electron transport chain to produce our ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, what about the fatty acids?"}, {"title": "Triglyceride Metabolism .txt", "text": "So the pathway that is followed by the fatty acids is slightly different."}, {"title": "Triglyceride Metabolism .txt", "text": "What happens to each fatty acid is the following."}, {"title": "Triglyceride Metabolism .txt", "text": "So the fatty acid goes onto the outer membrane of the mitochondria."}, {"title": "Triglyceride Metabolism .txt", "text": "So it goes onto the outer membrane."}, {"title": "Triglyceride Metabolism .txt", "text": "We use a single ATP molecule and we also use a coenzyme A to basically transform a fatty acid into acyl coenzyme A."}, {"title": "Triglyceride Metabolism .txt", "text": "So an acyl coenzyme A is essentially a fatty acid that is attached to a coenzyme A."}, {"title": "Triglyceride Metabolism .txt", "text": "And this basically activates our fatty acid."}, {"title": "Triglyceride Metabolism .txt", "text": "And now we can transport the fatty acid into the mitochondrial matrix using a special transport mechanism that involves a molecule known as carnitine."}, {"title": "Triglyceride Metabolism .txt", "text": "So carnitine is the molecule that helps transport our acyl coenzyme A that contains the fatty acid into the mitochondrial matrix."}, {"title": "Triglyceride Metabolism .txt", "text": "Now, once the fatty acid, specifically once inside the acyl coenzyme A is inside the mitochondrial matrix, the ACL coenzyme A molecule is shortened by two carbons via a series of four reactions that are known as beta oxidation because the cutting takes place on the beta carbon."}, {"title": "Triglyceride Metabolism .txt", "text": "So each time our acyl coenzyme A is shortened by two carbons, we basically produce a single NADH molecule, a single fadh two molecule, as well as an acetylco or an acetyl coenzyme A."}, {"title": "Triglyceride Metabolism .txt", "text": "So remember, an acyl coenzyme A and an acetyl coenzyme A are two different molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "So we take the acyl coenzyme A, it undergoes beta oxidation in the matrix to produce our acetyl coenzyme A."}, {"title": "Triglyceride Metabolism .txt", "text": "And the acetyl coenzyme A is the fuel in the citric acid cycle."}, {"title": "Triglyceride Metabolism .txt", "text": "So it goes into the citric acid cycle to produce NADH and Sadh, two molecules which then end up on the electron transport chain to produce our ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "And this process of beta oxidation of shortening our acyl coenzyme A of the fatty acid continues until we no longer have any carbons left."}, {"title": "Triglyceride Metabolism .txt", "text": "So this is the process by which we ultimately metabolize our triglycerides to form ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "Now the question is how many ATP molecules do we actually form when we metabolize our fats?"}, {"title": "Triglyceride Metabolism .txt", "text": "Well, let's take a look at the most common type of fatty acid in the human body known as palmitic acid."}, {"title": "Triglyceride Metabolism .txt", "text": "So palmitic acid is the most common fatty acid in the human body, and basically a single fatty acid of palmitic acid, or palmitate, basically is broken down into 106 ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "So we see that a single glucose forms a net result of 36 ATP molecules, but a single fatty acid actually forms a net result of 106 ATP molecules."}, {"title": "Triglyceride Metabolism .txt", "text": "So we see our fats store much more energy than our glucose molecule, and that's exactly why our body stores the majority of the energy in adipose tissue as our fat, our triglycerides."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "In nature."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "All living organisms, beginning with the very, very small ones, such as individual bacterial cells and ending with a very large complex ones such as human bodies that consist of trillions and trillions of individual cells."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "All living cells contain DNA as the carrier of genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And what that means is we have the DNA molecule that that is used to store the genetic information that is basically transcribed into the RNA molecule and then it's the RNA molecule that is ultimately used to synthesize the many different types of proteins that are used by that cell and needed by that cell to survive."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, in human cells, we have linear molecules of DNA and what that means is we have a beginning and we have an end."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "But in other organisms, for example, bacterial cells, they have circular DNA molecules."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And what that means is they don't have a beginning, they don't have an end, they are continuous, as we see in the following circle."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, linear DNA molecules and circular DNA molecules are actually relatively large and relatively long."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And if we zoom in into the cell of either bacterial cells or our own human cells, we're not going to see these DNA molecules existing in the following form."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Instead, the linear DNA molecules found in our own cells and the circular DNA molecules found in bacterial cells are going to condense via this process of super coiling."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, super coiling basically serves two important biological purposes."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Number one, we actually want to be able to fit that long DNA molecule into the nucleus of our own cells and into the cell structure of that biological cell."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And to do that, we have to basically condense the structure into this super coiled form, into this very compact form that is much, much smaller."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, the second function of super coiling is to basically affect the different types of processes found inside our body."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "For example, when inside our nucleus of the cell we replicate DNA, we have to unwind that double helix structure."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And when we unwind that double helix structure, the process of super coiling can basically stabilize that unwinding process."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And we'll discuss exactly how that takes place when we'll focus on DNA replication."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So the point is, inside the cells of these living organisms, these DNA molecules don't simply exist as linear DNA molecules or as circular DNA molecules."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Instead, they are usually super coiled into these super coils and superheles that are much more condensed and much more compact."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, as I mentioned earlier, all living organisms, including individual cells and those organisms containing many, many cells, all these cells contain DNA as the carrier of genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, although some viruses do contain DNA as that carrier of genetic information, other viruses, such as, for example, the tobacco mosaic virus TMV, contains RNA as the carrier of genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So this is in contrast to living organisms that contain DNA and always DNA as the carrier of the genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So what exactly is a virus?"}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Well, a virus is this non living agent that consists of a protein capsule and inside the protein capsule we have some type of genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, that genetic information can either be in a form of DNA like in living cells or in RNA but will never find both DNA and RNA."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "It's either this DNA or this RNA."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Never both."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, what these viruses basically do is because they cannot reproduce on their own accord what they do is they move from one host cell to a different whole cell."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "They infect these cells by injecting their genetic information and then once inside the cell they use the machinery of the cell to basically reproduce and form other viral agents."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "For example, if we look at the tobacco mosaic virus the tobacco mosaic virus is actually the first virus that we discovered and this tobacco mosaic virus consists of this protein capsite a helical protein capsite that consists of 2130 identical polypeptide subunits and these subunits form this helical protein capsule."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And inside that capsule we have a single stranded RNA molecule and it is given by 6390 nucleotides in length."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So this is the length of that particular RNA molecule inside this virus."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, once the tobacco mosaic virus actually infects that whole cell it injects the RNA molecule into that whole cell."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And a special thing about this RNA molecule is it contains the genetic information that codes for a special protein known as RNA directed RNA polymerase."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, remember, inside our bodies we take the DNA and we form the RNA molecule by using a special type of RNA polymerase."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "But inside these viruses this RNA polymerase actually transcribes RNA molecules from other RNA molecules and not DNA to RNA as it takes place inside our cells of the body."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So there are many examples of viruses in nature that follow this same pathway that is followed by the tobacco mosaic virus."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "That is, they form RNA agents or RNA molecules from other RNA molecules."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, another interesting category of viruses are the retroviruses and one example of a retrovirus is HIV."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So remember, HIV is that viral agent that causes AIDS in humans."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So all living organisms basically produce RNA from DNA."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So in our body, for example, we take DNA then we transcribe it into RNA and then the RNA is used to synthesize a variety of different types of proteins."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "But the special thing about these retroviruses is and that's actually where they obtain their name they are able to actually synthesize viral DNA molecules from RNA and that is in reverse of what happens in our own cells and all other living cells."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So, however, a category of viruses called retroviruses can synthesize DNA from RNA by using a special type of protein that is found in that retrovirus known as reverse transcriptase."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And so one example is the HIV agent."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So let's take a look at the following diagram to basically see how retrovirus actually works."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So inside the protein capsite of the retrovirus, we have two single strands of RNA molecules."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So retrovirus has two copies of a single stranded RNA molecule."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And once that retrovirus infects that whole cell, it injects these two individual RNA molecules into that hostel."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, because it carries that special enzyme known as reverse transcriptase, this enzyme basically binds onto either of these two viral RNA molecules and it begins to transcribe in the opposite direction to how it normally takes in our own cells."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So instead of going from DNA to RNA, this goes from RNA to DNA in reverse."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And so eventually, we synthesize these complementary viral DNA molecules and once they separate, once they anneal, actually right, so once these two blue strands actually separate, these two blue strands, because they're complementary with respect to one another, they can basically anneal."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And to anneal means to combine to form that double helix structure."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And once we form the viral double stranded DNA molecule, that DNA molecule is brought into the nucleus of the cell."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And inside the nucleus, a second type of special protein enzyme known as integrase, basically cuts the host DNA molecules."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So the green DNA is the host DNA, it cuts a section of that DNA molecule, it opens it up, and this double stranded DNA molecule that came from the virus basically injects itself integrates with that host DNA."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And this is how the majority of retroviruses actually work."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "So we conclude that although in all living cells, DNA molecules are the carrier of the genetic information, in some living organisms we have linear DNA molecules and in others we have circular."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, in any cell, we're never going to find these forms."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Instead, they're going to be super coiled into these compact structures."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "Now, unlike in living organisms, some viruses contain DNA as the carry of genetic information, but in others, it's the RNA that is used to carry that genetic information."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "And as we saw just a moment ago, some of these viruses can actually synthesize DNA molecules from RNA which is in reverse."}, {"title": "Circular DNA, RNA Genes and Viruses .txt", "text": "To have it normally takes inside our cells and inside the cells of all living organisms found in nature."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So inside developing fetus, there are two important shuns that are used by the circulatory system of that fetus to redirect blood away from the nonfunctional lungs and to the functional organs of that fetus, such as, for example, the brain."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, these two shuns include the foramen ovaly as well as the ductus arteriosis."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So let's briefly discuss how the blood actually actually travels within the heart of that vetus."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So we have the inferior venecrava and the superior venecrava."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And as the partially oxygenated blood makes its way via these two blood vessels and into the right atrium, once inside the right atrium, that blood goes into the left atrium via the Foramin or valley."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And that's because on the right side of the heart, we have a higher pressure than the left side as a result of those nonfunctional lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So the foramen or valley is like a one way door that opens this way because of a higher pressure being present inside the right atrium as compared to the left atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, a small amount of that blood will still make its way into the right ventricle."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And when that right ventricle contracts, it will pump that blood into the pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, inside the pulmonary trunk, we also have another type of duct known as the ductus arteriosis."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Remember the other type of duct that's known as the ductus venosis, but we're not going to focus on it in this lecture."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So we have the ductus arteriosis that connects the pulmonary trunk to the aorter."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And remember, inside that developing fetal heart, there's a higher pressure inside the pulmonary trunk than inside the order."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so what happens is most of that oxygenated blood will once again bypass the lungs, will be redirected away from the lungs and directly into the systemic circulatory system into the order."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, a tiny bit of that blood will still make its way into the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And that's important because the lungs do need a small amount of oxygen to keep on developing so that at birth, those lungs can actually function properly and efficiently."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So these are the two lungs that are used by the circulatory system of that fetus to basically redirect blood away from the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, what happens at birth?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Well, as soon as that fetus is bored and takes their first breath, what happens is the air rushes into the alveoli of the lungs and it displaces the fluid that is within the alveoli of the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And that decreases."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "It drops the resistance and pressure inside those lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And as soon as the pressure drops, now, the blood inside the right atrium can begin moving easily into the right ventricle, then into the pulmonary trunk and into the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so what that means is the pressure inside the right side of the heart will drop."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And because we have more blood rushing into the lungs, the lungs will pump more blood into the left side of the heart, into the left atrium, and so the pressure on the left side will increase."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so what happens at birth is we have a reversal in pressure taking place."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Before birth, the right side of the heart was at a higher pressure than the left side."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what that means is the pulmonary system was at a higher pressure than the systemic circulatory system."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "But after birth, we have a reversal of pressure."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "The left side is at a higher pressure than the right side."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what that means is inside the order, inside the systemic circulatory system, we're going to have a higher pressure than inside the pulmonary circulatory system."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, what that means is as soon as that individual is born, normally what happens is as a result of that reversal and pressure, the foraminal valley essentially shuts close."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And eventually, because the lungs are oxygenated and we produce a special type of protein known as bradycanin."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Bradycanin uses that oxygen, goes into the ductus arteriosis and begins to constrict the ductus arteriosis, eventually closing that duct off."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So normally within several minutes, the voramino valley is closed."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And normally within several hours, the ductus arteriosis is also closed."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, in some situations, in some conditions, however, the fetus can develop a condition known as either the patent ductus arteriosis or the patent for Raymond O'Valley."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And in both cases, what the patent means is we have an abnormality in which either one of these two ducts, either one of these two shuts do not actually close off."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "They remain open for the duration of that individual's lifetime unless it's actually surgically fixed."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So let's begin by discussing the patent ductus arteriosis."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So once again, normally what happens is as soon as the oxygen rushes into the lungs of that fetus, the lungs begin to produce the protein known as brady kinan."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And bradykinan only functions in the presence of plentiful oxygen."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So what brady kinan does is it moves into the ductus arteriosis that now contains a bunch of oxygen molecules and it uses that to close off and see loft the ductus arteriosis."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, suppose that individual of that fetus is born under hypoxic conditions and that means they do not have enough oxygen circulating inside their blood."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "In such a case, the bradyclinan cannot actually act effectively and efficiently because there is not enough oxygen."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So it will not be able to seal off that ductus arteriosis."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And that fetus develops a condition known as patent ductus arteriosis or PDA."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "That basically means that duct had not closed."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, what will happen in such a case?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Well, remember at birth, as we mentioned earlier, there is a reversal in pressure taking place."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so the pressure on the right side of the heart is lower than the pressure on the left side of the heart."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what that means is the pressure inside the systemic circulatory system is higher than the pressure inside the pulmonary circulatory system."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So what do we have at birth?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So basically, the ductus arteriosis does not close."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Yet we have a higher pressure inside the order, which is part of the circulatory system, than inside the pulmonary trunk, which is part of the pulmonary circulatory system."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what will happen is that blood, the fluid, will move down its pressure gradient from the order and into the pulmonary trunk because now we have a higher pressure inside the order compared to our pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so our blood, the oxygenated blood, will travel from the order into the pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so we have a mixing of oxygenated and deoxygenated blood taking place within the pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, what exactly does that mean?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Well, because some of that blood from the systemic circulatory system moves back into the pulmonary trunk, less of the oxygen will actually reach the tissues of that individual."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And as a result, that heart will need to pump harder and more to actually make sure that the tissues get enough oxygen."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So, PDA, or patent ductus arteriosis, causes oxygenated blood to move from the high pressure a order and into the low pressure pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And this means less oxygen will reach the tissues of that individual."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "What it also means is more blood will actually flow into the lungs, because if this oxygenated blood is mixing with the deoxygenated blood, the influx of blood into the pulmonary system will be greater."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And that will put more stress on the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "It will increase the pressure inside the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what that means is that feed, if that person will have more difficulty breathing as a result of the high pressure inside the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, of course, this situation can be surgically fixed."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, let's move on to the other type of abnormality that can arise as a result of the non closure of the forayman O'Valley."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So, normally, under normal conditions, what happens is as a result of the reversal in pressure, because we reverse the pressure at birth and the left side increases in pressure, it becomes greater than the right side of the heart."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "That one way valve essentially closes, but in some cases, it does not actually close."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And what that means is we can still have a movement of blood between the two atrium of the heart."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So, once again, during fetal development, there is a valve like structure that exists between the right and the left atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And this allows the oxygen rich blood to bypass those nonfunctional lungs within that developing fetus."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, normally at birth, this valve shuts close."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "But in some fetuses, the foramen ovaly fails to close properly, which leads to a permanent valve system that connects the two atrium of the heart."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And this condition is known as the patent for Raymond, or valley, and it is the most common type of atrial septal defect."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, what exactly is an atrial septal defect?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Well, septal simply means wall."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "The atria is referring to those two chambers of the heart, and a defect means it's an abnormality."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So normally, it closes."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "But in this type of defect, we have some type of abnormality that causes this valve to actually remain open."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so we have the movement of blood between the two atrium of the heart."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, normally this condition is actually not very dangerous because normally what happens is because we have a higher pressure on the left side of the heart, then on the right side of the heart, a tiny bit of that oxygenated blood inside the left atrium will go into the right atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so we have some of that oxygenated blood reaching the right atrium, and it will basically return back to the lungs via the pulmonary trunk."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, however, even though we have a tiny bit of blood going into the right atrium, there is still enough blood inside the left atrium to actually go into the left ventricle and eventually pump to the tissues and organs and systems of the body."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So normally, this is not a big problem."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "However, what it can cause is an embolism."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So what can happen is the blood inside the right atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "If the heart is actually undergoing some type of rigorous activity, so the person, let's say, running, and the heart has to pump more, then what can happen is the pressure inside the right atrium can be slightly greater than inside the left atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so some of that blood in the right atrium can move into the left atrium and then directly into the left ventricle and into the systemic circulatory system."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And this bypasses the lungs."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Now, why is this a problem?"}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "Well, as it turns out, the lungs not only oxygenate the blood, but they're also pretty good at breaking down blood clots."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And so what happens is, if there is a blood clot inside the right atrium and then it moves into the right ventricle and into the pulmonary, into our lungs, the lungs essentially act to break down different types of tiny blood clots."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "But if that blood clot isn't able to go into the lungs and goes directly into the left ventricle and then into the left atrium, then into the left ventricle, into our order, what happens is that blood clot isn't actually broken down because it bypassed the lungs as a result of this defect inside the wall between the two atrium."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "And now this blood clot can basically go into, let's say, some type of important organ, let's say the brain, and it could cause something called a stroke."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "This can lead to many, many problems."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "So although most of the time the patent for Raymond or Valley isn't dangerous, in some situations it can be very dangerous."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "On the other hand, the patent ductus arteriosis is a much more serious condition."}, {"title": "Patent Ductus Arteriosus and Patent Foramen Oval .txt", "text": "However, it can be fixed surgically when that fetus is actually born."}, {"title": "Polygenic Inheritance.txt", "text": "The final topic in our discussion on the principles of inheritance will be polygenic inheritance."}, {"title": "Polygenic Inheritance.txt", "text": "Now, in humans there are many different types of traits."}, {"title": "Polygenic Inheritance.txt", "text": "For example, the high trait or the skin color trait."}, {"title": "Polygenic Inheritance.txt", "text": "These different types of traits are affected or controlled by many different pairs of alleles down on different low side."}, {"title": "Polygenic Inheritance.txt", "text": "So polygenic inheritance is this phenomenon that basically describes this idea that multiple different allele pairs actually affect and control and have an additive effect on a given type of trait."}, {"title": "Polygenic Inheritance.txt", "text": "For example, the hydrate and the skin color trait."}, {"title": "Polygenic Inheritance.txt", "text": "Now, to demonstrate what we mean by polygenic inheritance, let's begin by assuming that the skin color trait in humans is controlled by three gene pairs."}, {"title": "Polygenic Inheritance.txt", "text": "So we have gene pair A, we have gene pair B and we have gene pair C. Let's suppose that these three different gene pairs are unlinked genes and what that means is they're located on different homologous chromosomes."}, {"title": "Polygenic Inheritance.txt", "text": "So let's suppose we have homologous chromosome pair number one, homologous chromosome pair number two and homologous chromosome pair number three."}, {"title": "Polygenic Inheritance.txt", "text": "Now, in pair number one we have the A traits."}, {"title": "Polygenic Inheritance.txt", "text": "So this can either be a upper case A or lowercase A."}, {"title": "Polygenic Inheritance.txt", "text": "And this can also be either a upper case A or lowercase A."}, {"title": "Polygenic Inheritance.txt", "text": "Now the second allele pair contains the B gene and likewise, we can either have uppercase B or lowercase B on each one of these individual chromosomes."}, {"title": "Polygenic Inheritance.txt", "text": "And finally, we have allele pairs number three, homologous pair number three that contains the final gene, gene three or gene C that also controls and effects and has an additive effect on the skin color trait in humans."}, {"title": "Polygenic Inheritance.txt", "text": "So we can also have uppercase C or lowercase C. Now, what do we mean by an uppercase C and a lowercase C?"}, {"title": "Polygenic Inheritance.txt", "text": "Well, notice that A, B and C are not complete dominance traits."}, {"title": "Polygenic Inheritance.txt", "text": "In fact, they're incompletely dominant genes."}, {"title": "Polygenic Inheritance.txt", "text": "And we'll see what that means in just a moment."}, {"title": "Polygenic Inheritance.txt", "text": "If you are not sure what we mean by incomplete dominance go back and watch my lecture on incomplete dominance and what it means for genes to be incompletely dominant."}, {"title": "Polygenic Inheritance.txt", "text": "So the capital letters represent incompletely dominant genes that express a dark color while our lowercase letters represent incompletely dominant genes that express the light skin color."}, {"title": "Polygenic Inheritance.txt", "text": "Now, since each gene, as we said earlier, has an additive effect, what that means is the more uppercase letters that we have in a given person, the darker the skin color of that person is."}, {"title": "Polygenic Inheritance.txt", "text": "So since each gene has an additive effect on the skin color, the more capital letters we have, the darker the skin is and vice versa."}, {"title": "Polygenic Inheritance.txt", "text": "The smaller the number of capital letters is, the lighter the skin color of that particular person."}, {"title": "Polygenic Inheritance.txt", "text": "So for example, if in a given individual all of these genes contain the uppercase letter, so these are uppercase A, these are uppercase B and these are uppercase C, then we have uppercase AA, uppercase BB, uppercase CC."}, {"title": "Polygenic Inheritance.txt", "text": "And this represents the darkest possible skin color and likewise if all of these are lowercase letters so lowercase A, lowercase A, lowercase B, lowercase B, lowercase lowercase C, lowercase C then we have the lightest possible skin color."}, {"title": "Polygenic Inheritance.txt", "text": "Now to further demonstrate how this added effect in polygenic inheritance actually works, let's carry out the following experiment."}, {"title": "Polygenic Inheritance.txt", "text": "Let's suppose we have a male individual that contains this genotype."}, {"title": "Polygenic Inheritance.txt", "text": "So we have these three pairs of homologous chromosomes and on each one of these individual chromosomes we only have uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "So we have uppercase A, uppercase A on this set of alleles we have uppercase B, uppercase B on the second set of alleles and uppercase C, uppercase C and let's suppose we mate this male individual with the female that is homozygous recessive for all of these different genes."}, {"title": "Polygenic Inheritance.txt", "text": "So we have lowercase A, lowercase A on the first set of chromosomes, lowercase B, lowercase B on the second set."}, {"title": "Polygenic Inheritance.txt", "text": "And lowercase C, lowercase C. Now, if we made these two individuals, then what we see is the offspring that is produced, the f one generation will be uppercase A, lowercase A."}, {"title": "Polygenic Inheritance.txt", "text": "And that's because one of these one of these one of these chromosomes, uppercase A will come from the male, and the other one, lowercase A will come from the female and so will produce uppercase A, lowercase A."}, {"title": "Polygenic Inheritance.txt", "text": "The same thing happens here."}, {"title": "Polygenic Inheritance.txt", "text": "When Meiosis takes place, the sperm cell receives one of the Uppercase B."}, {"title": "Polygenic Inheritance.txt", "text": "The Xcel receives one of the lowercase b."}, {"title": "Polygenic Inheritance.txt", "text": "They combine to form uppercase b, lowercase b."}, {"title": "Polygenic Inheritance.txt", "text": "And finally, these combine to form Uppercase C, Lowercase C. And so exactly half of the letters are Uppercase."}, {"title": "Polygenic Inheritance.txt", "text": "And what that means is since this is A very dark individual this is a very light individual because we have an intermediate case here this individual, the offspring will have A skin color that is somewhere in between the dark skin color and the light skin color."}, {"title": "Polygenic Inheritance.txt", "text": "Because here we have six uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "Here we have zero uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "Here we have one, two, three uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "So that means three is somewhere in between six and zero and so this will have an intermediate skin color."}, {"title": "Polygenic Inheritance.txt", "text": "Now let's suppose we take our individual, the f one generation and we made it with another individual that has the same exact genotype for the skin color genes."}, {"title": "Polygenic Inheritance.txt", "text": "So what exactly will be the distribution of the genotypes of our offspring, the f two generation?"}, {"title": "Polygenic Inheritance.txt", "text": "So what we basically have to do is this relatively long punished square."}, {"title": "Polygenic Inheritance.txt", "text": "So essentially we have eight different possibilities for the egg cell and a different possibilities for the sperm cell."}, {"title": "Polygenic Inheritance.txt", "text": "So each one of these basically describes its own unique sperm cell that contains its own unique genotype."}, {"title": "Polygenic Inheritance.txt", "text": "For example, this sperm cell contains all uppercase letters uppercase A, upper case B, uppercase C and this one contains uppercase A, upper case B and lowercase C and so forth."}, {"title": "Polygenic Inheritance.txt", "text": "And these are individual unique cases."}, {"title": "Polygenic Inheritance.txt", "text": "So just like in any punitive square."}, {"title": "Polygenic Inheritance.txt", "text": "We basically have to combine the Xcel with the sperm cell and we basically combine our genotype."}, {"title": "Polygenic Inheritance.txt", "text": "So we have uppercase A, uppercase A, upper case B, uppercase B, and uppercase C, uppercase C to form the zygote."}, {"title": "Polygenic Inheritance.txt", "text": "So uppercase A, uppercase A, upper case B, uppercase B, uppercase C, uppercase C, and we continue the process with all these different types of combinations."}, {"title": "Polygenic Inheritance.txt", "text": "For example, let's suppose we look at this one."}, {"title": "Polygenic Inheritance.txt", "text": "So for this particular zygote, we combine an excel that contains all lowercase letters, a sperm cell that contains all uppercase letters, and we form three uppercase letters and three lowercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "So uppercase A, lowercase A, upper case B, lowercase B, and uppercase C, lowercase C, and we do this with every single one of these squares."}, {"title": "Polygenic Inheritance.txt", "text": "So once we carry out the process, let's actually count up the squares that have all six upper case letters."}, {"title": "Polygenic Inheritance.txt", "text": "And notice if we go through each and every one of these, only one of these zygotes."}, {"title": "Polygenic Inheritance.txt", "text": "So one out of 64 possibilities will contain this case."}, {"title": "Polygenic Inheritance.txt", "text": "So this is the only zygote, the only square that contains all upper case six letters."}, {"title": "Polygenic Inheritance.txt", "text": "And so we place a six."}, {"title": "Polygenic Inheritance.txt", "text": "Now, by the way, there are a total of 64 cases because eight multiplied by eight gives us 64."}, {"title": "Polygenic Inheritance.txt", "text": "Now, if we continue the process and count up all the zygotes, all the possibilities where five letters are uppercase letters, we're going to get 123456."}, {"title": "Polygenic Inheritance.txt", "text": "So we see that six out of 64 possibilities will produce an offspring that has five uppercase letters and we continue the process."}, {"title": "Polygenic Inheritance.txt", "text": "Let's continue with three."}, {"title": "Polygenic Inheritance.txt", "text": "So in the case of three, we have, let's see, one, we have two, three, four, we have five, six, seven, we have 8910, we have 1112, 13, 14, 15, 16, 17, 18, 19 and 20."}, {"title": "Polygenic Inheritance.txt", "text": "So 20 out of 64 cases."}, {"title": "Polygenic Inheritance.txt", "text": "So there is a likelihood, 20 out of 64, that the offspring that is produced will have a genotype in which three of the letters are uppercase and three of the letters are lowercase."}, {"title": "Polygenic Inheritance.txt", "text": "So that means we're going to have an intermediate skin color."}, {"title": "Polygenic Inheritance.txt", "text": "And we continue the process with two uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "So we have one, we have two, we have three, four, five, we have six, we have seven, 8910, 1112, 13, 1415."}, {"title": "Polygenic Inheritance.txt", "text": "So 15 out of 64, we'll have only two uppercase."}, {"title": "Polygenic Inheritance.txt", "text": "If we continue with one uppercase, we'll see that we have 123456."}, {"title": "Polygenic Inheritance.txt", "text": "So 123456."}, {"title": "Polygenic Inheritance.txt", "text": "So six out of 64 will only have one uppercase letter."}, {"title": "Polygenic Inheritance.txt", "text": "And finally, just like there's a one out of 64 possibility of having all uppercase letters, there's a one in 64 possibility of having no uppercase letters."}, {"title": "Polygenic Inheritance.txt", "text": "And if we plot this, if we create a bar graph of this distribution, we get a normal distribution."}, {"title": "Polygenic Inheritance.txt", "text": "So we basically get this normal distribution that looks like a bell curve."}, {"title": "Polygenic Inheritance.txt", "text": "And so we have one out of 64 chance that six of them are uppercase and one out of 64 that none of them are uppercase."}, {"title": "Polygenic Inheritance.txt", "text": "Six out of 64 gives us the likelihood that five will be uppercase and six out of 64 gives likelihood that only one will be uppercase."}, {"title": "Polygenic Inheritance.txt", "text": "And we continue and notice that this highest bar basically describes the greatest likelihood."}, {"title": "Polygenic Inheritance.txt", "text": "It tells us that there is a greatest likelihood that the offspring produced from these two mating processes will give us an individual that contains three upper case letters and three lower case letters."}, {"title": "Polygenic Inheritance.txt", "text": "So it is most likely that the offspring that is produced between these two individuals that have the same exact skin color that individual will also have that same skin color."}, {"title": "Polygenic Inheritance.txt", "text": "So in this particular case this is the F one generation."}, {"title": "Polygenic Inheritance.txt", "text": "The F two generation is this entire distribution here."}, {"title": "Polygenic Inheritance.txt", "text": "So from this distribution we see that the F two generation offspring will be most likely the same exact skin color as these two individuals as the parents."}, {"title": "Polygenic Inheritance.txt", "text": "So this is what we mean by polygenic inheritance."}, {"title": "Polygenic Inheritance.txt", "text": "So we see that polygenic inheritance refers to the phenomenon by which multiple different allele pairs have a similar and an additive effect on the given trait."}, {"title": "Polygenic Inheritance.txt", "text": "And by additive we simply mean the genes are incompletely dominant with respect to one another."}, {"title": "Polygenic Inheritance.txt", "text": "So the greater the number of uppercase letters is the darker the skin is and vice versa."}, {"title": "Polygenic Inheritance.txt", "text": "If we have less uppercase letters that means the light of the skin color will be."}, {"title": "Cell Fractionation .txt", "text": "In order to study proteins, we have to obtain the proteins from some type of source."}, {"title": "Cell Fractionation .txt", "text": "And one of the most common types of sources are cells."}, {"title": "Cell Fractionation .txt", "text": "Now the question is, once we obtain our sample of cells, how do we extract that protein of interest from inside the cells?"}, {"title": "Cell Fractionation .txt", "text": "Well, we expose the cells to process known as cell fractionation."}, {"title": "Cell Fractionation .txt", "text": "And in cell fractionation there are two important steps."}, {"title": "Cell Fractionation .txt", "text": "In the first step we have to form a homogeneous."}, {"title": "Cell Fractionation .txt", "text": "And the way that we form a homogeneous is in the following manner."}, {"title": "Cell Fractionation .txt", "text": "We take a test tube and we place the cells inside the test tube as shown in the following diagram."}, {"title": "Cell Fractionation .txt", "text": "And then we expose the cells to some type of grinding or mixing process."}, {"title": "Cell Fractionation .txt", "text": "And what that does is it breaks down and ruptures the cell membranes of the cells, exposing all the different types of components and mixing all these different types of components found inside the cells."}, {"title": "Cell Fractionation .txt", "text": "For example, we have the nuclei, we have dorogynalle such as mitochondria, we have the ribosomes and so forth, all these different things mixed in inside our test tube."}, {"title": "Cell Fractionation .txt", "text": "And this is called a homogeneous."}, {"title": "Cell Fractionation .txt", "text": "Now once we form the homogeneous, we now expose the homogeneous to a process known as differential centrifugation and we conduct several centrifugation processes as we'll see in just a moment."}, {"title": "Cell Fractionation .txt", "text": "Now, if you don't know what differential centrifugation is, we're going to focus on the details of that process in the next lecture."}, {"title": "Cell Fractionation .txt", "text": "But what it basically does is it uses angular motion, it uses centripetal acceleration to basically separate the components inside the homogeneous based on their density."}, {"title": "Cell Fractionation .txt", "text": "So the more dense a certain component is, the lower along our test tube it will end up and the less density is, the higher up along a test tube it will actually be."}, {"title": "Cell Fractionation .txt", "text": "So in the first step after step one, we basically take our test tube with our homogeneous."}, {"title": "Cell Fractionation .txt", "text": "We place it into the baranas and it basically rotates and eventually it separates that mixture."}, {"title": "Cell Fractionation .txt", "text": "So the very dense material ends up at the bottom."}, {"title": "Cell Fractionation .txt", "text": "So this section that is known as the pellet and the rest ends up at the surface."}, {"title": "Cell Fractionation .txt", "text": "So higher up this entire section that is known as the supernatural."}, {"title": "Cell Fractionation .txt", "text": "Now in the first centrifugation process, our acceleration is 1000 g's, where g is simply the gravitational pull due to the earth 9.8 meters/second squared."}, {"title": "Cell Fractionation .txt", "text": "So 1000 G's basically means the molecules and things inside our test tube experience a gravitational or an acceleration that is 1000 times as high as the gravitational acceleration."}, {"title": "Cell Fractionation .txt", "text": "Now in the first step, because we're only using 1000 GS, we're going to separate things like the nuclei of the cells."}, {"title": "Cell Fractionation .txt", "text": "So in the pellet we're going to have the nuclei and above in a supernatin, we're going to have everything else."}, {"title": "Cell Fractionation .txt", "text": "So once we obtain this test tube, we basically remove the pellet and then we take the supernatin and we expose the supernatin to yet another centrifugation process."}, {"title": "Cell Fractionation .txt", "text": "But now we bump our acceleration, we increase it to 10,000 GS."}, {"title": "Cell Fractionation .txt", "text": "Once we do that, we basically form a pellet that now contains our mitochondria, which are smaller than nuclei."}, {"title": "Cell Fractionation .txt", "text": "And then we once again remove the pellet, we take the supernatin, we expose it to yet another centrifugation process, and now we increase the value of the acceleration to 100,000 GS."}, {"title": "Cell Fractionation .txt", "text": "And what that does is it basically creates this pellet that now contains very tiny microsomes."}, {"title": "Cell Fractionation .txt", "text": "And usually inside the supernatin are basically the proteins that we actually want to use."}, {"title": "Cell Fractionation .txt", "text": "Now, in every step of this process, we basically carry out some type of protein essay for that specific type of protein or enzyme that we actually want to study."}, {"title": "Cell Fractionation .txt", "text": "And whenever we have whenever we get the highest value for that protein activity, that's the fraction that we actually want to use."}, {"title": "Cell Fractionation .txt", "text": "That's what the source of protein is that we're going to use."}, {"title": "Cell Fractionation .txt", "text": "So once we obtain the source of a mixture of proteins and inside that mixture protein, we have that protein that we want to study that will act as a source."}, {"title": "Cell Fractionation .txt", "text": "And once we have the source, we now can use a variety of different types of specific purification processes."}, {"title": "Cell Fractionation .txt", "text": "So proteins can be generally proteins can be generally separated based on four important different types of properties."}, {"title": "Cell Fractionation .txt", "text": "So based on the size of the protein, based on the solubility of the protein, how well dissolves in a certain type of solvent, based on the charge found on that protein, and also based on the ability of that specific protein to bind to some specific type of biological molecule."}, {"title": "Cell Fractionation .txt", "text": "For example, certain types of proteins are able to bind to specific type of DNA sequences and DNA molecules, while other proteins cannot bind to those DNA molecules."}, {"title": "Cell Fractionation .txt", "text": "And using that property, we can separate them because of that ability to bind."}, {"title": "Cell Fractionation .txt", "text": "So there are eight important types of purification processes that you should be familiar with."}, {"title": "Cell Fractionation .txt", "text": "So in this lecture, we're simply going to go through these processes quickly."}, {"title": "Cell Fractionation .txt", "text": "But in the next several lectures, we're actually going to discuss them in much more detail."}, {"title": "Cell Fractionation .txt", "text": "So we have eight processes."}, {"title": "Cell Fractionation .txt", "text": "We have dialysis."}, {"title": "Cell Fractionation .txt", "text": "Now, the thing about dialysis is it doesn't actually allow us to separate different proteins, but what it allows us to do is it allows us to separate the proteins from other small molecules and ions by using a semipermeable membrane."}, {"title": "Cell Fractionation .txt", "text": "Now, salting out is basically the process by which we separate our protein based on its ability to form a precipitate at a specific type of salt concentration."}, {"title": "Cell Fractionation .txt", "text": "So, for example, one protein can precipitate at a concentration of salt, let's say around one molar, but another one will form a precipitate only at two molar and so forth."}, {"title": "Cell Fractionation .txt", "text": "So we can use salting out to basically separate different proteins."}, {"title": "Cell Fractionation .txt", "text": "Now, gel filtration chromatography is a technique that uses the size factor of proteins."}, {"title": "Cell Fractionation .txt", "text": "It can basically separate the proteins based on size."}, {"title": "Cell Fractionation .txt", "text": "And in gel filtration chromatography, we have this tube, and inside the tube, we have these special beads."}, {"title": "Cell Fractionation .txt", "text": "And so the proteins move along the tube and through the beads."}, {"title": "Cell Fractionation .txt", "text": "And the proteins that are largest will move fastest along the test tube."}, {"title": "Cell Fractionation .txt", "text": "And the ones that are smallest, because they get trapped inside those beads, they will move the slowest."}, {"title": "Cell Fractionation .txt", "text": "Now, in ion exchange chromatography, we separate our proteins based on their charge in affinity chromatography, this is where we basically separate our protein based on its affinity, on its ability to attract itself to specific types of other molecules."}, {"title": "Cell Fractionation .txt", "text": "So in our tube, we can basically form these different types of specific molecules along the tube."}, {"title": "Cell Fractionation .txt", "text": "And as the proteins are allowed to move along the tube, those proteins that do bind or are attracted to those molecules will bind to the surface of our tube."}, {"title": "Cell Fractionation .txt", "text": "But the ones that don't, the proteins that don't will essentially move straight down along our tube."}, {"title": "Cell Fractionation .txt", "text": "And we'll discuss that in much more detail in the next hour of electros."}, {"title": "Cell Fractionation .txt", "text": "Now, gel electrophoresis is something we spoke about already in biology."}, {"title": "Cell Fractionation .txt", "text": "So gel electrophoresis is the process by which we separate."}, {"title": "Cell Fractionation .txt", "text": "We use the charge on the protein to move that protein along an electric field, and we basically separate the proteins based on size."}, {"title": "Cell Fractionation .txt", "text": "So notice that gel filtration chromatography and gel electrophoresis, these two methods both use the size factor."}, {"title": "Cell Fractionation .txt", "text": "But the major difference between gel electrophoresis and gel filtration chromatography is in gel electrophoresis, all the proteins actually move along that region, while in gel filtration chromatography, the very small proteins essentially are trapped inside the beads of that system, as we'll see in a future lecture."}, {"title": "Cell Fractionation .txt", "text": "Now, in isoelectric focusing, this is where we separate our proteins based on their isoelectric point."}, {"title": "Cell Fractionation .txt", "text": "And the isoelectric point is that specific PH value at which the net charge on that protein is essentially neutral, and we'll see exactly is essentially zero, and we'll see exactly what that means once again in a future lecture."}, {"title": "Cell Fractionation .txt", "text": "Now, two dimensional electrophoresis basically combines the isoelectrofocusing method and the gel electrophoresis method."}, {"title": "Cell Fractionation .txt", "text": "So every time we conduct one of these protein purification processes, as well as following the cell fractionation process, we basically have to determine what the enzyme activity is and what the enzyme concentration is in that sample."}, {"title": "Cell Fractionation .txt", "text": "Because it's the enzyme activity and the concentration values that allows us to calculate the specific activity and recall it's a specific activity value that allows us to determine whether or not our sample is pure."}, {"title": "Cell Fractionation .txt", "text": "So basically, the greater this value is, the more pure our sample of protein is."}, {"title": "Cell Fractionation .txt", "text": "And every time we conduct these processes, at the end of the process, this value has to increase, because if it increases, that means our method was successful and we were able to purify our sample and produce a sample that contains more of the proteins that we actually want to study and less of the proteins that we don't want to study."}, {"title": "Types of Macromolecules .txt", "text": "Before we begin our discussion on the human digestive system, including the stomach, the small and large intestine, let's discuss the three different types of organic macromolecules that we ingest when we eat."}, {"title": "Types of Macromolecules .txt", "text": "So these organic macromolecules include carbohydrates proteins as well as lipids, also known as fats."}, {"title": "Types of Macromolecules .txt", "text": "So let's begin with carbohydrates hydrates."}, {"title": "Types of Macromolecules .txt", "text": "So carbohydrates are also known as sugars or polysaccharides."}, {"title": "Types of Macromolecules .txt", "text": "And carbohydrates consist entirely of carbon, of oxygen and of hydrogen."}, {"title": "Types of Macromolecules .txt", "text": "Now, carbohydrates basically exist in their polymer form when we actually ingest them in our food products."}, {"title": "Types of Macromolecules .txt", "text": "So what that basically means is carbohydrates exist of these connecting units we call monomers or monosaccharides."}, {"title": "Types of Macromolecules .txt", "text": "And before our body, our cells actually absorb these carbohydrates into the cells, we have to break down those carbohydrates, the polysaccharides, into their individual form, into their monosaccharides."}, {"title": "Types of Macromolecules .txt", "text": "And the way that our body breaks down these polysaccharides, these long chain carbohydrates, is by using specialized types of proteolytic enzymes that we're going to focus on in the next several lectures."}, {"title": "Types of Macromolecules .txt", "text": "Now, the process that these enzymes use is known as hydrolysis."}, {"title": "Types of Macromolecules .txt", "text": "That basically means they use water to basically cleave the bonds that connect the individual sugar monomers."}, {"title": "Types of Macromolecules .txt", "text": "So hydrolysis is used not only in carbohydrate breakdown, but also in the breakdown of proteins and lipids."}, {"title": "Types of Macromolecules .txt", "text": "In fact, hydrolysis is the most common type of catabolic process that exists inside the body."}, {"title": "Types of Macromolecules .txt", "text": "Catabolic simply means the breakdown of this is different than anabolic, which means the synthesis of."}, {"title": "Types of Macromolecules .txt", "text": "Now, although there are many different types of sugars that exist in nature, we have five member sugars, we have six member sugars and so forth."}, {"title": "Types of Macromolecules .txt", "text": "The most common type of sugar, monomer of sugar that is used by the body is glucose."}, {"title": "Types of Macromolecules .txt", "text": "In fact, when the majority of the cells take in that non glucose molecule, they normally convert, transform the non glucose into glucose."}, {"title": "Types of Macromolecules .txt", "text": "And this takes place in liver cells as well as intestinal cells in our intestines, in the liver, in our body."}, {"title": "Types of Macromolecules .txt", "text": "Now, glucose can be broken down and transformed into ATP molecules and ATP is used for energy."}, {"title": "Types of Macromolecules .txt", "text": "Now, in the process of glycolysis, we basically use glucose to form ATP as well as Pyruvate molecules and don't."}, {"title": "Types of Macromolecules .txt", "text": "And then those Pyruvate molecules are used in the creep cycle to form even more ATP molecules, the energy molecules that are used by the cell."}, {"title": "Types of Macromolecules .txt", "text": "Now, when our cell basically contains ample amounts, so enough ATP and it doesn't need to form any more ATP, it can basically take the glucose and store glucose in a polymer form known as glycogen."}, {"title": "Types of Macromolecules .txt", "text": "So our liver cells, muscle cells and other cells in the body store glucose in this polymeric form known as glycogen."}, {"title": "Types of Macromolecules .txt", "text": "And the individual sugars, the individual glucose monomers in glycogen are connected by special types of bonds known as alphaglycocitic linkages or alphaglycocitic bonds."}, {"title": "Types of Macromolecules .txt", "text": "Now, luckily, our body contains special proteolytic enzymes that are capable of cleaving the alphagly acidic linkages."}, {"title": "Types of Macromolecules .txt", "text": "So our body can easily break down the alphagly acidic bonds."}, {"title": "Types of Macromolecules .txt", "text": "However, other sugars other polymers of sugars."}, {"title": "Types of Macromolecules .txt", "text": "For example, in cellulose, which is found on plants, contains beta glycocitytic linkages."}, {"title": "Types of Macromolecules .txt", "text": "And our body does not contain the proteins to digest to break down these betaglycolytic linkages."}, {"title": "Types of Macromolecules .txt", "text": "So we can only break down the alphaglyic acidic linkages."}, {"title": "Types of Macromolecules .txt", "text": "Now, the process by which the majority of the cells in our body actually absorb the glucose across the cell membrane involves passive diffusion."}, {"title": "Types of Macromolecules .txt", "text": "And that basically means it doesn't actually need to use any type of ATP molecules."}, {"title": "Types of Macromolecules .txt", "text": "And that's because glucose normally travels across the cell membrane down its electrochemical gradient."}, {"title": "Types of Macromolecules .txt", "text": "However, certain specialized cells in our body use active transport to actually move our glucose against electrochemical gradient."}, {"title": "Types of Macromolecules .txt", "text": "And that means it uses these cells use ATP to actually move the glucose across."}, {"title": "Types of Macromolecules .txt", "text": "Now, two examples of these specialized types of cells are cells found in the kidneys and cells found in our small intestine."}, {"title": "Types of Macromolecules .txt", "text": "Now, in our kidneys, we want to make sure that none of the glucose actually ends up in the urine."}, {"title": "Types of Macromolecules .txt", "text": "And that's exactly why these kidney cells are specialized to have these active transport proteins that use ATP to move our glucose against electrochemical gradient, because we want to absorb all the glucose from our filtrate, from our urine."}, {"title": "Types of Macromolecules .txt", "text": "Now, in our small intestine, that is where we absorb most of our glucose molecules."}, {"title": "Types of Macromolecules .txt", "text": "And that's exactly why we want to be able to move the glucose across the cell membrane, regardless of what the electrochemical gradient of the glucose is."}, {"title": "Types of Macromolecules .txt", "text": "So this is our diagram that describes a small section of glycogen."}, {"title": "Types of Macromolecules .txt", "text": "So we have these many of these glucose molecules, our six member glucose molecules, and each one of these bonds is the alpha 114 glycocitic bond."}, {"title": "Types of Macromolecules .txt", "text": "Now, we also have so, notice that glycogen is not a straight chain polymer."}, {"title": "Types of Macromolecules .txt", "text": "It has kinks, it has these deviations, and these connecting bonds are the alpha one six glycosytic linkages."}, {"title": "Types of Macromolecules .txt", "text": "And our cells contain enzymes that can basically cleave both of these types of alpha bonds."}, {"title": "Types of Macromolecules .txt", "text": "Now, let's move on to our protein."}, {"title": "Types of Macromolecules .txt", "text": "So, proteins is yet another type of organic macromolecule that is also a polymer that we ingest when we eat our food."}, {"title": "Types of Macromolecules .txt", "text": "So proteins are another type of macromolecules that we ingest when we eat."}, {"title": "Types of Macromolecules .txt", "text": "So proteins are polymers that consist of individual units we call amino acids, which contain not only oxygen and carbon and hydrogen, but they also contain nitrogen."}, {"title": "Types of Macromolecules .txt", "text": "Now, the bonds that connect these individual monomers, our amino acids, are called peptide bonds."}, {"title": "Types of Macromolecules .txt", "text": "And proteins are usually called polypeptides, which means they consist of many of these peptide bonds and many of these amino acids."}, {"title": "Types of Macromolecules .txt", "text": "Now, just like we have specialized types of enzymes that break down our polymers of carbohydrates, of polysaccharides, we also have specialized types of enzymes in the stomach and a small intestine to basically break down these peptide bonds."}, {"title": "Types of Macromolecules .txt", "text": "So our body can use these proteolytic enzymes to catalyze the hydrolysis, the catabolic breakdown of our polypeptides into their constituent amino acids."}, {"title": "Types of Macromolecules .txt", "text": "And only then can our cells can actually ingest these amino acids into our body."}, {"title": "Types of Macromolecules .txt", "text": "So the majority of our proteins are ingested into the cells in the form of our monopeptides, our amino acids."}, {"title": "Types of Macromolecules .txt", "text": "But in some cases, we can also ingest bipeptides and tripepptides into our cells, as we'll see in the next several lectures."}, {"title": "Types of Macromolecules .txt", "text": "Now, proteins have many levels of structure, so we have the largest type of level, known as quaternary."}, {"title": "Types of Macromolecules .txt", "text": "And quaternary means we have several polypeptides that bond together via covalent bonds, our disulfide bridges, to form a single protein structure."}, {"title": "Types of Macromolecules .txt", "text": "We also have tertiary, which basically refers to the three dimensional structure of our protein."}, {"title": "Types of Macromolecules .txt", "text": "We have second there, which refers to either the beta pleated sheets or the alpha helixes."}, {"title": "Types of Macromolecules .txt", "text": "And we also have primary, which is basically the long sequence of amino acids inside the protein."}, {"title": "Types of Macromolecules .txt", "text": "Now, when we ingest the proteins, they usually come in either the tertiary or quarterly form."}, {"title": "Types of Macromolecules .txt", "text": "And what our body has to do is basically denature these proteins, basically break down the structure of the protein into the primary form, and we'll discuss how our body actually does this in the next several lectures."}, {"title": "Types of Macromolecules .txt", "text": "One of the ways is by using a very high acidity special type of cells known as parietal, cells in our stomach are capable of secreting gastric acid, hydrochloric acid that basically denatures our proteins."}, {"title": "Types of Macromolecules .txt", "text": "And once we denature them, our proteolytic enzymes can hydrolyze them via the process of hydrolysis, our catabolic reaction that breaks down these proteins."}, {"title": "Types of Macromolecules .txt", "text": "Now, our body uses 20 different types of amino acids."}, {"title": "Types of Macromolecules .txt", "text": "Now, all these 20 different types of amino acids are alpha amino acids."}, {"title": "Types of Macromolecules .txt", "text": "And alpha simply means that the residue is attached to our alpha carbon, that our group is attached to our alpha carbon with respect to our carbonyl group."}, {"title": "Types of Macromolecules .txt", "text": "Now, ten of these amino acids can actually be synthesized by our body without any problem, without actually having to ingest any type of food."}, {"title": "Types of Macromolecules .txt", "text": "But the other ten, which are known as essential amino acids, we cannot actually synthesize."}, {"title": "Types of Macromolecules .txt", "text": "We must actually ingest them from food products."}, {"title": "Types of Macromolecules .txt", "text": "And we need all 20 amino acids to basically survive, even if we are missing a single amino acid."}, {"title": "Types of Macromolecules .txt", "text": "That means we do not have the proper amount of amino acids in our body to synthesize all the proteins that are needed by the body to survive."}, {"title": "Types of Macromolecules .txt", "text": "So we need all these 20 amino acids to basically live on and survive and function effectively and efficiently."}, {"title": "Types of Macromolecules .txt", "text": "Finally, let's move on to the final organic type of macromolecule known as lipid."}, {"title": "Types of Macromolecules .txt", "text": "Now, by the way, organic simply means that it contains carbon."}, {"title": "Types of Macromolecules .txt", "text": "So all of these macromolecules contain a carbon component."}, {"title": "Types of Macromolecules .txt", "text": "So let's move on to lipids."}, {"title": "Types of Macromolecules .txt", "text": "Now, lipids are also known as fats."}, {"title": "Types of Macromolecules .txt", "text": "And unlike our carbohydrates and proteins, which are water soluble, so that means they are polar and which are polymers."}, {"title": "Types of Macromolecules .txt", "text": "So that means they consist of individual repeating units."}, {"title": "Types of Macromolecules .txt", "text": "Our lipids are not water soluble, so that means they do not dissolve in water they do not dissolve in a polar solvent."}, {"title": "Types of Macromolecules .txt", "text": "And we'll see what that means in just a moment."}, {"title": "Types of Macromolecules .txt", "text": "And lipids are not polymers."}, {"title": "Types of Macromolecules .txt", "text": "They are not composed of these individual units like the carbohydrates and proteins are."}, {"title": "Types of Macromolecules .txt", "text": "And there are many different types of examples of lipids that we can ingest into our body."}, {"title": "Types of Macromolecules .txt", "text": "So we have our steroids, and one example is cholesterol."}, {"title": "Types of Macromolecules .txt", "text": "We have triglycerides."}, {"title": "Types of Macromolecules .txt", "text": "We have our fatty acids that we can ingest."}, {"title": "Types of Macromolecules .txt", "text": "We can also ingest phospholipids."}, {"title": "Types of Macromolecules .txt", "text": "So basically, each one of these lipids serves its own unique purpose."}, {"title": "Types of Macromolecules .txt", "text": "For example, phospholipids and cholesterol are found in our membrane, while our fatty acids and triglyceride, triglycerides is the form that we store our fats inside our adipose cells."}, {"title": "Types of Macromolecules .txt", "text": "And fatty acids are those lipids that we use to actually break down and for ATP."}, {"title": "Types of Macromolecules .txt", "text": "So because lipids do not actually dissolve in water, and because the majority of the body and the cells are composed of water, that means lipids do not dissolve in our blood."}, {"title": "Types of Macromolecules .txt", "text": "They do not dissolve in our cytoplasm, the cell."}, {"title": "Types of Macromolecules .txt", "text": "And so what that basically means is when we ingest lipids, they're going to aggregate together."}, {"title": "Types of Macromolecules .txt", "text": "They're going to basically form these bundles, these fat bundles."}, {"title": "Types of Macromolecules .txt", "text": "Now, luckily, as we'll see in the next several lectures, our body has a way to deal with this."}, {"title": "Types of Macromolecules .txt", "text": "We can actually break down those clusters of lipids, and then we can use special enzymes to basically break our lipids."}, {"title": "Types of Macromolecules .txt", "text": "And we break the lipids usually into fatty acids."}, {"title": "Types of Macromolecules .txt", "text": "So we ingest that mostly in the form of triglyceride."}, {"title": "Types of Macromolecules .txt", "text": "So triglycerides consist of three fatty acids."}, {"title": "Types of Macromolecules .txt", "text": "So that's long carbon chains that are nonpolar the tails."}, {"title": "Types of Macromolecules .txt", "text": "And then we also have our glycerol component."}, {"title": "Types of Macromolecules .txt", "text": "So what this basically means is, because we ingest most of the fat in the form of triglycerides, before the triglycerides are actually absorbed by the cells, we have to break down our triglycerides into fatty acids and glycerol, and only then can our cells actually absorb those products."}, {"title": "Types of Macromolecules .txt", "text": "So since lipids do not actually dissolve in water, that means lipids do not dissolve in blood, nor do they actually dissolve in lymph."}, {"title": "Types of Macromolecules .txt", "text": "And what that means is we need specialized types of proteins to basically carry those lipids inside our blood system."}, {"title": "Types of Macromolecules .txt", "text": "Now, inside the blood, that carrier protein for fatty acids is known as albumin."}, {"title": "Types of Macromolecules .txt", "text": "And we'll discuss this in much more detail when we'll discuss our cardiovascular systems, our blood system."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Inside our body, we have two different proteins, myoglobin and hemoglobin, that carry out the function of bringing oxygen to the cells of our body, where that oxygen can then be used in a process called cellular respiration, aerobic cellular respiration, to produce ATP molecules."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, previously, we said that these two proteins contain heme groups, and it's the heme group group that is responsible for actually binding and holding on to the oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, in myoglobin, we have a single polypeptide chain, and so we have a single heme group."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "But in hemoglobin, because we have four different polypeptide chains, we have four different heme groups."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, one heme group can bind one oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And what that means is a single hemoglobin can bind four times as many oxygen molecules as myoglobin can."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, if hemoglobin can bind more of these oxygen molecules, why do we need myoglobin molecules in the first place?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And in general, why does our body need to use two different proteins to carry out the same function of bringing the oxygen to the cell?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Well, as it turns out, because these two proteins have slightly different structures, they have slightly different properties and therefore slightly different functions."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "As we'll see in just a moment, myoglobin is used to store the oxygen, while the hemoglobin is actually used to bring the oxygen continually from the lungs and to the tissues of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And we'll see exactly why that is."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So in just a moment."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, in biochemistry, we use something called the oxygen binding curve, also known as the oxygen dissociation curve, to basically describe the properties of myoglobin and hemoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And this is the graph shown on the board."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So the blue curve basically describes the myoglobin oxygen binding curve, while the red curve describes the hemoglobin oxygen binding curve."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So going this way, it's a binding curve, going backwards, it's a dissociation curve."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And so we can use O two binding curve or O two dissociation curve interchangeably."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "These two terms mean the same exact thing."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, on the graph, the y axis describes the fractional saturation of the protein."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "It tells us what fraction of the total number of proteins in our mixture is fully saturated, is bound to that oxygen, and it ranges from a value of zero to a value of one, where zero basically means none of the proteins contain oxygen, while one means 100% of the proteins or the proteins are bound to oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, the x axis describes the concentration of the oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And because oxygen is against, we commonly describe the concentration of oxygen by using the partial pressure of oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So PO two, and this is given in either millimeters of mercury or tor, these two units have the same exact quantities."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So one Tor is equal to 1 mercury."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So on this particular graph, we begin at 0 mercury and end up at 100 mercury."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And as we'll discuss in the next lecture, a value of 100 mmhg describes the partial pressure of oxygen inside our lungs, while a value of 40 mercury describes the partial pressure inside our resting tissue."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And we'll discuss much more of that in the next lecture."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So let's actually begin by describing what the meaning of these two curves are."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And let's begin with the blue curve that describes the oxygen binding curve for myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Notice for myoglobin, we have a simple binding curve."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And what that means is it shows that as we begin to increase the concentration ever so slightly, there is a sharp increase in that curve until it levels off and then essentially becomes flat."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, what that means is as soon as we begin to add a tiny amount of that oxygen into our mixture, all that oxygen begins to bind onto the myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Because the myoglobin has a very high affinity for that oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "It binds that oxygen strongly."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And that's why we have this sharp increase in that curve immediately after we begin increasing the concentration of that oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So we see that at a partial pressure of 2 million meter of mercury."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So let's take our marker out."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So, at this quantity here, which is about 2 million meter of mercury, if we basically draw a straight vertical line and eventually we hit the curve, we hit the curve at this value."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And this value describes a value of 0.5 fractional saturation of protein."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So at a value of 2 mercury, a very small amount of oxygen, 50% of all the myoglobin in our body in that mixture will contain oxygen balance of the heme group of the myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And this means that myoglobin binds to oxygens very readily."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "It has a very high affinity for oxygen, and it also means the following."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So, going this way, the oxygen is binding onto the myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "But going this way, the oxygen is dissociating."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Notice as we go this way, as we decrease the concentration of that oxygen, that myoglobin remains bound to that oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And the myoglobin only begins to unload or release that oxygen when the partial pressure drops to a very low quantity, and it essentially unloads it altogether."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "All the myoglobin unloads the oxygen very quickly and together when we drop that partial pressure to a certain value."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So myoglobin does not release oxygen until the partial pressure drops to a very low quantity."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, what is the physiological meaning behind this?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Well, what this means is our body can actually use the myoglobin for oxygen storage to basically store the oxygen until it really, really needs it, when the cells have a very low concentration of oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And that's exactly why myoglobin is the protein that is used by the muscle cells of our body to basically store the oxygen until that moment when we have very little oxygen found inside our body, when the lungs can no longer deliver the oxygen to the tissue of our muscle effectively and efficiently."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, why does my globin observe this behavior?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Well, it turns out because it turns out that myoglobin has these properties because it only consists of a single polypeptide chain."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Because it consists of only a single chain, it only consists of a single heme group."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And what that means is it does not bind oxygen cooperatively."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And we'll see exactly what that means in just a moment."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So what is the physiological consequence of this property of myoglobin?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Well, these properties of myoglobin as described here, makes it a perfect molecule to store the oxygen inside our cells."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "In fact, myoglobin, and that's why it's called mayo."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Myo means myocide, or muscle cell myoglobin, is used to store oxygen inside our muscle cells."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Myoglobin only releases that oxygen to the muscle cells when the concentration drops to a very small value."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And when it drops below a certain value, ultimately, all these myoglobin molecules in a cell will release that oxygen together."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And that's exactly what the sharp increase or decrease in that blue curve actually means."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now let's move on to hemoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Notice, unlike hemoglobin, unlike my globin, the curve for hemoglobin is not as sharp."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "In fact, we have this s shape curve, and this s shape is known as the sigmoidal shape curve."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And what the sigmoidal shape curve basically means is the binding affinity of hemoglobin for oxygen is much smaller than that for myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So we said earlier that a concentration of only 2 mercury is needed to actually bind 50% of that myoglobin to oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, in the case of hemoglobin, if we draw a straight line from the 50% mark, from the 0.5 mark, and we draw a vertical line down, this will give us a partial pressure of about 26 mercury."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So a concentration of 26 mercury is needed for exactly half of those hemoglobin molecules to become saturated to bind that oxygen, compared to the 2 mercury for the myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And what that means is that hemoglobin binds oxygen much less likely than the myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And so it has a lower affinity for oxygen than my globin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And once again, if we read the curve backwards, so going this way, the protein is binding the oxygen, but going backwards, the protein is dissociating that oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And so if we go this way, we see that our hemoglobin releases that oxygen much more readily than myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And that's exactly what makes hemoglobin much better at carrying the oxygen from the lungs and releasing it at the tissues and cells of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And that's exactly what the function of hemoglobin is."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So myoglobin is used to actually store that oxygen in the muscle cells, while hemoglobin is used to actually carry the oxygen from the lungs through the bloodstream into the tissues and cells of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And only when the hemoglobin isn't able to actually bring enough oxygen to our cells, only then does myoglobin begin to release that oxygen to the muscle cells of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So the sigmoidal curve is produced as a result of hemoglobin's ability to bind oxygen in a cooperative fashion."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So earlier we said that myoglobin binds oxygen in a non cooperative fashion, while hemoglobin binds it cooperatively."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So what do we mean by that?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And why does that actually occur?"}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Well, this means that the binding of oxygen at one heme group at one side on the hemoglobin makes the other unoccupied sites much more likely to bind oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So what that means is the different heme groups inside our hemoglobin actually interact with one another."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And so, for example, if we have a hemoglobin that contains fully unoccupied sites, when one of those heme groups binds oxygen, that will make the other three unoccupied sites much more likely to bind an oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And conversely, the release of oxygen from one side on the hemoglobin molecule makes to other occupied sites much more likely to unload those oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So, because hemoglobin consists of these four polypeptide chains, the four heme groups found on the four different chains can actually interact together."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "They can cooperate with one another to basically either release or bind that oxygen manner, that oxygen molecule in a cooperative fashion."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "Now, what this means physiologically, as I said earlier, it makes the hemoglobin a great carrier of oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So what that means is at the lungs, when our hemoglobin is in the lungs, it can easily bind that oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "But when it gets the cells and tissues of our body, it has no problem actually unloading and releasing that often to the cells of the tissues of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So we conclude that myoglobin does not bind oxygen cooperatively."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And this basically makes it a great storing molecule."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So it stores the oxygen in the muscle cells of our body because it only releases it when the concentration drops to very low value."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "On the other hand, because the hemoglobin consists of these four individual polypeptide chains, these polypeptide chains, the heme groups can interact with one another and they can basically induce the release or the binding of the oxygen."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And so this means if it makes it a perfect molecule to act as a carrier of oxygen inside our blood system, so that's exactly why hemoglobin is used by our body to basically take that oxygen in the lungs and bring it to the tissues of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "So we see that hemoglobin's cooperative behavior makes it a great oxygen carrier."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "It can readily bind that two in the lungs and has no problem releasing that oxygen inside the tissues of our body."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "And we'll discuss in much more detail what the physiological consequence is of hemoglobin and myoglobin."}, {"title": "Oxygen Binding Curve for Myoglobin and Hemoglobin.txt", "text": "In the next lecture, we're going to see exactly why it's hemoglobin and not myoglobin that is used as the oxygen carrier inside the red blood cells of our body."}, {"title": "Activation of Lymphocytes .txt", "text": "To gain a better understanding as to how our immune system actually works, let's take a look at the following diagram."}, {"title": "Activation of Lymphocytes .txt", "text": "At the following illustration."}, {"title": "Activation of Lymphocytes .txt", "text": "So, let's begin on this side."}, {"title": "Activation of Lymphocytes .txt", "text": "So, let's suppose some type of infection actually took place."}, {"title": "Activation of Lymphocytes .txt", "text": "And let's say that a bacterial cell got into our tissue."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, once the bacterial cell is inside the tissue of our body, infection begins."}, {"title": "Activation of Lymphocytes .txt", "text": "And the innate immune system is the first one to actually react."}, {"title": "Activation of Lymphocytes .txt", "text": "And what happens is special cells, immune cells known as mast cells and basophils begin to release chemicals such as histamine."}, {"title": "Activation of Lymphocytes .txt", "text": "And what that does is dilates our blood vessels and it brings specialized phagocytic immune cells known as macrophages, to the site of infection."}, {"title": "Activation of Lymphocytes .txt", "text": "So this is what a macrophage actually looks like."}, {"title": "Activation of Lymphocytes .txt", "text": "So, we have different types of organelles, for example, a nucleus."}, {"title": "Activation of Lymphocytes .txt", "text": "And we also have these digestive lysosomes, these tiny vesicles that carry digestive enzymes as well as an acidic environment."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, what the macrophage does is it engulfs our pathogen, in this case our bacteria, and it creates this vacuole within which we have that bacterial cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And some of these lysosomes fuse with this stagosome."}, {"title": "Activation of Lymphocytes .txt", "text": "And now this stackosome contains these digestive enzymes and acidic environment, as well as the bacterial cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And inside the phagosome, we begin the process of the breakdown and digestion of that bacteria."}, {"title": "Activation of Lymphocytes .txt", "text": "So the macrophage essentially engulfs that bacterial cell and begins the process of digestion."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, the macrophage is actually a type of cell we call APC, or antigen presenting cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And what that means is, after it kills off and breaks down that cell, it takes one of the antigens, one of the proteins or nucleic acids or polysaccharides from that bacteria, and it places it onto the surface of that cell."}, {"title": "Activation of Lymphocytes .txt", "text": "But it places it onto a special type of complex of proteins known as MHC, which we spoke about previously."}, {"title": "Activation of Lymphocytes .txt", "text": "So recall that MHC stands for the major histocompatibility complex."}, {"title": "Activation of Lymphocytes .txt", "text": "And this is a class two complex because it's used to actually communicate with other leukocytes, as we'll see in just a moment."}, {"title": "Activation of Lymphocytes .txt", "text": "So this antigen presenting cell aromacrophage creates the MHC class two complex."}, {"title": "Activation of Lymphocytes .txt", "text": "It places it on the surface and it takes an antigen which is shown in red, and it places it onto this region on the MHC class two complex."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, what happens next is another type of leukocyte."}, {"title": "Activation of Lymphocytes .txt", "text": "Another type of white blood cell can now interact and communicate with the macrophage."}, {"title": "Activation of Lymphocytes .txt", "text": "As a result of the presence of the MHC class two complex along with the antigen shown in red and a special type of T cell known as an inactivated helper T cell which is a CD four plus helper T cell begins to approach this MHC class two antigen."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, what do we mean by CD four?"}, {"title": "Activation of Lymphocytes .txt", "text": "Well, CD four is simply a special type of glycoprotein that is located on the membrane of T lymphocytes and specifically on the membrane of this inactivated helper T cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And what this CD Four glycoprotein does is it actually binds and interacts with MHC class two."}, {"title": "Activation of Lymphocytes .txt", "text": "We'll see that there is another type of CD glycoprotein we call CD eight glycoprotein."}, {"title": "Activation of Lymphocytes .txt", "text": "And that glycoprotein only interacts and binds with MHC class one complexes, as we'll see in just a moment."}, {"title": "Activation of Lymphocytes .txt", "text": "So we have an inactivated helper T cell, a type of Lymphocyte, T Lymphocyte that can now go on and bind to this MHC class two complex that contains that antigen."}, {"title": "Activation of Lymphocytes .txt", "text": "So we have the binding process takes place and when they bind and form this entire complex, the macrophage begins to release a special chemical known as interleukin one."}, {"title": "Activation of Lymphocytes .txt", "text": "And the interleukin one essentially goes on to and interacts with this inactivated helper T cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And what that does is it activates that helper T cell."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, once it's activated, it basically releases from this macrophage and it moves on and it finds a B Lymphocyte."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, remember, B Lymphocytes are part of our adaptive immune system, just like these helper T cells are."}, {"title": "Activation of Lymphocytes .txt", "text": "But the B Lymphocytes are part of the humoral immunity of our adaptive system while our T Lymphocytes and our helper T cells are part of the cell mediated immunity."}, {"title": "Activation of Lymphocytes .txt", "text": "So we see that the humoral immunity and the cell mediated immunity interact with one another to carry out the same exact function, to basically kill off these pathogens and kill off the infected cells of our body."}, {"title": "Activation of Lymphocytes .txt", "text": "So once we activate that helper T cell, it basically goes on and finds a B Lymphocyte that contains the MHC class two, class two complex along with that same antigen that was found on this macrophage."}, {"title": "Activation of Lymphocytes .txt", "text": "And they also bind and they also form a complex."}, {"title": "Activation of Lymphocytes .txt", "text": "And once they form a complex, these two cells begin to release these special chemicals known as cytokines."}, {"title": "Activation of Lymphocytes .txt", "text": "And what these cytokines do is they basically induce this T cell, the helper T cell, to begin to clone itself via the process of mitosis."}, {"title": "Activation of Lymphocytes .txt", "text": "So mitosis of the cell takes place and we form many of these cloned helper T cells."}, {"title": "Activation of Lymphocytes .txt", "text": "And these clone helper T cells begin to release another group of cytokines."}, {"title": "Activation of Lymphocytes .txt", "text": "And these cytokines go on."}, {"title": "Activation of Lymphocytes .txt", "text": "And then these cytokines induce these B Lymphocytes and T Lymphocyte cells to basically mature and differentiate into even more specialized cells."}, {"title": "Activation of Lymphocytes .txt", "text": "So these B Lymphocytes basically produce plasma cells as well as memory cells."}, {"title": "Activation of Lymphocytes .txt", "text": "While the T cell, when it reacts with the cytokines, it produces cytotoxic T cells, also known as killer T cells."}, {"title": "Activation of Lymphocytes .txt", "text": "And these cytotoxic T cells contain the glycoprotein CD eight, CD eight."}, {"title": "Activation of Lymphocytes .txt", "text": "And we'll see exactly what that means in just a moment."}, {"title": "Activation of Lymphocytes .txt", "text": "So let's take a look at these plasma cells."}, {"title": "Activation of Lymphocytes .txt", "text": "So these plasma cells have very extensive endoplasmic reticulum as seen in the following diagram."}, {"title": "Activation of Lymphocytes .txt", "text": "And that's because these plasma cells, their function is to basically form antibody."}, {"title": "Activation of Lymphocytes .txt", "text": "So remember, the plasma cells and the memory B cells are part of the humoral immunity, they're part of the antibody mediated immunity."}, {"title": "Activation of Lymphocytes .txt", "text": "And what that means is they're involved with forming and storing antibodies."}, {"title": "Activation of Lymphocytes .txt", "text": "So the plasma cells form antibodies that are complementary to these specific antigens that we spoke about earlier shown in red."}, {"title": "Activation of Lymphocytes .txt", "text": "So these antibodies are complementary to the antigens found on this bacterial cell."}, {"title": "Activation of Lymphocytes .txt", "text": "And these plasma cells form a bunch of these antibodies that can now move around our blood system and lymph system and they combine to the antigens of this bacterial cell."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, memory B cells, instead of forming these antibodies they essentially store these antibodies within the cell and they can essentially react with a bacterial cell of the same type that reinfects our body at some later time."}, {"title": "Activation of Lymphocytes .txt", "text": "So it's the memory B cells that essentially allow our immune system to be adaptive."}, {"title": "Activation of Lymphocytes .txt", "text": "It allows the adaptive immune system to actually learn from these pathogens that infect our cells of the body."}, {"title": "Activation of Lymphocytes .txt", "text": "And finally, our T cell differentiates into the cytotoxic T cell and this contains the CD eight glycoprotein on the membrane."}, {"title": "Activation of Lymphocytes .txt", "text": "Now, the CD eight glycoprotein basically is responsible for binding to the MHC class one, the major histocompatibility complex class one."}, {"title": "Activation of Lymphocytes .txt", "text": "And this is found on our infected cells of the body."}, {"title": "Activation of Lymphocytes .txt", "text": "And that's exactly why the cytotoxic T cells are those immune T cell immune cells of our body that are responsible for seeking out and locating the infected cells of our body."}, {"title": "Activation of Lymphocytes .txt", "text": "And once they bind to those infected cells they basically release special powerful proteins that are capable of digesting and breaking down the membrane of those cells lysing those cells and killing those cells."}, {"title": "Activation of Lymphocytes .txt", "text": "And that's exactly why the cell mediated immunity."}, {"title": "Activation of Lymphocytes .txt", "text": "The immune system that deals with our T lymphocytes is responsible for finding and killing off infected cells while the humoral immune system is responsible for killing off these bacterial cells, pathogens, toxins, parasites and so forth that infect our body."}, {"title": "Activation of Lymphocytes .txt", "text": "So this is a general overview, a very simplified overview of how our immune system actually works."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So let's continue our discussion on the different types of organelles found inside eukaryotic cells."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And let's focus on the endoplasmic reticulum and the Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, right outside the nucleus of most eukaryotic cells, and we say most because some eukaryotic cells, such as red blood cells, do not contain the endoplasmic reticulum nor or do they contain the Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, right outside the nucleus of most eukaryotic cells is a network of membraneous faults known as the endoplasmic reticulum, or simply the Er."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the membrane of the endoplasmic reticulum is a bilayer."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It's a phospholipid bilayer that separates the cytosol portion of our cell with the inside space of our Er."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the space the fluid inside our endoplasmic reticulum is known as the Er lumen, or this is thermal space."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the Er can basically be subdivided into two regions."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "We have the smooth Er and we have the rough Er."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And let's begin by discussing what the rough Er is and what the functions of the rough Er are."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So the membraneous folds found closest to the nucleus of our cell contain ribosomes embedded on the cytosol side of our endoplasmic reticular membrane."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "These ribosomes function to synthesize proteins that are ultimately either embedded into the cell membrane."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "These proteins are known as integral proteins, or they are destined to leave our cell altogether."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the membrane of the rough Er is actually physically connected to the membrane of the nucleus known as the nuclear membrane or the nuclear envelope."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And for this reason, we see that the perineuclear space, the space between the double layer of our nuclear envelope and the Er lumen, is actually physically connected as well."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And that makes sense, because inside our nucleus, in a region known as the nucleolus, we basically synthesize the ribosomal RNA subunits that are needed to create the ribosomes that end up in the rough endoplasmic reticulum."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, once the proteins in the rough endoplasmic reticulum are synthesized on the cytosol side, we basically take those synthesized proteins, we place them into the Er lumen, and then they travel through the rough Er lumen and eventually into the smooth Er lumen."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So now let's discuss the smooth endoplasmic reticulum."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, by the way, if this is our diagram of the eukaryotic cell, we have the nucleus, we have our rough endoplasmic reticulum that contains these folds."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "We have slightly smoother, more tubular folds on the smoothie R, and this is our Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So let's discuss the smoothie R, which is this section here."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the smoothie R contains folds that are slightly more tubular than the folds on the rough Er."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And this can be seen from this picture here."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, unlike the rough Er, the smooth Er does not contain ribosomes embedded in the membrane."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And that's exactly why we call it the smooth Er."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, since it doesn't contain any ribosomes inside our membrane, that means the smooth Er is not directly involved in synthesizing our proteins."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "However, it does contain some very important enzymes that are basically involved in creating glucose."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And this enzyme that I'm talking about is known as glucose six phosphatase."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So glucose six phosphatase is an enzyme that is important in the generation of glucose."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "But perhaps the most important or one of the most important functions of the smooth endoplasmic reticulum is the synthesis of different types of lipids."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And this includes fatty acids."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It includes phosphol lipids."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It also includes cholesterol."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "In fact, cholesterol can be transformed into the different types of steroids inside the smooth endoplasmic reticulum."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And finally, our smooth endoplasmic reticulum can also detoxify drugs."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It can undergo different types of oxidation reactions in which it detoxifies toxin and drugs such as, for example, alcohol."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So one might imagine that the cells in our liver contain very large smooth Er, and that's because in the liver, one of the main roles of our liver is to basically detoxify the different drugs and toxins that we ingest into our body."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, finally, let's move on to our Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So what exactly is the Golgi apparatus?"}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Where is it down?"}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And what are some of its functions?"}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So, the Golgi apparatus is a series of flattened membraneous sacs known as cystrone."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So if this is a smoothie r, the Gold Gipp apparatus is relatively close to our smoothie r. And notice it's also pretty large, so we can see it clearly under a microscope."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, once the proteins are synthesized on the cytosol side of our rough Er, they are injected, they are forced into our Er lumen, and they travel through the Er lumen into our smoothie r. And from the smoothie r, they are basically ejected into the cytosol by using some type of secretory vesicle."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So secretory vesicles carry our proteins from our rough Er and the smooth Er into the Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And all the proteins basically collect inside our Golgi apparatus."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And what the Golgi apparatus does is it basically organizes, it modifies, and it ships out all those proteins into the different parts of the cell, as well as the cell membrane and outside the cell."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So basically, one thing that I forgot to mention about the ruff Er is the proteins synthesized in the ribosomes of the rough Er are the proteins that eventually either end up in our cell membrane or they end up leaving the cell entirely."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And that means inside our ribosome, inside our rough Er, when we synthesize the proteins, we also add a special type of signal known as the signal sequence, or the peptide sequence onto the protein."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And that signal sequence basically signifies the fact that the protein's destination is either in the cell membrane or it's outside the cell."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And when the protein ends up in our Golgi apparatus, that sequence is modified."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So, basically, we can modify proteins in the Golgi apparatus either by adding carbohydrates on it or modifying in some other type of way."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "For example, we phosphorylate our proteins now, inside the Golgi apparatus, we also form several types of polysaccharides."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So our Golgi apparatus contains many important enzymes that are involved in forming different types of polysaccharides of sugars."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And one other important function of the Golgi apparatus is to basically create lysosomes."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So what happens is certain proteins that end up staying in our cytosol will basically leave the gold gaparatus in a vesicle, in a secretory vesicle, and that secretory vesicle becomes a lysosome."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, inside that lysosome, we contain the different types of modified proteins that are able to hydrolyze different types of products when they fuse with our lysosome."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "So we see that the Golgi apparatus is the organelle where we basically organize, modify, and ship all the proteins throughout the cell, throughout the membrane and outside the cell."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It's the place where we form lymphosomes."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It's also place where we form polysaccharides."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "We modify our proteins in many different ways."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "Now, the rough endoplasmic reticulum primarily functions to create our proteins that end up being placed either into the cell membrane or leave the cell entirely."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And our smooth er has several important functions."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It basically acts to de detoxify drugs and toxins."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "It acts to create or synthesize lipids, such as fatty acids, phospholipids and cholesterol, as well as create different types of steroids."}, {"title": "Endoplasmic Reticulum and Golgi Apparatus.txt", "text": "And it also acts to basically create a source of glucose by using glucose six phosphatase, our enzyme that creates glucose."}, {"title": "Nucleosides and Nucleotides.txt", "text": "A nucleic acid is a linear polymer of monomers we call nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now sometimes when describing nucleic acids, instead of using the word nucleotides, we sometimes use nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "But nucleotides and nucleotides are two different things."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So in this lecture we're going to discuss what the nucleotide and nucleotide is and what the difference between these two things things actually is."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So let's begin by describing nucleosides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So all a nucleocide is it's this unit."}, {"title": "Nucleosides and Nucleotides.txt", "text": "It's a molecule that consists of a sugar molecule attached covalently via a beta glycocitic bond to a base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this is one example of a nucleocide."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So in this particular nucleocide, the sugar is a ribosugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And what that means is this nucleocide will be found on the RNA molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now what about the base?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "Well, the base in this particular case is adenine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And the way that we name this nucleotide is simply adenosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now if this base was Guanine, then we'd call it guanosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "If this was cytosine we'd call it citadine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And if this was uracil, we'd call it uridine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now if we take and we remove this oh group, then we essentially change our sugar riboseuge into the deoxyribose sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And now this would no longer be adenosine, it would be deoxy adenosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And likewise, if this was deoxyribose and guanosine, we'd call it deoxyguanosine and so forth."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So these are the four nucleotides found in RNA and these are the four nucleotides found in DNA molecules."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And notice that the linkage between the carbon found on the sugar and the nitrogen found on our base is the beta glycosync linkage."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now this bond here is also coming out of the board."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And what that means is if this sugar molecule was found on the plane of the board, this entire base will be found above the plane of that sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And so what that means is the base group, in this case it's the adenine, lies above the plane of the sugar molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So when we normally draw nucleotides, this is how we portray our nucleotide."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So all a nucleotide is it's basically the nucleotide minus the phosphate group."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the way that we define a nucleotide is basically by saying we have a nucleotide that contains at least one phosphate group."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now before we go on to nucleotides, let's mention one more thing about nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So notice that the bond in a nucleotide that connects these two different molecules is always between carbon number one, one prime on the sugar and on nitrogen found on the base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now if the base is a purine and that means we have these two fuse rings, then this nitrogen number one will always be bound to carbon number one."}, {"title": "Nucleosides and Nucleotides.txt", "text": "If this base was a puridine when we have only a single ring, then a nitrogen would be nitrogen number one."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the bond always takes place between carbon number one and a nitrogen atom found on our base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now let's move on to nucleotide."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the only difference between a Nucleotide and a Nucleotide is in Nucleotides, we have the sugar and the base, as well as at least one of the phosphate groups attached to carbon number five on that sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, sometimes, as we'll see in just a moment, the phosphate group can also be attached to carbon number three."}, {"title": "Nucleosides and Nucleotides.txt", "text": "But usually in natural nucleotides found inside our body, we have the phosphate groups attached onto carbon number five."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So a nucleotide attached to one or more phosphate groups is called the Nucleotide."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And in most bio and in most biological nucleotides, the phosphate group is attached to the fifth carbon on that sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, perhaps one of the most prototypical examples the most famous examples of a nucleotide is adenosine five triphosphate or ATP."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is the molecule that our cells and our body uses to basically store and generate energy for different types of cellular processes."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So in this particular case, the sugar is a ribose sugar because we have that oh, group on the second carbon."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Notice that our base, just like in this case, is Adenine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And here, unlike here, we have the phosphate groups."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And for ATP, we have one, two, three of these phosphate groups."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And so we have a negative charge here, a negative charge delocalized here and two negative charges delocalized among those three oxygen atoms."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, how do we name Nucleotides?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "Well, this is our genetic formula that we basically have to use when we name the nucleotide that we're dealing with."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So we begin with the sugar base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So that's the nucleotide."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Then we move on to the type of linkage that exists between the sugar and the phosphate groups."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And then we move on to the number of phosphate groups that we have."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So if we have a single phosphate group that's monophosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "If we have two phosphate groups that's diphosphate three phosphate groups, as in this case, that's triphosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So let's take a look at the ATP molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So what type of sugar base?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "What type of nucleotide do we have in this particular case?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "Well, the sugar is a ribo sugar, and this base is anonyme."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And that means we have adenosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And that's exactly why this is adenosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, the linkage is between carbon number five on that sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And what that means is this is five prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And how many of these phosphate groups do we have attached to the five prime?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "And well, we have three phosphate groups."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And so that's exactly why this is adenosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Five triphosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Or simply five prime ATP."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Where A is adenosine, T is trip and P is phosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now let's look at another example."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Another type of biological molecule that we can find inside our body is the following molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this is quite different in four different ways."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this differs from the ATP in four different ways."}, {"title": "Nucleosides and Nucleotides.txt", "text": "First of all, the type of sugar difference in this particular case in this particular case, it's the ribosugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "In this particular case, it's the deoxyribosugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "The second difference is in this particular case, we have Guanine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "In this case, we have Adenine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And also notice that in this particular case, we have the prototypical linkage on a five prime N. But here we have the linkage on the three prime N. And unlike here, where we have three of these phosphate groups, we have one phosphate group here."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the way that we name this molecule is in the following manner."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So what type of sugar base, what type of nucleotide are we dealing here?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "Are we dealing here with?"}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the sugar is a deoxyribose, and that means we're dealing with one of these four choices."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Since we have Araguanine, that means we're dealing with deoxyguanosine."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So Deoxyguanosine is that sugar base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, the linkage is not between five prime carbon, it's between the three prime carbon."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And that means this is three prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And finally, because we have only one phosphate group, not three, this last part is monophosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So Deoxyguanosine is the nucleotide three prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Monophosphate is where that single phosphate group is actually attached to on that sugar."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now the shorthand way of writing that is three prime Dgmp, where D is deoxy, G is our guanassine, M is mono, and P is phosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this three prime basically tells us where that phosphate group is attached to on our sugar molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, in DNA molecules we have four types of nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "We have deoxy adenylate, we have deoxy, guanolate, and so forth."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So four of these different types of nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And notice that because we have the deoxy, that simply means we don't have that oxygen found on the second carbon."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And so if we want to describe the four different types of nucleotides on RNA molecules, we simply remove our deoxy term from this term, this term and this term."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, because we don't have a thymine in RNA, this will be different in RNA."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, the last thing I'd like to talk about is how we actually write down our sequence of nucleotides in a DNA molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So let's suppose we have the following three nucleotide nucleic acid."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So since we're dealing with our deoxyribosugar, this is a DNA molecule."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Now, the direction that we write our DNA molecule in is beginning at the five prime end and ending at the three prime end."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So to see what we mean by that, let's label our carbon."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is carbon prime one."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So one prime, two prime, three prime, four prime and five prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is the five prime N, and we can basically carry this same process out with all of these."}, {"title": "Nucleosides and Nucleotides.txt", "text": "This is four prime and this is five prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "The same thing here, one prime, two prime, three prime, four prime and five prime."}, {"title": "Nucleosides and Nucleotides.txt", "text": "There should be two H's, not one H right over here."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this should have an H, and this should have an H. Okay, so this here is the five prime N, and this here is the three prime N. And notice, just like in proteins in nucleic acids, we also have polarity."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So the five N is polar because we have this negative two charge as a result of the phosphate."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this N is also polar because we essentially have this oh group."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And so that's exactly why we have polarity along our nucleic acid."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So nucleic acids have polarity."}, {"title": "Nucleosides and Nucleotides.txt", "text": "We have the beginning, the five end and the end."}, {"title": "Nucleosides and Nucleotides.txt", "text": "The three end."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And the five end always contains at least one of these phosphate groups attached onto that carbon number five."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is the five end."}, {"title": "Nucleosides and Nucleotides.txt", "text": "This is the three end."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And instead of drawing out this entire nucleic acid every single time, this is the shortcut mechanism that we can basically use to write out this entire sequence."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is the beginning, the five N. And we simply write that type of base."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So we have Adenine A, we have Guanine that's G and we have citizen that's C. And every time you write this, we know this is the picture that we should be imagining inside our heads."}, {"title": "Nucleosides and Nucleotides.txt", "text": "So this is how you basically write our nucleic acids."}, {"title": "Nucleosides and Nucleotides.txt", "text": "And this is the major difference between nucleotides and nucleotides."}, {"title": "Nucleosides and Nucleotides.txt", "text": "Nucleotides incorporate the phosphate groups, but the nucleotides are basically the sugar molecule attached to our base minus those phosphate groups."}, {"title": "Testes.txt", "text": "The male gonads are known as testes."}, {"title": "Testes.txt", "text": "And testes are very two important roles."}, {"title": "Testes.txt", "text": "Firstly, they play a role as a reproductive organ."}, {"title": "Testes.txt", "text": "So that means they produce specialized types of cells known as sperm cells that are involved in our human reproduction cycle."}, {"title": "Testes.txt", "text": "And secondly, testes also play a role as an endocrine gland and that means they are capable, capable of releasing and producing specialized hormones that are required by our body."}, {"title": "Testes.txt", "text": "Now, in this lecture we're going to focus on the latter."}, {"title": "Testes.txt", "text": "We're going to focus on the endocrine capability of testes."}, {"title": "Testes.txt", "text": "Now, if we take a cross section of the testes we basically get the following diagram."}, {"title": "Testes.txt", "text": "And within this diagram we have a specialized section known as the Simoniferous tubules."}, {"title": "Testes.txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Testes.txt", "text": "So these tubules, shown in brown are the Simonerfrost tubules and if we examine the microscopic section of the simoniferous tubules, we basically get the following diagram."}, {"title": "Testes.txt", "text": "So within our Simoner PHOs tubules we have two very important types of cells that are involved in sperm production as well as in the production of our androgens the male sex hormones."}, {"title": "Testes.txt", "text": "So we have sirtoli cells which are these large cells shown that contain the blue nuclei as shown."}, {"title": "Testes.txt", "text": "And connecting these surtoli cells are the intercellular junctions, the tide junctions which basically create a watertight seal."}, {"title": "Testes.txt", "text": "Now, below our surtole cells, what keeps our surtoli cells together and attached to a membrane is this basement membrane layer."}, {"title": "Testes.txt", "text": "And below that we have these fibroblasts which are specialized types of cells that produce and release collagen that forms the extracellular matrix that surrounds our cells."}, {"title": "Testes.txt", "text": "Now, the other important types of cell that we have to know is our Ladic cell."}, {"title": "Testes.txt", "text": "This is also known as the intrastitial cell and these Ladic cells are shown in green."}, {"title": "Testes.txt", "text": "So we have the lady cells, we have these hertoli cells and we also have these red structures which are the capillaries that bring not only nutrients and oxygen but also important types of hormones to our testes, to our Simoniferous tubules of the testes."}, {"title": "Testes.txt", "text": "So in our discussion on the hypothalamus and the anterior pituitary gland, we said that the hypothalamus produces and releases a hormone known as GnRH, which stands for gonadotropin releasing hormone."}, {"title": "Testes.txt", "text": "And this hormone stimulates the interior pituitary gland to release two important types of hormones."}, {"title": "Testes.txt", "text": "We have the follicle stimulating hormone FSH and lee nizing hormone also known as LH."}, {"title": "Testes.txt", "text": "Now, when the luteinizing hormone is released into our bloodstream, it travels down to the capillaries of our simoniferous tubules and it attaches to the cell membrane of these latic cells and then basically stimulates these latic cells to release a special type of androgen known as testosterone."}, {"title": "Testes.txt", "text": "Now, testosterone is a steroid hormone and that means it is lipid soluble and it can easily pass across the cell membrane of target cells."}, {"title": "Testes.txt", "text": "So the receptor proteins of testosterone are found inside our cell."}, {"title": "Testes.txt", "text": "Now, testosterone has many important functions."}, {"title": "Testes.txt", "text": "Firstly, it basically stimulates and initiates the production of our sperm cells inside these regions between our surtoli cells."}, {"title": "Testes.txt", "text": "And we'll discuss what the function of sirtoli cells are in just a moment."}, {"title": "Testes.txt", "text": "Now, it also causes, it initiates secondary sex characteristics including the growth of pubic hair as well as underarmpit hair."}, {"title": "Testes.txt", "text": "And it also enlarges our larynx and that is what gives us a deeper voice when we're undergoing puberty."}, {"title": "Testes.txt", "text": "Now, it also is responsible for initiating the process of puberty."}, {"title": "Testes.txt", "text": "So basically our growth spurt, this involves the growth of not only our muscle, but also of bone."}, {"title": "Testes.txt", "text": "So it increases the bone and muscle mass in our body during the process of puberty."}, {"title": "Testes.txt", "text": "Now, it is also involved in actually preventing a condition known as osteoporosis."}, {"title": "Testes.txt", "text": "Osteoporosis is essentially the breakdown of our bone, our bone matrix, as a result of old age."}, {"title": "Testes.txt", "text": "And it also stimulates the closure of our epiphysical plate found in our long bone."}, {"title": "Testes.txt", "text": "So it's not only involved in actually elongating our bone, but it is also involved in ending the process of elongation in our long bones."}, {"title": "Testes.txt", "text": "Now, as time progresses and as our lady cells continually release our testosterone into our blood, that increases the level of testosterone in our blood."}, {"title": "Testes.txt", "text": "And as the blood testosterone level increases, the testosterone can actually go and inhibit the hypothalamus from releasing the gonadotropin releasing hormone and it can also inhibit the anterior pituitary gland from releasing our luteinizing hormone as well as the follicle stimulating hormone."}, {"title": "Testes.txt", "text": "And this type of pathway is known as negative feedback inhibition or negative feedback mechanism."}, {"title": "Testes.txt", "text": "Now, what about our follicle stimulating hormone and what about the surtoli cells?"}, {"title": "Testes.txt", "text": "Well, the surtoli cells are these cells shown here."}, {"title": "Testes.txt", "text": "Now, once the follicle stimulating hormone is released into our bloodstream, it travels to the capillaries of this region and it causes these surtoli cells to basically provide the nutrients needed to our sperm cells for them to actually develop into mature sperm cells."}, {"title": "Testes.txt", "text": "So in males, the follicle stimulating hormone stimulates the surtole cells to provide nutrients to the developing sperm cells."}, {"title": "Testes.txt", "text": "Now, as time progresses, what our surtole cells can do is they can basically release a glycoprotein hormone into our surrounding area, into our bloodstream known as Inhibit."}, {"title": "Testes.txt", "text": "And what Inhibit does is it goes into our bloodstream and it travels to our interior pituitary gland and it basically inhibits via a negative feedback loop, it inhibits the release of our follicle stimulating hormone from the interior pituitary gland."}, {"title": "Testes.txt", "text": "So to review what we just discussed, let's take a look at the following flow chart."}, {"title": "Testes.txt", "text": "So let's begin with our hypothalamus."}, {"title": "Testes.txt", "text": "So the hypothalamus produces a hormone known as GnRH, the gonadotropin releasing hormone which then travels to the anterior pituitary gland through the hypothesial portal system."}, {"title": "Testes.txt", "text": "And once it attaches to the endocrine cells in the interior pituitary gland, it causes those endocrine cells to release the follicle stimulating hormone and the lutenizing hormone."}, {"title": "Testes.txt", "text": "Now, the lee nizing hormone travels through our bloodstream and eventually attaches onto our lathic cells and it stimulates those Levic cells to release testosterone."}, {"title": "Testes.txt", "text": "At the same time the follicle stimulating hormone attaches onto our surtovi cells and it causes these cells to basically provide the nutrients to our developing sperm cells."}, {"title": "Testes.txt", "text": "While testosterone actually initiates the development of our sperm cells into mature sperm cells at the same time testosterone also causes these other different these other different effects."}, {"title": "Testes.txt", "text": "So for example, it's responsible for actually creating that growth sperm."}, {"title": "Testes.txt", "text": "It's responsible for giving us our secondary characteristics such as our enlarged langs, a deep voice, our pubic hair and other things of that nature."}, {"title": "Testes.txt", "text": "Now, when our concentration of testosterone is very high it can basically travel back into our hypothalamus and inhibit the release of GnRH."}, {"title": "Testes.txt", "text": "It can also inhibit the release of S, FSH and LH from the interior pituitary while the sertoli cells can basically create a protein hormone known as inhibit that goes on and negatively inhibits the release of SSH from our interior pituitary glands."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Previously, we saw how we can transform six of the 20 amino acids into pyruvate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now we're going to discuss how we can transform five of the 20 amino acids into a five carbon intermediate molecule we call alpha ketoglutrate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, remember that alpha ketoglutrate is actually intermediate of the citric acid cycle."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And what that means is when our liver, our, or hepatitocytes metabolize these five amino acids glutamate, glutamine, arginine, proline, or histidine, they ultimately form alpha key glutrate, which is then transformed into oxalo acetate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And the oxalo acetate can be used in gluconeogenesis to generate sugar molecules, glucose."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so that's exactly why these five amino acids are labeled as glucogenic."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So the strategy here is as follows."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So, if we begin with glutamate, glutamate can simply be metabolized directly into alpha key gluterate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "But if we have either one of these four amino acids shown here, they must first be metabolized into glutamate, and then glutrimate is in turn metabolized into alpha ketoglutrate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this is the strategy that our cells employ."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So let's take a look at how glutamate can be transformed into alpha ketoguterate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So what's the difference between glutamates and alpha ketoglutrates?"}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Well, on the glutamate, we have this alpha amino group, but on the alpha ketoglutrate, we don't."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Instead, the carbon is oxidized, and we have this carbon oxygen double bond between this carbon and this oxygen."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So ultimately, in this step, we basically want to remove this alpha amino group along with the h ion."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we ultimately want to remove an ammonium."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we want to undergo a deamination step in which we remove this ammonium, and we want to oxidize this carbon."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And that's exactly what happens in this step."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this step is catalyzed by glutamate dehydrogenase."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "It uses the oxidation reduction power of NAD plus to basically eliminate this group."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And then we attach an oxygen to form the carbon oxygen double bond."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this is our alpha ketoglutrate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, what about these other reactions here?"}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So let's take a look at the transformation of glutamine into glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So what's the difference between glutamine and glutamate?"}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Well, the only difference lies in this group here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So glutamate looks like this, but glutamine has this amino group attached onto this carbon instead of an oxygen."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so ultimately, we basically want to once again eliminate this amino group."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we want to eliminate ammonium, and we want to attach an oxygen."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so this is catalyzed by glutaminase, which uses water to basically remove this ammonium, and we form this oxygen as shown in this molecule."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we form our glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So in metabolizing glutamine to alpha ketoglutrate, we have to first form glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And then the glutamate is transformed into alpha ketoglutrate by the activity of this enzyme."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now let's move on to five histidine."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So histidine has a slightly more complex process in transforming it into glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So let's see what this process is."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this is what histidine looks like."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we have this five membered ring."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And by the activity of the enzyme histidine ammonia Lice, we essentially catalyze a simple elimination reaction in which this amino group acts as the Levin group."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "We have a pi bond that is formed between this carbon and this carbon, which basically acts to kick off this group here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And we form this intermediate molecule, Urakinate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we form a double bond between this carbon and this carbon, eliminating this Ammonium."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, in the next step, we have a simple hydration step."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "We have a water molecule that basically attacks this carbon here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we form a double bond between this carbon and the oxygen that is attached."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "We eliminate this pi bond and we also eliminate this pi bond here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we form this intermediate molecule."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "The third step is basically a hydrolysis step."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we have hydroxide, which basically acts as a nuclear file."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "It attacks this carbon, breaks this Sigma bond here, and we attach another oxygen onto this carbon here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And this nitrogen basically gains an H ion."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this is the molecule that we form in the third step."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, in the final step, we have THF."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So THF is tetrahydrofolate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And this is the molecule inside our body that is responsible for acting as a carrier for activated one carbon molecules."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And we'll talk about those in a later lecture."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "But basically, the tetrahydrofolate acts to basically take off this entire group."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So the carbon along with this nitrogen, so this nitrogen gains two more H ions."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "We basically form our glutamate and this THF, the tetrahydropholate abstracts this, forming this molecule here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So once the histidine is transformed into glutamate, then we simply undergo this step that is catalyzed by glutamate dehydrogenase to form the alpha ketoglutrates."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So that's five."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now let's look at four."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So, Proline, how do we transform proline into glutamates?"}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Well, this is the reaction process here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we begin with an enzyme, proline oxidase."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So, Proline oxidase takes proline, uses an oxygen to basically take off this age and this age, and we form a double bond between this nitrogen and this carbon."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we form this intermediate molecule here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, the problem with this intermediate molecule is we have a double bond between this atom and this atom."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And that greatly increases the energy of this molecule."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "It makes it very unstable."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "In fact, it becomes so unstable that in the presence of water, it basically spontaneously breaks."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So this ring spontaneously opens up and breaks."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so the oxygen here essentially attacks this carbon, forming this carbon oxygen double bond."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And the two HS go onto this nitrogen here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we formed this glutamate semiaaldehyde."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, the glutamate semi aldehyde is actually important, as we'll see in just a moment when we'll discuss Arginine, because Arginine also goes through this intermediate glutamate semi aldehyde."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, in the final step, we have an oxidation reduction reaction in which we essentially remove this H, attach an oxygen to form our glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So once we form the glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Again, the glutamate is then transformed into alpha keysagutrate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Now, I didn't show the mechanism on the board, but let's briefly talk about the mechanism by which arginine is transformed into glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So arginine is initially transformed into ornithine by the enzyme arginase."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And this is independent of the urea cycle because remember, in the urea cycle we also transform arginine into ornithine by the activity of arginase."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "But this happens separate of the urea cycle."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So once arginine is transformed into ornathene, the ornithine then acts as a substrate for the enzyme ornathene amino transfers phrase."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And what that enzyme does is it transforms that ornithine into glutamate semiaaldehyde, and then the glutamate semi aldehyde is transformed into glutamate via this step here."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so ultimately we form that glutamate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And then we use this process here to form the alpha key to gluterate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "So we see that these four amino acids are transformed into glutamate, and then glutamate is transformed into alpha key to glutorate."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And this can be used by our liver cells to actually generate glucose."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "And so that's why these five enzymes are known as glucose."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Sorry, these five amino acids are known as glucogenic."}, {"title": "Metabolism of amino acids to ketoglutarate .txt", "text": "Amino acids."}, {"title": "Smooth Muscle .txt", "text": "In the previous several lectures, we discussed two types of muscles in the human body."}, {"title": "Smooth Muscle .txt", "text": "We discussed the skeletal muscle and the cardiac muscle."}, {"title": "Smooth Muscle .txt", "text": "The final type of muscle found in the human body is the smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "And this will be the focus of this lecture."}, {"title": "Smooth Muscle .txt", "text": "So the smooth muscle is a type of muscle that is found in blood vessels and lymph vessels."}, {"title": "Smooth Muscle .txt", "text": "It's found in the bronchioles of the lungs, it's found in the stomach, the small and large intestine, we can find it in the iris portion of the eye."}, {"title": "Smooth Muscle .txt", "text": "We can also find in places like the bladder and the uterus, as well as other parts of the body."}, {"title": "Smooth Muscle .txt", "text": "Now, smooth muscles are innervated by the autonomic system, autonomic nervous system, just like the cardiac muscles."}, {"title": "Smooth Muscle .txt", "text": "And this basically means that just like cardiac muscle is involuntary, smooth muscle is also involuntary."}, {"title": "Smooth Muscle .txt", "text": "And that means we have no way to actually consciously control the movement of smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "Now, recalling our discussion on skeletal muscle and cardiac muscle, we said that these two types of muscles consist of individual units we call sarcomeres."}, {"title": "Smooth Muscle .txt", "text": "And these sarcomeres give skeletal and cardiac muscle striations."}, {"title": "Smooth Muscle .txt", "text": "Now, on the other hand, smooth muscles do not have these triations and that's because they do not consist of these units we call sarcomeres."}, {"title": "Smooth Muscle .txt", "text": "Instead, throughout the entire smooth muscle cell, we basically have a network of filaments that is responsible for the contraction of that muscle cell as a whole."}, {"title": "Smooth Muscle .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Smooth Muscle .txt", "text": "So, this is a diagram of a single smooth muscle cell."}, {"title": "Smooth Muscle .txt", "text": "We have the membrane shown in black, we have the nucleus shown in blue."}, {"title": "Smooth Muscle .txt", "text": "And notice we only have a single nucleus in any given smooth muscle cell."}, {"title": "Smooth Muscle .txt", "text": "And that means smooth muscle cells are unique nucleated, just like cardiac muscle cells."}, {"title": "Smooth Muscle .txt", "text": "Now, we also notice this network of three different types of filaments."}, {"title": "Smooth Muscle .txt", "text": "So we have the thin filament and the thick filament that are also found in the cardiac and skeletal muscle."}, {"title": "Smooth Muscle .txt", "text": "And we have a new type of filament known as the intermediate filament that is not found in skeletal and cardiac muscle."}, {"title": "Smooth Muscle .txt", "text": "Now, thin filament is composed of actin, the protein actin, while thick filament is composed of the protein myosin."}, {"title": "Smooth Muscle .txt", "text": "Now, the intermediate filament is composed predominantly of two types of proteins."}, {"title": "Smooth Muscle .txt", "text": "We have Desmond as well as a protein known as vimentin."}, {"title": "Smooth Muscle .txt", "text": "Now, we also have these regions we call the dense bodies, which are shown with these brown dots."}, {"title": "Smooth Muscle .txt", "text": "So the green portion are the intermediate filaments, the red portion are the thick filaments, the purple portion is a thin filament."}, {"title": "Smooth Muscle .txt", "text": "And these brown regions are called dense bodies."}, {"title": "Smooth Muscle .txt", "text": "And dense bodies are composed of a protein known as alpha Actinine."}, {"title": "Smooth Muscle .txt", "text": "So basically, the contraction of the thin filament and the thick filament shown in this diagram causes these dense bodies to basically move closer."}, {"title": "Smooth Muscle .txt", "text": "And these dense bodies are also connected to one another via these green sections."}, {"title": "Smooth Muscle .txt", "text": "Our intermediate filaments."}, {"title": "Smooth Muscle .txt", "text": "So when the thin filament slides along our thick filament, let's say these two dense bodies, they move closer together, and that brings these dense bodies and all the other dense bodies also closer together."}, {"title": "Smooth Muscle .txt", "text": "And notice some of these filaments are also attached to the membrane of the cell."}, {"title": "Smooth Muscle .txt", "text": "So when we have the contraction taking place, this network of filaments basically contracts uniformly, and that causes the entire cell to basically shrink inwards and become smaller in size."}, {"title": "Smooth Muscle .txt", "text": "So we have this contraction process taking place that is a result of this network of three types of filaments."}, {"title": "Smooth Muscle .txt", "text": "So once again, there are three types of filaments."}, {"title": "Smooth Muscle .txt", "text": "We have thin filaments, we have thick filaments, and we have intermediate filaments."}, {"title": "Smooth Muscle .txt", "text": "So the contraction of the thin and thick filaments causes our dense bodies to move closer, which causes the shortening of intermediate filaments found throughout the entire cell."}, {"title": "Smooth Muscle .txt", "text": "And since some of these filaments are connected to the membrane of the cell, what it ultimately causes is the contraction and the shrinking of the entire cell as a whole."}, {"title": "Smooth Muscle .txt", "text": "So basically, it contracts in the following fashion."}, {"title": "Smooth Muscle .txt", "text": "Now, there are two main types of arrangements of our muscle cells inside the human body."}, {"title": "Smooth Muscle .txt", "text": "One of these arrangements is known as the single unit smooth muscle, also known as the visceral smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "And the other type of arrangement is known as the multi unit smooth muscle arrangement."}, {"title": "Smooth Muscle .txt", "text": "So let's begin by defining what a single unit smooth muscle is."}, {"title": "Smooth Muscle .txt", "text": "So basically, this is the most common type of arrangement of smooth muscles inside our body."}, {"title": "Smooth Muscle .txt", "text": "So single unit smooth muscles consist of an innervating neuron that basically innervates a single or several cells in a group or a collection of cells as shown in the following diagram."}, {"title": "Smooth Muscle .txt", "text": "So we have a single neuron, the axon."}, {"title": "Smooth Muscle .txt", "text": "The axon splits into these two sections, these two groups."}, {"title": "Smooth Muscle .txt", "text": "And only one of these cells, this cell here and this cell here, is actually innervated by that neuron."}, {"title": "Smooth Muscle .txt", "text": "All the other cells, this cell, this cell and this cell and these other cells are not actually connected to our neuron directly."}, {"title": "Smooth Muscle .txt", "text": "So in our single unit smooth muscle, what we have are gap junctions."}, {"title": "Smooth Muscle .txt", "text": "So all these different types of cells that are connected are connected via these intracellular connections known as gap junctions."}, {"title": "Smooth Muscle .txt", "text": "And what these gap junctions do is they basically allow the movement of ions through the cells and that allows the propagation of our action potential."}, {"title": "Smooth Muscle .txt", "text": "So what that means is as our action potential travels through the axon from the autonomic nervous system, it basically innervates these two cells."}, {"title": "Smooth Muscle .txt", "text": "And these two cells basically undergo that contraction."}, {"title": "Smooth Muscle .txt", "text": "And that causes the action potential to spread through the other cells that are connected via the gap junction."}, {"title": "Smooth Muscle .txt", "text": "So that means this entire structure essentially contracts as a whole, as a single unit."}, {"title": "Smooth Muscle .txt", "text": "And that's why these are called single unit smooth muscles."}, {"title": "Smooth Muscle .txt", "text": "Now, single unit smooth muscles are found in places like the uterus."}, {"title": "Smooth Muscle .txt", "text": "Why well because when the woman is given birth the uterus has to contract as a single unit and that's why all the smooth muscles are arranged into this single unit smooth muscle arrangement."}, {"title": "Smooth Muscle .txt", "text": "Now other places where we find this type of arrangement is the stomach, the small intestinal bladder, as well as small arteries and veins."}, {"title": "Smooth Muscle .txt", "text": "Now the last thing I want to mention about this type of arrangement is the fact that just like certain cardiac cells in the heart are capable of displaying a type of activity known as myogenic activity, single unit smooth muscles can also exhibit the myogenic activity."}, {"title": "Smooth Muscle .txt", "text": "And what that basically means is these cells inside the single unit smooth muscle can basically contract without the input from our nervous system."}, {"title": "Smooth Muscle .txt", "text": "So even if we don't actually receive a signal from the nervous system, these cells can basically contract independently and that means they're myogenic."}, {"title": "Smooth Muscle .txt", "text": "So once again the single unit smooth muscle is the most common type of arrangement of smooth muscles in the human body."}, {"title": "Smooth Muscle .txt", "text": "Single unit smooth muscles consist of an innervating neuron that causes one or several of the smooth muscles to contract."}, {"title": "Smooth Muscle .txt", "text": "The action potential then travels through the other smooth muscles via gap junctions between adjacent cells."}, {"title": "Smooth Muscle .txt", "text": "So basically, as soon as the action potential is received by this cell, shown in red, is then split to the other cells and the same thing happens in this particular case."}, {"title": "Smooth Muscle .txt", "text": "So this red arrow basically describes the movement of our action potential."}, {"title": "Smooth Muscle .txt", "text": "So this sort of arrangement allows the group of smooth muscles to contract as a single unit as a whole."}, {"title": "Smooth Muscle .txt", "text": "Now single unit smooth muscles also display myogenic activity and this means that they can contract without the input of the nervous system."}, {"title": "Smooth Muscle .txt", "text": "And these types of arrangements are found in places like the uterus in our stomach, in the small intestine, as well as in small arteries and veins."}, {"title": "Smooth Muscle .txt", "text": "So now let's move on to the second type of arrangement known as the multiunit smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "Now the multiunit smooth muscle is a less common type of arrangement of our smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "So basically in this case, every single smooth muscle cell in this multi unit section is innervated by a neuron."}, {"title": "Smooth Muscle .txt", "text": "So we have each and every one of these smooth muscle cells is connected to some type of axon terminal of a neuron."}, {"title": "Smooth Muscle .txt", "text": "So we have these two neurons and each one of these cells are basically connected."}, {"title": "Smooth Muscle .txt", "text": "So what this basically means is if an action potential spreads to this axon and causes these three smooth muscle cells to contract, that does not mean that these neighboring cells, these cells will also contract."}, {"title": "Smooth Muscle .txt", "text": "So that means the contraction of these smooth muscles is independent of the contraction of these neighboring smooth muscles."}, {"title": "Smooth Muscle .txt", "text": "So this is what basically distinguishes the multi unit smooth muscle from the single unit or visceral smooth muscle."}, {"title": "Smooth Muscle .txt", "text": "Now where we find these types of smooth muscle muscles, well, we basically find them in the smooth muscle, in the iris of our eye."}, {"title": "Smooth Muscle .txt", "text": "We also find them in large arteries."}, {"title": "Smooth Muscle .txt", "text": "And we find them in places like our bronchioles found inside our lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "So far in our discussion on fetal circulation, we saw that the way that blood moves inside the developing fetus is different than the way the blood moves inside the adult circulatory system."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, the next question is what exactly happens to the circulatory system of that fetus as soon as the fetus is born, when that fetus takes their first breath?"}, {"title": "Fetal Circulation After Birth.txt", "text": "And more specifically, how exactly does the circulatory system of that fetus transition into the circulatory system of the fully functional adult individual?"}, {"title": "Fetal Circulation After Birth.txt", "text": "So, before we examine those questions, however, let's recall some important facts about the way that blood moves inside that developing fetus before the fetus is actually born."}, {"title": "Fetal Circulation After Birth.txt", "text": "So recall that inside the lungs, and more specifically, inside the alveoli of the lungs, we have a fluid."}, {"title": "Fetal Circulation After Birth.txt", "text": "And what that does is it creates a high resistance and a high pressure inside the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "And a similar thing exists in the liver."}, {"title": "Fetal Circulation After Birth.txt", "text": "So the lungs and the liver are not functional within that fetus."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so inside the lungs, we have a high resistance and a high pressure."}, {"title": "Fetal Circulation After Birth.txt", "text": "And the same thing is true inside the liver."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, if the blood were to actually move through the liver and through the lungs, that will greatly decrease the flow rate of that blood inside the fetal circulatory system."}, {"title": "Fetal Circulation After Birth.txt", "text": "And to prevent that from happening and to create a quick and efficient circulatory system of that fetus, what the fetus does is it redirects blood away from those two organs via special type of pathogeways, special types of Shuns known as the ductus arteriosis, the ductus venosis and the Forayman O'Valley."}, {"title": "Fetal Circulation After Birth.txt", "text": "So remember, it's inside the placenta where gas exchange and nutrient exchange takes place."}, {"title": "Fetal Circulation After Birth.txt", "text": "And as soon as that takes place, the oxygenated and nutrient filled blood will travel away from the placentum and towards this general direction via the umbilical vein."}, {"title": "Fetal Circulation After Birth.txt", "text": "And eventually, when it approaches the liver, there will be a Shunt that will exist between the umbilical vein and the inferior venocave."}, {"title": "Fetal Circulation After Birth.txt", "text": "And the Shunt is shown right here."}, {"title": "Fetal Circulation After Birth.txt", "text": "It's known as the ductus venosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so it's the ductus venosis that allows the blood to quickly and efficiently bypass the liver and enter thin fear of venecrava."}, {"title": "Fetal Circulation After Birth.txt", "text": "Eventually, then, fear of venocava connects with umbilical vein and connects with the superior venecva."}, {"title": "Fetal Circulation After Birth.txt", "text": "The partially oxygenated and deoxynated blood mixes and that goes into the right atrium of the heart."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, within the right atrium of the heart, we have another type of Shunk that exists."}, {"title": "Fetal Circulation After Birth.txt", "text": "This is known as the foray Mino valley."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, if we zoom in on the wall separating the right atrium and the left atrium, this is what we get."}, {"title": "Fetal Circulation After Birth.txt", "text": "So the pink section is the wall of the right atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "The purple section is the wall of that left atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And notice on the wall of the right atrium, we have a hole as well as a hole on the wall of the left atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And what this creates is a flap of wall that can open in the same way that a door can open."}, {"title": "Fetal Circulation After Birth.txt", "text": "So this only opens one way."}, {"title": "Fetal Circulation After Birth.txt", "text": "It only opens this way."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, this portion is known as a septum secumom."}, {"title": "Fetal Circulation After Birth.txt", "text": "This portion is known as the septum premium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this entire valve structure, door like structure that can open one way and close the other way is known as the foramen O valley."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, if the pressure is higher on the right atrium than on the left atrium, as it is in the case of that fetus, the pressure will create a force that will push on the septum."}, {"title": "Fetal Circulation After Birth.txt", "text": "Premium will push on this door and will open the door, allow the movement of blood from the right atrium to the left atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "So remember, inside the fetus, the reason we have a higher pressure in the right side of the heart in the right atrium than the left side of the heart, the left atrium, is because of the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "The lungs have a high resistance, create a high pressure to flow, and that causes a high pressure to exist in the pulmonary trunk as well as the right ventricle and the right atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so that's exactly why the blood will be shunted away from the lungs, will bypass the lungs and go directly from the right atrium into the left atrium, then into the left ventricle, and then into the order."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, of course, some amount of that blood will still leak into the right ventricle from the right atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And when this happens, the blood goes into the pulmonary trunk."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, when the blood is inside the pulmonary trunk, it also has a choice in the fetal circulatory system because we have this tiny passageway, this tiny shunt that connects the pulmonary trunk and the order."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this is known as the ductus arteriosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "And because once again, we have a high pressure inside the lungs and a low pressure inside the order, what happens is that oxygenated blood has a choice to bypass the lungs and go directly into the systemic circulation into the order via this duct known as the ductus arteriosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "So these three ducts basically allow the fetus to create a very quick and efficient way to move the blood within all the organs and tissues of the body."}, {"title": "Fetal Circulation After Birth.txt", "text": "And if it wasn't for these three ducts, the liver and the lungs would basically create a very slow blood flow and that oxnated blood would not be able to get to the brain and the other important organs and tissues of that developing fetus."}, {"title": "Fetal Circulation After Birth.txt", "text": "So this is what takes place within that fetal circulatory system."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, what happens as soon as that individual, as soon as that fetus is born?"}, {"title": "Fetal Circulation After Birth.txt", "text": "What happens during the first breath?"}, {"title": "Fetal Circulation After Birth.txt", "text": "Well, remember, the alveoli of the lungs are completely filled with the fluid."}, {"title": "Fetal Circulation After Birth.txt", "text": "But as soon as the first breath takes place, all that air that rushes into the alveoli of that lung displaces and removes pushes all that fluid out of the alveoli."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this expands the alveoli."}, {"title": "Fetal Circulation After Birth.txt", "text": "And by expanding the alveoli, that decreases the resistance and decreases the pressure inside the alveoli."}, {"title": "Fetal Circulation After Birth.txt", "text": "So as soon as the first breath is taken, what happens is we have a decrease in resistance and so a decrease in pressure which takes place within our lungs and that eventually also takes place within our liver."}, {"title": "Fetal Circulation After Birth.txt", "text": "So the liver begins to function following birth."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so the resistance as a result of that decreases."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, because we decrease the resistance and the pressure in the lungs, what happens is now the blood from the right atrium is more likely to move into the right ventricle and into the pulmonary trunk and then into the lungs, where the pressure is now is now low."}, {"title": "Fetal Circulation After Birth.txt", "text": "So air fills the alveoli of the lungs, expanding them."}, {"title": "Fetal Circulation After Birth.txt", "text": "This decrease in the resistance and the pressure in the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "And as a result, the blood rushes from the right side of the heart and into the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, as the blood moves along this side of the heart more easily the pressure inside the right atrium and the right ventricle decreases."}, {"title": "Fetal Circulation After Birth.txt", "text": "And that decreases the pressure on the right side of the heart."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, as we have more blood being pumped into the lungs, more blood is coming out of the lungs and moving into the left side of the heart."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so eventually what happens is the pressure on the left side of the heart increases."}, {"title": "Fetal Circulation After Birth.txt", "text": "So eventually the pressure on the right side will decrease, the pressure on the left side will increase and the pressure on the left side will become greater than the pressure on the right side of the heart."}, {"title": "Fetal Circulation After Birth.txt", "text": "And when that takes place, that's when the foramino valley closes."}, {"title": "Fetal Circulation After Birth.txt", "text": "So remember the septum prima, this wall will only open this way when the pressure inside the right atrium is higher than the pressure inside the left atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "But as soon as the first breath is taken, the pressure inside the right atrium drops, the pressure inside the left atrium increases."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so we have a reversal of the pressure differential."}, {"title": "Fetal Circulation After Birth.txt", "text": "And now, because the pressure on the left side of the atrium is greater, it will create a force that will point in this direction and that will close, shut this for a minute or valley."}, {"title": "Fetal Circulation After Birth.txt", "text": "And eventually what happens is this basically forms a closure and this also forms a closure."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so this is basically shut close."}, {"title": "Fetal Circulation After Birth.txt", "text": "So following birth, there is a reversal of the pressure differential."}, {"title": "Fetal Circulation After Birth.txt", "text": "That is, the pressure in the left atrium is greater, becomes greater than the pressure in the right atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this causes the septum premium to push against the septum sequandum which closes the forayman O'Valley."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this usually takes place within minutes following birth."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, this ultimately causes all that blood to be redirected from the right atrium into the right ventricle and eventually into the pulmonary section and then into the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so we have the closure of that wall, the closure of that one way door that exists within that developing fetus."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this is what we call the Foraymon O Valley, or the closure of the Foraymon ovaly."}, {"title": "Fetal Circulation After Birth.txt", "text": "So within minutes of taking the first breath, the Foraymon O valley is closed."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, let's move on to the ductus venosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "So what happens to the ductus venosis?"}, {"title": "Fetal Circulation After Birth.txt", "text": "Well, once that fetus is born, what the physicians do is they essentially clamp down the umbilical cord, and that causes the clamping of umbilical vein."}, {"title": "Fetal Circulation After Birth.txt", "text": "So at this particular location, we clamp down umbilical vein, and that creates a high resistance within this section."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so what happens is blood essentially stops flowing within this section of our blood vessel."}, {"title": "Fetal Circulation After Birth.txt", "text": "And eventually, this entire umbilical vein, this entire blood vessel, along with a ductus venosis, eventually diminishes in size, and the flow of blood decreases."}, {"title": "Fetal Circulation After Birth.txt", "text": "Eventually, it completely stops functioning."}, {"title": "Fetal Circulation After Birth.txt", "text": "It closes."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this usually takes place within days of the clamping process."}, {"title": "Fetal Circulation After Birth.txt", "text": "So following birth, the duct that's venosis also constricts and eventually diminishes in size to a non functional structure."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, what about the doctor's arteriosis?"}, {"title": "Fetal Circulation After Birth.txt", "text": "Remember, the doctor's arteriosis connects the pulmonary trunk to our aorter."}, {"title": "Fetal Circulation After Birth.txt", "text": "So what happens as soon as we take the first breath?"}, {"title": "Fetal Circulation After Birth.txt", "text": "Well, when we take the first breath, we have more blood flowing into the lungs, and the lungs decrease in pressure."}, {"title": "Fetal Circulation After Birth.txt", "text": "At the same time, we have more blood flowing into the order."}, {"title": "Fetal Circulation After Birth.txt", "text": "So the order increases in pressure."}, {"title": "Fetal Circulation After Birth.txt", "text": "And now we have a high pressure in the order, a low pressure in that pulmonary trunk."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so what happens is blood stops flowing from the trunk and to the order."}, {"title": "Fetal Circulation After Birth.txt", "text": "So eventually, the ductus arteriosis will also constrict and will also diminish in size until it stops functioning."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, to be more specific, what happens is as soon as the pressure inside the lungs increases and as soon as the oxygen is carried into the lungs, the lungs begin producing a special type of peptide, a special type of protein known as bradycanin."}, {"title": "Fetal Circulation After Birth.txt", "text": "And what brady kina does is it causes the constrictions of blood vessels when there is a high amount of oxygen."}, {"title": "Fetal Circulation After Birth.txt", "text": "So the bradyclin essentially travels into the ductus arteriosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "And because now we have a high oxygen content within that ductus arteriosis, the brady kinan basically causes the constriction of that ductus arteriosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so within hours, the ductus arteriosis will essentially constrict to a point where very little blood will actually flow between the pulmonary trunk and our eight order."}, {"title": "Fetal Circulation After Birth.txt", "text": "So, once again, following the expansion of lungs, they release a protein called bradyclin."}, {"title": "Fetal Circulation After Birth.txt", "text": "As oxygenated blood travels through the ductus arteriosis, that protein mixes with the oxygen, with the high oxygen content, and it causes the constriction of the ductus arteriosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "So as the pressure in the lungs falls below the systemic pressure, below the pressure inside our order, less blood flows via this constricted ductus arteriosis, and it eventually ceases to exist."}, {"title": "Fetal Circulation After Birth.txt", "text": "So we see that within minutes, the Forayman Or valley closes."}, {"title": "Fetal Circulation After Birth.txt", "text": "As a result, of the reversal and pressure between the right atrium and the left atrium."}, {"title": "Fetal Circulation After Birth.txt", "text": "Then within hours, the darkness arteriosis constricts."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so eventually, the blood ceases to flow from the pulmonary trunk into the order."}, {"title": "Fetal Circulation After Birth.txt", "text": "And finally, within days, as a result of that clamping process, the resistance inside the umbilical vein increases."}, {"title": "Fetal Circulation After Birth.txt", "text": "That causes less blood to flow inside the umbilical vein and inside the doctor's venosis."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this eventually becomes non functional and ceases to function and ceases to exist."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, another important change that takes place is the thickening of the left ventricle compared to the right ventricle."}, {"title": "Fetal Circulation After Birth.txt", "text": "So before that fetus is actually born, the size of the wall of the right ventricle is greater than the size of the wall of the left ventricle."}, {"title": "Fetal Circulation After Birth.txt", "text": "And that's because the right ventricle has to pump blood against a higher pressure to the lungs."}, {"title": "Fetal Circulation After Birth.txt", "text": "Now, what happens after birth is we have a reversal of pressure, and so the pressure in the lungs drops."}, {"title": "Fetal Circulation After Birth.txt", "text": "And so what eventually happens is that left ventricle will become thicker than the right ventricle."}, {"title": "Fetal Circulation After Birth.txt", "text": "And this is what we see in the adult circulatory system."}, {"title": "Fetal Circulation After Birth.txt", "text": "So these are the these are the sum these are important changes that take place within the circulatory system of the adult individual as soon as that fetus is actually born."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So since we're on the subject of polysaccharides, let's focus on a specific group of polysaccharides that exist inside our body that plays a very important role, as we'll see in just a moment."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And this group of polysaccharides is known as glycosaminoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So what exactly is a glycosaminoglycan?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, a glycosaminoglycan is a special type of polysaccharide that consists of repeating disaccharide units."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So we have two sugars that repeat again and again and again."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, one of these sugars is an amino sugar."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And what that means is it contains an amino group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And at least one of these sugars in the repeating disaccharide unit is actually modified with some type of negatively charged group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "For instance, a sulfate group or a carboxylate group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, to see exactly what we mean, let's take a look at the following four examples of glycosaminoglycans that we'll find inside our body."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So one of these glycosaminoglycans we actually discussed previously, so that is Heparin."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "We said heparin is this glycosaminoglycan that is produced and released by immune cells we call mast cells."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And we believe that heparin plays a role in immune lead, plays a role in actually helping our body fight off infectious agents."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "On top of that, heparin also acts as an anticoagulant."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So this is what the structure of that repeating disaccharide unit in Heparin actually looks like."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So on the first sugar, we have the carboxylate group that bears a negative charge and the sulfate group that also bears a negative charge."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "On the second unit, the second sugar of this disaccharide unit, we also have this sulfate group attached to this carbon, as we have in this particular case."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And we have the amino group that also contains this sulfate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So we see that heparin contains many of these negative charges and these negative charges give the heparin its functionality."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now the other three glycosaminoglycans we haven't yet discussed and we're going to focus on them in this lecture."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So we have conroytin six sulfate, or simply conjoitin sulfate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "We have keratin sulfate and we also have a hyaluronate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now let's take a look at conroytin sulfate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "In conjoitin sulfate, this is our disaccharide unit."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So once again, we have the meno group found here."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "We have the sulfate group and we have the carboxylate ion group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Here we have the carboxylate ion group and we have the amino group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And for this particular one, we have the amino group and we have this sulfate group."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now generally speaking, these glycosaminoglycans don't exist by themselves inside our body."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Usually the glycosaminoglycans actually covalently associate with proteins to form a category of modified proteins known as proteoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So what exactly is a proteoglycan?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, a proteoglycan is basically a protein molecule that has attached to some type of glycosaminoglycan or many glycosaminoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "In fact, usually the glycosaminoglycan is the predominant component of the proteoglycan."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And usually 95% of the proteoglycan by mass consists of glycosaminoglycans and only 5% consists of that protein component."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, what exactly are the functions of proteoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, proteoglycans, these protein, sugar, biomolecules have four important functions which I've listed on the board and the first two functions we're going to focus on in this lecture."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So function number one is it acts as joint lubricants."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Function number two, it basically functions in the structural components of tissues and that includes connective tissue, for instance, bone and cartilage."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Number three it functions to bind cells to extracellular matrix."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And number four it actually functions to move molecules through the extracellular matrix."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now one example of a well studied proteoglycan that we know a lot about is aggregate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And aggregate is found in the extracellular matrix of connective tissues such as Cartilage."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So if we examine Cartilage we have many different types of cells and surrounding the cells we have the extracellular matrix."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now the major component of Carthage is collagen."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So the major component of the exacerlic matrix is of course, collagen."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And collagen as we know, gives the exacer matrix its structure and it gives it tensile strength."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now the other major component of the extracellular matrix in Cartilage is aggregate."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "The example of the proteoglycan."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now aggregate, what it does is it acts as a lubricant and it asks to actually absorb the shock."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "It absorbs and dissipates impact forces as we'll see in just a moment."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So in the same analogous way that if we are in a car crash it's that airbag that acts to absorb the impact force."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "In this particular case, it's the aggregate that actually acts to absorb the impact force and prevent any type of damage to our tissue and to our body."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So the collagen gives tensile strength, support and structure and the agriculture helps dissipate impact forces."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "It absorbs those impact forces and lubricates the joints."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And to see exactly what that means, let's take a look at the structure of Agrican."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now the protein component of agriculture basically consists of three globular domains g one, g two and g three."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And these are shown on the board."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So this is glybular domain g one, glylor domain g two and glybular domain g three."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And this entire purple structure is that protein component of the aggregate of the proteoglycan."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, between g two and g three, we have this long section of amino acids, and it's the sequence of amino acids between the g two and the g three glybular domains of agriculture that basically are able to actually bind two important types of glycose aminoglycans, namely, the conjoitin six sulfate, which is shown in red, and the keratin sulfate, which is shown in brown."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So these red projections are conroytin six sulfate, the brown projections are the keratin sulfate and they're bound to the actual sequence of amino acids between the g three and the g two globular domains of agriculture."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, if we take a look at g one, the g one domain of aggregate is actually bound to this green fiber."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And the green fiber is actually the same Hyaluronate that we spoke about previously."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So this is the Hyaluronate backbone, which is another example of a glycos aminoglycan."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So these three different glycos aminoglycans are found within the connective tissue, in cartilage and inside our joints."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And together, these components play a role to basically absorb and dissipate the impact forces and prevent any type of damage."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "The question is, how is this actually achieved?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, to see how that is achieved, let's take a look at the following three diagrams."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And remember that these projections, the red projections and these brown projections all consist of these repeating disaccharide units."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And these repeating disaccharide units, this one and this one, contain these modified side chain groups that have negative charges."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now what does that mean?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, because these disaccharide units have been modified with these negatively charged groups, that means they will be attracted to water molecules."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Why?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, because water molecules are polar."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Water molecules contain a partial positive charge on the hydrogen ions."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And what that means when these Agrican molecules are in their initial position, we'll see that a bunch of water molecules will be absorbed and attached onto these glycosaminoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "The red ones are the conroytin sulfates and the brown ones are the keratin sulfates."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And so we're going to have non covalent interactions between the water molecules and these glycosaminoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So we see that the glycosaminoglycans, as a result of their negative charge, they will be able to actually absorb the water molecule."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And so this section will be lubricated with water."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, what happens when we apply some type of force?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So for instance, let's say I jump, and when I jump, what happens is the joints in the knees basically experience an impact force."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And what happens is a force is applied onto the agriculture."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And when a force is applied onto the aggregate, that basically forces all these water molecules to leave this section."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And that basically slightly deforms this agricent protein molecule, the proteoglycan."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And when this is essentially deformed, it absorbs some of that force."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, as soon as that force, as soon as that pressure is released, these water molecules will rush right back."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Why?"}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Well, because water will tend to move down its concentration gradient from a high to a low concentration."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And also the water molecules will essentially be attracted to these negatively charged groups on the glycosaminoglycans."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And so once the water is basically absorbed back into this area, that will basically cause these agricultants to basically spring back into their initial position."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And so together, this process allows the absorption of those different types of impact forces that prevents damage and it also allows the lubrication of the area."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And this is exactly what happens inside our joints."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Now, a medical condition known as osteoarthritis basically causes the breakdown and the degradation of these Agrican molecules and that's exactly what causes the pain that is due to osteoarthritis."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "So we see that polysaccharides are very important molecules."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "They don't only act as energy storage sources."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "They also act to basically give us structure."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "And they act to lubricate and prevent any type of damage."}, {"title": "Glycosaminoglycans and Proteoglycans .txt", "text": "Basically help absorb and dissipate the impact forces that we experience on a day to day basis."}, {"title": "Parathyroid Gland.txt", "text": "The next endocrine gland that we're going to focus on is the parathyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "Now the parathyroid gland consists of four tiny individual structures found on the back side of the thyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "So if we examine the front portion of the windpipe, we basically get the following diagram."}, {"title": "Parathyroid Gland.txt", "text": "So we have the thyroid cartilage, we have the atoms apple right beneath that and and right beneath that we have our thyroid gland that is shown in orange."}, {"title": "Parathyroid Gland.txt", "text": "Now if we examine the back side of this windpipe, we basically get the epiglottis, we have the pharynx and then we have the backside of our trachea as well as the back side of the thyroid gland shown in orange."}, {"title": "Parathyroid Gland.txt", "text": "And on the back side of the thyroid gland, we have these four individual structures that constitute the parathyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "So the parathyroid gland is found on the backside of the thyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "Now the blood vessel system and the lymph vessel system that basically provide the nutrients and the blood to our thyroid gland also provide the blood and our nutrients to the parathyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "So we see that the thyroid gland is very much connected to the parathyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "Now the next question is what are the hormones or hormone that is released by the parathyroid gland?"}, {"title": "Parathyroid Gland.txt", "text": "So we basically only have one hormone."}, {"title": "Parathyroid Gland.txt", "text": "The hormone is known as the parathyroid hormone."}, {"title": "Parathyroid Gland.txt", "text": "And this parathyroid hormone is produced in special cells inside the parathyroid gland known as the parathyroid chief cells or the parathyroid principal cells."}, {"title": "Parathyroid Gland.txt", "text": "And these cells basically produce and secrete the parathyroid hormone."}, {"title": "Parathyroid Gland.txt", "text": "Now, the parathyroid hormone is a peptide hormone and what that basically means is it is produced in the rough endoplasm reticulum of the chief cells and then it is modified in the golgi apparatus."}, {"title": "Parathyroid Gland.txt", "text": "Now, because it's a peptide hormone, that implies it's water soluble and so it is soluble in our blood."}, {"title": "Parathyroid Gland.txt", "text": "And that means we do not require any type of protein carrier to actually transport the parathyroid hormone in our blood system."}, {"title": "Parathyroid Gland.txt", "text": "Now, when the parathyroid hormone actually reaches its target cell, because it is not soluble in lipids, that means it cannot actually pass across the membrane of the target cell."}, {"title": "Parathyroid Gland.txt", "text": "Instead it binds onto the membrane of the target cell, it binds to special protein receptors and initiates a secondary messenger system that basically creates some type of change inside the cell."}, {"title": "Parathyroid Gland.txt", "text": "Now the question is, what exactly is the function, what is the purpose of the parathyroid gland or the parathyroid hormone?"}, {"title": "Parathyroid Gland.txt", "text": "Well, the function of the parathyroid hormone is basically the opposite of calcitonin."}, {"title": "Parathyroid Gland.txt", "text": "So previously we discussed a hormone that is produced by the thyroid gland known as calcitonin."}, {"title": "Parathyroid Gland.txt", "text": "And calcitonin is responsible for decreasing the concentration of calcium inside our blood."}, {"title": "Parathyroid Gland.txt", "text": "What the parathyroid hormone does is it increases the concentration of our calcium inside our blood."}, {"title": "Parathyroid Gland.txt", "text": "So this type of hormone is responsible for maintaining and regulating the concentration of calcium inside our blood."}, {"title": "Parathyroid Gland.txt", "text": "Now, the release or inhibition of the parathyroid hormone is controlled by the concentration of calcium inside of our blood."}, {"title": "Parathyroid Gland.txt", "text": "Now, when the blood calcium level drops, when it's relatively low, the parathyroid gland releases the parathyroid hormone."}, {"title": "Parathyroid Gland.txt", "text": "And this basically increases the concentration of calcium inside our blood as a result of three different things."}, {"title": "Parathyroid Gland.txt", "text": "So it basically does three important things."}, {"title": "Parathyroid Gland.txt", "text": "Firstly, it increases the activity rate of osteoclasts and decreases the activity of osteoblasts."}, {"title": "Parathyroid Gland.txt", "text": "So osteoblasts are those cells inside our bone that build the bone."}, {"title": "Parathyroid Gland.txt", "text": "It builds bone matrix by taking calcium from the blood and using that calcium to build the matrix."}, {"title": "Parathyroid Gland.txt", "text": "On the other hand, osteoclasts are those cells in the bone that resorb the bone."}, {"title": "Parathyroid Gland.txt", "text": "They break down the bone by breaking down the bone matrix and releasing the calcium and the phosphate ions into our blood."}, {"title": "Parathyroid Gland.txt", "text": "So what our parathyroid hormone does is it increases the activity of osteoclast, meaning it increases the rate of resorption of bone."}, {"title": "Parathyroid Gland.txt", "text": "So we break down more bone matrix and we release more calcium into our blood, thereby increasing the concentration of calcium in our blood."}, {"title": "Parathyroid Gland.txt", "text": "Now, the parathyroid hormone also actually affects our kidneys, so it increases the amount of calcium that is reabsorbed by our kidneys, and this increases the concentration of calcium in our blood and decreases the amount of calcium found in our urine."}, {"title": "Parathyroid Gland.txt", "text": "Now, it also affects our intestines."}, {"title": "Parathyroid Gland.txt", "text": "So what our parathyroid hormone does is it activates vitamin D, produces the active form of vitamin D in the kidneys, and then this vitamin D basically helps to absorb more calcium in our intestines."}, {"title": "Parathyroid Gland.txt", "text": "So notice these three things that we just mentioned are the opposite of what our calcitonin does released by the thyroid gland."}, {"title": "Parathyroid Gland.txt", "text": "So notice that the parathyroid hormone reverses the effects of calcitonin."}, {"title": "Parathyroid Gland.txt", "text": "So, whereas calciotonin actually decreases the concentration of calcium in our blood, the parathyroid hormone increases the concentration of calcium in our blood."}, {"title": "Parathyroid Gland.txt", "text": "Now, the remaining question is, how exactly do we control how much of our parathyroid hormone is released into our blood?"}, {"title": "Parathyroid Gland.txt", "text": "Well, there is actually a negative feedback mechanism that is in place to control the amount of parathyroid hormone inside our blood."}, {"title": "Parathyroid Gland.txt", "text": "So let's suppose, let's begin by supposing that inside our blood plasma, we have a low concentration of calcium."}, {"title": "Parathyroid Gland.txt", "text": "In such a case, this will basically trigger the parathyroid gland to release the parathyroid hormone."}, {"title": "Parathyroid Gland.txt", "text": "So we have a positive feedback loop here, a positive feedback loop here."}, {"title": "Parathyroid Gland.txt", "text": "And so, when we increase the amount of parathyroid hormone PTH in our blood, that basically does three things."}, {"title": "Parathyroid Gland.txt", "text": "It increases bone resorption, so it increases the rate of osteoclast and decreases the rate of osteoblasts."}, {"title": "Parathyroid Gland.txt", "text": "It increases the absorption of our kidneys, as well as increases the absorption of calcium in our intestines."}, {"title": "Parathyroid Gland.txt", "text": "And together, this basically increases the amount of calcium that is found inside our blood."}, {"title": "Parathyroid Gland.txt", "text": "Now, over time, as the concentration of calcium in our blood increases, this will create a negative feedback loop and it will cause our parathyroid gland to basically decrease in its release of PTH."}, {"title": "Parathyroid Gland.txt", "text": "And so, over time, this will stabilize and maintain the concentration of calcium in our blood serum, in our blood plasma."}, {"title": "Parathyroid Gland.txt", "text": "So the mount of PTH, the parathyroid hormone that actually circulates in our serum, is controlled via a negative feedback loop, as we just discussed."}, {"title": "Parathyroid Gland.txt", "text": "So basically, together, the calcitonin hormone released by the thyroid gland and the parathyroid hormone released by the parathyroid gland, these two hormones are responsible for regulating and maintaining the amount of calcium found inside our blood plasma."}, {"title": "Electron Transport Chain .txt", "text": "In the process of glycolysis, we produce NADH molecules and we also produce NADH molecules in pyruvate carboxylation and the citric acid cycle."}, {"title": "Electron Transport Chain .txt", "text": "In fact, in the citric acid cycle we also produce a similar molecule known as Fadh Two."}, {"title": "Electron Transport Chain .txt", "text": "Now, what exactly is the purpose of these two molecules?"}, {"title": "Electron Transport Chain .txt", "text": "Well, these these molecules basically play a role in transferring or transporting our electrons from glucose into a special region on the inner mitochondrial membrane known as the electron transport chain."}, {"title": "Electron Transport Chain .txt", "text": "And what the electron transport chain does is it basically transports electrons all the way to the final electron acceptor known as oxygen and we form water as a result."}, {"title": "Electron Transport Chain .txt", "text": "And this electron transport chain also establishes an electrochemical gradient that is used to synthesize ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "And it's the ATP molecule that is used by the cell as our energy source."}, {"title": "Electron Transport Chain .txt", "text": "So let's take a look at the structure of our electron transport chain."}, {"title": "Electron Transport Chain .txt", "text": "So the electron transport chain is shown in the following diagram."}, {"title": "Electron Transport Chain .txt", "text": "So we have the inner membrane of the mitochondria, which is a phospholipid bilayer."}, {"title": "Electron Transport Chain .txt", "text": "We have the outer membrane that is not shown."}, {"title": "Electron Transport Chain .txt", "text": "Let's imagine it's somewhere here."}, {"title": "Electron Transport Chain .txt", "text": "We have the space in between the two membrane shown here."}, {"title": "Electron Transport Chain .txt", "text": "That is the intermembrane space."}, {"title": "Electron Transport Chain .txt", "text": "And we also have this region, which is the mitochondrial matrix."}, {"title": "Electron Transport Chain .txt", "text": "And the citric acid cycle, as well as pyruvate decarboxylation takes place in the mitochondrial matrix."}, {"title": "Electron Transport Chain .txt", "text": "So the electron transport chain itself consists of a series of four protein complexes."}, {"title": "Electron Transport Chain .txt", "text": "We have protein complex one, two, three and four."}, {"title": "Electron Transport Chain .txt", "text": "And we also have a complex of proteins shown here that is known as ATP synthase that actually uses the electrochemical gradient to synthesize ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "So basically, protein complex one, protein complex three and four are used to establish the electrochemical gradient."}, {"title": "Electron Transport Chain .txt", "text": "And our ATP synthase uses that electrochemical gradient to synthesize our ATP molecule."}, {"title": "Electron Transport Chain .txt", "text": "So let's take a quick look at each one of these protein complexes and see what the function and the name of these protein complexes are."}, {"title": "Electron Transport Chain .txt", "text": "So let's begin with protein complex number one."}, {"title": "Electron Transport Chain .txt", "text": "Now, protein complex number one consists of many proteins."}, {"title": "Electron Transport Chain .txt", "text": "And together, protein complex number one is known as Nadhq oxidoreductase or NADH dehydrogenase."}, {"title": "Electron Transport Chain .txt", "text": "So it's called oxidoreductase because we have oxidation reduction reactions taking place."}, {"title": "Electron Transport Chain .txt", "text": "So what exactly is the purpose of protein complex Number One?"}, {"title": "Electron Transport Chain .txt", "text": "Well, NADH Dehydrogenase basically accepts the electrons from NADH molecules produced in glycolysis, pyruvate carboxylation and the citric acid cycle."}, {"title": "Electron Transport Chain .txt", "text": "So let's imagine that our NADH is produced in the citric acid cycle and then that NADH travels to protein complex number one and it gives the two electrons to protein complex number one."}, {"title": "Electron Transport Chain .txt", "text": "Now, when it donates those two electrons, those two electrons go onto a molecule known as Flavin mononucleotide, or FMN."}, {"title": "Electron Transport Chain .txt", "text": "So we reduce FMM, which is basically a group that is found on protein complex number one."}, {"title": "Electron Transport Chain .txt", "text": "And then those electrons basically travel via a series of groups, our iron sulfur groups, and eventually end up on a molecule known as Ubiquinon, shown by this Q circular symbol."}, {"title": "Electron Transport Chain .txt", "text": "So this is Ubiquinon, and Ubiquinon is basically an important electron carrier."}, {"title": "Electron Transport Chain .txt", "text": "So Ubiquinon is soluble inside our phospholipid bilayer membrane, and it can basically move along our membrane."}, {"title": "Electron Transport Chain .txt", "text": "So what this basically does is it accepts our electrons."}, {"title": "Electron Transport Chain .txt", "text": "And when Ubiquinone accepts our electrons, it is reduced."}, {"title": "Electron Transport Chain .txt", "text": "And that reduced version of Ubiquinone is known as Ubiquinol."}, {"title": "Electron Transport Chain .txt", "text": "Now, the most common Ubiquinone molecule in mammals and specifically in humans is coenzyme Q ten."}, {"title": "Electron Transport Chain .txt", "text": "So coenzyme Q ten is basically the specific Ubiquinone that is used by mammals and by humans."}, {"title": "Electron Transport Chain .txt", "text": "Now, once we reduce Ubiquinol to Ubiquinol, ubiquinol then travels from protein complex number one to protein complex number three."}, {"title": "Electron Transport Chain .txt", "text": "Now, actually, when this reaction takes place, when our electrons are transferred from NADH to our Ubiquinon to form Ubiquinol, we also actually pump four protons, four H ions from the mitochondrial matrix to the intermembrane space."}, {"title": "Electron Transport Chain .txt", "text": "And so we begin creating our electrochemical gradient."}, {"title": "Electron Transport Chain .txt", "text": "And our flavin mononucleotide also takes up two H ions from our matrix."}, {"title": "Electron Transport Chain .txt", "text": "Now, once Ubiquinol, the reduced version of Ubiquinon, travels to this protein complex number three, what happens is the main function of protein complex number three, also known as our cytochrome reductase or Q cytochrome C oxidore."}, {"title": "Electron Transport Chain .txt", "text": "Reductase basically functions to transfer those electrons from our carrier molecule, the Ubiquinol, to a different electron carrier known as cytochrome C. So cytochrome C is basically a small protein that is water soluble, that carries an electron from protein complex number three to protein complex number four."}, {"title": "Electron Transport Chain .txt", "text": "Now, also when our process within protein complex number three takes place, this pumps two hydrogen atoms from the mitochondrial matrix to our intermembrane space, and that further creates that electrochemical gradient."}, {"title": "Electron Transport Chain .txt", "text": "Now, when our electrons are transferred from Ubiquinon to cytochrome, cytochrome C then travels and attaches to protein complex number four, also known as cytochrome C oxidase."}, {"title": "Electron Transport Chain .txt", "text": "And the main function of protein complex number four is to basically use the electrons that is carried by cytochrome C to reduce our oxygen and form our water."}, {"title": "Electron Transport Chain .txt", "text": "Now, where exactly do we obtain the oxygen?"}, {"title": "Electron Transport Chain .txt", "text": "Well, by breathing in."}, {"title": "Electron Transport Chain .txt", "text": "So when we breathe in, when we inhale, we take an oxygen, and that's the same oxygen that is used by protein complex number four."}, {"title": "Electron Transport Chain .txt", "text": "Now, once we reduce our oxygen, this protein complex number four also transports four H plus ions from the mitochondrial matrix to the intermembrane space."}, {"title": "Electron Transport Chain .txt", "text": "And so we see that if we use one NADH molecule, we basically transport a total of ten four, two and two."}, {"title": "Electron Transport Chain .txt", "text": "So ten H plus ions into the intermembrane space, and that establishes an electrochemical gradient."}, {"title": "Electron Transport Chain .txt", "text": "Now, that means we have many more H plus ions found on the intermembrane space than in the mitochondrial matrix."}, {"title": "Electron Transport Chain .txt", "text": "And so that means our H plus ions will naturally and spontaneously want to flow from the intermembrane space to the mitochondrial matrix."}, {"title": "Electron Transport Chain .txt", "text": "However, because they have a positive charge, they're polar."}, {"title": "Electron Transport Chain .txt", "text": "And that means they cannot actually pass through our phospholipid bilayer because of the hydrophobic tails."}, {"title": "Electron Transport Chain .txt", "text": "And that's exactly where ATP synthase comes into play."}, {"title": "Electron Transport Chain .txt", "text": "So ATP synthase is basically a complex of proteins that create channels that allow the H plus ions to flow through these regions."}, {"title": "Electron Transport Chain .txt", "text": "So basically, our H plus ions begin to travel down their electrochemical gradient from a high concentration to a low concentration from a lot of charge to a very little charge."}, {"title": "Electron Transport Chain .txt", "text": "And as the H plus ions flow this way into the mitochondrial matrix, the ATP synthase also basically combines ADP adenosine diphosphate and a phosphate group to synthesize our ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "So basically, for a single NADH that is formed in either the citric acid cycle or pyruvate decarboxylation, one NADH produces three ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "However, if we examine the NADH molecule that is formed in glycolysis to actually get from the cytoplasm where glycolysis takes place and into the mitochondrial matrix, the NADH molecule has to transport via our mitochondrial inner and outer membrane and that requires energy."}, {"title": "Electron Transport Chain .txt", "text": "So for our NADH to get from the cytoplasm to the mitochondrial matrix we have to use a single ATP molecule."}, {"title": "Electron Transport Chain .txt", "text": "And that means the net result."}, {"title": "Electron Transport Chain .txt", "text": "So the net production of our NADH molecule that comes from glycolysis is not three, but only two ATP molecules because we had to use that one ATP molecule when we went from the cytoplasm into the mitochondrial matrix."}, {"title": "Electron Transport Chain .txt", "text": "So our NADH molecules produced in the mitochondrial matrix via the citric acid cycle or our pyruvate decreboxylation basically produces a net result of three ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "But the NADH produced in glycolysis produces a net result of only two ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "So let's basically summarize our results of what the electron transport chain is and how it actually works."}, {"title": "Electron Transport Chain .txt", "text": "So we have a series of four protein complexes one, two, three and four."}, {"title": "Electron Transport Chain .txt", "text": "And we also have our ATP synthase."}, {"title": "Electron Transport Chain .txt", "text": "Now, by the way, we still haven't discussed what protein complex two actually does."}, {"title": "Electron Transport Chain .txt", "text": "Protein complex two is known as our succinate oxidore reductase."}, {"title": "Electron Transport Chain .txt", "text": "And succinate oxidore reductase basically contains our enzyme, the protein involved in the citric acid cycle."}, {"title": "Electron Transport Chain .txt", "text": "So we know that in the citric acid cycle we form our fadh two molecule, our electron carrier."}, {"title": "Electron Transport Chain .txt", "text": "And that fadh two molecule is formed directly in protein complex number two."}, {"title": "Electron Transport Chain .txt", "text": "So protein complex number two, our succinate oxidore ductase, forms fadh two."}, {"title": "Electron Transport Chain .txt", "text": "And then that fadh two basically releases our electrons and those electrons are picked up by our Ubiquinone molecule."}, {"title": "Electron Transport Chain .txt", "text": "So Ubiquinon can also pick up except those electrons from protein complex number two."}, {"title": "Electron Transport Chain .txt", "text": "And then that Ubiquinol travels to protein complex number three."}, {"title": "Electron Transport Chain .txt", "text": "So let's go back and let's summarize our results."}, {"title": "Electron Transport Chain .txt", "text": "So high energy electron carriers called NADH molecules pass their electrons to flavin mononucleotide of complex number one which then shuttles those electrons via a series of iron sulfur groups and onto a molecule known as Ubiquinone."}, {"title": "Electron Transport Chain .txt", "text": "And the Ubiquitone in humans is known as coenzyme Q ten."}, {"title": "Electron Transport Chain .txt", "text": "Now, fadh two is itself synthesized in protein complex number two."}, {"title": "Electron Transport Chain .txt", "text": "And our fadh two transfers those electrons also to a molecule, our Ubiquinon."}, {"title": "Electron Transport Chain .txt", "text": "Now, once we reduce the Ubiquinon, once it gains those electrons, it becomes Ubiquinol, and it travels onto complex number three, where it transfers the electrons to yet another electron carrier that is water soluble, a small protein known as cytochrome C. Now, cytochrome C moves onto complex number four, where it transfers those electrons to complex number four."}, {"title": "Electron Transport Chain .txt", "text": "And these electrons are used to actually reduce oxygen and form water."}, {"title": "Electron Transport Chain .txt", "text": "Now, in the process, protein complex one, three, and four all release protons."}, {"title": "Electron Transport Chain .txt", "text": "They pump protons from the mitochondrial matrix into the intermembrane space, thereby establishing the electrochemical gradient."}, {"title": "Electron Transport Chain .txt", "text": "Notice that protein complex number two is not a proton pump."}, {"title": "Electron Transport Chain .txt", "text": "And that means it does not actually pump any H ions into the intermembrane space."}, {"title": "Electron Transport Chain .txt", "text": "Now, the entire purpose of creating this electrochemical gradient is to basically create a high concentration of our H plus ions as well as a high amount of charge in the intermembrane space."}, {"title": "Electron Transport Chain .txt", "text": "And that allows these H plus ions to move down their electrochemical gradient from a region of high concentration to low concentration from a region of high charge to low charge through these channels in our ATP synthase."}, {"title": "Electron Transport Chain .txt", "text": "And when these H ions move, we synthesize ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "So for one NADH coming from the citric acid cycle or Pyruvate decarboxylation, we form three ATP molecules."}, {"title": "Electron Transport Chain .txt", "text": "But for our NADH coming from glycolysis, we only synthesize two."}, {"title": "Electron Transport Chain .txt", "text": "Once again, because we have to use ATP to transport the NADH from the cynoplasm to the mitochondrial matrix."}, {"title": "Citric Acid Cycle .txt", "text": "The first step of cell respiration is glycolysis."}, {"title": "Citric Acid Cycle .txt", "text": "Glycolysis is basically the transformation of glucose into two pyruvate molecules."}, {"title": "Citric Acid Cycle .txt", "text": "Now, if there is oxygen present in the cell, then the cell can undergo reaction known as aerobic cellular respiration, in which the two pyruvate molecules formed in the cytoplasm of the cell via the the process of glycolysis are then transported into the mitochondrial matrix of the mitochondria of that cell."}, {"title": "Citric Acid Cycle .txt", "text": "And once within the mitochondrial matrix, the two pyruvate molecules are transformed into two acetylcoenzyme A molecules via a process known as pyruvate decarboxylation."}, {"title": "Citric Acid Cycle .txt", "text": "Now, once we form the two acetylcoenzion A molecules in the mitochondrial matrix, they will then enter a cycle known as the citric acid cycle, also known as the crept cycle, also known as the tricarboxylic acid cycle, or simply TCA."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the citric acid cycle is basically a series of eight steps, a series of eight reactions, as shown in the following diagram."}, {"title": "Citric Acid Cycle .txt", "text": "We have 123-4567 and eight."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the entire purpose of the citric acid cycle is to basically take the energy that is stored within our acetyl coenzyme A and transfer that energy in the form of high energy electrons to our electron carrying molecules, our NADH and Fadh, too."}, {"title": "Citric Acid Cycle .txt", "text": "So the citric acid cycle doesn't actually directly form ATP molecules."}, {"title": "Citric Acid Cycle .txt", "text": "What it actually does is it forms these NADH and fadh two molecules, the high energy electron carriers that will then be used by the electron transport chain to synthesize the ATP molecules."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the way that we described our citric acid cycle on the diagram is for a single acetyl coenzyme A."}, {"title": "Citric Acid Cycle .txt", "text": "But because glucose produces two acetyl coenzyme A, ultimately that means that this cycle will actually take place twice for any single glucose molecule."}, {"title": "Citric Acid Cycle .txt", "text": "So a single glucose molecule breaks down to two pyruvates."}, {"title": "Citric Acid Cycle .txt", "text": "And since each pyruvate creates that acetylco enzyme A, we have two of these acetylcoenzymes A."}, {"title": "Citric Acid Cycle .txt", "text": "So this citric acid cycle takes place twice for any given glucose molecule, and this citric acid cycle takes place within the mitochondrial matrix of the mitochondria found within the cell."}, {"title": "Citric Acid Cycle .txt", "text": "So let's take a look at each one of these eight steps."}, {"title": "Citric Acid Cycle .txt", "text": "And we're not going to focus too much on the detail, because each one of these steps is actually pretty complicated."}, {"title": "Citric Acid Cycle .txt", "text": "It contains many enzymes and many intermediates."}, {"title": "Citric Acid Cycle .txt", "text": "So we're going to simply paint the general picture of this cycle."}, {"title": "Citric Acid Cycle .txt", "text": "Let's begin with step number one."}, {"title": "Citric Acid Cycle .txt", "text": "Now, in step number one, we take our acetylcoenzyme A, and we mix it with a four carbon molecule known as oxaloacetate."}, {"title": "Citric Acid Cycle .txt", "text": "So the oxalo acetate is a four carbon molecule that when we mix it with acetyl coenzyme A, we form a molecule known as citral coenzyme A, and then that citral coenzyme A reacts with an H 20 molecule to release the coenzyme A cofactor and to produce a six carbon citrate molecule."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the fact that this contains six carbons makes sense because our oxyloacetate contained four carbons, and the acetyl portion of the acetyl coenzyme contains two carbons."}, {"title": "Citric Acid Cycle .txt", "text": "So when we combine these, we form the six carbon citrate molecule."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the question is, what exactly is the point of forming our citrate molecule?"}, {"title": "Citric Acid Cycle .txt", "text": "Well, basically, the reason we form a six carbon molecule is because this citric acid cycle involves two decarboxylation processes."}, {"title": "Citric Acid Cycle .txt", "text": "And so we have to add two carbon atoms, and that's exactly what we do in cytrate."}, {"title": "Citric Acid Cycle .txt", "text": "So step one, oxalo acetate and acetyl coenzyme A react to form citro coenzyme A, which then reacts with water to form the citrate."}, {"title": "Citric Acid Cycle .txt", "text": "The purpose of this step is to create a molecule that will ultimately undergo the decarboxylation reactions."}, {"title": "Citric Acid Cycle .txt", "text": "Now let's move on to step number two."}, {"title": "Citric Acid Cycle .txt", "text": "In step number two, we see that the citrate cannot actually undergo the decarboxylation directly because the hydroxyl group on citral is not positioned on the correct location."}, {"title": "Citric Acid Cycle .txt", "text": "And so what we do is we use a special type of enzyme that transforms the citrate into ISO citrate, which basically is an isomer of this molecule."}, {"title": "Citric Acid Cycle .txt", "text": "So now the isocytrate is able to undergo the decarboxylation reaction."}, {"title": "Citric Acid Cycle .txt", "text": "So basically, I group step one and step two into the same stage."}, {"title": "Citric Acid Cycle .txt", "text": "Let's call that stage one because these two steps involve preparing our molecule for decarboxylation."}, {"title": "Citric Acid Cycle .txt", "text": "So let's call these two steps stage one."}, {"title": "Citric Acid Cycle .txt", "text": "Now let's move on to stage two, which basically involves step three, step four and step five."}, {"title": "Citric Acid Cycle .txt", "text": "In these steps, as we'll see in just a moment, we have the decarboxylation reactions taking place, and we also form the only molecule that has the high energy phosphate group, our GTP, in this stage."}, {"title": "Citric Acid Cycle .txt", "text": "So let's begin with step three."}, {"title": "Citric Acid Cycle .txt", "text": "So in step three, once we form our six carbon isocytes or citrate, that undergoes a decarboxylation reaction, that means we release our carbon dioxide in step three, and we also use our NAD plus and we reduce it into the NADH, and we also form an H plus ion."}, {"title": "Citric Acid Cycle .txt", "text": "Now, we also form because we lose a single carbon that leaves as the carbon dioxide."}, {"title": "Citric Acid Cycle .txt", "text": "We go from a six carbon molecule to a five carbon molecule known as alpha keto gluterate."}, {"title": "Citric Acid Cycle .txt", "text": "Now, once we form the alpha ketoglutrate, that further undergoes a decarboxylation reaction."}, {"title": "Citric Acid Cycle .txt", "text": "So we release yet another carbon dioxide."}, {"title": "Citric Acid Cycle .txt", "text": "So that means we go from a five carbon to a four carbon molecule known as succinctal coenzyme A."}, {"title": "Citric Acid Cycle .txt", "text": "Now, the coenzyme A release in step one reacts with this molecule and goes into the process."}, {"title": "Citric Acid Cycle .txt", "text": "That's why we have the succinl coenzyme A, and we also once again, reduce an NAD into our NADH."}, {"title": "Citric Acid Cycle .txt", "text": "We also release the H plus ion as in step number three."}, {"title": "Citric Acid Cycle .txt", "text": "Now let's move on to step number five."}, {"title": "Citric Acid Cycle .txt", "text": "In step number five, we basically transfer a phosphate group from the succinil coenzyme A onto the GDP, where GDP is basically guanosine diphosphate, and we form our guanosine triphosphate."}, {"title": "Citric Acid Cycle .txt", "text": "So we see that this is the only step in the citric acid cycle in which we actually produce a high phosphoryl transfer potential molecule basically our GTP."}, {"title": "Citric Acid Cycle .txt", "text": "And that GTP is ultimately transformed into an ATP molecule via an enzymatic reaction."}, {"title": "Citric Acid Cycle .txt", "text": "So I label these three steps as stage number two."}, {"title": "Citric Acid Cycle .txt", "text": "So, stage number one is the preparation step."}, {"title": "Citric Acid Cycle .txt", "text": "We create that molecule that is capable of undergoing the two decarboxylation reactions."}, {"title": "Citric Acid Cycle .txt", "text": "In stage two, we basically have the two decarboxylation reactions, and we also have the only reaction that produces the high phosphoryl transfer potential molecule, the GTP."}, {"title": "Citric Acid Cycle .txt", "text": "Now, we also use the phosphate to form that GTP, and we basically released the coenzyme A that went into the reaction in step number four."}, {"title": "Citric Acid Cycle .txt", "text": "Now, stage number three are basically steps six, seven and eight."}, {"title": "Citric Acid Cycle .txt", "text": "And the entire purpose of these steps is to basically regenerate our molecule, the oxalo acetate, the four carbon molecules that we'll need to use again to basically undergo the reaction."}, {"title": "Citric Acid Cycle .txt", "text": "This process the cycle a second time because we have that second acetyl, coenzyme A."}, {"title": "Citric Acid Cycle .txt", "text": "So the final three steps six, seven and eight of the citrix cycle involves the regeneration of our oxalo acetate molecule."}, {"title": "Citric Acid Cycle .txt", "text": "The question is, how exactly does this take place?"}, {"title": "Citric Acid Cycle .txt", "text": "So, let's begin with our succinate."}, {"title": "Citric Acid Cycle .txt", "text": "The succinate looks something like this."}, {"title": "Citric Acid Cycle .txt", "text": "We have the carbon 1234, and these two H atoms shown in purple will basically react with a single fad molecule."}, {"title": "Citric Acid Cycle .txt", "text": "And that fad molecule will be reduced."}, {"title": "Citric Acid Cycle .txt", "text": "It will take these two H atoms, as well as a single electron from each one of these atoms, which will end up on this molecule known as our fadh two high energy electron carrier."}, {"title": "Citric Acid Cycle .txt", "text": "And once these two leave, we form a pi bond between carbon one and carbon two, as shown."}, {"title": "Citric Acid Cycle .txt", "text": "And this is known as the fumerate molecule."}, {"title": "Citric Acid Cycle .txt", "text": "Next, we take the fumerate."}, {"title": "Citric Acid Cycle .txt", "text": "We basically input a water molecule, and that water molecule basically goes onto these two carbons."}, {"title": "Citric Acid Cycle .txt", "text": "So an H goes onto this carbon, and then the hydroxyl goes onto this carbon, as shown."}, {"title": "Citric Acid Cycle .txt", "text": "And this is our malate molecule."}, {"title": "Citric Acid Cycle .txt", "text": "So malate is shown here."}, {"title": "Citric Acid Cycle .txt", "text": "And finally, to form the final product to regenerate our oxalo acetate, we have an NAD plus that is reduced."}, {"title": "Citric Acid Cycle .txt", "text": "So it takes our H, which basically is this H here."}, {"title": "Citric Acid Cycle .txt", "text": "Once we take that H, we form our NADH."}, {"title": "Citric Acid Cycle .txt", "text": "And we also remove this H here to basically form a pine bond between the oxygen and our carbon."}, {"title": "Citric Acid Cycle .txt", "text": "And this is the final molecule, the four carbon oxalo acetate."}, {"title": "Citric Acid Cycle .txt", "text": "So, in the process of regenerating our oxalo acetate in step six, seven and eight, we also actually produce the high energy electron carrying molecules."}, {"title": "Citric Acid Cycle .txt", "text": "We produce a single fadh two in step six and a single NADH in step eight."}, {"title": "Citric Acid Cycle .txt", "text": "And we also use a water molecule in step number seven."}, {"title": "Citric Acid Cycle .txt", "text": "Now, this step, this cycle takes place twice because we have two acetyl coenzyme A molecules coming from a single glucose."}, {"title": "Citric Acid Cycle .txt", "text": "And that means the final product will be all these products multiplied by two."}, {"title": "Citric Acid Cycle .txt", "text": "So the final product of the citric acid cycle, when one glucose produces the two acetyl coenzyme A molecules are four carbon dioxides."}, {"title": "Citric Acid Cycle .txt", "text": "So one, two, that's two multiplied by two."}, {"title": "Citric Acid Cycle .txt", "text": "So four, we have six NADH."}, {"title": "Citric Acid Cycle .txt", "text": "So we have one NADH formed here, one formed here and one formed here."}, {"title": "Citric Acid Cycle .txt", "text": "That's three multiplied by two."}, {"title": "Citric Acid Cycle .txt", "text": "We have two fadhs, so we have one coming in step six multiplied by two."}, {"title": "Citric Acid Cycle .txt", "text": "So we have two of those."}, {"title": "Citric Acid Cycle .txt", "text": "We have two GTP, one formed."}, {"title": "Citric Acid Cycle .txt", "text": "In our step number six, we have four H plus ions."}, {"title": "Citric Acid Cycle .txt", "text": "So we have one, two."}, {"title": "Citric Acid Cycle .txt", "text": "We multiplied that by two, we form four."}, {"title": "Citric Acid Cycle .txt", "text": "And we also have our two coenzyme A molecule."}, {"title": "Citric Acid Cycle .txt", "text": "So these are the final products of our citric acid cycle when basically, we have one glucose that produces two acetyl coenzymes A that go into this cycle inside the mitochondrial matrix."}, {"title": "Citric Acid Cycle .txt", "text": "So once again, the entire purpose of the citric acid cycle is not to actually directly synthesize our ATP molecules, but it's to transfer the energy from the CETO coenzyme A in the form of the highenergy electron."}, {"title": "Citric Acid Cycle .txt", "text": "So we produce these electron carriers that are then used by the electron transport chain, which we'll discuss in the next lecture, to synthesize our ATP molecules."}, {"title": "Structure of Skin.txt", "text": "The skin, along with our hair and nails, is part of the integratory system of the human body."}, {"title": "Structure of Skin.txt", "text": "It basically covers our body."}, {"title": "Structure of Skin.txt", "text": "Now, the skin is an organ."}, {"title": "Structure of Skin.txt", "text": "In fact, it is the largest organ of the human body by mass as well as by size."}, {"title": "Structure of Skin.txt", "text": "And the fact that the skin is an organ means it consists of the four different types of tissues that can necktive tissue, epithelial tissue, muscle tissue and nervous tissue."}, {"title": "Structure of Skin.txt", "text": "And these four different types of tissue work together to carry out a specific set of functions."}, {"title": "Structure of Skin.txt", "text": "Now, in the next lecture we're going to focus on the function of the skin."}, {"title": "Structure of Skin.txt", "text": "But in this lecture, we're going to focus on the structure of the skin."}, {"title": "Structure of Skin.txt", "text": "So let's begin by looking at the following diagram that describes a cube region of our skin."}, {"title": "Structure of Skin.txt", "text": "Now notice that the skin consists of three different sections."}, {"title": "Structure of Skin.txt", "text": "We can divide the skin into three different regions."}, {"title": "Structure of Skin.txt", "text": "The outermost section of the skin is known as the epidermis."}, {"title": "Structure of Skin.txt", "text": "The middle portion is known as the dermis, and the lowest portion is known as the hypodermis, or the subcutaneous layer."}, {"title": "Structure of Skin.txt", "text": "Now let's begin by discussing the epidermis, the outermost portion of the skin."}, {"title": "Structure of Skin.txt", "text": "The epidermis actually consists of four different types of cells."}, {"title": "Structure of Skin.txt", "text": "The cells that predominate in our epidermis are the caroteneocides."}, {"title": "Structure of Skin.txt", "text": "They make up 95% of the cells found within the epidermis."}, {"title": "Structure of Skin.txt", "text": "And what these cells do is they release a protein known as carotene."}, {"title": "Structure of Skin.txt", "text": "And carotene is responsible for making the skin impermeable to water."}, {"title": "Structure of Skin.txt", "text": "Now the other three types of cells found in the epidermis include the melanocytes."}, {"title": "Structure of Skin.txt", "text": "And these melanocytes are responsible for producing a skin pigment known as melanin, which basically gives the skin its color."}, {"title": "Structure of Skin.txt", "text": "The more melan we have in our skin, the darker our skin is."}, {"title": "Structure of Skin.txt", "text": "We also have cells known as Langerhon cells."}, {"title": "Structure of Skin.txt", "text": "And these cells are involved in our immunity."}, {"title": "Structure of Skin.txt", "text": "They protect our body from bacterial agents."}, {"title": "Structure of Skin.txt", "text": "And finally, we also have Merkel cells which are believed to be involved in sensation."}, {"title": "Structure of Skin.txt", "text": "Now these four different types of cells found in the epidermis are spread among the five different layers found within the epidermis."}, {"title": "Structure of Skin.txt", "text": "So we can actually subdivide our epidermis into five different layers."}, {"title": "Structure of Skin.txt", "text": "So these layers go as follows."}, {"title": "Structure of Skin.txt", "text": "The lowest layer in the epidermis is the stratum basal."}, {"title": "Structure of Skin.txt", "text": "The next layer is the stratum spinosum, followed by the stratum granolasum, followed by the stratum lucidum, followed by the stratum corneum."}, {"title": "Structure of Skin.txt", "text": "Now stratum simply is another word for layer."}, {"title": "Structure of Skin.txt", "text": "So we have five different layers found within the epidermis."}, {"title": "Structure of Skin.txt", "text": "Now the next question is where exactly are these four cells found within these five layers?"}, {"title": "Structure of Skin.txt", "text": "So within the stratum basil, we have two types of cells."}, {"title": "Structure of Skin.txt", "text": "We have the melanocytes and we also have our Mercol cells."}, {"title": "Structure of Skin.txt", "text": "So let's take a look at the following diagram."}, {"title": "Structure of Skin.txt", "text": "This lowest portion is the stratum basil."}, {"title": "Structure of Skin.txt", "text": "And within the stratum."}, {"title": "Structure of Skin.txt", "text": "Basil we have the mercal cells shown here."}, {"title": "Structure of Skin.txt", "text": "We also have these green cells, our melanocytes."}, {"title": "Structure of Skin.txt", "text": "Now these other purple cells are our stem cells."}, {"title": "Structure of Skin.txt", "text": "And these stem cells found within the Stratum basil are responsible for differentiating for becoming our caroteneocides."}, {"title": "Structure of Skin.txt", "text": "So these stem cells differentiate into caroteneocides."}, {"title": "Structure of Skin.txt", "text": "And as these caroteneocides progress, as they begin to secrete produce our carotene, they begin to move up along the epidermis."}, {"title": "Structure of Skin.txt", "text": "So eventually they move up into this section, which is the Stratum spinosum."}, {"title": "Structure of Skin.txt", "text": "So these rat cells are basically the living keratinocytes."}, {"title": "Structure of Skin.txt", "text": "Now the keratinocytes continue to move up along the epidermis and as they move deeper and farther up along the epidermis, they slowly begin to die off."}, {"title": "Structure of Skin.txt", "text": "And that's because the epidermis doesn't actually contain any blood vessels."}, {"title": "Structure of Skin.txt", "text": "And that means as the keratino sides move higher up, they cannot actually obtain the nutrients needed to actually continue living."}, {"title": "Structure of Skin.txt", "text": "And so that's exactly why they eventually lose their nuclei and the organelles and they die."}, {"title": "Structure of Skin.txt", "text": "They become nothing but bundles of keratin."}, {"title": "Structure of Skin.txt", "text": "And carotene is very important in not only giving our skin its strength, but also making the skin impermeable to water."}, {"title": "Structure of Skin.txt", "text": "In fact, this entire upper layer of the epidermis, which consists of about 20 to 30 layers of dead cells, consists of nothing but cells that contain carotene."}, {"title": "Structure of Skin.txt", "text": "No nuclei, no organelles, only our carotene."}, {"title": "Structure of Skin.txt", "text": "And this makes our skin impermeable to water."}, {"title": "Structure of Skin.txt", "text": "Now, within our Stratum spinosum, we also have the Langerhond cells that are responsible for basically protecting our skin from bacterial agents."}, {"title": "Structure of Skin.txt", "text": "So if we look at the following diagram, we have the stem cells merkel cells, melanocytes in the Stratum basil."}, {"title": "Structure of Skin.txt", "text": "Within our spinosum we have these living caroteneocides as well as these Langerhon cells shown in blue."}, {"title": "Structure of Skin.txt", "text": "Now, in this diagram, I skip the Stratum granolosum and I also skip the Stratum lucidum."}, {"title": "Structure of Skin.txt", "text": "I go directly to the Stratum corneum, this brown layer that consists of these dead carotenesites that contain the keratin, that gives the skin strength and makes it waterproof, impermeable to water."}, {"title": "Structure of Skin.txt", "text": "Now let's move on to this middle layer of our skin known as our dermis."}, {"title": "Structure of Skin.txt", "text": "Now, our epidermis is connected to the dermis via a basement membrane that consists of a network of proteins."}, {"title": "Structure of Skin.txt", "text": "And just like we can divide the epidermis into five layers, we can divide the dermis into two layers."}, {"title": "Structure of Skin.txt", "text": "This upper layer of the dermis is known as our papillary layer, and this next layer is known as our reticular layer."}, {"title": "Structure of Skin.txt", "text": "Now let's begin by discussing the papillary layer."}, {"title": "Structure of Skin.txt", "text": "This layer basically consists of a connective tissue that has extensions that extend into the dermis."}, {"title": "Structure of Skin.txt", "text": "And this papillary layer basically connects our epidermis to our dermis."}, {"title": "Structure of Skin.txt", "text": "Now, what about the reticular layer?"}, {"title": "Structure of Skin.txt", "text": "This is the layer that also consists of a very dense connective tissue."}, {"title": "Structure of Skin.txt", "text": "It consists of collagen fibers that provide the skin with strength, as well as our elastin fibers that give the skin its flexibility and elasticity."}, {"title": "Structure of Skin.txt", "text": "On top of that, our reticular layer also contains many important structures."}, {"title": "Structure of Skin.txt", "text": "For example, it contains our blood vessels and that includes the arteries that bring the blood to the cells of the skin as well as the veins that take away the deoxygenated blood filled with waste products back into our blood system."}, {"title": "Structure of Skin.txt", "text": "We also contain the roots of the hair follicles and these hairs, which also consist of carotene, basically move all the way to the outside of our body."}, {"title": "Structure of Skin.txt", "text": "So these are our hairs that extend to the outside and these are the hair roots."}, {"title": "Structure of Skin.txt", "text": "Now, we also have oil glands, also known as sebaceous glands and oil is produced to basically make the hair impermeable to water."}, {"title": "Structure of Skin.txt", "text": "We also have these green structures which are the sweat glands."}, {"title": "Structure of Skin.txt", "text": "And remember, sweat is another method by which we excrete our waste products to the outside."}, {"title": "Structure of Skin.txt", "text": "Sweat is also the method by which we regulate the amount of heat found inside our body."}, {"title": "Structure of Skin.txt", "text": "So when we basically want to take the heat and move it to the outside we do it via the process of sweating as we'll see in the next lecture."}, {"title": "Structure of Skin.txt", "text": "Now, we also have smooth muscle in our dermis and the smooth muscle is found around the roots of the hair follicles and that's because this smooth muscle is responsible for erecting our hair giving us goosebumps."}, {"title": "Structure of Skin.txt", "text": "So once again the reticular layer is the lower portion of the dermis it is much thicker than the papillary layer and consists of a highly dense connective tissue made of collagen and elastin fibers these fibers give the skin its strength and elasticity."}, {"title": "Structure of Skin.txt", "text": "Now the reticular portion also contains blood vessels, sebaceous glands, sweat glands the root of the hair follicles receptors such as for example pressure receptors as well as smooth muscle."}, {"title": "Structure of Skin.txt", "text": "Now finally let's move on to the lowest portion of the skin the hypodermis also known as the subcutaneous layer."}, {"title": "Structure of Skin.txt", "text": "Basically this is the layer that insulates our body it contains the adipose cells, our fat cells as shown in the following diagram."}, {"title": "Structure of Skin.txt", "text": "So these orange cells are the adipose cells found in the hypodermis."}, {"title": "Structure of Skin.txt", "text": "Now we also have a network of fibers within this region for example we have the collagen as well as elastin fibers and what the subcutaneous layer does what the hypodermis does is it allows the dermis to basically stick to the rest of our body."}, {"title": "Structure of Skin.txt", "text": "So this is the lower, most portion of the skin."}, {"title": "Structure of Skin.txt", "text": "It contains cells such as macrophages and adipose cells."}, {"title": "Structure of Skin.txt", "text": "So macrophages are those immune cells that engulf different types of detrimental debris and or our bacterial cells they basically take off the waste products and ensure that the waste product and bacterial agents do not harm the skin in any way."}, {"title": "Structure of Skin.txt", "text": "Now this layer insulates the organism and connects the skin to the body and it also contains a network of protein and fibers so this layer is also very elastic and very strong."}, {"title": "Proximal Convoluted Tubule .txt", "text": "The Proximal Convoluted tubule is a segment of our nephron that connects the Bowman's capsule, this cup shaped structure of the nephron, to the Proximal straight tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this entire tubular section is known as the Proximal Convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, right below the Proximal stray tubule is a U shaped structure not shown, known as the Loop of Henley."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And we'll discuss that and its function in the next lecture."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this entire segment, the Proximal convolute Tubule, is located entirely in the renal cortex of the kidney, in the outer portion of the kidney, below the renal medulla."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is the cortex and this is the medulla that is not shown."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, what exactly is the function of the Proximal Convoluted tubule?"}, {"title": "Proximal Convoluted Tubule .txt", "text": "Well, there are three important functions that we should consider."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Function number one, as we'll see in just a moment, it basically reabsorbs important nutrients and electrolytes that are secreted into our filtrate when our blood plasma travels across the glumerolus and into our Bowman's capsule, and we'll see what those nutrients and electrolytes are."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So our Proximal convolute reabsorbs those nutrients from our filtrate back into our blood system via these capillaries that run along our Proximal convolute, the peritubular capillaries."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, the second function of the Proximal Convoluted tubule is that in secretion, it secretes certain types of molecules and ions that are no longer needed by our body."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And this includes things like hydrogen ions as well as bicarbonate ions, as we'll see in just a moment."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, the final function of our Proximal Convoluted tubule is to actually prevent the movement of waste products from the filtrat found inside the lumen of the Proximal convolute and into our blood system."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So the Proximal convolute not only reabsorbs and secretes molecules and ions, but it also prevents the movement of waste products from actually returning and moving back into our blood plasma, such as, for example, urea."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, if we zoom in on any section of the Proximal Convoluted tubule, if we examine the inner lining of that tubule, we're going to see epithelial cells."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So the inner wall lining of the Proximal Convoluted tubule contains many of these epithelial cells that are connected by special types of junctions known as tide junctions."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And what these tide junctions do is they basically prevent the movement of these waste products from the lumen of our Proximal Convoluted tubular from the filtrate back into our blood plasma of these peritubular capillaries."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, all the surrounding tissues found around the Proximal Convoluted tubule is known as our interstituum."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So what the Proximal Convolutes do is they prevent the movement of these waste products from the filtrate back into our interstituum."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, these epithelial cells basically contain foldings on the membrane, and these foldings are known as the microvilli."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And the microvilli greatly increases the surface area of the inner lining of our Proximal Convoluted tubule, and this increases the rate of reabsorption as well as secretion along the entire Proximal Convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, the epithelial cell membranes also contain special type of integral proteins found within our membrane."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And these integral proteins aid they allow the movement of our ions and molecules across the membrane."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we have two types of movement that takes place inside the proximal convoluted tubial."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We have active transport, which utilizes ATP, and we have passive transport which does not utilize ATP."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So let's take a look at the following diagram that basically describes several of these epithelial cells binding together to form the membrane the lining of our proximal convolute tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we have these epithelial cells that are connected, and these are our tie junctions that prevent the movement of waste products from the lumen of the proximal convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "This is where the filtrate is found to the interstituum of our renal cortex, to these peritubular capillaries that are found within our interstituum."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, this side of the membrane that faces the lumen portion is known as the apical side, and this other side across it is known as the basil lateral side."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we have ions that enter via our apical side, eventually travel down through the basil lateral side, and will enter the peritubular capillaries."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So now let's actually discuss how the absorption and secretion takes place across our cell membrane of the epithelial cells found within the proximal convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And let's discuss which molecules and ions are reabsorbed and which ones are secreted."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, the proximal convoluted tubule of that nephron basically is responsible for absorbing about 70% of all the sodium and water that is found within our filtrate."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And it also basically absorbs 100% of our amino acids and glucose molecules that end up in our filtrate when the blood plasma travels from our glomerulus to our Bowman's capsule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So the proximal convolute tubel is responsible for absorbing nearly 70% of the sodium and water found in the filtrate back into our blood system via these peritubular cavities."}, {"title": "Proximal Convoluted Tubule .txt", "text": "It also absorbs in normal cells 100% of the glucose and amino acids in our glomerul filtrate."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So let's zoom in on any one of these cells."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We basically get the following diagram."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is the microvilli membrane of, let's say, this cell right here."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So, if we examine the membrane, we'll see these transport proteins that we spoke of earlier."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We have different types of proteins that basically move different types of molecules across our membrane."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, this is the apical side."}, {"title": "Proximal Convoluted Tubule .txt", "text": "This is this side of the membrane that points towards the lumen of the proximal convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is where our filtrate is actually found."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So as the filtrate moves this way, we have the passive and active transport of different types of molecules and ions."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So the first transport that we should discuss is found on this protein membrane."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is an ATPase."}, {"title": "Proximal Convoluted Tubule .txt", "text": "It basically uses one ATP molecule and transforms that into an ATP."}, {"title": "Proximal Convoluted Tubule .txt", "text": "At the same time, it pumps three sodium ions basically against its electrochemical gradient and into the lumen of the proximal convolute tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "At the same time, it brings two potassium ions from the lumen to our cytoplasm of the epithelial cell of the proximal convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is an example of active transport."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Not only does it utilize ATP, it also moves the sodium against its electrochemical gradient."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, the entire purpose of using this Atpas pump is to create an electrochemical gradient for sodium."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So as a result of the action of this ATPase pump, we create a very high potassium, a very high sodium concentration on the lumen side of our cell."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And what that does is it builds this concentration of sodium and allows the passive transport of sodium down its electrochemical gradient."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this protein membrane basically moves one of the sodium ions down its electrochemical gradient from a high to a low concentration."}, {"title": "Proximal Convoluted Tubule .txt", "text": "At the same time, it also moves an H ion from the cytoplasm to our lumen."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So it secretes an H and it basically absorbs the sodium as a result of the concentration gradient created by this Atpas pump."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Likewise, because of this Atpas pump, this cotransport protein basically moves one sodium down its electrochemical gradient."}, {"title": "Proximal Convoluted Tubule .txt", "text": "At the same time, it brings our glucose molecule or amino acid molecule from the lumen to our cytoplasm."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we have the absorption of our we have the coabsorption of our sodium along with the glucose or our amino acids."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So these are the two nutrients that are reabsorbed back by our body, and these are the two electrolytes that are reabsorbed by our body."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, we haven't shown it in the diagram, but chloride ions are also reabsorbed by our body, so they move from the lumen into the cytoplasm."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, finally, we have the movement of bicarbonate, just like this moves from the cytoplasm to the lumen."}, {"title": "Proximal Convoluted Tubule .txt", "text": "This also moves this way into our lumen."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So these two ions are secreted."}, {"title": "Proximal Convoluted Tubule .txt", "text": "These two ions are absorbed, while glucose and amino acids are the two nutrient molecules that are also absorbed."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, notice that as all these ions, as these ions and this ion basically moves into the cytoplasm of our epithelial cell, that increases the concentration of solute inside our cell and that also increases our osmotic pressure."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And that will basically allow the passive transport of our water across the membrane from the lumen side to our cytoplasm."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Why does the water move this way?"}, {"title": "Proximal Convoluted Tubule .txt", "text": "Well, because it moves into an area where we have a high concentration of solute."}, {"title": "Proximal Convoluted Tubule .txt", "text": "And that concentration solute was basically built due to the movement of these ions into our cell."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we see that potassium, sodium, water, glucose and amino acids are all reabsorbed by our cell."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, once they are reabsorbed by the cell, they move across the cell and they basically move across the bacillateral membrane this side of our cell, they move into our instertuum, and then they move into the peritubular capillaries, where they basically move into our bloodstream system."}, {"title": "Proximal Convoluted Tubule .txt", "text": "At the same time, the h and the bicarbonate ions move into our filtrate, and they are carried all the way across this region, into the proximal stray tubule, along the loop of Henley, then along our distal convoluted tubule, eventually along our collecting duct, which empties it out into our ureter, that travels into the urinary bladder, where it is stored."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Eventually, it is secreted by our body."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So this is the function of our proximal convoluted tubule."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we conclude that what is reabsorbed back into our bloodstream from our filtrate are sodium ions, as well as potassium and chloride ions, water, glucose and amino acids."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, why do we want to reabsorb these in the first place?"}, {"title": "Proximal Convoluted Tubule .txt", "text": "Well, because our body does not want to waste things like amino acids and glucose, because we need that to build important things."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We need glucose for ATP."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We need amino acids to build our proteins."}, {"title": "Proximal Convoluted Tubule .txt", "text": "Now, we secrete our H plus and Bicarbonate because we don't want to basically increase or decrease our PH of the blood by too much."}, {"title": "Proximal Convoluted Tubule .txt", "text": "So we see that one important function of our proximal convoluted tubule to regulate the PH of our blood."}, {"title": "Proximal Convoluted Tubule .txt", "text": "We don't want to build the concentration of H plus because we don't want to make our blood too acidic."}, {"title": "Introduction to Membrane Transport .txt", "text": "The next topic that we're going to focus on will be membrane transport."}, {"title": "Introduction to Membrane Transport .txt", "text": "So how exactly do molecules make their way across the cell membrane from one side to the other side of that cell membrane?"}, {"title": "Introduction to Membrane Transport .txt", "text": "Well, the method that they use to cross the membrane really depends on the properties of those molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "So to begin, let's focus on nonpolar and small molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "So remember, the cell membrane consists predominantly of a hydrophobic region."}, {"title": "Introduction to Membrane Transport .txt", "text": "So the entire core of the membrane, this entire rest section, is hydrophobic nonpolar because of the presence of these hydrocarbon tails, part of the phospholipid molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, because a non polar molecule can easily dissolve in a hydrophobic non polar solution, what that means is if a small non polar molecule wants to make its way across the cell membrane, all it has to do is dissolve inside that cell membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "And this process, by which a small non polar molecule will move down its concentration gradient from a high till low potential through the core of that membrane by dissolving in that cell membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "This is known as simple diffusion."}, {"title": "Introduction to Membrane Transport .txt", "text": "And to demonstrate this, let's examine the cell membrane of the cells found inside our lungs."}, {"title": "Introduction to Membrane Transport .txt", "text": "So inside the cells of our lungs, we know we have a high concentration of carbon dioxide inside and a low concentration on the outside."}, {"title": "Introduction to Membrane Transport .txt", "text": "Conversely, we have a low concentration of oxygen on the inside but a high concentration of oxygen on the outside."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, both carbon dioxide and oxygen are small non polar molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "And what that means is these two molecules will have no problem making their way and dissolving into that hydrophobic red core of that membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so these oxygen molecules will naturally move spontaneously move from a high potential concentration to a low potential concentration from the outside to the inside."}, {"title": "Introduction to Membrane Transport .txt", "text": "They will pass and dissolve inside and through that membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "Likewise, these carbon dioxide, being non polar will also dissolve and move through that membrane via simple diffusion."}, {"title": "Introduction to Membrane Transport .txt", "text": "But they will move from the inside to the outside down their concentration gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, what about if the molecule is polar?"}, {"title": "Introduction to Membrane Transport .txt", "text": "So what if it has some type of charge?"}, {"title": "Introduction to Membrane Transport .txt", "text": "So, for instance, let's say we're looking at ions."}, {"title": "Introduction to Membrane Transport .txt", "text": "For instance, we can look at sodium ions, chloride ions, potassium ions."}, {"title": "Introduction to Membrane Transport .txt", "text": "We can look at calcium ions and so forth."}, {"title": "Introduction to Membrane Transport .txt", "text": "Or we can look at molecules that don't have a charge yet they are very polar."}, {"title": "Introduction to Membrane Transport .txt", "text": "For instance, sugar molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "Sugar molecules are large enough and polar enough to not be able to pass across the membrane via simple diffusion."}, {"title": "Introduction to Membrane Transport .txt", "text": "So in this case, if a molecule is polar and large, for example, sugars and sodium ions and so forth, they will not be able to simply dissolve inside that hydrophobic core."}, {"title": "Introduction to Membrane Transport .txt", "text": "And in this particular case, they have to use another method."}, {"title": "Introduction to Membrane Transport .txt", "text": "And what they use is these integral proteins, transmembrane proteins that exist inside our cells."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have one integral protein shown here and another one shown here."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, these are also known as transport membrane proteins because we find the proteins in the membrane and their function is to transport move these molecules across the two sides of the membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, we can categorize, we can break down these membrane proteins, transport membrane proteins into two types."}, {"title": "Introduction to Membrane Transport .txt", "text": "We have membrane channels and we also have membrane pumps."}, {"title": "Introduction to Membrane Transport .txt", "text": "So let's begin by focusing on membrane channels."}, {"title": "Introduction to Membrane Transport .txt", "text": "So let's suppose we're going to focus on a specific type of ion."}, {"title": "Introduction to Membrane Transport .txt", "text": "Let's say the sodium ion."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, we know that on the outside of the cell we have a higher concentration of sodium ions than on the inside of the cell."}, {"title": "Introduction to Membrane Transport .txt", "text": "And what that means is if we did not have this cell membrane, these sodium ions would move down their electrochemical gradient from a high electric potential to a low electric potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "And this is essentially analogous to a marker moving from a high gravitational potential to a low gravitational potential in the following manner."}, {"title": "Introduction to Membrane Transport .txt", "text": "So essentially, from physics, we know that because there's a positive charge on the outside and a negative charge on the inside, there will be an electric field that exists across the cell membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so this electric field that points this way from the outside to the inside will create, will exert an electric force that will try to pull on these sodium ions."}, {"title": "Introduction to Membrane Transport .txt", "text": "Let's focus on this sodium ion here."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have a force that is exerted on this ion."}, {"title": "Introduction to Membrane Transport .txt", "text": "Let's call that force E because it's the force due to the presence of this electric field."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, by the second law of motion, we know that if this is the only force acting on the sodium, then it will move in this direction."}, {"title": "Introduction to Membrane Transport .txt", "text": "The problem is, it's not the only force."}, {"title": "Introduction to Membrane Transport .txt", "text": "We have this barrier, a hydrophobic barrier that will not be able to or that the sodium ion will not be able to pass across."}, {"title": "Introduction to Membrane Transport .txt", "text": "And this is analogous to the following situation."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have a barrier, the hydrophobic membrane, that prevents the sodium ion from actually moving down its potential gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "In this case, we have gravitational potential gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "So from a high gravitational to a low gravitation."}, {"title": "Introduction to Membrane Transport .txt", "text": "But it can't move because of the presence of this barrier, the hydrophobic core."}, {"title": "Introduction to Membrane Transport .txt", "text": "So what we have happening is we have another force that points in the opposite direction, the force due to the presence of this hydrophobic barrier."}, {"title": "Introduction to Membrane Transport .txt", "text": "Let's call that simply FH."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so these two forces point an equal and opposite direction."}, {"title": "Introduction to Membrane Transport .txt", "text": "So they're equal in magnitude, they point in opposite directions."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so this marker is not going to move in the same way that the sodium ion is not going to move because of the presence of the hydrophobic barrier."}, {"title": "Introduction to Membrane Transport .txt", "text": "That sodium, because it contains a full positive charge, it cannot dissolve in the non polar hydrophobic core."}, {"title": "Introduction to Membrane Transport .txt", "text": "So what these membrane channels do is they essentially create a passageway in that membrane that basically doesn't contain that hydrophobic core."}, {"title": "Introduction to Membrane Transport .txt", "text": "And what that means is what that channel does is it removes that hydrophobic core so that now that marker can move down its gravitational potential in the same way that the channel creates this passageway that doesn't contain the hydrophobic regions anymore."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so now it moves down its potential gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we essentially remove that force that existed due to these hydrophobic regions."}, {"title": "Introduction to Membrane Transport .txt", "text": "Remove that force, we only have the electric force."}, {"title": "Introduction to Membrane Transport .txt", "text": "So now these will move down their potential gradient from a high electric potential to a low electric potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, because these channels essentially create these passageways that essentially lack the hydrophobic core, what these channels do is they facilitate the spontaneous diffusion of these ions, in some cases, molecules down their electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "So this type of transport is known as facilitated the fusion."}, {"title": "Introduction to Membrane Transport .txt", "text": "And because they don't use any energy molecules, for instance, ATP molecules, to carry out the process, this type of transport is known as passive transport."}, {"title": "Introduction to Membrane Transport .txt", "text": "So it doesn't use any ATP."}, {"title": "Introduction to Membrane Transport .txt", "text": "So let's summarize our results."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have certain ions which contain full, positive or negative charges and molecules which are very polar or large."}, {"title": "Introduction to Membrane Transport .txt", "text": "These cannot move across the cell membrane because they cannot dissolve inside the hydrophobic nonpolar region of that membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, channels are essentially these pathogeways that allow these ions or molecules to move and bypass the non polar core of that membrane, so they can cross that cell membrane without ever interacting with that hydrophobic core of the membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "So in this particular case, we saw that all the sodium ions can spontaneously move down their electrochemical gradient, just like the market can move spontaneously down its gravitational potential gradient from a high to a low."}, {"title": "Introduction to Membrane Transport .txt", "text": "We have this barrier, the hydrophobic core, that prevents the movement of those sodium ions, just like my hand prevents the movement of this marker down its potential gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "And channels essentially remove that hydrophobic core and allow those ions to move down that passageway that does not contain that hydrophobic core."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so what that means is this type of movement is known as facilitated diffusion."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, since channels move ions and molecules down their electrochemical gradient, no energy is actually used."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so what that means is this mode of transport is known as passive transport."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, we have many different types of examples of channels that exist inside our body."}, {"title": "Introduction to Membrane Transport .txt", "text": "And two examples that we're going to focus on in future lectures will be voltage gated channels and gap junctions."}, {"title": "Introduction to Membrane Transport .txt", "text": "So voltage gated channels are used by our neurons to basically create that action potential, while gap junctions are used by, for instance, our cardiac muscle cells to create this forceful contraction of the heart."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now let's move on to membrane pump."}, {"title": "Introduction to Membrane Transport .txt", "text": "So what exactly is the major difference between membrane channels and membrane pump?"}, {"title": "Introduction to Membrane Transport .txt", "text": "So, both of these types of transport, membrane proteins basically move large and polar molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "But the difference is the channels do not use energy and they always move down their electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "From a high to a low potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "But membrane pumps actually use energy to actually move these molecules against their electrochemical gradient from a low potential to high potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "And this is analogous to basically moving this marker from a low potential to a high potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "So this marker will never, by itself spontaneously move from a low to high potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "To actually get it to move from here to here, I have to take this mark or move it along this line."}, {"title": "Introduction to Membrane Transport .txt", "text": "So I have to apply force, I have to move this and do works, I have to transfer energy."}, {"title": "Introduction to Membrane Transport .txt", "text": "And in the same exact way, these membrane pumps utilize energy to move these ions and molecules against their electrochemical gradient from a low to a high potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "And because they use energy, we call them active transporters."}, {"title": "Introduction to Membrane Transport .txt", "text": "So this type of mode of transport is known as active transport."}, {"title": "Introduction to Membrane Transport .txt", "text": "So unlike channels, pumps utilize energy."}, {"title": "Introduction to Membrane Transport .txt", "text": "So the energy can be the energy stored in the chemical bonds of ATP molecules."}, {"title": "Introduction to Membrane Transport .txt", "text": "Or some types of pumps can also actually absorb light energy."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have these pumps that utilize energy to move ions and molecules across a membrane."}, {"title": "Introduction to Membrane Transport .txt", "text": "And they use energy because they have to move them against the electrochemical gradient from a low potential to a high electric potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so these pumps are known as active transport as they use these ATP molecules and energy to actively move these molecules against their electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, there are two types of membrane proteins."}, {"title": "Introduction to Membrane Transport .txt", "text": "We have two types of membrane pumps."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have membrane pumps that use ATP molecules as the energy source molecules and they use them directly."}, {"title": "Introduction to Membrane Transport .txt", "text": "And these are known as Atpas."}, {"title": "Introduction to Membrane Transport .txt", "text": "So pumps that utilize ATP directly, hydrolyzed ATP, are known as Atpas."}, {"title": "Introduction to Membrane Transport .txt", "text": "We also have membrane pumps that we call secondary transporters or co transporters."}, {"title": "Introduction to Membrane Transport .txt", "text": "And we'll discuss these and what they are just in a moment."}, {"title": "Introduction to Membrane Transport .txt", "text": "So let's begin with Atpas."}, {"title": "Introduction to Membrane Transport .txt", "text": "So let's suppose we take the sodium ions one more."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we have a high concentration, a low concentration electric field lines basically point in the direction."}, {"title": "Introduction to Membrane Transport .txt", "text": "That means these sodium ions want to move naturally from a high potential to a low potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "But now we're looking not at a channel, but at an ATPase, a pump that uses ATP."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so what this does is it uptakes an ATP molecule from the inside, it hydrolyzes that ATP molecule."}, {"title": "Introduction to Membrane Transport .txt", "text": "And that creates a conformational change in the structure of that pump."}, {"title": "Introduction to Membrane Transport .txt", "text": "And once that conformational change takes place, it basically forces a sodium ion to move against its electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "From the inside a low potential, to the outside a high potential."}, {"title": "Introduction to Membrane Transport .txt", "text": "So the pump actually uses energy stored in the chemical bonds of ATP and moves the sodium against the electric field lines against this electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "And so that's exactly what a pump is, an Atpas."}, {"title": "Introduction to Membrane Transport .txt", "text": "And we're going to look at many different types of examples of Atpas."}, {"title": "Introduction to Membrane Transport .txt", "text": "So two types of examples that we're going to look at are the ptype, Atpas and the ABC transporter, which is also an ATP ace."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, all types of pumps are energy transducers and what that basically means is they transform energy from one form to another."}, {"title": "Introduction to Membrane Transport .txt", "text": "So in the case of ATP Aces, they transform the energy stored in the chemical bonds of ATP into the energy stored in establishing that electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we see that membrane pumps are responsible for actually using ATP or energy to create establish these electrochemical gradients."}, {"title": "Introduction to Membrane Transport .txt", "text": "And then the membrane channels use these gradients to basically move these molecules spontaneously from one side to the other side down that electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "So we said a moment ago that we have two types of pumps."}, {"title": "Introduction to Membrane Transport .txt", "text": "We have ATP Aces and we also have second air transporter."}, {"title": "Introduction to Membrane Transport .txt", "text": "So really briefly, what exactly is a secondary transporter?"}, {"title": "Introduction to Membrane Transport .txt", "text": "Well, a secondary transporter is a pump that doesn't use ATP directly."}, {"title": "Introduction to Membrane Transport .txt", "text": "What it does instead is it uses the electrochemical gradient of one molecule to move a second molecule against its electrochemical gradient."}, {"title": "Introduction to Membrane Transport .txt", "text": "An example that we're going to focus on are the lactose transporters that we find and equalize cells."}, {"title": "Introduction to Membrane Transport .txt", "text": "Now, of course, we also have many different types of secondary transporters that we find inside our own cells of the body, as we'll see in a future electrom."}, {"title": "Cleavage and Blastulation .txt", "text": "Embryological development are a series of complex and intricate processes that ultimately allow the zygote following fertilization to develop into the billions and billions of cells that make up the adult individual."}, {"title": "Cleavage and Blastulation .txt", "text": "And in this lecture we're going to discuss the first two processes of embryological development."}, {"title": "Cleavage and Blastulation .txt", "text": "We're going to focus on cleavage as well as blaster."}, {"title": "Cleavage and Blastulation .txt", "text": "But first, let's begin by taking a look at the following diagram that describes the structure of the female reproductive system."}, {"title": "Cleavage and Blastulation .txt", "text": "So we have the ovary, we have the fallopian tube and we have the uterus."}, {"title": "Cleavage and Blastulation .txt", "text": "Now what happens inside the ovary?"}, {"title": "Cleavage and Blastulation .txt", "text": "Well, inside the ovary we have the development of that oocide."}, {"title": "Cleavage and Blastulation .txt", "text": "The oocide is found inside the follicle."}, {"title": "Cleavage and Blastulation .txt", "text": "So the primary follicle becomes a secondary follicle."}, {"title": "Cleavage and Blastulation .txt", "text": "In the process we produce estrogen."}, {"title": "Cleavage and Blastulation .txt", "text": "And the estrogen, what it does is it begins the thickening of the lining of the uterus."}, {"title": "Cleavage and Blastulation .txt", "text": "It initiates the thickening of the endometrium that is needed for implantation to actually take place."}, {"title": "Cleavage and Blastulation .txt", "text": "So eventually when you form the mature secondary follicle, ovulation takes place and that follicle ruptures, releasing that secondary oocide, the xcel, into the pericneal cavity."}, {"title": "Cleavage and Blastulation .txt", "text": "And from the Peric neal cavity the secondary oocide moves into our fallopian tube."}, {"title": "Cleavage and Blastulation .txt", "text": "This structure right here."}, {"title": "Cleavage and Blastulation .txt", "text": "Now the fallopian tube basically acts as a passageway and allows the movement of the secondary oocide, the excel, along this canal and into the uterus."}, {"title": "Cleavage and Blastulation .txt", "text": "So inside the fallopian tube, the cells that line the fallopian tube contains cilia and the wavelike motion of the cilia allows the movement of that oocide along the fallopian tube."}, {"title": "Cleavage and Blastulation .txt", "text": "In addition, the peristalsis, the contraction of the muscle along the fallopian tube also allows the movement of that oicide along that canal and to the uterus."}, {"title": "Cleavage and Blastulation .txt", "text": "Now let's suppose that this particular individual undergoes sexual intercourse so that sperm cells are deposited into the vaginal cavity."}, {"title": "Cleavage and Blastulation .txt", "text": "From the vaginal cavity those sperm cells move into the uterus and eventually make their way into the fallopian tube."}, {"title": "Cleavage and Blastulation .txt", "text": "And at this portion, at the thickest portion of the fallopian tube a single sperm cell will combine with this secondary OSI."}, {"title": "Cleavage and Blastulation .txt", "text": "And this is the process of fertilization."}, {"title": "Cleavage and Blastulation .txt", "text": "So fertilization takes place within this section."}, {"title": "Cleavage and Blastulation .txt", "text": "Now following fertilization we have an influx of calcium ions into the cytoplasm of that form zygote."}, {"title": "Cleavage and Blastulation .txt", "text": "And what the influx of calcium ions does is it initiates a set of metabolic processes."}, {"title": "Cleavage and Blastulation .txt", "text": "For example, it initiates the Cortical reaction and this leads to the formation of a membrane that basically is impermeable to sperm cells."}, {"title": "Cleavage and Blastulation .txt", "text": "So no other sperm cell can actually make its way into that xcel."}, {"title": "Cleavage and Blastulation .txt", "text": "Now the influx of calcium ions also initiates other metabolic processes such as protein synthesis."}, {"title": "Cleavage and Blastulation .txt", "text": "And eventually this leads to the process of mitosis."}, {"title": "Cleavage and Blastulation .txt", "text": "So the zygote begins to divide following, shortly afterwards, the process of fertilization."}, {"title": "Cleavage and Blastulation .txt", "text": "Now why would the zygote actually want to or need to divide?"}, {"title": "Cleavage and Blastulation .txt", "text": "Well, because the entire organism contains cells."}, {"title": "Cleavage and Blastulation .txt", "text": "The building blocks of the organism are cells."}, {"title": "Cleavage and Blastulation .txt", "text": "And that means we have to take that single cell zygote and develop as many cells as possible."}, {"title": "Cleavage and Blastulation .txt", "text": "And that's exactly why mitosis begins to take place shortly following fertilization."}, {"title": "Cleavage and Blastulation .txt", "text": "So right about here, we have the first mitotic process take place and the unicellular zygote begins to undergo mitosis."}, {"title": "Cleavage and Blastulation .txt", "text": "It replicates the DNA and then cytokinesis takes place."}, {"title": "Cleavage and Blastulation .txt", "text": "And we form a structure that contains two identical cells that are equal size and which have the same exact genetic information."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, by definition, a zygote only consists of one cell."}, {"title": "Cleavage and Blastulation .txt", "text": "And as soon as we form these two cells, this is no longer a zygote, but now we refer to it as the developing embryo."}, {"title": "Cleavage and Blastulation .txt", "text": "So this is a two cell embryo, which is found right about here."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, following this process, two cells are not enough."}, {"title": "Cleavage and Blastulation .txt", "text": "We have to produce hundreds of cells."}, {"title": "Cleavage and Blastulation .txt", "text": "And so what happens is these two cells begin to divide via the same process, mitosis."}, {"title": "Cleavage and Blastulation .txt", "text": "So they produce a four celled embryo."}, {"title": "Cleavage and Blastulation .txt", "text": "And so now we have these four identical cells that contain the same exact genetic information."}, {"title": "Cleavage and Blastulation .txt", "text": "And this process doesn't stop here."}, {"title": "Cleavage and Blastulation .txt", "text": "It continues."}, {"title": "Cleavage and Blastulation .txt", "text": "Eventually, we form a structure that consists of 32 identical cells that all carry the same exact genetic information."}, {"title": "Cleavage and Blastulation .txt", "text": "At this point, these individual cells are called blastomirs."}, {"title": "Cleavage and Blastulation .txt", "text": "And this entire structure is called the morala."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, what the morala is, is this spherical structure of identical cells."}, {"title": "Cleavage and Blastulation .txt", "text": "And this is a structure that is, that exists during the process of cleavage."}, {"title": "Cleavage and Blastulation .txt", "text": "So everything we discussed so far, which are basically very quick and very rapid mitotic divisions, this process is known as cleavage."}, {"title": "Cleavage and Blastulation .txt", "text": "And during cleavage, the cells, individual cells, do not actually grow."}, {"title": "Cleavage and Blastulation .txt", "text": "In fact, the cells get smaller and smaller."}, {"title": "Cleavage and Blastulation .txt", "text": "But these cells are identical."}, {"title": "Cleavage and Blastulation .txt", "text": "They carry the same exact genetic information and they are of equal size."}, {"title": "Cleavage and Blastulation .txt", "text": "So what exactly is the purpose of cleavage?"}, {"title": "Cleavage and Blastulation .txt", "text": "Well, the purpose of cleavage is to actually partition that zygote into many identical cells so that we can use these identical cells later on as the building blocks to actually form that developing embryo and eventually form that organism, the adult organism."}, {"title": "Cleavage and Blastulation .txt", "text": "So this is the process of cleavage."}, {"title": "Cleavage and Blastulation .txt", "text": "Now let's move on to the process known as blastulation."}, {"title": "Cleavage and Blastulation .txt", "text": "So this structure here, the morala, will continue dividing these individual cells."}, {"title": "Cleavage and Blastulation .txt", "text": "The blastomirs will continue to divide via mitosis until we form a sphere that consists of hundreds of cells."}, {"title": "Cleavage and Blastulation .txt", "text": "And inside the sphere, we're going to have a hollow cavity that will consist of fluid."}, {"title": "Cleavage and Blastulation .txt", "text": "And this entire structure is called the blastula."}, {"title": "Cleavage and Blastulation .txt", "text": "And this process is known as blastulation."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, in humans and other mammals, the blastula is also known as a blastocyst."}, {"title": "Cleavage and Blastulation .txt", "text": "And the inner cavity, the fluid filled cavity of that structure is known as a blastoceal."}, {"title": "Cleavage and Blastulation .txt", "text": "So this is the process of blastulation."}, {"title": "Cleavage and Blastulation .txt", "text": "So the morala, the individual cells of the morala will continue to divide via the process of mitosis."}, {"title": "Cleavage and Blastulation .txt", "text": "And eventually they will begin to organize themselves into this threedimensional structure shown here known as the blastocyst, or the blastula so notice we have three important components of the blastocyst."}, {"title": "Cleavage and Blastulation .txt", "text": "We have this outer structure of cells known as the trophy blast."}, {"title": "Cleavage and Blastulation .txt", "text": "We have this inner collection of cells found on one side known as the inner cell mass."}, {"title": "Cleavage and Blastulation .txt", "text": "And then we have this hollow cavity that contains a fluid that is used to basically provide the nutrition to these cells that the cells need to actually grow and develop."}, {"title": "Cleavage and Blastulation .txt", "text": "And this cavity is known as a blastoceal."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, what exactly is the function of the inner cell mass and the trophy blast?"}, {"title": "Cleavage and Blastulation .txt", "text": "Well, the trophy blast will eventually develop into the coriane and the placenta of the fetus, while the inner cell mass, these cells here, shown in light purple, will eventually develop into the actual organism, into the tissues, into the organs and the systems of that individual."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, notice, everything we've discussed so far was actually before implantation took place."}, {"title": "Cleavage and Blastulation .txt", "text": "So during fertilization, the zygote begins to move."}, {"title": "Cleavage and Blastulation .txt", "text": "It undergoes the first mitotic division."}, {"title": "Cleavage and Blastulation .txt", "text": "And right about here, we form that marula, or the Morola."}, {"title": "Cleavage and Blastulation .txt", "text": "And what this morala consists of is these 32 identical cells that carry the same exact genetic information of which are of equal size."}, {"title": "Cleavage and Blastulation .txt", "text": "And eventually, as this structure moves its way and makes its way into the actual space of the uterus, it develops into the blastula via the process of blastulation."}, {"title": "Cleavage and Blastulation .txt", "text": "So this is this structure right here, and eventually what happens is five to eight days following fertilization, that blastula will implant itself onto the endometrium, the lining of that uterus that was prepared by the two hormones, estrogen as well as progesterone, that were released by the corpus luteum."}, {"title": "Cleavage and Blastulation .txt", "text": "Now, only if implantation actually takes place can the Blasphema develop into the next structure."}, {"title": "Cleavage and Blastulation .txt", "text": "And we're going to focus on that in the next lecture."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So once we successfully purify that protein of interest, what do we do next?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Well, logically speaking, if we don't know anything about that protein that we just isolated, what we want to do first is we want to actually determine what the amino acid composition is within that protein."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we want to know what types of amino acids are found within that protein and how many of each amino acid is found within that protein."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So how do we calculate this information?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "How do we find this information?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So this is what we're going to look at in this lecture."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we're going to begin by assuming we know what our protein is."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So let's suppose we have a six amino acid polypeptide."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we have alanine, arginine, phenylalanine, glycine, aspartate, and glycine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Now, of course, usually you don't know what that protein actually is, but in this lecture, I give you the composition of that protein to basically show you how this method actually works."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So once we have that beaker, and inside that beaker, we have the solution that consists of only this type of protein."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "What do we do first?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Well, ultimately, what we want to do is we want to separate the amino acids, the different amino acids, into different compartments."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And then we want to count up how many amino acids are found within each compartment."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "But to actually separate our amino acids, we first have to break the bonds holding these amino acids together in that polypeptide chain."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So in the first step, we basically want to break the bonds."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And the way we break the peptide bonds is we take this peptide, we place it into a solution that consists of six molar hydrochloric acid at a temperature of 110 degrees Celsius."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And we wait for about 24 hours."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And what will happen is that will hydrolyze and break down the peptide bonds separating these amino acids."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so following the addition of our peptide into this solution, at this temperature, for 24 hours, we're going to have a solution that consists of these individual constituent amino acids floating around in that water."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Now, what exactly is the next step?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So once we separated these amino acids, now we want to actually separate them into these individual compartments."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So how exactly do we separate them into individual beakers?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we're going to basically use a procedure that we spoke about earlier."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We're going to use the ion exchange chromatography technique."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And this technique basically separates our molecules based on their net charge."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So remember, these different amino acids will contain different side chain groups, and that means they will contain different properties such as the net charge."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we'll see exactly how that is useful in just a moment."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So let's suppose that this is our setup."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So this is the funnel placed on top of our column."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Inside the column, we have these specially formed gel beads that essentially contain a charge."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So in this case, we're going to use negatively charged beads."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So this is our ion exchange chromatography technique."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And we take the beaker that consists of these amino acids in their individual form and we essentially pour it into our funnel so that eventually they end up in this column."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And because these have charges, they will interact with the charges found inside our column."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so what will happen is they're going to bind the different sections of our column."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So for example, we see that Alamine is somewhere here."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We see that Aspartate is here."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We see that Glycine is here and here and so forth."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Now, once these are actually down, right, what will happen next?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Well, the binding process differs for each one of these amino acids."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And that's because they have different charge values and they have different types of side chain groups."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And what that means is when we actually wash our column down with some type of material, when we wash them down, they will basically detach depending on what the concentration, what the PH, and what the volume is of that particular buffer."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we can use a buffer, for example, sodium side trait of increasing PH to basically wash down our column."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And as we wash down the column, these amino acids will begin to elude at different rates."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So the identity of the amino acid can be determined based on the volume of the buffer and the PH of the buffer that is needed to actually elude that amino acid."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we essentially have these values that we can find in a textbook and then we can actually determine what the values that we use are, and then we can compare them to those textbook values and see exactly what amino acid we are dealing with."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So, to see what we mean, let's suppose we use a buffer at a relatively low PH, and we use a very small amount of that volume before we see that one of those amino acids actually eludes."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so if we know if we calculate how much volume we used and what the PH of that is, and we compare to our textbook value, we'll see that the first amino acid was this green amino acid, which is aspartate."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So d. Now we continue our process, we continue pouring and we increase the amount of volume and we might change our PH."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And then once we see that a second amino acid loops, then we write down how much volume we use and what the PH of that buffer was."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We compare it to our textbook value and we see that it is this quantity here."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So the x axis basically describes the volume of the buffer that is added in order to loot that amino acid."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So in this area, we have a very acidic buffer that we use."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "In this area, it's not as acidic."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So as we go this way, the acidity of our buffer basically decreases."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "It becomes more basic."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "At the same time, the volume increases going in that direction."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we see that the second amino acid basically is our g, and that's glycine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Then we see that the next one in line is Alanine, because this much volume is basically used at a specific type of PH."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And we continue our process until we see that the next one is phenylalalamine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And finally, all the way here, we have the r, which is arginine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And that makes sense because arginine is the most basic and aspartate is the most acidic."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So step two basically allows us to actually separate our amino acids into different containers."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And now we know what amino acid is found in which one of our containers, so we know which amino acids we have."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "The next question is, how many of each amino acids do we have in that beaker?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we want to count up those amino acids, and that's exactly what we do in step three."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So now that we know the types of amino acids involved, we must determine what the quantity of each one is in our polypeptide."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And the way that we're going to do that is use a special type of molecule known as ninhydran."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So here we have our five beakers that we basically separated in step two."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So in beaker one, we basically have arginine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "In beaker two, we have glycine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "In beaker three, we have aspartate."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "In beaker four, we have phenoalamine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And in beaker five, we have alanine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we know which amino acids we have because we were able to compare to our textbook standard value, as shown in this diagram."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "The next question is, what is the concentration?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "How many of these amino acids are found in each one of these solutions?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So what we do is we take each one of these solutions."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We basically add this special molecule known as ninhydrin."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And what ninhydrate does is it reacts with that amino acid to form a special type of molecule that is able to absorb a particular frequency or a particular wavelength of light."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And for 19 of the 20 amino acids, it basically produces a very, very dark blue color or a very, very dark purple color."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we place them in hydrogen, it reacts with our amino acid, and then we basically heat it and we produce a mixture."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Now, once we heat that, we can then take a sample out of that beaker, and we can place it into a special apparatus that essentially collects or determines how much light that solution can absorb."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And we do that because after heating the solution of Ninhydrate and the amino acid, we can test the solution for light absorption, because the higher the concentration of that amino acid is inside that solution that contains ninhydrin, the more light our solution actually absorbs."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "For example, let's suppose we take this first beaker."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We add the hydrant to it and we heat it."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so this will turn dark blue or dark purple."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And then we take a pipette."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "We take a small sample out of that mixture, and we place it into a special apparatus that is able to absorb light or determine how much light is actually absorbed."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so we shine light at a specific wavelength, it absorbs them, and we determine how much is absorbed."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And we do it with every one of these beakers."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And then we plot it on an x y axis, where the y axis is the absorption of light, and the x axis is the type of amino acid we actually use."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so what we see is the higher our value is, the higher this slope is, the higher our absorption is."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And because in this protein, we have one alanine, one arginine, one phenylalanine, and one aspartate, the height of these values will be exactly the same."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "But because we had two glycine amino acids, what that means is this will be twice as high as any other one of these slopes."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so what that means is we have twice as many of the glycine."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So in this case, we have one, two as these other ones."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So we have one, one, one, and two."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "And so in this manner, by using this step three, we can basically determine what the relative amount is of each one of these amino acids in our protein."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "So now we know what the composition is, we know what types of amino acids we have, and we also know how many of each one do we you have."}, {"title": "Amino Acid Composition in Proteins .txt", "text": "What exactly is the next step?"}, {"title": "Amino Acid Composition in Proteins .txt", "text": "Well, in the next lecture, as we'll see, the next step is to actually determine what the specific sequence is of those amino acids inside that polypeptide chain."}, {"title": "Circulation in Fetal Heart .txt", "text": "As we know, the way that blood moves inside the circulatory system of the developing Fetus is quite different than the way that blood moves inside the circulatory system of the fully functional adult individual."}, {"title": "Circulation in Fetal Heart .txt", "text": "So in this lecture we're going to discuss, we're going to focus on the way that blood moves inside the heart of that developing Fetus."}, {"title": "Circulation in Fetal Heart .txt", "text": "So let's begin inside the inferior venacava."}, {"title": "Circulation in Fetal Heart .txt", "text": "So we know that along the inferevenicaver, we have the partially oxygenated blood that is moving along and eventually moves into the right atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "But before it moves into the right atrium of the heart, the partially oxygenated blood that moves along the inferior venecrava eventually combines with the deoxygenated blood that is moving along the superior venecave and which is coming from the extremities found on the upper side of that developing Fetus."}, {"title": "Circulation in Fetal Heart .txt", "text": "So we have the deoxygenated blood is moving along our superior venecaa."}, {"title": "Circulation in Fetal Heart .txt", "text": "It eventually combines and mixes with the blood that is coming from this, the inferior venecrava."}, {"title": "Circulation in Fetal Heart .txt", "text": "So we have the partially oxygenated blood is moving along the inferior venecrava, and eventually it combines and it goes into the right atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, once inside the right atrium of the heart, what does the blood do next?"}, {"title": "Circulation in Fetal Heart .txt", "text": "Well, normally, in the fully functional adult individual, the blood will go into the right ventricle."}, {"title": "Circulation in Fetal Heart .txt", "text": "But what happens in the lungs is it doesn't actually go or the majority of it doesn't go into the right ventricle."}, {"title": "Circulation in Fetal Heart .txt", "text": "Instead, it passes along the wall of that atria, and it goes into this section here, the left atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, the reason for that is because if we examine inside the lungs, inside the alveoli of the lungs, those alveoli are completely filled with the fluid."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so because of that, there will be a high resistance and a high pressure inside the lungs."}, {"title": "Circulation in Fetal Heart .txt", "text": "And because of this high pressure in the lungs, and because the lungs are not functional inside that developing Fetus, this blood will move into the left atrium and not into the left ventricle."}, {"title": "Circulation in Fetal Heart .txt", "text": "So because on the right side of the heart we have a higher pressure then on the left side of the heart, as a result of the high pressure inside the lungs, the majority of that blood, the partially oxygenated blood, will move from the right atrium, this chamber here, via the pharamino valley and into the left atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, what exactly is this for amino valley?"}, {"title": "Circulation in Fetal Heart .txt", "text": "Well, in that developing Fetus, the wall that is separating the two atria contains this one way door, a valve system."}, {"title": "Circulation in Fetal Heart .txt", "text": "And if we push against that valve system, it essentially opens up."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so because of the higher pressure, it pushes against this forraminal valley, the valve, and it basically pops open and the blood flows into the left atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "And as a result, what that means is the partially oxygenated blood is able to actually bypass those nonfunctional high pressure lungs."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, of course, a tiny amount of that blood will still get into the right ventricle of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "So a portion of that blood does, in fact, move into the right ventricle of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "And actually that's important because when that heart of that fetus is developing, we have to be able to develop the wall of those ventricles."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so a tiny portion of the blood goes into the ventricle, meaning this right ventricle can actually now contract."}, {"title": "Circulation in Fetal Heart .txt", "text": "And as it contracts, it develops the wall of the ventricle."}, {"title": "Circulation in Fetal Heart .txt", "text": "So that partially oxygenated blood goes into the left of the right ventricle, the right ventricle contracts, and then it sends that partially oxygenated blood into the pulmonary trunk."}, {"title": "Circulation in Fetal Heart .txt", "text": "So it moves this way, then it moves via this valve system and into the pulmonary trunk."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, once inside the pulmonary trunk, what happens next?"}, {"title": "Circulation in Fetal Heart .txt", "text": "Well, this is the second difference between the fully functional adult heart and this developing fetal heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "So we have another type of shunt known as the ductus arteriosis."}, {"title": "Circulation in Fetal Heart .txt", "text": "And because of the ductus arteriosis, and because the pressure inside the pulmonary trunk is higher than the pressure inside this eight order, what happens is to minimize the amount of partially oxygenated blood from going into the lungs, we have the blood going via this duct and into our eight order."}, {"title": "Circulation in Fetal Heart .txt", "text": "So the majority of the blood that actually flows into the pulmonary trunk from the right ventricle goes directly into the systemic circulatory system, into the order bypassing our lungs."}, {"title": "Circulation in Fetal Heart .txt", "text": "Now, of course, the lungs do need oxygen."}, {"title": "Circulation in Fetal Heart .txt", "text": "They do need a tiny bit of oxygen to actually develop over time so that once that fetus is born, those lungs can function effectively and efficiently."}, {"title": "Circulation in Fetal Heart .txt", "text": "So a tiny amount of oxygenated blood does actually pass along aropulmonary arteries and eventually reaches the capillaries of the lungs."}, {"title": "Circulation in Fetal Heart .txt", "text": "So these are the capillaries of the lungs."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so once the oxygen is deposited into our lungs, what happens is that deoxygenated blood returns via these pulmonary veins and it returns into the left vet, or the left atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "So it travels this way along these pulmonary veins, and eventually it connects and it deposits into the left atrium of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so we see that we have a mixing of the oxygenated blood coming in from the right atrium and the deoxnated blood that is coming from the lungs and that mixes within the left atrium."}, {"title": "Circulation in Fetal Heart .txt", "text": "Then that blood moves into the left ventricle of the heart."}, {"title": "Circulation in Fetal Heart .txt", "text": "And when the left ventricle of the heart contracts, it forces all that blood to move into the systemic circulatory system, more specifically into this blood vessel here, known as our aorter."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so now we have the mixing of this partially oxygenated blood with this partially oxygenated blood coming in from the pulmonary trunk."}, {"title": "Circulation in Fetal Heart .txt", "text": "And then the blood moves into the upper extremities, as well as along the following canal and down here into the lower extremities."}, {"title": "Circulation in Fetal Heart .txt", "text": "And so this is the way that our blood actually travels within our developing Fetus, and we see that it's quite different than the way that blood moves inside the fully functional adult heart."}, {"title": "Interferons.txt", "text": "One important aspect of the innate immune system that I forgot to mention previously are a group of biological molecules known as interferon."}, {"title": "Interferons.txt", "text": "So the question that we're going to briefly address in this lecture is how exactly does our innate nonspecific immune system deal with pathogens that ultimately end up making their way into the cells of our body such as viruses and other intracellular parasites."}, {"title": "Interferons.txt", "text": "So let's take a look at the following diagram."}, {"title": "Interferons.txt", "text": "Let's suppose some type of virus infects our cell and this is the infected cell shown in red."}, {"title": "Interferons.txt", "text": "So the virus injects some type of RNA or DNA into that cell infecting that cell."}, {"title": "Interferons.txt", "text": "Now, how exactly does our innate non specific immune system deal with these types of viral and parasitic infections?"}, {"title": "Interferons.txt", "text": "Well, what happens is the infected cell begins to produce a biological molecule known as an interferon and we have many different types of interferons."}, {"title": "Interferons.txt", "text": "So these purple molecules here are the interferon."}, {"title": "Interferons.txt", "text": "So the infected cell begins to produce these interferons and the cell releases these interferons to the surrounding environment."}, {"title": "Interferons.txt", "text": "Now, what's the function of these interferons?"}, {"title": "Interferons.txt", "text": "Well, basically we have a bunch of healthy nearby cells shown in blue and we also have other wide blood cells that are in close proximity."}, {"title": "Interferons.txt", "text": "For example, we have the natural killer cell and we also have aromacrophages which play a role in the innate immune response."}, {"title": "Interferons.txt", "text": "So what these interferons do is they ultimately bind onto the membrane of these healthy blue cells and they prepare those cells for that viral infection."}, {"title": "Interferons.txt", "text": "For example, they ensure that these blue cells, healthy cells begin to produce special types of proteins that essentially are antiviral proteins."}, {"title": "Interferons.txt", "text": "They block viral replication from actually taking place."}, {"title": "Interferons.txt", "text": "So when this infected cell actually lyses it breaks open and releases the newly formed viruses."}, {"title": "Interferons.txt", "text": "And these viruses eventually make their way to these healthy cells."}, {"title": "Interferons.txt", "text": "These nearby healthy cells have already mounted a defense and are ready for that viral attack."}, {"title": "Interferons.txt", "text": "Now, on top of that, these interferons can also actually bind to these other specialized leukocytes, these other specialized white blood cells."}, {"title": "Interferons.txt", "text": "So we have macrophages and we have natural killer cells."}, {"title": "Interferons.txt", "text": "So once the interferon interacts with the natural killer cell it essentially guides that killer cell to this infected cell."}, {"title": "Interferons.txt", "text": "And what the natural killer cells ultimately do is they destroy the infected cells and they also destroy cancer cells."}, {"title": "Interferons.txt", "text": "Now, these interferons can also find these macrophages and they can guide the macrophages to the infected cell and these macrophages can ultimately engulf and degrade those infected cells."}, {"title": "Interferons.txt", "text": "Now, on top of that, one other important aspect of these interferons is if the infection is too far along and the cell cannot be saved then what the interferon can actually do is they can initiate stimulate the cell death of that infected cell."}, {"title": "Interferons.txt", "text": "For example, by breaking the Lysosomes and releasing the hydrocytic environment into the cytoplasm of that infected cell."}, {"title": "Interferons.txt", "text": "And that will ultimately kill off our cells."}, {"title": "Interferons.txt", "text": "So this is the method by which the innate, the nonspecific immune system of our body deals with viruses and other intracellular parasites that actually infect ourselves."}, {"title": "Interferons.txt", "text": "They use these biological molecules we call interferons."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Previously, in our introduction to the field of biotechnology, we mentioned a specific type of molecule known as a restriction enzyme or restriction endonuclease."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, restriction enzymes are these natural biological molecules found inside many prokaryotic cells, such as bacterial cells."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And what the biological purpose of these molecules is, is to protect those cells from different types of foreign pathogenic DNA molecules."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "For instance, if a virus that carries DNA infects a bacterial cell, the bacterial cell can protect itself by using these restriction enzymes."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And what these restriction restriction enzymes do is they bind onto that viral DNA molecule and they cleave it."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "They cut it up into smaller nonfunctional fragments."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, biochemists can actually extract and clone these restriction enzymes from these bacterial cells and prokaryotic cells, and we can use them for a variety of different purposes as we'll discuss in the next several electros."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So there are four purposes I've listed on the board."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we can use them to analyze and study some DNA molecules that we're interested in."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "We can also actually use them to determine the actual sequence of nucleotides of very, very long DNA molecules."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So if we have a long DNA molecule, we can use these restriction enzymes to cut the molecule to smaller fragments and then we can determine what the sequence is of the smaller fragments."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And by piecing together, by determining the order of the fragments, we can then determine what the order of the sequence of nucleotides is in that long DNA molecule."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, we can also use restriction enzymes to create recombinant DNA molecules and then we can actually clone and amplify those molecules if we want to."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And there are many other purposes, as we'll see in the next several lectras."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now let's move on to the mechanism of action."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "How exactly does this cleaving process take place?"}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So restriction enzymes are these proteins found in these natural biological system cells."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And they cleave via the process of hydrolysis phosphodiastor bonds that hold nucleotides together."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And these restriction enzymes basically cleave two phosphodiastor bonds in a single double helix DNA molecule and they cleave at specific palindromic sequences."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, to see what we mean by all that, let's take a look at a specific type of restriction enzyme that is found in E. Coli bacterial cells known as ECoR one."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, this restriction enzyme basically cleaves at this location and this location along the following palindromic sequence."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So notice we have a double stranded DNA molecule."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "We have one strand, and then we have the complementary lower strand."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And notice the blue section basically describes the palindromic sequence where this eco r one actually cleaves."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we have GAATTC."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And then if we read this this way, we get also GAATTC."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So palindromic simply means if we read it this way, it will be the same as if we read it this way along the complementary strand if we read it in this direction."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we go from five to three on this tran and from five to three on this strand."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so it reads the same exact sequence."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And notice that it cleaves between the ga on this side, and that means it will cleave between the ga on the opposing palindromic sequence."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So this and this is where it will use the process of hydrolysis to basically break the phosphodia ester bonds."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so this is one phosphodiaester bond and a second phospholester bond that it will break."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so once it cleaves those two phosphodiast bonds, we basically produce the following two fragments of DNA."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And notice in this particular case, we have these staggered or uneven regions that we form."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And these are commonly known as sticky ends because if we stick them back together, because they're complementary, they will essentially form those hydrogen bonds."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so we reform that strand that we essentially broke this into."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So notice that the restriction enzyme cuts at a palindromic sequence shown in blue."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "The cut sides are symmetrically positioned along the two strands of DNA."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we cut this region between the ga and this region also between our ga. Now, another way of saying that our mechanism of action is along a palindromic sequence is to basically say that the way we cut our double stream DNA molecule is to form a molecule that is characterized by a two fold rotational symmetry."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So this should be rotational symmetry."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So one interesting property of the majority of the cleavages that take place is that they are characterized by two fold rotational symmetry."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Now, to see what we mean by two fold rotational symmetry, let's take a look at the following diagram."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So, let's suppose we take just this blue sequence."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we have Gaaptc and then we have Cttaag."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So this side we're going to label in black."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we have five prime and we have three prime."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "This side we're going to label in purple."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we have three prime and we have five prime."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we add our ECoR, one restriction enzyme, and it cleaves."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "It breaks the phosphodiester, the bond here and the phosphodies, the bond here."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so we produce the following two fragments with these two sticky ends."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So what do we mean by a two fold rotational symmetry?"}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So, what we mean by that is if we take this molecule and we rotate it first about the x axis, 180 degrees, and then about the Y axis, also by 180 degrees."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So if we make the two types of rotations, a two full rotation, then at the end we will produce that same molecule."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So to see what we mean, let's actually conduct our rotation."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we make the cleavage."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So what we get is one fragment contains the five prime N in black with the G and the three prime N. So Cttaa and then the other end contains the three prime Aattc and the five prime in purple given by G. So if we make the first rotation by 180 degrees along the y axis."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So we basically flip it this way."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "These two will end up on this side and these two will end up on this side."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So the three will end up here."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "The five will end up here."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "The black five will end up here, the black three will end up here."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so will these corresponding sequences."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So here we have Cttaa."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Here we have g. Here we have g. And here we have Cttaa."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And now if we rotate this fragment 180 degrees along the X axis going this way, we essentially flip it this way."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Then what we get is the three will go on the bottom, this five will go on the top, this five will go in the bottom, this three will go on the top."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And so will these sequences."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And notice what we get after the two fold rotation, the 180 degree rotation about the Y and the X axis."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "We essentially produce a molecule that is exactly like this molecule here."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And that's exactly what we mean by a palindromic sequence."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "So this is what we usually see when we're dealing with these restrictions."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "Restriction enzymes."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "When restriction enzyme enzymes actually cleave the double stranded DNA molecules, they cleave it in such a way so that they produce this two fold rotational symmetry."}, {"title": "Restriction Enzymes and Palindromic Sequences .txt", "text": "And what that basically amounts to is they cleave at palindromic sequences as the one described in this particular example."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "In prokaryotic cells, such as bacterial cells, operons are used to regulate gene expression."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what about in eukaryotic organisms?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "How do eukaryotic cells, such as the cells found in our body, actually regulate gene expression?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Well, because eukaryotic cells are so much more complex than prokaryotic cells, we see that the method by which gene genes are regulated in eukaryotic organisms is much more complex than that in prokaryotic organisms."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And there are many different levels at which gene regulation and gene expression can actually take place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And in this lecture, we're going to focus on the most common method of regulating genes in eukaryotic cells, and this is on the level of transcription itself, so by actually changing the rate at which transcription takes place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So in this lecture, we're going to briefly discuss the different components that are found along a eukaryotic gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this basically describes a diagram of a basic eukaryotic gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And we have five important components."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "We have exxons, we have introns, we have our transcription start site, we have promoters, and we have enhancers."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So let's begin by discussing what we mean by exons and introns."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So, in any eukaryotic gene, we have those segments of DNA that actually do code for a polypeptide, and those segments that do not code for a polypeptide."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So in this particular diagram, these are the exons, they are segments of DNA that do code for a polypeptide."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "While these orange sections are the introns, they do not code for anything useful."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And eventually, during the process of RNA splicing, these sections are actually removed from that mRNA molecule and only these exons are actually left."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what about this segment right over here?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this green segment is known as the transcription start side, and this is where transcription actually begins."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So a special protein complex that consists of twelve proteins known as RNA polymerase two bind onto the start side, the transcription start side, and this is where initiation actually takes place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "This is where we begin the process of transcription."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this is our transcription start site."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this is our start site, this is exon number one, this is exxon number two and exxon number three, this is, let's say, intro number one, and this is intron number two."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So we have introns exxon's a start site."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what about this segment and this segment here?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So, together this entire region is known as the promoter."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So just like operons in prokaryotic cells contain promoters, so do these Eukaryotic genes, but the promoters of Eukaryotic genes are much more complex."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So we have different parts of the promoter, so the promoter can be broken down into the core promoter, which is basically shown in pink, this is our core promoter, and these remaining promoters are known as the upstream promoters."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, notice that the core promoter, this entire segment, is found upstream to the left of the start side."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "In fact, usually this is located about 40 basis to the left of our start side."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, this core promoter basically doesn't change from one eukaryotic gene to another eukaryotic gene, so it remains consistent."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "In fact, the most common type of core promoter is the Tata box core promoter."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And the reason we call it Tata box is because the sequence of nucleotides is Tata, and that doesn't change when we go from one eukaryotic gene to another."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So that recurs between different or that recurs within different types of eukaryotic genes."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what's so special about the Tata box?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "What's so special about the core promoter in general?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this is where all the different types of transcription factors and regulatory proteins actually bind to, and they form a complex that consists of over 50 different types of proteins."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And this complex is necessary for transcription to actually take place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So we have this complex of proteins that binds onto our Tata box and then basically calls upon other proteins, those other proteins bind, forming a larger complex and so forth."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And eventually that interacts with the protein found at the start side and that initiates the process of RNA transcription."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So two important types of proteins you should be familiar with is transcription factor two D and transcription factor two B."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, transcription factor 2D is itself a complex of many proteins, and one of the important proteins within the transcription factor 2D is known as the Tata binding protein or TBP."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And this is the protein that actually binds to the sequence Tata found on the core promoter."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, we also have the transcription factor to be, and this is the protein that is needed for the interaction to take place between the RNA polymerase, two protein found on the start side, and the task of binding protein."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So that's why we need the transcription factor two B."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So we see that the core promoter is where the majority of the proteins actually congregate when they actually bind."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what about these other upstream promoters?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So these are known as the upstream promoters."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "What's so special about the upstream promoters?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Well, these are also segments of DNA that allow the binding of different types of regulatory proteins."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So they can either be proteins that activate transcription or proteins that repress transcription, inhibit transcription from taking place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, unlike the core promoter, which doesn't really change when we go from one eukaryotic gene to another, we see that the number and the types of upstream promoters do vary between different types of eukaryotic genes."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, the final type of section that we're going to focus on is known as the enhancer."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this section is known as the enhancer, and notice it is found much farther away from our gene than anything else."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "In fact, the enhancer is usually found thousands of bases upstream or downstream our gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, what's so special about the enhancer?"}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Well, basically, the enhancer can also bind special transcription factors."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And when a transcription factor bind onto the enhancer, the enhancer will essentially loop around and bind onto the protein complex found on the promoter."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And this interaction will stimulate transcription and increase the rate of transcription of this gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So the enhancers are segments of DNA that are typically located far away from the gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "They can be either upstream, they can be either downstream, or they can also be, in some cases, inside that gene itself."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "Now, enhancers bind special transcription factor proteins that increase the rate of transcription."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And how that takes place is this entire complex essentially loops around."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this is our enhancer."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "This is the transcription factor."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So the transcription factor that bonds onto our enhancer, and then this entire complex."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So the transcription factor bounces the enhancer bind onto the protein complex found on the promoter."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And once that binding takes place, that stimulates the transcription of that particular gene."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "It increases the rate at which transcription actually takes place."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "So this is one method by which eukaryotic cells actually regulate the rate of their transcription."}, {"title": "Gene Regulation in Eukaryotes .txt", "text": "And we'll focus on this in much more detail when we'll get into biochemistry."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So far, in our discussion on carbohydrate molecules, we focus on the individual monomers of sugars we call monosaccharides."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, we're going to discuss how we can actually connect these individual monosaccharides together to form larger carbohydrate molecules."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And to begin in this lecture, we're going to focus on disaccharides."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, generally speaking, what exactly is a disaccharide?"}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Well, a disaccharide is a carbohydrate that consists of two individual monosaccharides which are connected by a special type of linkage, a special type of bond we call the Oglycocitic bond, which we introduced in the previous lecture."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, to demonstrate what types of disaccharides we can have and the types of Oglycocitic bonds that we can have in nature, let's take a look at the three most common types of disaccharide."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So, these are maltose, lactose, and sucrose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So let's begin with maltose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And this is what a single maltose disaccharide actually looks like."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So, a maltose disaccharide consists of an alpha D glucose in its cyclic form, bound to another alpha D glucose, also in its cyclic form."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And the binding takes place between carbon number one of the first glucose and carbon number four of the second glucose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, both of these molecules have the alpha an American figureation, and more specifically, because carbon number one of this first glucose have the alpha and American figureation."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So this oxygen basically points in the opposite direction downward, with respect to where this group points upward."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Then this special type of Oglyacidic bond in maltose is called the alpha glycocitic linkage, or glycocitic bond."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So alpha designates the configuration of this first anomary carbon of glucose number one."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "One four means we have a bond between the first carbon on the first glucose and the fourth carbon on the second glucose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So, in malatose, 2D glucose monosaccharides are linked via an Oglycocitic bond that exists between the first carbon of the first glucose and the fourth carbon of the second glucose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And as I just said, since carbon one of the first glucose has the alpha anemeric arrangement, we call the bond an alpha 114 glycositic bond."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, where exactly does maltose actually come from?"}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Well, maltose itself is formed when we actually break down starch, and starch is the polysaccharide that is stored in plants."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And we'll discuss starch in much more detail in the next lecture."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So when we ingest starch, we break down starch into these maltose disaccharides."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And when maltose makes its way into the brush border of our small intestine, we have these special digestive enzymes we call maltase molecules."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And maltase is the enzyme that is responsible for digesting and breaking down these alpha one four glycocitic bonds within maltose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So when maltose arrives, when maltose arrives at the brush border of the small intestine, an enzyme called maltase hydrolyzes, maltose disaccharides into their individual glucose constituents, and then those glucose molecules can be ingested into the cell."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, let's move on to the second common type of disaccharide we call lactose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And lactose is a disaccharide that is found in milk."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So lactose is disaccharide that is found in milk and which consists of two individual monosaccharides."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "The first monosaccharide is a galactose, and more specifically, it's the beta deglactose, while the second molecule, the second monosaccharide, is the alpha deglucose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So let's take a look at the structure of this lactose molecule."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So notice the linkage, just like in this particular case, is also between the first carbon of the first sugar molecule and the fourth carbon of the second sugar molecule."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "But notice that our bond on this anomaly, carbon of the first sugar, is or has the beta arrangement."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And what that means is this bond points upward in the same direction as this group, which also points upward."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And that's why we call it the beta anamer of D galactose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And because of this, this linkage is known as the beta one four glycositic bond."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So we have a bond between carbon 104, but because this points up, not downward, this is the beta arrangement."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And so we have the beta one four glycocitic bond."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, in humans, we also have an enzyme, or at least most people have an enzyme known as lactase that breaks down this lactose into the individual constituents, galactose and glucose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "In bacterial cells, the enzyme is called beta galactose, sedase."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And so these two enzymes are responsible for breaking down this same energy source in different organisms, one in humans and the other in bacterial cells."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And finally, let's take a look at sucrose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, sucrose is what we call table sugar."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And sucrose is the mobile form of carbohydrates that is found in plants."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And we obtain sucrose from cane plants or beet plants."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So sucrose, just like lactose and maltose, is a disaccharide."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And sucrose consists of two individual monosaccharides."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "One of them is the glucose, and the other one is fructose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And fructose exists as a five membered sugar."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So sucrose is a disaccharide that consists of an alpha glucose bound to a beta fructose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, unlike in this particular case, in this particular case where the bond is between carbon one and carbon four, the bond in sucrose is between the two anameric carbons on the two different sugar molecules."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And this happens to be a bond between carbon one of glucose, the first sugar, and carbon two of the second sugar, the fructose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So this is alpha D glucose in its cyclic form."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So we have carbon 12345 and six."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And the arrangement here is the alpha arrangement, because this bond points downward in the opposite direction to where this group actually points to."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, this is our beta defruptose, and this is carbon number one of the beta D fructose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So this is carbon number two, carbon number three, four, five and six."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And notice that this entire group points downward, which is the same direction as this group point."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So this group points downward, this group points downward."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And so for the fructose, this is the beta anamer because of the arrangement of this anomeric carbon."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So this carbon one is the anameric carbon of glucose and this carbon two is the animeric carbon of fructose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And because we have a bond between two anameric carbons, this is called the alpha twelve glycosytic linkage."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And because both of these anomeric carbons essentially have a bond, like shown by the blue linkage here, this sucrose, this disaccharide, is an example of a non reducing sugar."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So what exactly is a non reducing sugar?"}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Well, as we discussed previously, a non reducing sugar is a sugar that, when mixed with some type of oxidizing agent, will not react via an oxidation reduction reaction."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "On the other hand, if we have a reducing sugar, when a reducing sugar is in the presence of some type of oxidizing agent, it will be oxidized."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "It will react in an oxidation reduction reaction."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, Maltose and lactose are examples of reducing sugars."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And that's because if we examine this sugar here and this sugar here, if it opens up into its open chain form, it will have an aldehyde group."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And aldehyde groups are capable of reacting with oxidizing agents."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "On the other hand, in sucrose, because both of these anumericarbons are essentially occupied as a result of this bonding, none of these sugars will be able to open up into their open chain confirmation that contains a free aldehyde or a free ketone group."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And that means, because there is a lack of this reactivity, this will be a non reducing sugar."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So sucrose is an example of a non reducing sugar, while maltose and lactose are examples of reducing sugars."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So again, unlike Malcolm and Lactose, which are reducing sugars, sucrose is a non reducing sugar because neither glucose nor fructose within this sucrose molecule can be transformed into an open chain confirmation with a free aldehyde or a free ketone group."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And so these cannot be oxidized in the presence of an oxidizing agent."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "Now, just like we have an enzyme, narrow small intestine, that breaks down maltose and lactose, we also have an enzyme, narrow small intestine, that breaks down sucrose."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "And this enzyme is called sucrase."}, {"title": "Disaccharides (maltose, lactose, and sucrose) .txt", "text": "So sucrose is broken down by an enzyme we call sucrase that is found on the brush border of our small intestine."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Many of the processes that take place inside our cells and generally in nature sometimes actually have negative effects."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And the electron transport chain is no exception."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So even though the electron transport chain is very useful to our cells because it allows us to establish a proton gradient across the inner membrane of the mitochondria which ultimately allows us to generate these high I energy ATP molecules the electron transport chain also sometimes produces these harmful byproduct molecules that can cause damage to ourselves."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And because these harmful byproduct molecules are actually oxygen derivative molecules we call them reactive oxygen species."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, before we actually talk about these molecules in slightly more detail let's remember what happens on the normal conditions in complex four of the electron transport chain."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So, remember, the entire point of the electron transport chain is to actually take those high energy electrons produced by creating the NADH molecules and fadh two molecules and using those electrons to create a proton gradient."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And the final accept of electrons is diatomic oxygen."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And in complex four of the electron transport chain a total of four electrons and four protons are combined into diatomic oxygen to completely reduce that diatomic oxygen into water molecules."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And water molecules are harmless to the cell."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And the water molecules can be used in a variety of different ways."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But under certain conditions, the oxygen is only partially reduced into some type of molecule."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So if oxygen, for instance, only gains one electron we form a radical molecule known as the superoxide an ion if it accepts two electrons."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So one and two, we form the peroxide molecule."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "In fact, when we discussed complex four, we said that a peroxide bridge is formed between the copper B atom and the heme A three group."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, these two types of molecules are very, very reactive."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And if somehow complex four releases either this molecule or this molecule they can cause damage to the components of our cells because of their reactivity."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So they can react with things like nucleic acids, so DNA molecules or they can react with other proteins and enzymes and they can disrupt their functions and that can cause damage to our cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we see that in complex four, on the normal conditions, when a total of four electrons are transferred to diatomic oxygen we form two water molecules which are harmless to the cell."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But if oxygen only gains one or two electrons this can lead to the production of molecules such as superoxide ions or peroxide ions."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And if these are released by complex four, that can cause damage to our cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And because of that, we call these reactive oxygen species."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "They're highly reactive and they can cause damage to the cells of our body."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So Ros stands for reactive oxygen species."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, of course, the electron transport chain isn't a perfect process and these molecules will, in fact, form."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And that's exactly why, as we'll see in just a moment, we have enzymes that can actually control the formation of these harmful byproducts."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So generally speaking, if these reactive oxygen species produce are not actually controlled, ros can actually react with cell components and cause something called oxidative damage."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "In fact, it's oxidative damage that is linked to the process of aging."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we age partially as a result of these reactive oxygen species."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "On top of that, oxidative damage has also been linked to a variety of different types of medical conditions and medical abnormalities."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "For instance, things like ischemia, diabetes, cervical cancer, liver damage as a result of alcohol overconsumption, emphysema and many other disease has been linked to this process of oxidative damage."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "The fact that these peroxide and superoxide anions react with components of our cells such as DNA and proteins and that can actually cause detrimental effects."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, there are many different ways by which the cells of our body can actually destroy or convert these peroxide and superoxide molecules into safer molecules."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, the first thing that I should mention is complex four, which actually produces a peroxide bridge as an intermediate molecule doesn't simply let go of these molecules."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So these complexes, these enzymes which basically reduce things like oxygen molecules, actually hold on to these molecules very tightly and they only let go under certain conditions."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we see that complex four holds the oxygen and its derivatives very tightly."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "It only releases it upon the conversion of these molecules into safer molecules as in this case, into water."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But for the few ros molecules that are released in the process or for instance, when we form the peroxide in complex four, if the complex four accidentally releases the peroxide, we do have certain methods that our cells use to actually help us remove these harmful molecules from our body."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And these methods includes using these special protective enzymes to find, to locate these ros molecules and to basically convert the ros molecules into something that are safer."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So let's discuss two very important types of protective enzymes used by our human cells and many other eukaryotic cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we have an enzyme known as superoxide, this mutates, and an enzyme known as catalase."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "In addition, we also have many different types of vitamins used by our body that actually allows us to control the amount of these reactive oxygen species that we find inside our cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So let's begin by focusing on super oxide, this mutate."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So this is the enzyme that basically locates and converts superoxide radical species like the one basically discussed right here."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So this is the general reaction that basically is catalyzed by super oxide, this mutase."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But as we'll see in just a moment, the superoxide, this mutate that is used by ourselves basically carries out a two step process."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But this is the general process."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we essentially take two of these superoxide anions."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "We use two H plus ions."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "We react them to form a single hydrogen peroxide molecule which is actually itself an unsafe molecule."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And we'll see what is done with this in just a moment."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But we also form this diatomic oxygen and this diatomic oxygen is in fact a safe molecule."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, inside eukaryotic cells, the cells of our own body we actually have two forms of super oxide this mutase."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "One form depends on manganese and the other form depends on copper and zinc atoms."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So the manganese containing this mutase is found in the mitochondria of our cells while the copper and zinc dependent this mutase is actually found in the cytoplasm of our body."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "But either one of these two enzymes basically catalyze the following two step process."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So in process one we have the oxidized version of this mutate that reacts with a single superoxide ion."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So it essentially releases a diatomic oxygen and it keeps a single electron so that we oxidize or we reduce it into the reduced this mutase version."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, the reduced dismutase then reacts with another superoxide anion as well as with two H plus ions."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And this allows us to basically oxidize this, reduce this mutate back into the oxidized version."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we regenerate that enzyme and we also form this hydrogen peroxide."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, hydrogen peroxide in itself is also a very reactive molecule and it can be very dangerous and that's exactly where the second enzyme comes into play."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Our cells also contain an enzyme known as catalase."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And catalase is actually a protein that contains a heme group."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And what this does is it takes two of these hydrogen peroxide molecules react them to form two water molecules as well as a single diatomic oxygen molecule."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And these two molecules are completely harmless."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "They're safe inside our cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So these two molecules can be used in a variety of different ways."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "For instance, the oxygen can be used by the electron transport chain to generate ATP molecules and water molecules can be used in a variety of different types of processes."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "For instance, hydrolysis processes."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "Now, one last thing I'd like to mention is the fact that exercise so if we continually exercise on a daily basis that can actually be very beneficial."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "And one benefit of exercising is that exercising actually increases the concentrations, the levels of these enzymes, protective enzymes inside our cells."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So as we exercise we increase the levels of superoxide this mutates and Catalyte and catalyst because exercising actually increases the likelihood that we're going to produce these reactive oxygen species."}, {"title": "Reactive Oxygen Species and ETC .txt", "text": "So we see that exercise increases the amount of protective enzymes found in our cells such as superoxide dismutase which can increase our cells ability to actually find and remove these harmful reactive oxygen and species."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Within our body."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "There's a great number of different types of neurons that are found within the nervous system."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, these neurons differ from one another not only in their size and shape, but they also differ in the speed at which they move the action potential along the axon of that neuron."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, some of these neurons in our body are capable of moving action potential potentials at speeds over 100 meters/second, while other neurons are capable of moving action potentials at speeds of only 1 meter/second."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "The question is, what exactly determines the speed at which that action potential moves along the axon of the neuron within our body?"}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, let's begin by recalling some physics."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, if we study the movement of the action potential along the axon from a physics perspective, we see that the action potential is nothing more than a moving electric current and the axon is nothing more than a biological wire."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So recall that what determines the velocity with which the current moves inside the wire is the resistance of that wire to the flow of that current."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, resistance itself depends on three important factors."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So recall that the resistance of an electric current moving inside a wire depends on the cross sectional area of that wire, its thickness."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "It depends on the length of that wire, and it also depends on an internal property known as the resistivity, which basically depends on the type of material that that wire is made of."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So this equation basically summarizes what we just said."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So this equation describes the relationship between the resistance as well as the length, the area and our resistivity."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So the resistance of the wire is equal to the product of our resistivity row multiplied by L, the length divided by a it's cross sectional area."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And from this equation, we see that if we increase the length, we increase the numerator, and so we increase our resistance."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And because the resistance is high, that means the velocity will be low."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "On the other hand, if we increase the area, the denominator will increase, and that will decrease the resistance."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And so it will increase the velocity of that current inside that wire."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So this equation tells us that a wire that is thick and which is short will propagate the current at a higher velocity because the resistance will be lower."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now we can actually treat the axon as if it was that wire, and we can treat the action potential as if it was that moving electric current."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "In fact, an action potential is a moving electric current."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So from this same equation, we can see that an axon with a larger diameter will propagate that action potential much quicker because the larger diameter means we have a larger area and a thicker area."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And so that means a lower resistance."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "At the same exact time."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "If we decrease the length of that axon, we decrease the L. And so we decrease our resistance and we increase the speed of the movement of that action potential inside our axon."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And this is summarized in these two diagrams."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So in diagram A we have an axon that is thick and that is short."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "In diagram two, in diagram B we have a long axon that is very thin."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, from our discussion above we see that diagram B describes the axon that would ultimately propagate that action potential at a much greater rate than diagram B because in A we have a large area and a small length and that would decrease the resistance inside that axon."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now of course, because the size of our body is limited, that means the length and the thickness of that axon is also limited."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "That is, we cannot actually make our axon too thick or too short or too long."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, instead of actually increasing the area or increasing the area or decreasing the length of the axon, the way that our body increases the speed at which our action potential moves along the axon is by using a special type of insulating material."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So special types of cells known as glial cells found inside the nervous system cover the axon of the neuron with a special insulating material known as the myelin."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And this myelin or myelin sheath basically increases the speed at which our neuron propagates that action potential as we'll see in just a moment."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So basically, our nervous system can be broken down into two categories."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "We have the central nervous system so that's the brain and the spinal cord and we also have our peripheral nervous system."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And both of these categories contain their own glial cells."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So schwann cells are the cells found in the peripheral nervous system while oligodendrocytes are those glial cells found in the central nervous system."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And what these cells do is they move around the axon of the neuron and they basically cover that neuron at specific sections with a layer of insulating myelin."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, because the myelin is insulating, what that means is no action potential can actually be generated on the cell membrane where it is covered with that myelin material."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, just because the cell membrane is actually covered with that myelin material, that does not mean that no electric signal can travel through that axon."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "In fact, even though this section, let's say this section of the axon is covered with the myelin, our electric current can still travel through the cytoplasm to the cytosol of our cell and that's exactly how that signal will get from one node to the next node as we'll see in just a moment."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So instead, the current moves through the cytosol of the axon until it reaches a part of the membrane that is not myelinated."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And these gaps where we do not have any myelination as shown on this diagram and this diagram, so these are the gaps and these are the gaps here."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "These are known as nodes of Ranvia."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So basically at the nodes of Ranvia, we do not have any myelination."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "In fact, we have a great number of sodium voltage gated channels."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And because we have such a great number of voltage gated channels, sodium voltage gated channels at the nodes of Ramvia, that will greatly increase our sensitivity to depolarization."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So, to see what we mean by this, let's take a look at the following diagram."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So, this diagram basically describes how our action potential moves along an axon that is myelinated, as shown in this diagram."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So this is our cell body, these are the dendrites, and this is our axon."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "If we take a cross section of this axon, we basically get the following diagram."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So, let's suppose we stimulate our axon hillock, as shown, and an action potential is generated at the axon hillock as it begins to move along, eventually it gets to the cell membrane that contains the myelin natived sheath."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And so, as soon as it gets to that sheath, no more action potential can actually travel through the cell membrane."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Instead, that electric signal will propagate at a much quicker rate through the cytoplasm of the cell."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So this is the cytoplasm, this is the outside region, these are the myelinated sheets, and these are the nodes of Ranveer."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Remember, the nodes of Ranvir are gaps that occur at regular intervals between the segments of the myelin sheet."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And these gaps contain a great number of sodium channels."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So, as this electrocurrent moves into this node, what happens is this signals the depolarization process and the voltage gated sodium channels open up and our flux influx of sodium ions goes into our cell and that depolarize the cell and creates the action potential."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Now, that basically amplifies our electric signal and sends it through the cytoplasm because the action potential cannot travel through this myelin native cell membrane."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And so it really quickly travels to the next node, creates that depolarization, creates that action potential."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "Once again, that action potential cannot actually travel through the cell membrane."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And so the signal travels through the cytoplasm until it gets to the third node."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And this continues."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And this jumping process in which our action potential jumps from one node to the next node, to the third node, this process is known as saltatory conduction."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And saltatory conduction greatly speeds up the movement of our action potential because instead of the action potential actually moving through the entire membrane, which would slow it down, it basically moves only through these certain sections known as the note of Ranvia."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And this greatly speeds up the process of the propagation of that action potential."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "So, on top of increasing the thickness of our axon and decreasing the length of that axon, another way that our body can speed up the propaganda of that action potential is by using these cells, glial cells to myelinate or insulate certain sections of the axon."}, {"title": "Myelination and Saltatory Conduction .txt", "text": "And that leads to this propagation mechanism known as salt tory conduction."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So when we introduced enzymes, we said that what enzymes do is they catalyze, they speed up the rates of reactions."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And the way that they speed up the rates of reactions is by decreasing the energy of the transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So in that particular reaction, that the enzyme catalyzes, once that substrate is inside the active side, when the reaction takes place inside the active, active side, what the active side does is it stabilizes the transition state and decreases the energy of that transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And that's exactly what lowers the activation energy that gives energy of activation."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So enzymes catalyze reactions by stabilizing the transition state within that particular reaction."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And remember, transition states are these structures that are so high in energy that they exist only for a very short period of time."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So in that energy diagram, the transition state is the topmost portion of that energy diagram."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, previously we discussed different types of enzyme inhibitors and we said that a very good enzyme inhibitor is an inhibitor that resembles the structure of that substrate."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So if the inhibitor of some particular enzyme resembles the structure of the substrate that binds into the active side of the enzyme, then what that inhibitor can do is because it has a similar shape to the substrate, it can easily accommodate itself into that structure of the active sites."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So we previously saw that a good way to inhibit the activity and the functionality of enzymes is to create an inhibitor that resembles that natural substrate of that particular enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now because of the argument that we just mentioned earlier."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So, since enzymes active sites essentially stabilize the structure of the transition state, then that must imply that a much more effective and a much better inhibitor of an enzyme would be an inhibitor that resembles not the structure of the substrate, but rather the structure of that transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And these types of inhibitors are known as transition state analogues or transition state inhibitors."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So we see that these transition state analogs are molecules that resemble the structure of the transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And because enzymes ultimately stabilize the energy and the structure of the transition state, these are very, very potent, very effective inhibitors."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So let's take a look at two examples."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So let's begin by examining an enzyme found in bacterial cells known as proline raysimase."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And proline raysimase basically catalyzes the transformation, the isomerization reaction of Lproline into Dproline."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, the difference between Lproline and Dproline lies in the stereochemistry of this carbon."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "On this particular molecule, the H atom points into the board."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "But in this particular case, the H atom is coming out of the board."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so that's the difference between Lproline and Dproline."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And proline raysimase basically catalyzes the transformation of these two molecules back and forth."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, if we examine the transition state when going from Lproline to Dproline, this is what we see."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "This is the structure of that high energy transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And notice that in this transition state, this carbon atom has planar."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So it's trigonal planar."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And what that means is these three bonds."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So this Covalent bond, this Covalent bond and this Covalent bond all lie along the same plane."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And that's what we mean by trigonal planearity."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So there is trigonal plane narrative within this molecule."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And what that means is so if the H atom is added on the top side, we basically form this Dproline."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "But if the H atom is added from the bottom side, we're going to form that Lproline."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So from the discussion above, if we can somehow build a molecule that is a transition state analog that resembles the structure of this particular molecule, then that means that transition state analog will be a very potent inhibitor of this enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "The proline resumes because that transition analog, that transition state analog will be able to accommodate quite easily into the active side of that enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So once again the transition state of this reaction, that's the isomerization of Lproline to deprolene contains an alpha carbon that has planar or trigonal planar, that is trigonal planar."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And it turns out that if we use a molecule known as parole two carboxylic acid which basically also contains trigonal planarity on that carbon as seen in the following diagram, then this will be a very, very potent inhibitor and this is in fact a transition state analog for this enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So let's take a look at parole two carboxylic acid and compare the structure to the transition state of this particular reaction."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So notice this carbon has trigonal planarity and so does this carbon."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So because we have this double bond, that means these three bonds will all lie along the same exact plane."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so these two molecules in fact resemble one another much more than this molecule resembles that substrate."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And because of that, because this inhibitor resembles the transition state much more than it does that actual substrate molecule, this will be a much more potent, much better inhibitor."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "In fact, this molecule here, the transition state analog, parole two carboxylic acid binds 160 times more likely to the enzymes active side, to the proline raysimase active side than the proline molecule itself."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so if given a chance, this will be much more likely to bind into the active side than this substrate molecule or this substrate molecule."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Another example is shown on this side of the board."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So the enzyme methyl Thio adenosine nucleusidase is basically the enzyme that catalyzes the hydrolysis of the bond between this carbon on the sugar molecule and this nitrogen on the base."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And this reaction is known as deadenylation."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So this enzyme catalyzes the deadenylation reaction, basically the breaking of this particular bond in this molecule."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so by the same argument, if we are able to build a molecule, a transition state analog that resembles the structure of the transition state in this reaction, in this deadenylation reaction, then we can build a very, very potent inhibitor to this enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "In fact, we can build this molecule that will act as a transition state analog."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And notice there is a great deal of similarity between this molecule and this transition state."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, the final question that I want to discuss is what exactly is the usefulness of this transition state analog?"}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So one usefulness is the ability to build a molecule that is a very good inhibitor to some particular type of enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So for instance, if a bacterial cell, if a bacteria infects our body, then one way to inhibit the activity of that bacterial cell is to inhibit in some way some type of enzyme by using transition state analogues."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, another important application of transition state analogs is the following."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "We can actually create antibodies that have specific catalytic capabilities by using these transition state analogues."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So we can now build antibodies with specific catalytic capabilities by using transition state analogues as antigens."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And to demonstrate how this actually works, let's discuss the biosynthesis process, the biosynthesis of the heme groups."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So remember, in proteins such as hemoglobin and myoglobin, we have these important prosthetic groups known as heme groups."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And at the center of the heme group is the protiporphine ring."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So the protoporphine ring basically is that organic part of that heme group that actually carries, that holds that iron atom."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, in the process of the synthesis of this protoporphine ring, of the hemegroup, the final step is to basically use a special enzyme known as ferrokeletase to basically catalyze the insertion of that se atom, the metal atom, into the center of the protiporphine ring."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, normally, the protoporphine ring has a planar shape, so the shape of it is relatively planar."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "But to actually fit that fe atom, the metal atom, into the center of that protoporphine, what this enzyme does, what the ferrocalitase does is it basically bends the shape of that protoporphine ring and then that exposes the electrons, the lone pair of electrons that can now bind that fe atom."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so what the ferrocalitase does is it basically catalyzes the bending of that planar shape of the protoporphrine molecule."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And that allows the fitting, that allows the insertion of that fe atom into that hin group, into that protoporphrine."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Now, how can we use this to basically build an antibody with a specific type of catalytic ability?"}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "Well, normally, the protoporphrine has a planar shape and we see that what this enzyme does is it basically bends the shape."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so the transition state of the protoporphine ring has to be bent in shape."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So the transition state of the protoporphrin basically has a bent shape."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So that means if we can somehow build a transition state analog that has the protoporphine with the bent shape, that means that type of molecule will be much more likely to bind into the active side of that particular enzyme, the ferrokeletate."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So in fact, what we can do is we can methylate one of the nitrogen atoms in that ring."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And by methylating this nitrogen that creates stere hindrance and that forces the bending of that protoporphin ring."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And now that we have formed this transition state analog whose structure resembles the transition state structure in that particular catalytic process, we can now expose, we can use this molecule, this transition state analog, as an antigen, essentially expose it to a plasma cell."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "The plasma cell will, in turn, basically begin building antibodies that contain an active side that has a complementary structure to this particular antigen."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And so, once we build that antibody, the antibody will be easily able to fit those protoporphrine molecules into the antibody active side."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And that antibody will, in turn, have the catalytic ability to basically transform or insert that se atom into the centering of that particular protoporphine."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So we see that transition state analogs are not only useful in actually inhibiting and blocking the ability of enzymes to catalyze reactions, but we can also use these transition state analogues to actually build antibodies that have catalytic capabilities."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And these antibodies are commonly known as enzymes, where AB stands for antibody and the zine part stands for the enzyme."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "So, abzymes are these antibodies that contain catalytic capabilities that can basically catalyze their different types of reactions."}, {"title": "Transition State Analogs and Catalytic Antibodies .txt", "text": "And the way that we build them is by using these transition state analogues as antigen molecules."}, {"title": "Enzymes .txt", "text": "The majority of the chemical reactions and biological processes that take place within the human body are governed by a class of biomolecules known as enzymes."}, {"title": "Enzymes .txt", "text": "Now, virtually all enzymes are proteins, some enzymes are in fact RNA molecules and we'll discuss those separately."}, {"title": "Enzymes .txt", "text": "Now enzymes are these protein molecules that assist is the chemical reactions that take place within the human body."}, {"title": "Enzymes .txt", "text": "So before we discuss the major chemical processes that take place within the human body such as glycolysis, fermentation or cell respiration, let's discuss and define what the role of the enzyme is within the human body."}, {"title": "Enzymes .txt", "text": "So enzymes are biological molecules, are proteins that increase the rate of the reaction."}, {"title": "Enzymes .txt", "text": "They increase the speed of that reaction by decreasing the activation energy of that reaction."}, {"title": "Enzymes .txt", "text": "Now recall that the activation energy is basically the amount of energy that must be inputted into our reaction to overcome that energy barrier, to basically reach that transition state and transform the reactants to the product."}, {"title": "Enzymes .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Enzymes .txt", "text": "So the y axis is the energy, the x axis is the reaction progress, it's the time."}, {"title": "Enzymes .txt", "text": "So we have the reactants and this is the energy of the reactants."}, {"title": "Enzymes .txt", "text": "We have the products, this is the energy of the products."}, {"title": "Enzymes .txt", "text": "Now for the forward reaction going this way, we see that the reactants are at a higher energy level than the products and that means this is an exothermic reaction."}, {"title": "Enzymes .txt", "text": "So going this way in the forward direction we have an exothermic reaction and energy is released into the surroundings."}, {"title": "Enzymes .txt", "text": "Now for the reactants to actually transform into the products, we have to input enough energy."}, {"title": "Enzymes .txt", "text": "Specifically, we have to input this amount of energy, which is our activation energy, it's the activation barrier."}, {"title": "Enzymes .txt", "text": "So basically, if we input this amount of energy, the reactants can basically reach the transition state and then convert to the product."}, {"title": "Enzymes .txt", "text": "And what protein enzymes do, what enzymes do is they basically bind to the reactants in some form or way and they actually lower the activation energy by basically providing a completely different reaction pathway."}, {"title": "Enzymes .txt", "text": "So the rate of chemical reactions depends on its activation energy and enzymes increase the rates of reactions by decreasing the activation energy."}, {"title": "Enzymes .txt", "text": "The activation energy is the amount of energy that must be added to our system, to our reaction, to transform the reactants to the transition state and then to our products."}, {"title": "Enzymes .txt", "text": "So basically, this is the first important point that we must know about enzymes."}, {"title": "Enzymes .txt", "text": "So enzymes increase the rate of the full reaction, but they also increase the rate of the reverse reaction."}, {"title": "Enzymes .txt", "text": "So this is a very important point that most people sometimes miss."}, {"title": "Enzymes .txt", "text": "So if we look at the following diagram, we have the full reaction going this way and we also have the reverse reaction going this way."}, {"title": "Enzymes .txt", "text": "Now for the full reaction, this is the activation energy."}, {"title": "Enzymes .txt", "text": "For the reverse reaction, this is our activation energy."}, {"title": "Enzymes .txt", "text": "It's the energy difference between the transition state and the energy of the product."}, {"title": "Enzymes .txt", "text": "So we have an exothermic reaction going this way and an endothermic reaction going in reverse."}, {"title": "Enzymes .txt", "text": "And we see that when the enzyme actually lowers the activation energy."}, {"title": "Enzymes .txt", "text": "So this is our uncatalyzed reaction that does not involve the enzyme."}, {"title": "Enzymes .txt", "text": "And this is the graph for the catalyzed reaction that does involve that enzyme."}, {"title": "Enzymes .txt", "text": "Remember, enzymes are basically catalysts."}, {"title": "Enzymes .txt", "text": "So we see that when we lower the activation energy, we not only lower the activation energy for the full reaction going this way, we also decrease the activation energy for the reverse reaction."}, {"title": "Enzymes .txt", "text": "So that is a very important point to remember about how the catalyst, our enzymes, basically lower the activation energy."}, {"title": "Enzymes .txt", "text": "Now let's move on to the second important point that we must always remember about enzymes, biological catalysts, that basically speed up reactions that take place within our bodies."}, {"title": "Enzymes .txt", "text": "So, although enzymes increase the rate of the reaction, although they do in fact affect the kinetics of the reaction, they do not affect the thermodynamics of that reaction."}, {"title": "Enzymes .txt", "text": "And what that means is the concentration of the products that are produced at the end of the catalyzed reaction is exactly the same as the concentration of products that are produced for the uncatalyzed reaction."}, {"title": "Enzymes .txt", "text": "So at equilibrium, for the catalyzed version, we still have the same exact concentrations of reactants and products that are left over and formed."}, {"title": "Enzymes .txt", "text": "So, although enzymes increase the rate of reaction, they do not increase or decrease how much product is actually formed."}, {"title": "Enzymes .txt", "text": "That means that for catalyzed reactions, the same concentration of product is reached at equilibrium as for the uncatalyzed reaction."}, {"title": "Enzymes .txt", "text": "So that means what our enzyme actually does is it increases the rate of the reaction."}, {"title": "Enzymes .txt", "text": "It basically decreases the time at which we reach equilibrium."}, {"title": "Enzymes .txt", "text": "But the concentration of reactants and products is exactly the same."}, {"title": "Enzymes .txt", "text": "It's unchanged at equilibrium."}, {"title": "Enzymes .txt", "text": "So equilibrium is reached faster, but the actual concentrations of the reactants and products at equilibrium does not change."}, {"title": "Enzymes .txt", "text": "Now let's move on to the third important fact about enzymes."}, {"title": "Enzymes .txt", "text": "So, biological enzymes, biological catalysts do not change the energy of the products, nor do they actually change the energy of our reactants."}, {"title": "Enzymes .txt", "text": "And that means the change in enthalpy or the change in Gibbs free energy of the overall reaction does not exactly change."}, {"title": "Enzymes .txt", "text": "So, to see what we mean, let's take a look at the following two graphs, which are basically these graphs here."}, {"title": "Enzymes .txt", "text": "So notice that we have the reactants and the products."}, {"title": "Enzymes .txt", "text": "So this line is the energy for the reactants."}, {"title": "Enzymes .txt", "text": "This line is the energy for our products."}, {"title": "Enzymes .txt", "text": "And this is our uncannilized reaction."}, {"title": "Enzymes .txt", "text": "So we do not have the enzyme here."}, {"title": "Enzymes .txt", "text": "This graph, however, represents the same reactants and the same products."}, {"title": "Enzymes .txt", "text": "But now we have that enzyme."}, {"title": "Enzymes .txt", "text": "So basically, we lower the activation energy."}, {"title": "Enzymes .txt", "text": "But notice that the energy of the reactants and products does not change."}, {"title": "Enzymes .txt", "text": "So when we calculate the change in Gibbs, the energy of this reaction or our change in enthalpy between the products and our reactants, we see that it's exactly the same as for the uncatalyzed and the catalyzed case."}, {"title": "Enzymes .txt", "text": "So we see that enzymes do not actually affect the energy of the products, nor do they affect the energy of the reactants."}, {"title": "Enzymes .txt", "text": "And finally, the final important point to remember about enzymes is that enzymes are not actually used up."}, {"title": "Enzymes .txt", "text": "They are not actually consumed in any reaction."}, {"title": "Enzymes .txt", "text": "And if the enzyme is altered in some way, and usually they are, they are regenerated, the final enzyme is exactly the same as the initial enzyme that basically went into that reaction."}, {"title": "Enzymes .txt", "text": "So enzymes themselves are not actually consumed during reactions, although they might alter in some way."}, {"title": "Enzymes .txt", "text": "For example, when the reaction binds to the active side of our enzyme, it might change its shape ever so slightly."}, {"title": "Enzymes .txt", "text": "But at the end of the reaction, our enzyme is always regenerated in the same form as it basically went in to our reaction."}, {"title": "Enzymes .txt", "text": "So this is a very important property of enzymes because that means a very small quantity of enzymes can be used to basically speed up many reactions at the same exact time."}, {"title": "Enzymes .txt", "text": "We do not have to actually use up our enzyme and create new enzymes because one enzyme can basically react with many different reactants."}, {"title": "Enzymes .txt", "text": "So that is expressed in the following expression."}, {"title": "Enzymes .txt", "text": "So let's suppose we have reactants A and B."}, {"title": "Enzymes .txt", "text": "We place our enzyme, that enzyme basically takes A and B and reacts them."}, {"title": "Enzymes .txt", "text": "It decreases the activation energy to form product C and D. But the actual enzyme on the product side is exactly the same as the enzyme on the reactant side."}, {"title": "Enzymes .txt", "text": "They are not actually used up or destroyed in any way or form."}, {"title": "Enzymes .txt", "text": "So these are the four important points that you must always remember about the role of enzymes in the human body."}, {"title": "Enzymes .txt", "text": "So enzymes affect kinetics."}, {"title": "Enzymes .txt", "text": "They do not affect thermodynamics."}, {"title": "Enzymes .txt", "text": "That means they only increase the speed or the rate of the reaction by decreasing the activation energy."}, {"title": "Enzymes .txt", "text": "They do not affect the energy values of the products or the reactants."}, {"title": "Enzymes .txt", "text": "And they do not affect the concentration of the products and reactants that exist at equilibrium."}, {"title": "Enzymes .txt", "text": "They do not affect equilibrium, they simply increase the time."}, {"title": "Enzymes .txt", "text": "They basically decrease the time at which equilibrium is achieved."}, {"title": "Enzymes .txt", "text": "Equilibrium is achieved faster with enzymes, but the concentrations are exactly the same as before without the enzyme."}, {"title": "Enzymes .txt", "text": "And the final thing we have to know is enzymes themselves aren't used up."}, {"title": "Enzymes .txt", "text": "They are not consumed, they are not destroyed."}, {"title": "Enzymes .txt", "text": "They might be changed ever so slightly, but at the end that same enzyme is regenerated."}, {"title": "Enzymes .txt", "text": "And that means that the enzyme can be used over and over again to basically assist with that same type of reaction."}, {"title": "Enzymes .txt", "text": "Now, in the next lecture we're going to discuss two important models that are used to describe how enzymes actually interact with our reactants, also known as the substrate."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "All living organisms found on Earth, and this includes both eukaryotes as well as prokaryotes, need three different things to actually survive and grow."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And these three things are energy, carbon, as well as electrons."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now, why exactly do our organisms need these three different things?"}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Well, basically, they need energy to power the different types of processes that take place within that organism."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "They need carbon to create the biomolecules used by those organisms, and they need electrons to basically undergo oxidation reduction reactions that are used to create different types of molecules."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "For example, if we examine the human body, humans need energy to basically power different types of processes."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And one particular process is basically the creation of an electrochemical gradient on our nerve cell, and that creates an action potential that propagates and sends electrical signals."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Humans basically need a carbon source to create different types of biomolecules, such as our proteins, that are used throughout the human body."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And humans need electrons to basically create ATP energy molecules, our adenosine triphosphates that are used by the cell."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So we see that all these three things are needed by humans, but are also needed by every single type of living organism that exists on Earth."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And because these three things, energy, carbon, electrons are needed by all the organisms, we can categorize organisms by how they actually obtain these three things."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So we can categorize organisms by how they obtain their carbon source."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We can categorize organisms by how they obtain the energy source, and we can also categorize organisms by how they obtain their electron source."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So let's begin with carbon."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So, basically, humans are examples of heterotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Heterotrophs are those organisms that must obtain their organic carbon source from an outside organism."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "For example, we have to obtain our carbohydrates proteins, as well as lipids, from other types of organisms."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So that's exactly why we need to eat food products, animal products, as well as plant products to obtain these organic carbon containing things."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So humans are examples of heterotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We obtain our carbon source from other organisms."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now, the other side of the spectrum are autotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Autotrophs are examples of organisms that can actually create or synthesize energy containing carbon molecules, organic molecules from inorganic starting materials, such as carbon dioxide."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So the prime example of Odotropes are plants."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Plants are basically able to use inorganic carbon dioxide, mix it with water to actually form the carbohydrate sugar molecules."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So that's an example of autotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Autotrophs obtain their carbon source from inorganic materials, while out of heterotrophs need to obtain the organic carbon from other organisms."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now let's move on to our energy source."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So, once again, let's use humans as our example."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Humans are examples of chemotrophs because they basically obtain their energy source by breaking down macromolecules, such as sugars, lipids, and proteins."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We basically store that energy in molecules known as ATP or adenosine triphosphate."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now, the other type of molecule, the other type of organism that basically uses light as the energy source are known as phototrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So basically, plants are example of phototrophs because they use the energy stored and light to basically synthesize carbohydrate molecules."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So they combine carbon dioxide, our inorganic carbon source, with water, and by using our light, they synthesize our carbohydrates as well as oxygen."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So phototrophs are those organisms that use light as their energy source to power the different processes inside that organism."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "While chemo tropes obtain their energy by basically breaking down or oxidizing either inorganic or organic matter."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "In the case of humans, we basically oxidize our organic matter."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We oxidize our macromolecules such as sugars, lipids, and proteins."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now, the final way by which we can categorize organisms is by the source of electrons."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So those organisms that basically obtain their electrons form organic materials such as sugars, proteins, or lipids."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And this includes us humans."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "These types of organisms are known as organotropes, while those organisms that obtain their electron source from non organic or inorganic materials, those are known as lithotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So basically, we have the source by which we obtain our carbon."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We have either autotrophs or heterotrophs."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Autotrophs basically means we create or synthesize our organic molecules from inorganic starting materials such as carbon dioxide."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Heterotropes means to actually obtain that organic material, we cannot synthesize it."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We have to obtain it from other organisms."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And this includes humans, while this include plants."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Now, the energy source can be broken down into two types."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "We have phototrophs, which only use light as the energy source, and for example, plants use light energy to synthesize our carbohydrates, while chemotrophs are those that actually obtain our energy source by breaking down or oxidizing either organic or inorganic matter."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "And finally, we can also categorize based on electron source."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "So we have organotropes, which basically means we obtain our electrons from organic materials such as sugar, as proteins and lipids, while inorganic, while our organisms that obtain our electrons from inorganic starting materials."}, {"title": "Autotrophs and Heterotrophs .txt", "text": "Those types of organisms are known as lithotropes."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Thus far in our discussion on enzymes, we kept our discussion very general."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "We generalized the idea of what enzymes actually do."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So we said that enzymes are these biological catalysts that speed up the rates of all different types of reactions that take place inside ourselves."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And we said that the way that they achieve this is by basically binding that substrate muscle molecule into a special environment we call the active side."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And inside the active side, there's a conformational change that takes place and that stabilizes not only the substrate molecule, but it also stabilizes the transition state in that particular reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And by stabilizing the transition state, that releases a certain amount of binding energy into the environment and that decreases the energy of that transition state."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "It lowers the energy of the transition state and that's what lowers the activation energy."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And by lowering the activation energy, we speed up the rate of that particular reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So this is the general mechanism by which enzymes actually function."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, we know the general idea of what enzymes actually do, but what exactly happens inside the active sites of these enzymes?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So we have all these different types of enzymes down inside our body."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "They all carry out the same general idea."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "They basically decrease the activation energy of the reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "But how exactly is that achieved?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And what are some mechanisms, what are some methods that enzymes use to achieve this decrease in activation energy?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So four of these methods are listed on the board and we have many more, but these are the four most important ones."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And enzymes can use one of these methods or they can use a variety of these different methods."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So let's begin by focusing on the first one we call Covalent catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So in some enzymes, such as, for example, trypsin chymatrypsin, other digestive enzymes, as well as the enzyme we're going to focus in this lecture, glycopeptide transpeptidase."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "In some enzymes inside the active side, we have catalytic residues, these amino acids, part of the active side of the enzyme that are responsible for actually forming a temporary Covalent bond."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, why would we want to form a Covalent bond?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Well, one reason is to basically keep that substrate molecule in place inside the active side."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So many enzymes contain active sites with catalytic residues that can form temporary Covalent bonds with the substrate molecule and that can be used to basically keep that molecule in place for the time being until that reaction actually takes place."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, at the end of the reaction, because we always have to regenerate our enzyme, the enzyme is never used or depleted or changed in any reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "We have to break that bond."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And that's exactly why we call this bond a temporary or a transient Covalent bond."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, in our discussion on irreversible suicide inhibitors, we discussed penicillin."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And we said that penicillin is an antibiotic that affects a specific bacterial enzyme found in bacterial cells known as glycopeptide transpeptidase."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And when we discussed this molecule, we said that inside the active site of glycopeptide transpeptidase is this catalytic residue, namely this serene molecule."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And the serene amino acid basically plays the catalytic role of actually forming a Covalent, a temporary Covalent bond between the oxygen and this carbon."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So in this reaction, in the first step, this molecule actually forms a bond between the oxygen and this carbon, kicking off this terminal amino acid to form the following temporary transient acid intermediate molecule."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, at the end of the reaction, of course, this bond is actually broken, but we formed the bond to basically keep this group attached into the active side so that another substrate can move in and grab this group."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So the bacterial enzyme glycopeptide transpeptidase, utilizes Covalent catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And as we'll see in just a moment, another enzyme that we can basically label as using Covalent catalysis is Kymatrypsin."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And this is an important digestive enzyme that exists inside our digestive system."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And we'll discuss much in much more detail what chymatrypsin actually does inside the active side."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now let's move on to method number two catalysis by proximity and catalysis by orientation."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So if we recall the collision theory from basic chemistry based on the collision theory, for a reaction to actually take place, what must happen?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Well, first of all, those two substrate molecules that are about to react must actually collide."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So they must collide, they must collide with enough energy and they must collide with the proper orientation."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So only when the collision actually takes place with the proper orientation and with the right amount of energy do we actually form the product molecule."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, what the active side does, what enzymes actually do is they bring the substrate molecules into this very small region of space that creates a microenvironment for that reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So inside the active side, we create a microenvironment that not only brings those substrate molecules in close proximity, but it also orients those substrate molecules in the proper orientation so that reaction can actually take place."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "For instance, if we go back to Covalent catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Another reason why covalent contalisis might take place is because once we attach this group onto the active side, that orients that group in just the proper orientation for the next step in the reaction to actually take place."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So many biological reactions involve two or more substrate molecules."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And this implies that for a reaction to actually take place, they must be close enough and must also have the proper orientation."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And what active sites of enzymes provide is they provide that small region of space, that microenvironment that brings the substrate close enough for the collisions to actually take place at a high enough frequency."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "In addition, the active sites may also orient the molecules in the proper orientation for that bond to actually form and for us to form those products."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, method number three is called acid based catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And in acid based catalysis, we basically have a transfer of an Hion."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, there are many residues that are involved or there are specific residues found in active sites that might be involved in a transfer of an H ion."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And one specific residue is the histidine amino acid."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So the histidine molecule has a PH that is relatively close to the normal physiological PH."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And many enzymes inside our body, as we'll see in the next several lectures, utilize histidine to actually transfer H ion."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So active sites may contain residues such as histidine that can participate in transferring hydrogen ions."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, why would we want to transfer an H ion?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Well, in some cases, if we transfer an H ion from one molecule to another molecule we basically create a strong nucleophile."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And that strong nucleophile might be needed in that particular biological reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So by transferring hydrogen ion the active site may activate a nucleophile that is required in that catalysis process."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, by transferring an H ion we can also actually stabilize different types of groups that might be found inside the active site that contain charges."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And the transfer of H ions can also be used to increase the electrostatic interactions that take place within that active site and that can interstabilize things like the transition state inside that chemical reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, one particular example of an enzyme that uses acid based catalysis is Chimetrypsin."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Inside Chimotrypsin, inside the active side, we have a Serene residue that acts as a nuclear foile."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "But to create a strong nuclear file what must happen is the H atom the H ion from the oxygen of Serene must be taken away."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And so what happens is a nearby histidine in the active side participates in actually taking away that H atom."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And so we see that the H atom is transferred onto this nitrogen and the positive charge is now essentially delocalized among these different atoms in the histidine side chain."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "But this one now contains a full negative charge."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And now this became a very strong nucleophile."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And this can participate in forming covalent, a temporary covalent bond."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So as we'll see in the next several lectures, chimetrypsin, which this basically describes, uses not only acid based catalysis but it also uses covalent catalysis in decreasing the activation energy of that particular chemical reaction."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "That is, what it participates in is breaking different types of peptide bonds breaking different types of proteins that we ingest into our body."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And finally, the final mechanism by which our enzymes can decrease the activation energy and therefore increase the rates of reactions is called metal ion catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So, what's so special about metal ions or metal atoms?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Well, many enzymes and many proteins inside our body."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "For example, when we spoke about myoglobin and hemoglobin we saw that these proteins use metal atoms and in fact, enzymes utilize metal atoms as cofactors."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Now, what's so special about these metal atoms?"}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "Well, metal atoms have the ability to lose electrons very easily."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And by losing electrons, they gain a positive charge."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So because they are deficient electrons, they have a positive charge."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And this positive charge can be used to interact with different types of molecules found inside the active side."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And so the positive charges on metal ions, as we'll see in more detail in the future lectures, they can be used to basically stabilize the transit transition states as well as the intermediate molecules that are formed within that active side."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "They can also be used to assist in actually forming a strong nucleophile."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "For instance, one will discuss carbonic and hydrates."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "We'll see that in carbonic and hydrates, inside the active side, we have a zinc metal atom that is used to actually form a strong nucleophile, the hydroxide nucleophile."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And finally, this metal atom can actually be used to hold that substrate molecule in place."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So in the same way that we can use covalent contalisis to basically orient that substrate and hold it in place, we can also use the positive charge of these metal atoms to actually bring the substrate molecules in the proper orientation and hold them in place inside the active side so that reaction can actually take place at a reasonably high rate."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So we see that our enzymes inside our body use a variety of different types of methods and mechanisms to basically carry out the general reaction of decreasing the activation energy of that biological process."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "So we can have covalent catalysis, we can have catalysis by proximity, we can have acid based catalysis, and we can also have metal ion catalysis."}, {"title": "Mechanisms of Enzyme Catalysis .txt", "text": "And we'll discuss many examples of enzymes that utilize these different methods in the next several electrics."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So far in our discussion on genetic abnormalities, we focused on a specific type of abnormality of chromosomes known as anne ploid."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, aniploid is the condition in which the nucleus of our body has either an extra copy of a chromosome or lacks a copy of a chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "In the former case, it's called a trisomy, in the latter case, it's called anosomy."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So a monosomic cell is a cell that lacks a chromosome, while a trisomic cell is a cell that has an extra copy of a chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, we said that anuploid is commonly a result of something called nondisjunction that can take place either in mitosis or meiosis."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So now we're going to focus on other types of chromosomal abnormalities that can arise due to different types of conditions."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "For example, excessive exposure to X ray."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So if the cells of our body, for example, are exposed to X ray radiation, then what can happen is a segment of the chromosome can actually break off."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And once that segment actually breaks off, it can do one of four different things."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "We can either have an inversion take place, we can have a deletion, we can have a duplication or translocation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's discuss what these actually mean."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And let's begin by looking at inversion."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's suppose this is our normal chromosome and this is a specific segment of the DNA that is about to break off."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's suppose this chromosome is exposed to some type of radiation, for example, X ray radiation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And eventually the X ray radiation breaks the bonds within this section and this section."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so we have the breakage of that particular segment of DNA."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, what happens during inversion is once this breaks off, it basically reverses its orientation and so it flips."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So here the purple section is upward, and here the purple section points downward."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And now it can basically reattach itself into this section of the chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so we have this altered chromosome in which we still have this entire segment of DNA within the chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "But now the order is actually reversed."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So in inversion, the detached segment of that particular chromosome reverses its orientation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "It becomes opposite and then reattaches onto that original chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So this is the same original chromosome that we begin with."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now let's move on to deletion."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So deletion is relatively simple."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "What happens is, in deletion, our detached segment, once it breaks off, it basically moves away and it does not reattach itself onto that original chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So if the detached fragment of DNA does not reattach itself onto that original chromosome, this is known as a deletion with respect to that original chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, what about duplication?"}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Remember, in deployed organisms, every single chromosome comes with a homologous pair."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So in humans, we have 46 chromosomes, but we have 23 homologous pair of chromosomes."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's suppose this is our homologous pair of chromosomes."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So this chromosome is homologous with respect to the second one, which means they carry genes that code for the same exact types of traits."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, what exactly do we mean by duplication?"}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's suppose ves is our gene that is about to break off."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So it is exposed to some form of radiation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "The bonds are broken, this part detaches."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now, when this part detaches, instead of going back onto this segment chromosome, it moves onto the first chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And because this is a homologous chromosome, it contains similar genes."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "We have a duplication take place on this chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So here we have a duplication, because this attaches onto this section right here."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And here we have a deletion, because this segment that broke off does not actually return to this particular chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So when duplication takes place, deletion also takes place, as we see in this particular example."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So if a segment of DNA breaks off and attaches onto a homologous chromosome, because that homologous chromosome carries those same types of genes, we say that we have a chromosomal duplication take place."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And finally, let's examine translocation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So translocation is the process by which a segment of that chromosome breaks off and moves onto and attaches onto a non homologous chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So, let's suppose we have a homologous pair number one, and we have a homologous pair number two."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So what this means is these are homologous with respect to one another, these are homologous with respect to one another, but these are non homologous."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And what that means is they don't actually carry the same genes that code for the same trait."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So let's suppose this segment shown in purple actually breaks off."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Once it breaks off, instead of going onto this original chromosome or onto the homologous chromosome, as we saw in this case, this segment can move on and attach itself onto a completely different non homologous chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Let's suppose this one right over here."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so this one attaches, let's say, somewhere right here."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so we formed the following, the following chromosome pair."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So basically, right over here, we have the process of deletion that took place that we discussed earlier."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And right over here we have the process of translocation that took place."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So basically, that segment of DNA that originally came from this chromosome moved on to this non homologous chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So aside from the abnormality we call anuploid, we can also have these other four types of chromosomal abnormalities."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "We can have inversion, we can have deletion, we can have duplication and translocation."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So in either case, we have a segment of that chromosome breaking off."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And in inversion, once that chromosome segment breaks off, it flips, it reverses its orientation and reinserts back into that original chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "In deletion, we have that broken off detached chromosome segment, basically moves away and never reattaches onto that particular original chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "In the case of duplication, we're dealing with a homologous pair of chromosomes."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so we have chromosome number one, and it's Homologous chromosome number two."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So we have a segment of, let's say, the second one break off, and then it moves on to that Homologous chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So we say that's a duplication, because this chromosome already carries those similar types of genes, and that's why we have a duplication taking place."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "Now in a translocation, we basically have the breaking off of that segment."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "And so that segment, once it breaks off, it moves on to a non Homologous chromosome, attaches to that non Homologous chromosome."}, {"title": "Chromosomal Depletion, Inversion, Duplication and Translocation .txt", "text": "So these are the four different types of chromosomal abnormalities that are not a result of nondisjunction."}, {"title": "Adaptive Immune System .txt", "text": "When one of the many different types of barriers of our body are breached for example we have a cut in our skin and our pathogen makes its way into the tissue of our body."}, {"title": "Adaptive Immune System .txt", "text": "Infection begins."}, {"title": "Adaptive Immune System .txt", "text": "And as soon as infection begins the innate immune system uses nonspecific defense mechanisms such as the process of inflammation."}, {"title": "Adaptive Immune System .txt", "text": "And what inflammation does is it ultimately localizes our infection to that specific region."}, {"title": "Adaptive Immune System .txt", "text": "It calls upon macrophages and oleukocytes that essentially engulf the pathogens as well as our infected cells."}, {"title": "Adaptive Immune System .txt", "text": "Now, while this process is taking place and while the innate immune system is preventing the spreading of this pathogen of this infection the adaptive immune system also known as the quiet immune system the other part of our immune system begins to mobilize itself."}, {"title": "Adaptive Immune System .txt", "text": "It begins to gear up to basically help fight that infection."}, {"title": "Adaptive Immune System .txt", "text": "Now, we know the innate immune system begins to act immediately following infection but our adaptive immune system actually takes several days before it is actually fully active and fully functional."}, {"title": "Adaptive Immune System .txt", "text": "Now, unlike the innate immune system which uses nonspecific mechanisms the adaptive immune system actually uses specific defense mechanisms because it uses antigens and antibodies as we'll see in just a moment."}, {"title": "Adaptive Immune System .txt", "text": "Now, the innate immune system cannot actually learn from infections but as we'll see in just a moment the adaptive immune system can actually learn from the different types of infections and pathogens that infect the body."}, {"title": "Adaptive Immune System .txt", "text": "Now, the adaptive immune system can be subdivided into two categories into two divisions."}, {"title": "Adaptive Immune System .txt", "text": "We have the antibody mediated immunity or the humoral immunity and we also have the cell mediated immunity."}, {"title": "Adaptive Immune System .txt", "text": "And these two systems work together to basically carry out that same exact function to fight off our pathogens that infected our body."}, {"title": "Adaptive Immune System .txt", "text": "So let's begin with the antibody mediated immunity."}, {"title": "Adaptive Immune System .txt", "text": "Now, the leukocytes involved the white blood cells involved in the antibody mediated immunity are the beetleympicides."}, {"title": "Adaptive Immune System .txt", "text": "Now, beet lymphocytes not only form in the bone marrow but they also mature in our bone marrow."}, {"title": "Adaptive Immune System .txt", "text": "And once they are released into our plasma into our lymph they travel and are stored within the lymph nodes of our body."}, {"title": "Adaptive Immune System .txt", "text": "Now, when infection takes place the B lymphocytes are released from the lymph node and they travel through our lymph system through our blood system and they travel inside our tissues."}, {"title": "Adaptive Immune System .txt", "text": "Now, before we actually discuss these B lymphocytes let's backtrack and go back to the process of inflammation."}, {"title": "Adaptive Immune System .txt", "text": "So when the innate immune system carries out inflammation it basically calls upon macrophages."}, {"title": "Adaptive Immune System .txt", "text": "So this is our macrophage."}, {"title": "Adaptive Immune System .txt", "text": "Now, what the macrophage does is it engulfs and breaks down these different types of pathogens."}, {"title": "Adaptive Immune System .txt", "text": "And what it also does is it takes the antigens of these pathogens and places the antigens on the surface on the membrane of the macrophage."}, {"title": "Adaptive Immune System .txt", "text": "The question is what for?"}, {"title": "Adaptive Immune System .txt", "text": "Well, because as it turns out the B lymphocytes as well as the T lymphocytes as we'll see in just a moment contain these receptors on the membrane of the lymphocytes."}, {"title": "Adaptive Immune System .txt", "text": "So the B lymphocytes contains the B cell receptors and when the B lymphocyte approaches our macrophage, if the B cell receptor complements this antigen we can have the binding process take place."}, {"title": "Adaptive Immune System .txt", "text": "They will form a complex and that will ultimately call upon a cell involved in the cell mediated immunity known as the helper T cell."}, {"title": "Adaptive Immune System .txt", "text": "And what the helper T cell does is it releases a special type of chemical or special types of chemicals which basically help the B lymphocyte undergo mitosis and differentiate into two different types of cells."}, {"title": "Adaptive Immune System .txt", "text": "So the B lymphocytes form plasma cells and memory B cells."}, {"title": "Adaptive Immune System .txt", "text": "And the memory B cells are the same cells that we spoke about earlier that are involved in the process of learning."}, {"title": "Adaptive Immune System .txt", "text": "So plasma cells are those specialized cells that are factories for antibodies."}, {"title": "Adaptive Immune System .txt", "text": "So they have extensive endoplasm reticulum that essentially forms many, many antibodies."}, {"title": "Adaptive Immune System .txt", "text": "And these antibodies that are formed by the plasma cell are specific and they complement the antigen that the B lymphocyte initially was bound to."}, {"title": "Adaptive Immune System .txt", "text": "And because we have many, many different types of plasma cells we have many different types of antibodies that are produced for each one of these different antigens that came from each one of these different types of pathogens."}, {"title": "Adaptive Immune System .txt", "text": "Now, what exactly is the purpose of these antibodies and what are these antibodies in the first place?"}, {"title": "Adaptive Immune System .txt", "text": "Well, antibodies are specialized proteins."}, {"title": "Adaptive Immune System .txt", "text": "They are also known as immunoglobulins immune means immunity and globulants mean protein."}, {"title": "Adaptive Immune System .txt", "text": "So these antibodies circulate along our blood system and our lymph system until they basically bind to the specific antigen that is found on another pathogen or let's say, some type of bacterial cell."}, {"title": "Adaptive Immune System .txt", "text": "Now, once our antibody binds onto that antigen it can do two things."}, {"title": "Adaptive Immune System .txt", "text": "It can either call upon other leukocytes, for example, macrophages, to come and engulf that pathogen or it can begin to aggregate and form this very large insoluble complex in a process known as agglutination."}, {"title": "Adaptive Immune System .txt", "text": "So antibodies are very, very important and they're involved in the adaptive immune system."}, {"title": "Adaptive Immune System .txt", "text": "And that's exactly why we call it an adaptive immune system because we have these other types of cells known as memory B cells and we also have actually memory T cells as we'll see in a moment."}, {"title": "Adaptive Immune System .txt", "text": "And what these memory cells do is they store a copy of that antibody on the membrane of that memory cell."}, {"title": "Adaptive Immune System .txt", "text": "And so these memory B cells swim around and circulate our blood system."}, {"title": "Adaptive Immune System .txt", "text": "Now lymph system and if that same type of pathogen ever reinfects our body these memory b cells as well as memory T cells of the cell mediated immunity can actually recognize these pathogens immediately and begin a very quick and effective response that can ultimately kill off that reinfecting pathogen."}, {"title": "Adaptive Immune System .txt", "text": "So these are the two types of cells that come from our B lymphocyte."}, {"title": "Adaptive Immune System .txt", "text": "But these B lymphocytes must associate with the helper T cells to actually become these two different types of cells."}, {"title": "Adaptive Immune System .txt", "text": "So these two different divisions although they are divisions, they have to work together to actually carry out this process of defending and protecting our body from pathogens."}, {"title": "Adaptive Immune System .txt", "text": "Now, the humoral immunity system is actually very effective against bacterial cells, different types of parasites, fungi, viruses, as well as toxins that enter our tissue of our body."}, {"title": "Adaptive Immune System .txt", "text": "Now, let's move on to our cell mediated immunity."}, {"title": "Adaptive Immune System .txt", "text": "Now, the cell mediated immunity also involves a special type of leukocyte known as the Tea lymphocytes."}, {"title": "Adaptive Immune System .txt", "text": "So belymphocytes are the humoral immunity but T lymphocytes are part of our cell mediated immunity."}, {"title": "Adaptive Immune System .txt", "text": "Now, T lymphocytes also are formed inside the bone marrow but T lymphocytes mature inside the thymus, which is basically a glam found in this region of our body."}, {"title": "Adaptive Immune System .txt", "text": "And what the Thiamis does is it basically checks, it tests these premature T lymphocytes and it ensures that the T lymphocytes don't actually attack our own cells of the body."}, {"title": "Adaptive Immune System .txt", "text": "And that's an important process because if the T lymphocytes do attack the cells of our body, what the thymus does is it ultimately Detroit these T lymphocytes."}, {"title": "Adaptive Immune System .txt", "text": "Now, one very important type of T lymphocyte that we spoke about earlier is the helper T cell."}, {"title": "Adaptive Immune System .txt", "text": "So once infection begins, some of these T lymphocytes differentiate into our helper T cells."}, {"title": "Adaptive Immune System .txt", "text": "Now, what exactly is the purpose of helper T cells?"}, {"title": "Adaptive Immune System .txt", "text": "Well, helper T cells help differentiate other cells of our immune system and they also release special types of chemicals known as interferons as well as interleukins."}, {"title": "Adaptive Immune System .txt", "text": "And these chemicals are involved in differentiating our cells as well as in promoting the process that defends our body from pathogens."}, {"title": "Adaptive Immune System .txt", "text": "For example, we know that helper T cells help differentiate the B lymphocytes into these plasma cells and memory B cells."}, {"title": "Adaptive Immune System .txt", "text": "Now, memory B cells help our immune system with learning and the plasma cells produce our antibodies that basically float and circulate around our blood system."}, {"title": "Adaptive Immune System .txt", "text": "Now, what the helper T cells also do is they also help differentiate T lynthesize into a special type of soldier cell we call the killer T cell or the cytotoxic T cell."}, {"title": "Adaptive Immune System .txt", "text": "Now, these cytotoxic T cells basically travel to the infected area and they can use the antibody found on their cell membrane and bind to special antigen portions, specific antigen portions found on the infected cell or pathogen cell."}, {"title": "Adaptive Immune System .txt", "text": "And they can basically release these very powerful proteins, proteolytic proteins that essentially drill holes inside those infected cells, killing those cells."}, {"title": "Adaptive Immune System .txt", "text": "And these powerful proteins are known as perforance."}, {"title": "Adaptive Immune System .txt", "text": "So basically the T lymphocy, with the help of the helper T cell differentiates into these soldiers cytotoxic T cells that contain these receptors."}, {"title": "Adaptive Immune System .txt", "text": "And when these receptors locate the specific type of antigen found on the infected cell, they bind, they form a complex."}, {"title": "Adaptive Immune System .txt", "text": "And once they form a complex, they begin to release these powerful proteins that drill holes in these infected cells and kill off those infected cells."}, {"title": "Adaptive Immune System .txt", "text": "And they can also release chemicals, these green dots that essentially call upon macrophages."}, {"title": "Adaptive Immune System .txt", "text": "And these macrophages basically come next to this infected cell and once the cell dies off the macrophage essentially engulfs that cell and breaks it down into different types of things."}, {"title": "Adaptive Immune System .txt", "text": "Now, two other types of cells that T lymphocytes can differentiate into our memory T cells that function in the same way as memory B cells and we can also form something called suppressor cells or suppressor T cells."}, {"title": "Adaptive Immune System .txt", "text": "And these cells are involved in using a negative feedback mechanism to essentially regulate and tone down our functionality of the immune system."}, {"title": "Adaptive Immune System .txt", "text": "So our cell mediated immunity is very effective against cells that have been infected by these different types of pathogens."}, {"title": "Adaptive Immune System .txt", "text": "So these are the major differences between the antibody mediated immunity and the cell mediated immunity."}, {"title": "Adaptive Immune System .txt", "text": "But these two different divisions must actually work together to carry out that same function."}, {"title": "Adaptive Immune System .txt", "text": "They cannot exist by themselves."}, {"title": "Adaptive Immune System .txt", "text": "For example these B lymphocytes need the helper T cells to actually differentiate and produce our antibodies."}, {"title": "Adaptive Immune System .txt", "text": "And the cell mediated immunity means these antibodies to actually function properly."}, {"title": "Adaptive Immune System .txt", "text": "And that means these two different systems must work together to carry out that same function."}, {"title": "Modification of Carbohydrates .txt", "text": "Carbohydrates molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "So individual monosaccharides can be modified in a variety of different ways by ourselves."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, generally speaking, why would ourselves want to modify sugar molecules?"}, {"title": "Modification of Carbohydrates .txt", "text": "Well, by modifying sugar molecules, the cells can actually change and alter the properties and the functionalities of sugar molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "And this is crucial in many different processes that take place inside our body."}, {"title": "Modification of Carbohydrates .txt", "text": "And one very important process in which we modify sugar molecules is in the process of glucose metabolism, as we'll see briefly in just a moment."}, {"title": "Modification of Carbohydrates .txt", "text": "So there are two modifications of sugars that we're going to focus on in this lecture."}, {"title": "Modification of Carbohydrates .txt", "text": "We're going to begin by discussing phosphorylation of sugars and then we're going to move on to glycosidation of sugars."}, {"title": "Modification of Carbohydrates .txt", "text": "So whenever our cells actually uptake sugar molecules, the first step in the breakdown of glucose in glucose metabolism is to phosphorylate glucose, is to basically transform the glucose into glucose six phosphates."}, {"title": "Modification of Carbohydrates .txt", "text": "So on the reactant side, we have the beta anomer of the cyclic form of glucose."}, {"title": "Modification of Carbohydrates .txt", "text": "So we have carbon 12345 and six."}, {"title": "Modification of Carbohydrates .txt", "text": "And this is the anameric carbon and it's the beta anomer because the hydroxyl group on carbon one points in the same direction as this group attached to carbon number five."}, {"title": "Modification of Carbohydrates .txt", "text": "So in the process of phosphorylation, when we transform glucose into glucose six phosphate, we essentially add the phosphoryl group onto carbon number six, as shown in this diagram."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, what's the major difference between the glucose and the glucose six phosphate?"}, {"title": "Modification of Carbohydrates .txt", "text": "Well, the major difference is the presence of this modified group."}, {"title": "Modification of Carbohydrates .txt", "text": "And this group contains a net negative charge, specifically a charge of negative two."}, {"title": "Modification of Carbohydrates .txt", "text": "So compared to this glucose molecule, which has a net charge of zero, this molecule has a net negative charge."}, {"title": "Modification of Carbohydrates .txt", "text": "And whenever a system in nature contains charge, what that means is its energy is higher, it's less stable and it's more reactive."}, {"title": "Modification of Carbohydrates .txt", "text": "So essentially bifus formulating a glucose molecule and transforming it into glucose expositate, our cells increase the reactivity of the glucose molecule and that allows it to basically undergo further processes and ultimately break down and form the ATP energy molecules that our cells use as the major energy source."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, the second reason why we phosphorylate glucose molecules is to increase the polarity of the glucose molecule."}, {"title": "Modification of Carbohydrates .txt", "text": "So compared to this unmodified glucose, the phosphorylated glucose contains a higher charge and so it is more polar."}, {"title": "Modification of Carbohydrates .txt", "text": "And because this molecule is more polar, it is much less likely to actually spontaneously leave the cell."}, {"title": "Modification of Carbohydrates .txt", "text": "Why?"}, {"title": "Modification of Carbohydrates .txt", "text": "Well, because around the cell we have the cell membrane which consists predominantly of non polar lipid molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "And so this highly polar glucose phosphate cannot spontaneously leave the cell because it cannot pass across the non polar bilayer membrane surrounding the cell."}, {"title": "Modification of Carbohydrates .txt", "text": "So once again, the first step in glucose metabolism involves modifying the glucose by adding phosphoryl group onto carbon number six."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, phosphorylation of glucose gives it a net negative charge and transforms it into an anion."}, {"title": "Modification of Carbohydrates .txt", "text": "And this is done for two reasons."}, {"title": "Modification of Carbohydrates .txt", "text": "The first reason is to prevent the glucose from spontaneously exiting the cell."}, {"title": "Modification of Carbohydrates .txt", "text": "And the second reason is to basically increase its energy, make it less stable, more reactive, so that it can form more linkages and can actually break down and form those ATP molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, let's move on to the process of glycosidation."}, {"title": "Modification of Carbohydrates .txt", "text": "And before we actually examine what that is, let's begin once again with this same beta animal of glucose."}, {"title": "Modification of Carbohydrates .txt", "text": "So we essentially have the beta D glucose molecule in its cyclic form."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, even though the cyclic form is more stable and it's going to predominate at equilibrium, we're still going to form a very tiny amount with less than 1% of the open chain of this deglucose molecule."}, {"title": "Modification of Carbohydrates .txt", "text": "And in the open chain we see that we have the aldehyde."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, what's the big deal about the aldehyde group?"}, {"title": "Modification of Carbohydrates .txt", "text": "Well, from organic chemistry we know that when an aldehyde group is in the presence of some type of oxidizing agent, for example a copper ion with a charge of positive two, that will basically undergo an oxidation reduction reaction."}, {"title": "Modification of Carbohydrates .txt", "text": "So this will basically act as the reducing agent and the C two, the oxidizing agent, while that will act as the oxidizing agent and what we'll have is, will form a carboxylic acid."}, {"title": "Modification of Carbohydrates .txt", "text": "So the thing about this unmodified z glucose molecule is that it contains an aldehyde group when the glucose exists in its open chain form and the aldehyde group is reactive when in the presence of oxidizing agents."}, {"title": "Modification of Carbohydrates .txt", "text": "And when that happens, when we'll have some type of oxidizing agent in the presence of the unmodified glucose in its open chain form, will transform that glucose into a carboxylic acid."}, {"title": "Modification of Carbohydrates .txt", "text": "And such sugar molecules, unmodified sugar molecules that can basically react with oxidizing agents to form the carboxylic acids, these are known as reducing sugars because they act as reducing agents."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, under certain circumstances, our cells don't actually want this reaction to take place."}, {"title": "Modification of Carbohydrates .txt", "text": "And what our cells do is they essentially remove that aldehyde group by reacting it in the process we call glycosidation, which basically transforms that glucose molecule into a glycoside."}, {"title": "Modification of Carbohydrates .txt", "text": "So what happens is we can basically undergo the process in the presence of alcohol."}, {"title": "Modification of Carbohydrates .txt", "text": "So let's suppose we have the simplest alcohol methanol."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, under acidic conditions, for example, in the presence of some type of acid, let's say HCL."}, {"title": "Modification of Carbohydrates .txt", "text": "So hydrochloric acid, what will happen is the hydrochloric acid will basically protonate this hydroxyl group."}, {"title": "Modification of Carbohydrates .txt", "text": "This will basically depart, forming a carbocation intermediate."}, {"title": "Modification of Carbohydrates .txt", "text": "And then this can act as a nucleophile attacking this carbon either from the top side or bottom side."}, {"title": "Modification of Carbohydrates .txt", "text": "And ultimately we form a mixture of these two molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "These two products and these two products are known as glycosides."}, {"title": "Modification of Carbohydrates .txt", "text": "So this is the methyl beta D glucocide and this is the methyl alpha deglucouranicide."}, {"title": "Modification of Carbohydrates .txt", "text": "And notice the difference between these two molecules is simply the orientation, the stereo chemistry of this group attached to carbon number one, in the beta case, this points in the same direction as this group."}, {"title": "Modification of Carbohydrates .txt", "text": "And the alpha case, it points in the opposite direction of this group here."}, {"title": "Modification of Carbohydrates .txt", "text": "So these two products are animals."}, {"title": "Modification of Carbohydrates .txt", "text": "We have the alpha and the beta anomer and they're called glycosides."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, this bond shown red the bond between the animary carbon number one on that glucose molecule and this oxygen that is part of this methanol is known as the Oglycocitic bond."}, {"title": "Modification of Carbohydrates .txt", "text": "We call it the Oglycocitic bonds."}, {"title": "Modification of Carbohydrates .txt", "text": "That basically differentiate from the anglyacitic bond that we'll talk about in just a moment."}, {"title": "Modification of Carbohydrates .txt", "text": "So the O simply means the bond is between carbon and oxygen and not between carbon and nitrogen, as the case is in the end glycositic bond."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, what's the entire point of carrying out this reaction?"}, {"title": "Modification of Carbohydrates .txt", "text": "Why do our cells actually want to create these glycosides?"}, {"title": "Modification of Carbohydrates .txt", "text": "Well, by creating the glycosides, we essentially remove the hydroxyl group and we remove the hydroxyl group and we replace it with this group that came from that methanol alcohol."}, {"title": "Modification of Carbohydrates .txt", "text": "And by replacing it with this group, we essentially remove the presence of an aldehyde from the open chain form."}, {"title": "Modification of Carbohydrates .txt", "text": "And if there is no aldehyde presence in the open chain form, then that means when either of these glycosides are in the presence of oxidizing agents for example, the cupric acid that we spoke of earlier the Cu two."}, {"title": "Modification of Carbohydrates .txt", "text": "Plus the copper ion with the two plus charge."}, {"title": "Modification of Carbohydrates .txt", "text": "These will not react in the presence of oxidizing agents and they will not play the role of being the reducing sugars because in the open chain form they do not contain the aldehyde group."}, {"title": "Modification of Carbohydrates .txt", "text": "And so these are known as non reducing sugars because they will not act as reducing agents in the presence of an oxidizing agent."}, {"title": "Modification of Carbohydrates .txt", "text": "So, unlike the unmodified D glucose, as we spoke about just a moment ago, the glucose glycoside does not react in the presence of oxidizing agents."}, {"title": "Modification of Carbohydrates .txt", "text": "And this is because it cannot be converted into an open chain form with an aldehyme group."}, {"title": "Modification of Carbohydrates .txt", "text": "And such unreactive sugars are known as non reducing sugars."}, {"title": "Modification of Carbohydrates .txt", "text": "So inside our cells, under certain cases, we want to keep the glucose in its unmodified form because we want to be able to react glucose in some way to basically form a bond."}, {"title": "Modification of Carbohydrates .txt", "text": "But under certain circumstances, we want to be able to transform glucose into a glycoside to prevent it from actually reacting with other types of reactive oxidizing agents."}, {"title": "Modification of Carbohydrates .txt", "text": "Now, another way that we can transform the glucose into a glycoside is by reacting with amines."}, {"title": "Modification of Carbohydrates .txt", "text": "And we actually spoke about this type of reaction when we discussed DNA and RNA molecules."}, {"title": "Modification of Carbohydrates .txt", "text": "So when a ribose molecule or a deoxyribose molecule, in the case of DNA molecules, react with some type of nitrogenous base, which is actually an amine, we form a nucleuside."}, {"title": "Modification of Carbohydrates .txt", "text": "So this is what we call a glycocidation with amines reaction."}, {"title": "Modification of Carbohydrates .txt", "text": "So the anemary carbon of deglucose."}, {"title": "Modification of Carbohydrates .txt", "text": "So carbon number one can react in the presence of amines to form not an Oglycocitic bond, but the Nglycocitic bond, because in this case, the bond is between the carbon number one and a nitrogen atom."}, {"title": "Modification of Carbohydrates .txt", "text": "So if we take, for instance, this same glucose molecule that we spoke of earlier, the beta D glucopyronose, and we reacted in the presence of some type of amine, we basically replaced the hydroxyl group with the amine group."}, {"title": "Modification of Carbohydrates .txt", "text": "And so now this bond in red is known as the Amglycocitic bond."}, {"title": "Modification of Carbohydrates .txt", "text": "And we'll see many examples of these types of reactions in the lectures to come."}, {"title": "Modification of Carbohydrates .txt", "text": "So the major point of this lecture is the fact that sugars can be modified in a variety of different ways."}, {"title": "Modification of Carbohydrates .txt", "text": "And by modifying the sugar molecules, our cells can actually control the properties and the reactivities of these sugar molecules."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "In our discussion on DNA molecules we mentioned that DNA is the biological molecule that stores the genetic information that is found within the cell and the DNA molecule are found inside the nucleus of our cell."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now, the genetic information that is stored within our DNA can be used to ultimately produce and synthesize our proteins and enzymes that are used by the cell."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "However, the DNA itself is not directly involved in protein synthesis."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Instead, our DNA must first be transcribed into a molecule known as RNA and it's the RNA that is directly involved in the synthesis of our protein molecule."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So in this lecture we're going to basically differentiate between RNA and DNA molecules and we're going to discuss the different types of RNA molecules that exist within our cell."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now, what exactly is RNA?"}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "RNA stands for ribonucleic acid and RNA is very similar to DNA in that it is also a polymer that consists of individual units known as nucleotides."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And just like in DNA our nucleotides in RNA also consist of three important parts."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "We have a sugar, we have a phosphate group and we also have a nitrogenous base."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now let's begin by differentiating the type of sugar that exists in DNA and RNA molecules."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So recall in DNA molecules the sugar that is involved is the deoxyribose sugar and the sugar looks something like this."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Notice that on the deoxyribo sugar the second carbon does not have a hydroxyl group."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "However, the RNA molecules contain the ribose sugar and unlike the deoxyribose the ribosugar actually does contain the hydroxyl group found on the second carbon."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So this is the ribosugar that is found on RNA molecules and that's exactly why our RNA stands for ribonucleic acid while DNA stands for deoxyribose nucleic acid."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now let's begin by let's move on to our nitrogenous base."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So there are four different types of nitrogenous bases that are found in DNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we have guanine and anine which are the two types of purines and we also have the thymine as well as our cytosine."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And the thymine and the cytosine are the two types of pyrimidines that exist in DNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now RNA nucleotides also contain adenine guanine as well as cytosine."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "However, thiamine is not found in RNA molecules."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "In RNA molecules the thymine is replaced with the uracil nitrogenous base and the major difference between the thymine and the uracil is the composition of atoms."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So notice this carbon contains the methyl group on thymine but this carbon does not."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And this carbon contains the nitrogen the amine group while this carbon contains our carbon oxygen double bond."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So this is the major difference between the thymine and our uracil nitrogenous base."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So in DNA molecules we have the thymine but in RNA molecules the thymine is replaced with our uracil."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now recall that in DNA the thymine combines or pairs with the adenine."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "In RNA the adenine actually pairs with the uracil because we no longer have the thionine."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So in RNA molecules."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Our adenine pairs with your cell while the guanine pairs with our cytosine."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now what other differences exist between our DNA and RNA biological molecules?"}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Well, another important difference between DNA and RNA is that RNA exists mostly as a single strand."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we do find double stranded RNA molecules but our RNA molecules predominantly exist in the single strand form."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "However, recall that DNA molecules actually exist predominantly as the double stranded form."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we have our double helix basically in DNA our two single strands of DNA align antiparallel and they hydrogen bonds to form our double helix."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "But the RNA exists predominantly in the single strand form and this is exactly what allows our RNA molecule to actually pass through the nuclear pores."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So unlike DNA which stays within the nucleus of our cell mRNA molecules can actually move from the nucleus to the cytoplasm through the nuclear pores that are found inside the nuclear membrane of the nucleus."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now as we mentioned earlier, there are different types of RNA molecules that exist and each one of these RNA molecules serves its own primary purpose."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So let's discuss the different types of RNA molecules and what their primary function is."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And let's begin with the messenger RNA or mRNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So within the nucleus of our cell our DNA can be transcribed."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "It can undergo a process known as transcription which we'll discuss in detail in the next several lectures."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And DNA can be transcribed into our messenger RNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now messenger RNA, once it's actually formed, it can be modified in several important ways and ultimately our messenger RNA will end up in a cytoplasm of the cell where the messenger RNA will combine with the ribosomes of the cell and the messenger and the ribosomes will basically combine to synthesize our proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we see that the ribosomes can basically translate the genetic information that is stored within the mRNA and using that genetic information that came from the DNA we can synthesize our proteins through a process known as translation which we'll discuss in much greater detail in the next several electrodes."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now in eukaryotic cells our eukaryotic mRNA is usually used to synthesize a single protein."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "But in prokaryotic organisms a single mRNA molecule can be used to synthesize many different proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now let's move on to the second type of RNA known as rRNA which stands for ribosomal RNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now ribosomal RNA is synthesized in a specific section of the nucleus known as the nucleolus."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And once we synthesize our rRNA from the DNA that rRNA can transfer into the cytoplasm and it can combine with special types of proteins to form the ribosomes."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we see that ribosomal RNA are specialized RNA molecules that combine with proteins to form ribosomes."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So ribosomes contain RNA and RNA basically form an integral part of these ribosomes."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And recall in our discussion on ribosomes we said that ribosomes are the machinery that is used to synthesize our proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And finally, let's move on to the final type of RNA known as tRNA, which stands for transfer RNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now, when our mRNA combines with the ribosomes, what happens is our mRNA contains a three sequence nucleotide that is known as the codon."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And the codon basically stands for some type of amino acid."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "Now, in order to bring that amino acid from some location inside our cytoplasm into the ribosome, we have to have some type of molecule."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And the molecule that brings the amino acid into that ribosome is our transfer RNA."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So transfer RNA are specialized molecules that collect the proper or appropriate amino acid and bring it into the ribosome where that amino acid is then attached to the growing polypeptide chain."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we see that all three of these different types of RNA molecules are synthesized inside the nucleus and they're all involved in the process in the synthesis of our proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And each one of these different types of RNA molecules serves its own unique function."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So the messenger RNA basically contains the genetic information, the codons, that basically code for our protein, the ribosomal."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "RNA are integral parts of ribosomes which are the machinery that basically synthesize our proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And the transfer RNAs are those RNA molecules that collect the proper amino acid and ultimately bring it into our ribosome so that we can add that amino acid to the growing peptide chain."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "So we see it's not the DNA molecule but it's the RNA, a molecule that is directly involved in the synthesis of our proteins."}, {"title": "mRNA, rRNA, and tRNA .txt", "text": "And we'll discuss the processes of transcription and translation in the next several lectures that involve these different types of molecules."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "The three structures that begin and allow the movement of food along our digestive canal, also known as the elementary canal, are the oral cavity, also known as aroma, the pharynx, as well as Aristophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So let's briefly discuss what the function is and what takes place within each one of these structures."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And let's begin with the oral cavity."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, the oral cavity cavity is also known as the mouth."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And what the mouth does is initiates two important processes."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "One called mechanical digestion and the other one called chemical digestion."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, mechanical digestion is the process by which we break down the large food particles into much smaller food particles."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, mechanical digestion does not actually break down any chemical bonds."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "It does not break any covalent bonds that actually hold those macromolecules together."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "What it actually does is it simply increases the surface area of the food on which the proteolytic enzymes found in the mouth, in our stomach and small intestine can actually act on."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this makes the process of digestion the breakdown much more efficient and effective."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, what actually initiates and creates mechanical digestion is the movement of the muscles and the teeth found inside our mouth."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this is known as chewing, or mastication."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, this chewing process, the chewing of food, actually transforms our food into a spherical mass we call the bolus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this shape of the bolus basically allows the movement of the spherical bolus along our cylinder known as Aristophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So the stophagus, as we'll see in just a moment, is a tube that has a cylindrical shape."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And the bolus, the fact that our chewing process creates this bolus is helpful because the bolus, the sphere of food, can easily move along Aristophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, let's move on to chemical digestion."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So chemical digestion is the process by which our proteolytic enzymes actually break down and cleave the chemical bonds that hold our macromolecules together."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So basically, these proteolytic enzymes catalyze the reaction known as hydrolysis."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "It's a catabolic reaction that breaks down our chemical bonds using water."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So the two types of proteolytic enzymes found in the mouth are amylase, also known as Tylen, as well as lipase, also known as lingual lipase."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, amylase is a proteolytic enzyme that catalyzes the breakdown of carbohydrates, specifically of starch."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "It breaks down our carbohydrate, known as starch, into our maltose, as well as dextrin."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "On the other hand, lipase is a proteolytic enzyme that catalyzes the hydrolysis, the breakdown of fats, of lipids into their constituents."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So we see that in the mouth we initiate the actual chemical breakdown of not only carbohydrates, but also of fats."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, proteins are not actually broken down inside our mouth so we increase the surface area via mechanical digestion but we do not actually chemically break down our proteins in the mouth."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, special types of glands known as salivary glands secrete a substance of fluid known as saliva in our mouth."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And saliva consists of many different things."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, saliva consists predominantly of water."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "About 95% of saliva consists of water and that's because the process of hydrolysis that is catalyzed by amylase and lipase and other protein enzymes in our stomach as well as in our small intestine require water to actually break those bonds and that's why we have so much water in our saliva."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, other components of saliva include these proteolytic enzymes, it includes glycoproteins, it includes mucus, it also includes special antibacterial molecules, enzymes such as lysozymes."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "These lysozymes basically attack and break down the cell walls of bacterial cells and that kills off our bacteria."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, what saliva also does is it actually lubricates our bolus, our food and that allows the movement of the bolus along Aristophagus with a minimal amount of friction and that ensures that the movement of arabolis along the esophagus doesn't actually hurt, it is not actually painful."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now let's move on to our pharynx."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "The pharynx is basically the passageway that connects our oral as well as nasal cavity to our windpipe as well as to our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, because we have this connection, this intersection between the windpipe and our esophagus, we basically have a flap of cartilage known as epiglottis that separates the windpipe from Aristophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So what the windpipe does is it allows the movement of air from the mouth from the nose or mouth to our lungs while what our esophagus allows us to do is it allows us to actually move the food from the mouth to our stomach."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now what this epiglottis does is when we initiate the process of swallowing, when we begin swallowing our food, our epiglottis basically closes our windpipe and that allows our food bowls to actually move along the pharynx and right into our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So the pharynx is the passageway that connects the nasal and the oral cavity to our windpipe, our larynx and the trachea as well as to our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "It allows not only the movement of air into and out of the lungs but it also allows the movement of our food bowls into our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, in order to actually prevent the movement of the food into our windpipe, a cartilage in this flap called the epiglottis forms a protective barrier that keeps the food out of the larynx."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So as the tongue and other voluntary muscles found in the mouth initiate the process of swallowing wing, this reflex creates the movement of that epiglottis and the epiglottis basically shuts close and that prevents the movement of our bolus into our air passageway into the larynx."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, we have a special type of circular muscle that basically connects, that separates our esophagus as well as the pharynx and this is known as our esophageal sphincter."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this esophageal sphincter relaxes and opens and allows the movement of that bolus into our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So now let's move on to our esophagus."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So the esophagus is a relatively long and relatively narrow passageway, a cylindrical passageway that allows the movement of our bolus, the food from the pharynx and into our stomach."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So the esophagus is a relatively long and narrow passageway that connects the pharynx to our stomach."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "It runs along and in the back of the windpipe and it's found in front of our spinal cord."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, the upper portion of our esophagus consists of skeletal muscle while the rest of it consists of involuntary smooth muscle."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this basically means that although we can actually initiate the process of swallowing and we can actually voluntarily control the movement of food into the upper region of the esophagus, the rest of that movement is controlled, involuntary."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "We cannot actually control it consciously."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And this process by which our smooth muscle is found in our esophagus creates a wavelike motion and allows that bolus of food to actually travel along our esophagus is known as peristaltis."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "So peristalis is the wavelike contraction of our smooth muscle that propels and allows that food to actually move down our esophagus and ultimately to our stomach."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "Now, once at the bottom of our esophagus there's another sphincter known as the cardiac sphincter that actually opens up and allows the movement of that bolus from the esophagus and into our stomach."}, {"title": "Oral Cavity, Pharynx, and Esophagus.txt", "text": "And as we'll see in the next lecture in our stomach we begin the digestion of our proteins."}, {"title": "Diagonal Electrophoresis.txt", "text": "In this lecture, we're going to finish our discussion on protein sequencing."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now, previously we focused on proteins that consist of a single polypeptide chain and we discussed how we can sequence the amino acids in those types of proteins."}, {"title": "Diagonal Electrophoresis.txt", "text": "But we know many proteins inside our body."}, {"title": "Diagonal Electrophoresis.txt", "text": "For example, hemoglobin have more than one polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "So they have have quotinary structure."}, {"title": "Diagonal Electrophoresis.txt", "text": "And the question is, if a protein has quotinary structure, if a protein consists of two or more polypeptide chains, how do we sequence these types of proteins?"}, {"title": "Diagonal Electrophoresis.txt", "text": "So how do we determine the amino acid sequence in proteins that consists of two or more polypeptide subunits?"}, {"title": "Diagonal Electrophoresis.txt", "text": "So there are three steps that we essentially have to follow."}, {"title": "Diagonal Electrophoresis.txt", "text": "In step one, what we want to do is we want to take our quarterly structure and break it down."}, {"title": "Diagonal Electrophoresis.txt", "text": "We want to denature our protein."}, {"title": "Diagonal Electrophoresis.txt", "text": "We want to break down the non covalent interactions and the disulfide bonds that exist between those two polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we need to expose the quadrinary structure to a denaturing solution."}, {"title": "Diagonal Electrophoresis.txt", "text": "For example, we can use urea or guanidine hydrochloride to basically break down those non covalent interactions holding our two polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then if we have disulfide bonds between our two polypeptide chains, we want to expose them to beta mercapto ethanol to basically break down those covalent interactions."}, {"title": "Diagonal Electrophoresis.txt", "text": "So let's suppose we're dealing with a protein that consists of two individual subunits, two polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "We have the green one and we have the blue one."}, {"title": "Diagonal Electrophoresis.txt", "text": "And these red lines are basically our disulfide bonds."}, {"title": "Diagonal Electrophoresis.txt", "text": "So if we take this protein and place it into a solution that contains urea and betama captive ethanol, we're going to denature the structure and separate these two polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we are going to have a mixture of the green individual chain and the blue individual chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "And notice that in this particular example, the blue one is greater than our green one."}, {"title": "Diagonal Electrophoresis.txt", "text": "So the next step is step number two."}, {"title": "Diagonal Electrophoresis.txt", "text": "So once we separate that structure, once we separate these polypeptide chains, once we have the mixture of these two different types of polypeptide chains, the next question is how do we purify our mixture and isolate these two polypeptide chains into different compartments, into different beakers, for example?"}, {"title": "Diagonal Electrophoresis.txt", "text": "Well, we have to use some type of purification method now because in this case, the size of this is greater than the size of this."}, {"title": "Diagonal Electrophoresis.txt", "text": "We can use gel electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "So."}, {"title": "Diagonal Electrophoresis.txt", "text": "SDS Page."}, {"title": "Diagonal Electrophoresis.txt", "text": "Also known as SDS polyacrylamide gel electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "And the reason we use this setup is because it allows us to separate the two polypeptide chains based on their size and mass."}, {"title": "Diagonal Electrophoresis.txt", "text": "So here we have the electrophoresis setup."}, {"title": "Diagonal Electrophoresis.txt", "text": "We basically take the mixture of these two proteins, we put them inside the well and we wait some time."}, {"title": "Diagonal Electrophoresis.txt", "text": "And what will happen is, because this has a greater size, it will experience a greater resistance as it travels down to the bottom of our gel."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so what happens is after some time passes, this will migrate less than the smaller green protein."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so we're going to form two bands."}, {"title": "Diagonal Electrophoresis.txt", "text": "One of the band, the green band, corresponds to this protein and the second band corresponds to this larger polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "So once we form these two bands, we can now isolate these two proteins."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we take out this protein, place them into beaker one."}, {"title": "Diagonal Electrophoresis.txt", "text": "We take out the second protein, the second polypeptide chain, and place it into beaker number two."}, {"title": "Diagonal Electrophoresis.txt", "text": "So now we have two beakers with these two different polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "And now all we have to do in step three is do exactly what we did follow the same exact procedures that we followed with those individual polypeptide chains, as we discussed previously."}, {"title": "Diagonal Electrophoresis.txt", "text": "So what that means is, for example, let's suppose we take that beaker number one that contains our green polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "What we have to do is we have to expose that polypeptide chain to proteolytic molecules that cleave our peptide at specific locations."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we essentially cut up and divide this long fragment, this long polypeptide chain, into many small fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we take each one of these fragments and we run egman degradation on each one of these fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "And that allows us to basically determine exactly what that sequence is of each one of these fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we repeat the process with a different proteolytic enzyme."}, {"title": "Diagonal Electrophoresis.txt", "text": "And eventually we can basically find what the order is of these different fragments in that polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we repeat the process with this larger blue polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "At the end, we basically are able to sequence what those amino acids are and how they're arranged in that polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "So once again, once we isolate the two subunits, we can now determine what the sequence of amino acid is separately."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we take, for example, this mixture."}, {"title": "Diagonal Electrophoresis.txt", "text": "We expose it to or this polypeptide chain."}, {"title": "Diagonal Electrophoresis.txt", "text": "We expose it to proteolytic enzymes."}, {"title": "Diagonal Electrophoresis.txt", "text": "We cut up into these many fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "Then we run the eggman degradation process to determine what the specific sequence is of each one of these fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we repeat the process with the different proteolytic enzyme."}, {"title": "Diagonal Electrophoresis.txt", "text": "We get a different set of fragments and we again run admin degradation to find the sequence."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we use the two sets of fragments to basically find what the correct order is of these fragments with respect to one another."}, {"title": "Diagonal Electrophoresis.txt", "text": "And in that manner, we can basically find what the sequence is of amino acids in this polypeptide."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then we repeat that with the blue polypeptide."}, {"title": "Diagonal Electrophoresis.txt", "text": "And at the end, we know exactly what the sequence of amino acid is in this protein that consists of these two polypeptide chains."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now, the final piece of information that we need to know is where exactly are these disulfide bonds?"}, {"title": "Diagonal Electrophoresis.txt", "text": "So we want to answer the following question how do we determine the position of the sulfide bonds in that protein that contains these disulfide bridges."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we have to follow three different steps."}, {"title": "Diagonal Electrophoresis.txt", "text": "And what we use is a special process known as diagonal electrophoresis which is basically two different applications of the gel electrophoresis process as we'll see in just a moment."}, {"title": "Diagonal Electrophoresis.txt", "text": "So let's suppose this is the protein and in the protein we have these two polypeptides and they are connected to one another at two locations by disulfide bond."}, {"title": "Diagonal Electrophoresis.txt", "text": "So this is disulfide bond number one and disulfide bond number two."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now what we want to do initially is we want to take this protein and expose it to some type of proteolytic enzyme."}, {"title": "Diagonal Electrophoresis.txt", "text": "And we want to make sure that that proteolytic enzyme does not break these disulfide bonds."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we take our protein, we expose it to our proteolytic chemical."}, {"title": "Diagonal Electrophoresis.txt", "text": "And what that proteoly chemical does is it cleaves at different sections on these two polypeptides."}, {"title": "Diagonal Electrophoresis.txt", "text": "For example, let's say it cleaves."}, {"title": "Diagonal Electrophoresis.txt", "text": "Let's erase these for a moment so that we're not confused."}, {"title": "Diagonal Electrophoresis.txt", "text": "So that proteolytic chemical, for example, let's say cleaves at this location."}, {"title": "Diagonal Electrophoresis.txt", "text": "Then it cleaves at this location."}, {"title": "Diagonal Electrophoresis.txt", "text": "It also cleaves at this location."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so we produce the following four different fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we break this bond here, we produce fragment number one."}, {"title": "Diagonal Electrophoresis.txt", "text": "So let's label this fragment as fragment number one."}, {"title": "Diagonal Electrophoresis.txt", "text": "Then we cleave this bond here, we produce this fragment number two."}, {"title": "Diagonal Electrophoresis.txt", "text": "And we also produce, once we cleave this section here we produce this fragment number four."}, {"title": "Diagonal Electrophoresis.txt", "text": "And notice that because the protolytochemical leaves our disulfide bonds intact these red bonds aren't broken."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so this entire fragment number three actually consists of this green section that came from the green polypeptide and the blue section that came from that blue polypeptide."}, {"title": "Diagonal Electrophoresis.txt", "text": "And we do this for a specific region because this is an important part of the process of diagonal electrophoresis as we'll see in just a moment."}, {"title": "Diagonal Electrophoresis.txt", "text": "So these are basically our steps in diagonal electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now once we have these four fragments in our mixture in our solution we now place them onto a sheet and we run electrophoresis on that sheet along the horizontal direction."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we now place the fragments onto the corner of a sheet and we run electrophoresis along the horizontal direction."}, {"title": "Diagonal Electrophoresis.txt", "text": "So essentially we place them onto the corner and they begin to migrate."}, {"title": "Diagonal Electrophoresis.txt", "text": "And once again the ones that are heaviest, the ones that are largest will essentially migrate the least."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so because fragment three is the largest this will basically travel the least distance."}, {"title": "Diagonal Electrophoresis.txt", "text": "And because fragment two is the smallest it will travel the greatest distance."}, {"title": "Diagonal Electrophoresis.txt", "text": "And then four is slightly smaller than what is it one."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so four will be here and one will be here."}, {"title": "Diagonal Electrophoresis.txt", "text": "So following electrophoresis in the horizontal direction this is our distribution of proteins, of bands that we actually get."}, {"title": "Diagonal Electrophoresis.txt", "text": "And notice that protein three consists of a blue section, this section and the green section, this section here."}, {"title": "Diagonal Electrophoresis.txt", "text": "So let's call this blue section, let's call it three B."}, {"title": "Diagonal Electrophoresis.txt", "text": "And let's call this green section, three A because that will become important in just a moment."}, {"title": "Diagonal Electrophoresis.txt", "text": "So this is step A of diagonal electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "What do we do in step B?"}, {"title": "Diagonal Electrophoresis.txt", "text": "Well, now in step B, once we have the separation of these four fragments, we now want to expose the sheet that contains these separated proteins to special type of chemicals."}, {"title": "Diagonal Electrophoresis.txt", "text": "So we essentially vaporize the chemical and we expose our sheet to this chemical that essentially breaks our disulfide bond."}, {"title": "Diagonal Electrophoresis.txt", "text": "So the sheet is now exposed to a chemical, namely a performic acid."}, {"title": "Diagonal Electrophoresis.txt", "text": "So the vaporized version of formic acid and that performic acid breaks those disulfide bonds."}, {"title": "Diagonal Electrophoresis.txt", "text": "And now these fragments that were initially connected are no longer connected because these two bonds are broken by the vaporized performic acid."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now let's move on to C. So now these two have been broken."}, {"title": "Diagonal Electrophoresis.txt", "text": "And now in step C, we run a second round of gel electrophoresis on that same sheet under the same conditions."}, {"title": "Diagonal Electrophoresis.txt", "text": "But now we run it in a perpendicular direction."}, {"title": "Diagonal Electrophoresis.txt", "text": "Instead of running it this way, we run it going up."}, {"title": "Diagonal Electrophoresis.txt", "text": "And that's exactly why we have these two axes on the following graph."}, {"title": "Diagonal Electrophoresis.txt", "text": "So the x axis describes the horizontal electrophoresis, the first round of electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "And this is the second round of electrophoresis."}, {"title": "Diagonal Electrophoresis.txt", "text": "So now they begin to migrate up."}, {"title": "Diagonal Electrophoresis.txt", "text": "Now what happens is at the end of our experiment, this is what we basically see."}, {"title": "Diagonal Electrophoresis.txt", "text": "This is our diagonal line that gives this name the diagonal electrophoresis procedure."}, {"title": "Diagonal Electrophoresis.txt", "text": "So because segment or fragment two, four and one do not consist of two or more fragments, they are individual fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "But because this one consists of two fragments, we're going to see the following distribution."}, {"title": "Diagonal Electrophoresis.txt", "text": "So one, four and two are simply single fragments."}, {"title": "Diagonal Electrophoresis.txt", "text": "Nothing has happened to them."}, {"title": "Diagonal Electrophoresis.txt", "text": "They traveled as shown, this distance here, this distance here and this distance here."}, {"title": "Diagonal Electrophoresis.txt", "text": "So because two is the smallest, it traveled greatest along this vertical direction."}, {"title": "Diagonal Electrophoresis.txt", "text": "Four is this segment here."}, {"title": "Diagonal Electrophoresis.txt", "text": "And because four is slightly smaller than one, it travels farther than one."}, {"title": "Diagonal Electrophoresis.txt", "text": "But notice what happened to three, because three, after we exposed the two performic acid has been separated because these two bonds broke."}, {"title": "Diagonal Electrophoresis.txt", "text": "Three now consists of three A and three B that are not connected."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so when we run gelature freezes along the vertical direction, what happens is they will actually separate because three A is much smaller than three B."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so three A will essentially travel higher up than three B and three B because it is the largest out of all."}, {"title": "Diagonal Electrophoresis.txt", "text": "These fragments will be found lowest along the vertical direction."}, {"title": "Diagonal Electrophoresis.txt", "text": "And so now we know that there exists disulfide bonds between these two fragments, three A and three B."}, {"title": "Diagonal Electrophoresis.txt", "text": "And once we know that, we can basically cleave them further and determine what the sequence is by using the admin degradation process as we discussed here."}, {"title": "Diagonal Electrophoresis.txt", "text": "And once we know the sequence, once we know where those 16 amino acids are, we can determine how these 16 amino acids are actually connected."}, {"title": "Diagonal Electrophoresis.txt", "text": "So this is how we basically know what the position is of our disulfide by running this special type of procedure known as diagonal electrophoresis."}, {"title": "Polyclonal Antibodies .txt", "text": "Antibodies are macromolecules produced by the cells of our body and the cells of other organisms and they serve a protective function."}, {"title": "Polyclonal Antibodies .txt", "text": "So they are part of the immune system of that particular organism."}, {"title": "Polyclonal Antibodies .txt", "text": "So whenever pathogenic agents some type of infectious agent, for example, a bacterial cell makes its way into the organism, that organism responds by using its immune immune system to basically produce these special molecules we call antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "And what an antibody is it's basically this very highly specialized type of protein that has a high affinity for a specific type of pathogenic antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, what exactly is an antigen?"}, {"title": "Polyclonal Antibodies .txt", "text": "Well, an antigen is any type of molecule that comes from that infectious agent that invaded that body."}, {"title": "Polyclonal Antibodies .txt", "text": "So an antigen could be, for example, a sugar molecule, a polysaccharide that came from that infectious agent."}, {"title": "Polyclonal Antibodies .txt", "text": "It can also be a nucleic acid or it can be a protein."}, {"title": "Polyclonal Antibodies .txt", "text": "And in this lecture we're going to assume our antigen is a protein."}, {"title": "Polyclonal Antibodies .txt", "text": "Now how exactly does the binding process between an antibody and an antigen actually take place?"}, {"title": "Polyclonal Antibodies .txt", "text": "Well, in our body we have five categories of antibodies and antibodies are also known as immunoglobulins."}, {"title": "Polyclonal Antibodies .txt", "text": "And that's because immuno means it's part of our immune system and globulin means the spherical shape, the globelike shape of that particular antibody."}, {"title": "Polyclonal Antibodies .txt", "text": "So immunoglobulin g is one of the five different categories of antibodies that we have inside our body."}, {"title": "Polyclonal Antibodies .txt", "text": "And the shape of immunoglobulin g is shown here."}, {"title": "Polyclonal Antibodies .txt", "text": "So immunoglobulin g consists of four polypeptide chains."}, {"title": "Polyclonal Antibodies .txt", "text": "Two of these chains are large and we call them heavy chains."}, {"title": "Polyclonal Antibodies .txt", "text": "They're the purple ones and the other two are light chains."}, {"title": "Polyclonal Antibodies .txt", "text": "They're shown in blue."}, {"title": "Polyclonal Antibodies .txt", "text": "So these blue chains are connected, the purple chains by disulfide bonds."}, {"title": "Polyclonal Antibodies .txt", "text": "And these two heavy chains are connected to each other, but also by disulfide bonds as shown by these red bonds."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, on that antibody we have a specific region known as the antigen binding side."}, {"title": "Polyclonal Antibodies .txt", "text": "And the antigen binding side contains a specific sequence of amino acids that has a high affinity for that antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, if these are the antigens, the antigens also contain a sequence of amino acids that basically bind to that antigen binding side of the antibody."}, {"title": "Polyclonal Antibodies .txt", "text": "So every antigen contains an epitope, which is a specific sequence of amino acids that binds onto the antigen binding side of that immunoglobulin of that antibody."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, once that binding process takes place, we form the antibody antigen complex."}, {"title": "Polyclonal Antibodies .txt", "text": "Now what takes place next?"}, {"title": "Polyclonal Antibodies .txt", "text": "Well, once this binding process takes place it elicits a series of different responses by our immune system."}, {"title": "Polyclonal Antibodies .txt", "text": "And one way that our immune system responds is by using a special type of immune cell known as a plasma cell to basically manufacture and produce antibodies that bind to that specific antigen that the antibody was bound to."}, {"title": "Polyclonal Antibodies .txt", "text": "So if this is our antigen that the antibody is bound to, then the plasma cells will produce more antibodies that will bind to this specific antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, oftentimes what happens is let's talk about these plasma cells for a moment."}, {"title": "Polyclonal Antibodies .txt", "text": "So the thing about plasma cells is any individual plasma cell will only produce a single type of antibody."}, {"title": "Polyclonal Antibodies .txt", "text": "So we have this one to one correlation between the plasma cell we're talking about and the antibody that it produces."}, {"title": "Polyclonal Antibodies .txt", "text": "So it only produces a single type of antibody."}, {"title": "Polyclonal Antibodies .txt", "text": "Now the thing about antigens is many antigens contain many epitopes."}, {"title": "Polyclonal Antibodies .txt", "text": "So many regions where antibodies can actually be bound to."}, {"title": "Polyclonal Antibodies .txt", "text": "In this particular case we only show one epitope."}, {"title": "Polyclonal Antibodies .txt", "text": "But in this case we show one, two, three different types of epitopes and the plasma cells of our body realize that and our immune cell, what it does to basically create a more effective response is once the antibody antigen complex is formed that signals different types of plasma cells to proliferate and form more plasma cells."}, {"title": "Polyclonal Antibodies .txt", "text": "And these different types of plasma cells begin to produce different types of antibodies that might have a slightly different type of mass and slightly different type of property."}, {"title": "Polyclonal Antibodies .txt", "text": "But all these antibodies produced will bind to that same type of antigen and these are known as polyclonal antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "So polyclonal simply means we have poly so many different types of plasma cells and so we produce many different types of antibodies but all these antibodies will still bind to that same type of antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "The only difference is they will bind to different locations on that antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "That's what we mean by polyclonal antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "So this binding process takes place, it tells our plasma cells which types of antibodies to produce."}, {"title": "Polyclonal Antibodies .txt", "text": "It tells them exactly what type of epitopes are found on that antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "And then the different types of plasma cells produce let's say antibody one, two and three."}, {"title": "Polyclonal Antibodies .txt", "text": "And then antibody one binds onto epitope one as shown here."}, {"title": "Polyclonal Antibodies .txt", "text": "Antibody two binds onto the second epitope as shown here."}, {"title": "Polyclonal Antibodies .txt", "text": "And the third one binds to this third epitope as shown here."}, {"title": "Polyclonal Antibodies .txt", "text": "So these three antibodies are our polyclonal antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "So many antigens have several epitopes."}, {"title": "Polyclonal Antibodies .txt", "text": "Polyclonal antibodies are a mixture of these different types of antibodies which have slightly different properties that all bind to that specific antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "But they bind two different locations, two different epitopes on that particular antigen."}, {"title": "Polyclonal Antibodies .txt", "text": "Now how do we produce polyclonal antibodies?"}, {"title": "Polyclonal Antibodies .txt", "text": "For example, if I'm a biochemist in the laboratory how can I produce these polyclonal antibodies and actually study them?"}, {"title": "Polyclonal Antibodies .txt", "text": "Well, it turns out that it's not that difficult to produce these polyclonal antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "So basically we take some type of organism with a functioning immune system, for example a mouse and we inject that mouse with our fluid that contains those antigens."}, {"title": "Polyclonal Antibodies .txt", "text": "For example, one type of antigen is two, four Dinitrophenol."}, {"title": "Polyclonal Antibodies .txt", "text": "So we can inject two, four Dinitrophenol into the mouse, into the blood of the mouse by using a syringe."}, {"title": "Polyclonal Antibodies .txt", "text": "So we inject once we wait three weeks, we inject the second time, we wait three weeks."}, {"title": "Polyclonal Antibodies .txt", "text": "And after a total of six weeks we take another syringe and we draw blood from that mouse."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, that blood will now contain the polyclonal antibodies against that antigen, against the two four Dinitrophenol."}, {"title": "Polyclonal Antibodies .txt", "text": "And now we can use the different types of purification techniques that we spoke about previously to basically isolate and study the polyclonal antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "For example, we can undergo self fractionation and differential centrifugation to basically isolate all the proteins from that blood mixture."}, {"title": "Polyclonal Antibodies .txt", "text": "And then we can use some type of purification technique."}, {"title": "Polyclonal Antibodies .txt", "text": "For example, we can use affinity chromatography, Angela Traffrees to basically isolate those polychrome antibodies and study them so we see that it's not that difficult to actually isolate and form these poly antibodies."}, {"title": "Polyclonal Antibodies .txt", "text": "Now, in the next lecture, we're going to discuss something called monoclonal antibodies and those are actually difficult to synthesize."}, {"title": "Polyclonal Antibodies .txt", "text": "It took us a while to basically realize how we can synthesize monoclonal antibodies as we'll see in the next lecture."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "The large green ones and the intermediate orange ones."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Now, over time, as a result of what we discussed earlier, we're going to see the following arrangement take place."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "So, because those large proteins will have a smaller velocity, smaller rate of movement, as a result of the increase in the drag force in the coefficient, what that means is these green proteins will be found higher up as compared to our intermediate orange proteins, which will be somewhere in the middle."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And those very tiny proteins, the purple ones, will find it easier to move along these channels and pores because of its physical size, because of that smaller drag force."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And so, over time, we basically see three different bands form."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "At the top, we have the green band."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Somewhere in the middle, or somewhere on the bottom, we have this purple band."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And somewhere in the middle, we have our orange band."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "So this band is the collection of these green proteins."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "This band is the collection of these intermediate proteins, and this band is a collection of these very tiny proteins."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And although each and every individual protein will follow its own unique pathway through these channels and pores, because their rates will be exactly the same."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "So for any given protein that is of equal size, because their rate will be the same, they will end up at the same exact location along our gel."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "So we have the large proteins, intermediate and the small proteins."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Now, the final question is, what is the difference between gel electrophoresis and gel filtration chromatography?"}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Because both of these techniques do the same exact thing."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "They basically separate the proteins based on size."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "But what's the major difference between these two methods?"}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Well, in gel atrophies all of these proteins in the mixture are forced to move through the porous gel."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "But in the case of gel filtration chromatography, only the small proteins are actually forced to move through the beads that are composed of that porous gel."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "In gel filtration chromatography, the large proteins are not forced to move through the porous beads."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "Instead, they can simply travel through the space around the beads."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And because of that, in gel filtration chromatography, it's the larger protein that makes its way down to the column first, because it doesn't experience a large drag force like the small molecules that do travel to the beads do."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And so that is the major difference between these two techniques."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "In gel electrophoresis, all the molecules have to move through the pores gel, and so they all feel the drag force."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "But in gel filtration chromatography, it's only the small molecules that can fit into those gel beads, and so they feel a drag force, but the larger proteins move through the space around the beads, and so it's they don't feel a force, a drag force like the small molecules do."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "And that's exactly why these concepts are basically reversed."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "In gel electrophoresis, the large molecules remain at the top, but in gel filtration chromatography."}, {"title": "SDS Polyacrylamide Gel Electrophoresis .txt", "text": "The large molecules go to the bottom, but the small ones remain at the top."}, {"title": "Urea cycle .txt", "text": "So at last, let's discuss the urea cycle."}, {"title": "Urea cycle .txt", "text": "So where does the cycle actually take place and why does it take place in the first place?"}, {"title": "Urea cycle .txt", "text": "So the urea cycle occurs predominantly in our hepatitis, in our liver cells, and to a smaller extent also takes place in our kidneys."}, {"title": "Urea cycle .txt", "text": "So why does it actually take place?"}, {"title": "Urea cycle .txt", "text": "Well, the urea cycle gives us a way to transform a toxic byproduct of amino acid metabolism, namely ammonium, into less toxic form urea that can then be mobilized and transported to the kidneys, where the kidneys excrete the urea via urine."}, {"title": "Urea cycle .txt", "text": "So that's what the urea cycle is."}, {"title": "Urea cycle .txt", "text": "Now, let's take a look at the details of this cycle."}, {"title": "Urea cycle .txt", "text": "And let's begin by summarizing the cycle on this side."}, {"title": "Urea cycle .txt", "text": "And then let's take a look at the details of each step."}, {"title": "Urea cycle .txt", "text": "So ultimately, we can break down the cycle into five steps."}, {"title": "Urea cycle .txt", "text": "Two of these steps, step one and two, take place in the matrix of the mitochondria of that liver cell."}, {"title": "Urea cycle .txt", "text": "And the other three steps three, four and five take place in a cytoplasm of that hepatocyte, the liver cell."}, {"title": "Urea cycle .txt", "text": "So let's suppose we have metabolism of amino acids that takes place inside the hepatocide."}, {"title": "Urea cycle .txt", "text": "Now, this also takes place outside the liver, but ultimately all the ammonium ends up inside the liver, inside the matrix of that mitochondria."}, {"title": "Urea cycle .txt", "text": "And so the extra ammonium basically is used."}, {"title": "Urea cycle .txt", "text": "It's combined with carbon dioxide that comes from bicarbonate, as we'll see in just a moment."}, {"title": "Urea cycle .txt", "text": "And using two ATP molecules, we form a high energy molecule, a molecule that has a high transfer potential known as carbon oil phosphate."}, {"title": "Urea cycle .txt", "text": "Now, this takes place in the matrix of the mitochondria."}, {"title": "Urea cycle .txt", "text": "We have an amino acid called ornithine that actually formed in step five of the urea cycle that moves into the matrix of the mitochondria."}, {"title": "Urea cycle .txt", "text": "And the ornithine is combined with the carbon acid or the carbon phosphate to form the citrulline."}, {"title": "Urea cycle .txt", "text": "And citrulline is yet another amino acid."}, {"title": "Urea cycle .txt", "text": "So ultimately, even though these two are amino acids, they're not actually used in protein synthesis."}, {"title": "Urea cycle .txt", "text": "Remember, these aren't part of the 20 amino acids that our body uses to synthesize proteins."}, {"title": "Urea cycle .txt", "text": "Now, once we form citrulline in step two, that moves into the cytoplasm of the cell, and in a cytoplasm, we combine the citrulline with aspartate to form argininosuxnate."}, {"title": "Urea cycle .txt", "text": "Now, an important point must be made about step three."}, {"title": "Urea cycle .txt", "text": "So we saw that the first amino group that ends up in the urea came from this free ammonia."}, {"title": "Urea cycle .txt", "text": "But the second amino group that ends up on the urea comes from aspartate."}, {"title": "Urea cycle .txt", "text": "Now, once we form arginosuxanate, that is then broken down into arginine and fumarate."}, {"title": "Urea cycle .txt", "text": "So what happens in step four?"}, {"title": "Urea cycle .txt", "text": "So ultimately, the second amino group that came from aspartate ends up on the arginine when this reaction happens, but the carbon skeleton that was found on the aspartate essentially ends up on the fumerate."}, {"title": "Urea cycle .txt", "text": "In fact, the carbon skeleton of the aspartate is fumerate."}, {"title": "Urea cycle .txt", "text": "Now, fumerate is important because fumerate is the link."}, {"title": "Urea cycle .txt", "text": "It's the bridge between the urea cycle and gluconeogenesis, the production of glucose."}, {"title": "Urea cycle .txt", "text": "So remember, in the liver we have gluconeogenesis and in gluconeogenesis we can ultimately form malate from fumerate."}, {"title": "Urea cycle .txt", "text": "And malate is transformed in gluconeogenesis to oxalo acetate."}, {"title": "Urea cycle .txt", "text": "And it's oxyloacetate that is used to form glucose."}, {"title": "Urea cycle .txt", "text": "So we see that link, the bridge between ureacycle and gluconeogenesis, the production of glucose is this fumarate."}, {"title": "Urea cycle .txt", "text": "So we recycle the carbon skeleton and aspartate to fumerate and then use that to form glucose and gluconeogenesis."}, {"title": "Urea cycle .txt", "text": "But the nitrogen containing group that ends up on the argininosochtenate as a result of the aspartate stays on the molecule to form arginine."}, {"title": "Urea cycle .txt", "text": "Now, in the final step, step five, where we form the urea, we essentially hydrolyze the arginine by using a water molecule."}, {"title": "Urea cycle .txt", "text": "We remove that urea and we also form the ornithine, the amino acid that ultimately is recycled back into the matrix of mitochondria to ultimately help this cycle continue taking place."}, {"title": "Urea cycle .txt", "text": "So if we look on this molecule, the oxygen shown in blue came from the water."}, {"title": "Urea cycle .txt", "text": "This carbon came from this carbon dioxide."}, {"title": "Urea cycle .txt", "text": "This nitrogen here came from the aspartate and this nitrogen came from this free ammonium."}, {"title": "Urea cycle .txt", "text": "So once we formed the urea, it then moves via the bloodstream to our kidneys and the kidneys ultimately excrete that via urine."}, {"title": "Urea cycle .txt", "text": "Now, let's actually look at the details of each one of these steps and let's begin with step number one."}, {"title": "Urea cycle .txt", "text": "So in step number one, the enzyme that catalyzed the step is carbon phosphate synthetase."}, {"title": "Urea cycle .txt", "text": "So this carboil phosphate synthetase ultimately utilizes two ATP, two ATPs in this three step process."}, {"title": "Urea cycle .txt", "text": "So we begin with a carbon dioxide, but actually the carbon dioxide is in the form of Bicarbonate."}, {"title": "Urea cycle .txt", "text": "So remember, carbon dioxide in our body exists as Bicarbonate."}, {"title": "Urea cycle .txt", "text": "Now, Bicarbonate is a stable molecule and we have to increase its energy and that's where we use the first ATP."}, {"title": "Urea cycle .txt", "text": "So we phosphorylate the carbon to form carboxy phosphate."}, {"title": "Urea cycle .txt", "text": "And now this is high enough in energy to actually react with our ammonia."}, {"title": "Urea cycle .txt", "text": "Now, notice I said ammonia and not Ammonium."}, {"title": "Urea cycle .txt", "text": "Why is that?"}, {"title": "Urea cycle .txt", "text": "Well, because the carbon, well, phosphate synthetase uses the ammonia as a substrate and not ammonium."}, {"title": "Urea cycle .txt", "text": "So remember, inside our body we have ammonium that exists in somewhat of an equilibrium with its ammonia."}, {"title": "Urea cycle .txt", "text": "And so Ammonium transforms into ammonia and then that is used as a substrate by carbon, well phosphate synthetase to basically combine this ammonia with this carbon here, kicking off this orthophosphate."}, {"title": "Urea cycle .txt", "text": "And so we form the carbonic acid and then the second ATP comes into play."}, {"title": "Urea cycle .txt", "text": "And this basically attaches the phosphate here, attaches onto this oxygen to basically form the carbon oil phosphate as we have it here."}, {"title": "Urea cycle .txt", "text": "And so this molecule is high in energy, it has a high transfer potential because of this anhydrate bond shown here."}, {"title": "Urea cycle .txt", "text": "And so what that means is this molecule is now ready to react with the ornasene in step number two."}, {"title": "Urea cycle .txt", "text": "But before we go to step number two."}, {"title": "Urea cycle .txt", "text": "I have to mention that this carbon oil phosphate synthetase enzyme will only become active in the presence of a molecule known as an acetyl glutamate."}, {"title": "Urea cycle .txt", "text": "So we have to have an acetyl glutamate to actually activate the carbon well phosphate synthetase to allow it to undergo these reactions and produce carbon well phosphate."}, {"title": "Urea cycle .txt", "text": "And because this enzyme lies in the matrix of the mitochondria, this step takes place in the matrix of the mitochondria."}, {"title": "Urea cycle .txt", "text": "Now step two also takes place in the matrix of the mitochondria because the enzyme ornithine transcarbomolase lies in the matrix of the mitochondria."}, {"title": "Urea cycle .txt", "text": "And so what this enzyme does is it takes this product of reaction one and it transfers this carbon group kicking off the orthophosphate, it transfers this group onto ornathine to form citrulline."}, {"title": "Urea cycle .txt", "text": "So this is what ornithine looks like."}, {"title": "Urea cycle .txt", "text": "And ultimately this group here, minus this oxygen and this phosphate group is transported onto this nitrogen of the ornathine to form the citrulline."}, {"title": "Urea cycle .txt", "text": "And then the citrulline moves into the cytoplasm of the cell."}, {"title": "Urea cycle .txt", "text": "So that's where we go to step three."}, {"title": "Urea cycle .txt", "text": "So in step three now, we want to add the second amino group and that comes from Aspartate."}, {"title": "Urea cycle .txt", "text": "So this is aspartate here."}, {"title": "Urea cycle .txt", "text": "Ultimately we want to transfer this group here."}, {"title": "Urea cycle .txt", "text": "And so the enzyme argininosuxnate synthetase, it uses an ATP, it hydrolyzed that ATP to form amp and Pyrophosphate."}, {"title": "Urea cycle .txt", "text": "And that energy is used to form a bond between this nitrogen here and ultimately this carbon here."}, {"title": "Urea cycle .txt", "text": "And we kick off this oxygen here."}, {"title": "Urea cycle .txt", "text": "And so we form argininosuccinate."}, {"title": "Urea cycle .txt", "text": "And now we have a positive charge that is essentially delocalized among these three nitrogen atoms here."}, {"title": "Urea cycle .txt", "text": "So once we form this, we also actually form this Pyrophosphate."}, {"title": "Urea cycle .txt", "text": "And the Pyrophosphate, because it's unstable, will actually hydrolyze."}, {"title": "Urea cycle .txt", "text": "And so what that means is we not only use one ATP in this step, but we actually use two equivalent ATP molecules because the hydrolysis of Pyrophosphate basically is equivalent to hydrolyzing a single ATP molecule."}, {"title": "Urea cycle .txt", "text": "And so here we actually use two and not one ATP molecules."}, {"title": "Urea cycle .txt", "text": "So once we form Argine succinate, that is then used in step four."}, {"title": "Urea cycle .txt", "text": "And so now what we want to use is we want to basically transform or remove the carbon skeleton that came from Aspartate."}, {"title": "Urea cycle .txt", "text": "So we want to keep this nitrogen group shown here on this structure."}, {"title": "Urea cycle .txt", "text": "But we want to remove this carbon skeleton and recycle that carbon skeleton."}, {"title": "Urea cycle .txt", "text": "And so that's what happens in step four."}, {"title": "Urea cycle .txt", "text": "The enzyme argininosuxinase basically catalyzes the removal of this carbon skeleton to form fumarate."}, {"title": "Urea cycle .txt", "text": "And we also form arginine as shown here."}, {"title": "Urea cycle .txt", "text": "Now the fumarate is again the link, it's the bridge between urea cycle and gluconeogenesis."}, {"title": "Urea cycle .txt", "text": "This can be used by the liver cell, the hepatocide, to actually form glucose."}, {"title": "Urea cycle .txt", "text": "But arginine continues onto step five."}, {"title": "Urea cycle .txt", "text": "And in step five, what we ultimately want to do here is we want to remove this group here."}, {"title": "Urea cycle .txt", "text": "We want to attach an oxygen to form that urea and the resulting carbon skeleton that is formed is that ornithine amino acid that ultimately goes back into the matrix and is reused to continue this urea cycle."}, {"title": "Urea cycle .txt", "text": "And so the enzyme arginase uses a water molecule to essentially attack and hydrolyze this bond here, breaking this bond, forming the ornithine as well as that urea."}, {"title": "Urea cycle .txt", "text": "And so we see the oxygen came from this water."}, {"title": "Urea cycle .txt", "text": "In step five, the carbon came from the bicarbonate."}, {"title": "Urea cycle .txt", "text": "In step one, this nitrogen came from step three, that aspartate."}, {"title": "Urea cycle .txt", "text": "And this nitrogen essentially came from this step also."}, {"title": "Urea cycle .txt", "text": "Step one, the free ammonium."}, {"title": "Urea cycle .txt", "text": "And so the urea is then transported into the bloodstream, moved into the kidneys and it's removed by the kidneys via urine."}, {"title": "Urea cycle .txt", "text": "Now, if we sum up all these steps, this is the net reaction that we get."}, {"title": "Urea cycle .txt", "text": "So a single carbon dioxide molecule, a single free ammonium to water molecule."}, {"title": "Urea cycle .txt", "text": "So one water molecule came from here and a second water molecule came from transforming the carbon dioxide into bicarbonate."}, {"title": "Urea cycle .txt", "text": "We have three ATPs and an aspartape."}, {"title": "Urea cycle .txt", "text": "So two ATPs are used here and one ATP is used here and we generate urea."}, {"title": "Urea cycle .txt", "text": "Two ATPs, we have an amp, we have an orthophosphate, Pyrophosphate and fumarate."}, {"title": "Urea cycle .txt", "text": "And as I said before, because we have the Pyrophosphate and it basically breaks down that's equivalent to using one more ATP."}, {"title": "Urea cycle .txt", "text": "And so instead of having three total, we have four equivalent ATPs used per one cycle of urea."}, {"title": "Urea cycle .txt", "text": "And we also generate that fumar rate which is then used by the liver to potentially form glucose molecules via gluconeogenesis."}, {"title": "Urea cycle .txt", "text": "So this is the urea cycle, the method by which our body, the liver specifically, is able to transform the toxic byproduct of amino acid metabolism, the free ammonium into a less toxic urea form which is then mobilized, delivered to our kidneys and excretive via the kidneys, via our urine."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Every single nephron within our kidneys contains a structure known as the renal corpuscle."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And the renal corpuscle is involved in filtering our blood as we'll see in just a moment."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So if we take a look at the nephron and we zoom in on this structure, we get the diagram of the renal corpuscle."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So the renal corpuscle is found in this segment of the nephron."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now the renal corpusol actually consists of two different structures."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "We have this cup shaped structure right here which is the Bowman's capsule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And within the cavity of this Bowman's capsule we have a network of blood capillaries known as the glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So our a fair arterial brings and carries the oxygenated blood filled with nutrients as well as waste products into the glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And the blood that travels through that glomerulus basically is filtered."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So about 20% of that blood enters the space of the Bowman's capsule through a region known as our filtration layer that we're going to discuss in just a moment."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And the rest of that blood, about 80% of it, is carried via and into the effing arterial that carries the rest of that blood to the vase erecta, the second capillary system of our nephron."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Remember, the nephron contains a portal system, two capillary networks."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "The glomerolus is the first capillary network and the base erectecta is the second capillary network."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So let's take a look at our glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So the glomerulus consists of two types of specialized cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So lining the capillaries of the glomerulus are cells known as endothelial cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And endothelial cells are basically involved in filtration."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "They contain tiny pores, tiny federations that are responsible for allowing the movement of small particles and molecules across this layer and into the Bowman's space."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So this region here inside the Bowman's capsule is known as the Bowman's space."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now by the way, this section here is the beginning of the proximal convoluted tubule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So these cells here are the cells of the proximal convoluteutubial."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So the filtrate flows into the Bowman space and then into the lumen of our proximal convolute."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now the other type of cell that is found in the glomerulus is known as the mesongal cell and the mesongal cells are shown in orange."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "The mesonial cells are modified smooth muscle cells that are responsible for contracting our blood vessels inside our glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And that speeds up or slows down the movement of the blood plasma through our glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So this is our glomerulus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now what about the Bowman's capsule?"}, {"title": "Filtration in Renal Corpuscle.txt", "text": "The Bowman's capsule consists of a parietal layer of cells which is this outer layer of cells found on both sides as well as an inner layer of cells that is known as the visceral layer."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And the visceral layer contains a specialized type of filtration cell known aside the potato side, as we'll see in just a moment, contains very small slits that actually allow the filtration of our blood."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So we also have this section known as the juxtaglomerol apparatus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And this is nothing more than a collection of three types of cells that are involved in controlling and regulating the process of filtration and movement of the blood plasma through our renal corpus cell."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So we have the macula densa, which are the cells found on this side of the distal convolute."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So this is a cross section of the distal convolute."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "It's coming out of the board and bringing blood this way."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, these cells are the granular cells, also known as the juxtaglomeral cells, and these are the agranial cells, also known as the laces cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And we'll talk about the function of these cells in just a moment."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So let's take a look at our filtration layer."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So if we take a cross section, if we look at this section here, we get the following diagram."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So, as the blood travels through the blood capillaries of the glomerulus, we basically have a layer of different cells known as our filtration membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So this is a three layer membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So these rest cells are the endothelial cells of the blood vessels that contain the tiny pores, the tiny holes that allow the movement of small molecules, such as water molecules, amino acids, glucose molecules, as well as electrolytes, such as sodium ions, potassium ions, and other things."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, this purple section is the basement membrane that is shown in this diagram."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "It's this purple outline that goes all the way around our Bowman's capsule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So this purple layer is the basement membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "It consists of a network of proteins, and it contains a negative overall charge."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And what that basically means is negatively charged particles such as chloride ions will find it very difficult to actually pass across the basement membrane because of that propulsion between the negative charge of the chloride ion and the negative charge of the basement membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So we see that positively charged particles will be attracted across, but negatively charged particles will tend to stay within the blood vessels of Araglomerilus."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, these cells, shown in brown, are the potocides."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "They form the visceral layer of the Bowman's capsule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And these poticides have small extensions that extend into the basement membrane and connect with that basement membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And between the potocides, we have these very tiny slits, very tiny holes that also allow the movement of small particles across the membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So we have a three layer filtration membrane that allows the movement of certain type of particles across our membrane and into the space of the Bowman's capsule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, this type of filtration process that takes place inside the renal corpuscle is known as ultra filtration or glomeryl filtration."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And the normal rate at which our filtration takes place inside the renal corpuscle is 125 ML every single minute."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, let's go on to these cells and let's discuss the function of granular cells and maguladensa cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So the structure known as the juxtaglomerol apparatus consists of these three types of cells, granular cells or extra, or our juxtaglomerol cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Our immaculate densa as well as our agranial cells or our laces cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, the granule cells are involved in secreting a type of proteolytic enzyme known as Renan."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And Renin is involved in the Rena angiotensin aldestroone pathway that is involved in controlling the blood volume and blood pressure inside our body."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, the macula density cells are found on our proximal convolutubial and they're found in close proximity to the granule cells."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And these macular density cells are basically important because they are able to actually sense the concentration of sodium chloride inside the distal convoluted tubule."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And they are also responsible for stimulating the granular cells to release that green and proteolytic enzyme that is responsible for controlling our blood volume and blood pressure."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, the function of the agranial cells is not yet known."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So let's summarize our discussion of the renal corpuscle."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So, we see that the renal corpuscle is involved in filtering our blood."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "About 20% of the blood that enters the globe, marylus, through the Afair Narteriol, is actually filtered into the Bowman space and travels into the proximal convoluted tubule of our nephron."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "The other 80% basically leaves via the Ethernet arterial and travels to the second capillary network system known as the Vasa rectan."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "Now, this membrane separating the space of the Bowman's capsule and the space the lumen of the capillaries inside the glomerulus consists of a membrane that has three layers."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "We have a layer of endothelial cells that contain tiny pores, and we have a layer of potocides that contains tiny slits."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And these tiny pores and slits allows the movement of only relatively small particles and molecules across our membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And this basement membrane contains an overall negative charge and it basically allows the movement of positively charged ions and molecules across the membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So we conclude that things like sodium ions, potassium ions, amino acids, glucose, water, very small proteins and urea are all going to be filtered across this membrane."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "But large proteins such as albumin, red blood cells or platelets these things will not be able to pass across these small holes and they will remain inside the blood vessel and will eventually go into our Ethernet arterial and will return to the blood system of our body."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "And by this method, our renal corpuscle is capable of filtering and removing some of that waste products from the blood plasma and into the filtrate."}, {"title": "Filtration in Renal Corpuscle.txt", "text": "So, once the blood plasma enters the Bowman's capsule, it is known as Arifiltrate, and it contains many different types of waste products, such as urea, that are ultimately excreted by our body."}, {"title": "ABO Blood Types Part II.txt", "text": "And so does I be lowercase IO."}, {"title": "ABO Blood Types Part II.txt", "text": "Now, what about blood type AB?"}, {"title": "ABO Blood Types Part II.txt", "text": "So to form blood type AB, the male parent has to be A."}, {"title": "ABO Blood Types Part II.txt", "text": "The female parent has to be B, or vice versa."}, {"title": "ABO Blood Types Part II.txt", "text": "This male has to be B, and this female has to be A."}, {"title": "ABO Blood Types Part II.txt", "text": "And only then will we form blood type AB."}, {"title": "ABO Blood Types Part II.txt", "text": "And finally, to form blood type O, both of these have to be recessive, meaning they both have to lack these genes that code for either one of these antigens."}, {"title": "ABO Blood Types Part II.txt", "text": "And so in that case, if we have recessive and recessive, we form lowercase IO, lowercase IO, and that gives us blood type O."}, {"title": "ABO Blood Types Part II.txt", "text": "So these are the four different types of blood groups that humans actually have."}, {"title": "ABO Blood Types Part II.txt", "text": "And we see that at knowing how the immune system actually works and the fact that it produces antibodies is crucial to actually understanding how and why blood transfusion actually takes place and how it works."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "Transform into that product will not be as high."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And that's exactly why the K cat is lowered in the case in the presence of a noncompetitive inhibitor."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And finally, what about the Km value?"}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And this is and this is perhaps the difficult part of understanding how this actually affects that enzyme kinetic."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So why does the Km remained constant?"}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So the Km, in the presence of a non competitive inhibitor, remains constant."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "How can this remain constant, and yet the VMAX is lowered?"}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "Well, the reason that the Km remains constant is because the inhibitor, by binding onto that enzyme, even though it changes the shape of the active side of the enzyme, and so it changes the efficiency, the Kcat value of that enzyme, it does not change the likelihood that that particular substrate is going to bind onto the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So it doesn't matter if the inhibitor is bound to that enzyme or not."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "In either case, the substrate will have no problem actually binding onto that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So we see that in this particular equation, if we have the inhibitor bound onto that enzyme, the substrate is just as likely to bind onto that enzyme as it is to bind onto that enzyme in the absence of that inhibitor."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So this reaction takes place just as likely as this reaction takes place."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And because of that, the affinity of that particular substrate for the active side does not change."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And so Km remains the same."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So Michael is constant, describes the ability of the substrate to bind to the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And notice that the substrate can bind or dissociate from the active side regardless of whether or not that inhibitor is bound."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And this simply was not true for the case of on competitive inhibition."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "In on competitive inhibition, once the inhibitor binds onto the enzyme substrate complex, it blocks that substrate from leaving the active side, and that increases the affinity of the substrate for the active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And so that decreases that apparent Km value."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "In this case, we saw that the Km value increased because we need a higher concentration of S to reach that same particular rate."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "But in this particular case, that substrate is just as likely to bind until the enzyme in the absence as in the presence of that inhibitor."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And so the Km value does not actually change."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "So this is how these three reversible inhibition processes actually affect enzyme kinetics."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "In the case of competitive inhibition, we see that the VMAX does not actually change because we can ultimately overcome that inhibition by increasing the concentration of S, the K Cab, the turnover number doesn't change because the efficiency of that active side, the fully functional active side, does not change."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And we saw that the Km value actually is increased because we require a higher concentration to reach the rate of VMAX divided by two."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "Now, in uncompetitive inhibition, we saw that the VMAX actually decreases, and that's because at any given time, some of those enzyme substrate complexes are going to have an inhibitor present to them, and that will decrease the number of fully functional enzymes, and so that will lower that VMAX."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "Now, the Kcat is not changed because the active site's ability to basically convert the substrate into the product does not change."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And we said that the Km decreases because once the inhibitor binds onto that complex, it prevents that substrate from leaving that active side, and that essentially increases its affinity for the active side, increases the substrate's affinity for the active side, and decreases the Km."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "Now, in the case of non competitive inhibition, we said that the V max is lowered because we have less functional enzymes."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And the Kcat is also lowered because once the inhibitor binds onto that enzyme, it changes the shape of that active side."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "It no longer makes it a perfect fit for that substrate."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And so the efficiency of that active side is lowered."}, {"title": "Enzyme Kinetics of Reversible Inhibition (Part II) .txt", "text": "And that's why Kcat is lowered, but because that's substrate is just as likely to bind for the active side of the enzyme in the absence as in the presence of that inhibitor, the Km, the mechanics constant does not actually change in the presence of a non competitive inhibitor."}, {"title": "Phospholipids .txt", "text": "Lipids are biological molecules which are insoluble in water, and that's because they contain a large hydrophobic nonpolar region that does not allow them to actually dissolve in an aqueous environment."}, {"title": "Phospholipids .txt", "text": "Now, although we have many different types of lipids that exist in nature, the lipids that we're going to focus on are the lipids that will find in the cell membranes of eukaryotic cells as well as bacterial cells."}, {"title": "Phospholipids .txt", "text": "And there are three lipids that will find in cell membranes."}, {"title": "Phospholipids .txt", "text": "So we'll find phospholipids glycolipids as well as cholesterol molecules."}, {"title": "Phospholipids .txt", "text": "Now, in this lecture, we're going to focus only on phospholipids."}, {"title": "Phospholipids .txt", "text": "So there are two types of phospholipids."}, {"title": "Phospholipids .txt", "text": "We have phosphoglycerides and we also have spingolipids."}, {"title": "Phospholipids .txt", "text": "And we'll see exactly what the difference is between these two phospholipids in just a moment."}, {"title": "Phospholipids .txt", "text": "First, let's discuss the constituents, the components that make up any phospholipids."}, {"title": "Phospholipids .txt", "text": "So let's take a look at the following list."}, {"title": "Phospholipids .txt", "text": "Number one, we'll always find a platform molecule, a molecule that acts as the backbone of attachment for the other groups, in the case of the phosphoglycerides will have a glycerol that acts as a backbone."}, {"title": "Phospholipids .txt", "text": "In the case of the spingolipids, will have a slightly different platform molecule known as a spinocine."}, {"title": "Phospholipids .txt", "text": "Now, they always have fatty acids."}, {"title": "Phospholipids .txt", "text": "In the case of spingolipids, we have one fatty acid."}, {"title": "Phospholipids .txt", "text": "In the case of phosphoglycerides, we have more than one fatty acids."}, {"title": "Phospholipids .txt", "text": "They always contain a phosphate group."}, {"title": "Phospholipids .txt", "text": "And most of the time, the phosphate group is attached onto some type of modified alcohol."}, {"title": "Phospholipids .txt", "text": "And that's why we have a star."}, {"title": "Phospholipids .txt", "text": "We won't always find this attachment."}, {"title": "Phospholipids .txt", "text": "We'll find it most of the time."}, {"title": "Phospholipids .txt", "text": "Now, both types of phospholipids, these phosphoglycerides and fingal lipids, are antipathic molecules."}, {"title": "Phospholipids .txt", "text": "And what that means is they have a nonpolar component and they have a polar component."}, {"title": "Phospholipids .txt", "text": "So basically, the fatty acids give the phospholipids, the hydrophobic non polar properties."}, {"title": "Phospholipids .txt", "text": "But it's these two groups, the phosphate and the alcohol, that give them the water loving hydrophilic polar quantities and so qualities."}, {"title": "Phospholipids .txt", "text": "And so that's exactly why we call phospholipids amphipathic, because they have groups that can associate with polar and non polar environments."}, {"title": "Phospholipids .txt", "text": "So let's begin with phosphoglycerides."}, {"title": "Phospholipids .txt", "text": "And this is basically a diagram that describes what a phosphoglyceride actually looks like."}, {"title": "Phospholipids .txt", "text": "So by definition, when a phospholipid contains a glycerol as the platform molecule, we call such a phospholipid phosphoglyceride."}, {"title": "Phospholipids .txt", "text": "So what exactly is a glycerol?"}, {"title": "Phospholipids .txt", "text": "Well, basically a glycerol is a three carbon alcohol molecule."}, {"title": "Phospholipids .txt", "text": "So we have one, two, three carbons."}, {"title": "Phospholipids .txt", "text": "And each one of these carbon is attached onto an oxygen that was part of the hydroxyl of that alcohol group."}, {"title": "Phospholipids .txt", "text": "But after we combine these molecules, we remove that H atom."}, {"title": "Phospholipids .txt", "text": "And so we simply have these oxygens, as shown in the following diagram."}, {"title": "Phospholipids .txt", "text": "Now, we also have two fatty acids."}, {"title": "Phospholipids .txt", "text": "So fatty acid number one is attached onto carbon number one."}, {"title": "Phospholipids .txt", "text": "Fatty acid number two is attached onto carbon number two."}, {"title": "Phospholipids .txt", "text": "So we see that there's an Esther bond that exists between the oxygen of this carbon and the carbon of that carboxylic acid, of that fatty acid."}, {"title": "Phospholipids .txt", "text": "And notice that these two fatty acids don't have to be the same exact length."}, {"title": "Phospholipids .txt", "text": "So they can have the same number of carbon atoms or they can be different."}, {"title": "Phospholipids .txt", "text": "And that's why I have M and M. So N can be equal to M, or they can be different integers."}, {"title": "Phospholipids .txt", "text": "Now, what about the third carbon?"}, {"title": "Phospholipids .txt", "text": "The third carbon contains an oxygen that is basically attached onto that phosphate component."}, {"title": "Phospholipids .txt", "text": "And notice in this particular case, we don't have anything else attached onto our phosphate group."}, {"title": "Phospholipids .txt", "text": "So we don't have this alcohol."}, {"title": "Phospholipids .txt", "text": "And this is exactly why."}, {"title": "Phospholipids .txt", "text": "This phosphoglyceride is an example of the simplest type of phosphoroglyceride in which that phosphate group is not actually modified with an alcohol."}, {"title": "Phospholipids .txt", "text": "And the name for this phosphoglyceride is phosphatide."}, {"title": "Phospholipids .txt", "text": "So the simplest phosphoglyceride in which that phosphate group is not modified with the alcohol, is known as a phosphotide."}, {"title": "Phospholipids .txt", "text": "And although we'll find these phosphotide inside our cell membrane, we'll only find them in very, very small quantities."}, {"title": "Phospholipids .txt", "text": "Now most of the time this phosphate group is actually modified with some type of alcohol."}, {"title": "Phospholipids .txt", "text": "Usually the alcohol is either a choline, acerine or enochetol."}, {"title": "Phospholipids .txt", "text": "And we have other common groups, but these are very common groups."}, {"title": "Phospholipids .txt", "text": "So we have the choline, which contains this alcohol component."}, {"title": "Phospholipids .txt", "text": "We have a serine, which is also an amino acid that contains this alcohol."}, {"title": "Phospholipids .txt", "text": "And we have this cyclohexane derivative in which each one of these carbons contains an alcohol."}, {"title": "Phospholipids .txt", "text": "So this is known as inositole."}, {"title": "Phospholipids .txt", "text": "So let's suppose we want to basically combine a choline with the following molecules."}, {"title": "Phospholipids .txt", "text": "So in that particular case, this is basically what we produce."}, {"title": "Phospholipids .txt", "text": "And this is a much more common type of phospholipid, more specifically phosphlyceride that will find in the cell membrane."}, {"title": "Phospholipids .txt", "text": "So notice here we have a bond that is formed between this phosphate, this phosphorus atom of the phosphate group, and this oxygen of this choline."}, {"title": "Phospholipids .txt", "text": "So we can basically replace this with a serene in which there will be a bond between this phosphorus atom and this oxygen."}, {"title": "Phospholipids .txt", "text": "Or we can remove this and basically attach this phosphorus atom to this oxygen here."}, {"title": "Phospholipids .txt", "text": "Either case, we basically form a modified version of this molecule here."}, {"title": "Phospholipids .txt", "text": "Now let's move on to our sphingolipids."}, {"title": "Phospholipids .txt", "text": "So what's the difference between a phosphorglyceride and a spingolipid?"}, {"title": "Phospholipids .txt", "text": "Well, in the case of phosphorglycerides, this component was a glycerol."}, {"title": "Phospholipids .txt", "text": "But in the case of spingolipids, the platform molecule, that backbone is a much more complex alcohol molecule that basically looks like this."}, {"title": "Phospholipids .txt", "text": "So instead of having this three carbon alcohol, we have this more complex alcohol in which we have a primary alcohol, a secondary alcohol, we have this long unsaturated hydrocarbon component that contains this double bond."}, {"title": "Phospholipids .txt", "text": "And we also have this amino group that contains a positive charge."}, {"title": "Phospholipids .txt", "text": "This is this fingersine that acts as a platform molecule that attaches all these other components."}, {"title": "Phospholipids .txt", "text": "So one example of a single lipid that we're going to find around the membranes of nervous cells."}, {"title": "Phospholipids .txt", "text": "So nerve cells is basically a finger myelin molecule."}, {"title": "Phospholipids .txt", "text": "And in this particular case, the nitrogen is attached onto that carboxylic acid of that particular fatty acid."}, {"title": "Phospholipids .txt", "text": "So this bond is basically this bond here."}, {"title": "Phospholipids .txt", "text": "And notice unlike in this case where we have two of these fatty acids, we only have one fatty acid in this particular case."}, {"title": "Phospholipids .txt", "text": "Now this is the oxygen attached onto this phosphate."}, {"title": "Phospholipids .txt", "text": "And in this particular case, it's the primary oxygen, not the secondary oxygen."}, {"title": "Phospholipids .txt", "text": "Because we have a primary and a secondary, it's the primary attached onto the phosphorus atom of that phosphate group."}, {"title": "Phospholipids .txt", "text": "And just like in this case, we can have an attached between the p and the oxygen of that alcohol."}, {"title": "Phospholipids .txt", "text": "We have the same thing here, except this molecule is now found on this region here."}, {"title": "Phospholipids .txt", "text": "So this is also choline that we have in this particular case."}, {"title": "Phospholipids .txt", "text": "We call this the sphingomyeline."}, {"title": "Phospholipids .txt", "text": "So we see that we have two types of phospholipids."}, {"title": "Phospholipids .txt", "text": "We have the phosphoroglycerides and we have the spingolipid."}, {"title": "Phospholipids .txt", "text": "And basically what differentiates these two is the type of platform molecule that connects the other components, the fatty acids, the phosphate group and in most cases that alcohol components."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "In humans, as well as many other deployed organisms, a process known as crossing over can take place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, crossing over takes place during meiosis."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that means crossing over occurs when we form gametes sex cells."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, what exactly is the purpose?"}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "What's the importance of crossing over?"}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Well, as we'll see in just a moment, crossing over a lot allows us to produce sex cells."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "It allows us to produce gametes that carry genetic information that is slightly different than genetic information found inside our somatic cells."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that's exactly why I, for example, don't look exactly like either of my parents."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that's exactly why I have my own set of unique fingerprints."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "It's because crossing over allows those gametes to obtain genetic information that is unique to that specific sex cell."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, in our discussion of crossing over, we're going to focus on a type of organism we call the fruit fly."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, in fruit flies, we're going to study two different traits."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "We're going to examine the structure of the wings and we're going to discuss the color trait of that fruit fly."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, in fruit flies, we have two types of wings that can form."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "We have normal wings and we have vestigial wings."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Likewise, we have two different types of colors."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "We have the gray color and we have black color."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, it turns out that normal wings that we're going to designate with blue uppercase V is dominant over the recessive vestigial wing, which we're going to designate with purple lowercase V. And by the same token, the color gray is dominant over the color black."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So the color gray, we're going to designate with red uppercase B."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And the color black, we're going to designate with orange lowercase B."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, the normal wings and our color, the wing gene and the color gene are linked to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And what that basically means is they are found on the same exact chromosome."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So to see what we mean by that, let's take a look at the following diagram."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this is basically a homologous chromosome pair."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And what that basically means is one of these chromosomes came from the male parent and the other chromosome came from the female parent."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And both of these chromosomes carry genes that code for the protein that expresses the same type of traits."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, notice along each one of these chromosomes, let's suppose along the darker green chromosome, we have two genes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And this red gene is linked to the blue gene in the same exact way that this orange gene is linked to the purple gene."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So whenever two or more genes are found on the same chromosome, they are said to be linked to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this gene right here, uppercase V, is linked to this here uppercase B, while this is linked to this right over here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, let's suppose that this particular fruit fly that has this homologous chromosome pair wants to produce gametes, so it wants to undergo reproduction and that means it wants to produce gametes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And the first step in producing gametes is to replicate the DNA during interface."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So once we replicate the DNA, we form the following two homologous chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So now, instead of having a single chromatid, we have two cystochromatids is a cystochromatid to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And because DNA replication produces identical pieces of chromosome, that means these two are identical chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "By the same exact analogy, this is identical to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So these two are cystochromatids with respect to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So these two are cystochromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "These two are cystochromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, these, with respect to one another, are homologous chromosomes in the same way that these two were homologous chromosomes up here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But now, once DNA replication took place, we form these two identical pairs of cystochromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So these are identical to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "These are identical to one another, but these are different with respect to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But we call them homologous because they still carry those genes that code for the same exact traits."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So we have the wing structure and the color and the wing structure and the color traits."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So we know that during meiosis one, in our discussion on meiosis one, we said that during ProPhase one of meiosis, we have a process known as synapses taking place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So the synapses is basically the intertwining of the chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And when the chromosomes intertwined, when they overlap onto one another, we have crossing over taking place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And what crossing over is it's the exchange of genetic information of chromosomal pieces among two noncystochromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So, remember, these two are cystochromatids with respect to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "These two are cystochromatids with respect to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But this one here and this one here are noncystochromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "That's because they are not identical to one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, when crossing over actually takes place, we form genetically different chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "We form recombinant chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So, once again, during meiosis one, synapses between the homologous non synthetic chromatins."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So let's say this one right here and this one right here takes place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that allows the exchange of genetic information in a process known as crossing over, and that produces genetically recombinant chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So basically, during ProPhase one of meiosis, these two homologous chromosomes that have been replicated basically approach one another."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And now this right here can basically overlap with this right here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And when this interlapping or overlapping takes place, this is known as synapses."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So we have this overlaps onto this right over here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, when the overlapping takes place, then we can exchange in the process known as crossing over."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And this dark green piece that came from this here goes onto the light green piece onto this chromatid right over here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And likewise, this lighter green section of the chromosome that came from this homologous chromosome goes on to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "At the end, we formed the following pair of homologous chromosomes in which this is no longer identical to this, and this is no longer identical to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And at this point, we call these recombinant chromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Why?"}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Well, because none of these are actually identical as in the case of this, where this one was identical to this and this one was identical to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now each one of these are genetically unique."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this is basically what happens during ProPhase one of meiosis."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now let's fast forward to metaphase one of meiosis."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "During metaphase one of meiosis, these recombinant chromosomes basically align along the equator along the midsection of that particular somatic cell."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this is the midsection and this homologous but recombinant chromosome pair have now aligned itself along the equator and now a process known as segregation will take place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So these will basically separate onto opposite poles."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Eventually, cytokinesis will produce two different cells and this is the reduction step where we go from the two N number to the N number of chromosomes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now let's suppose now we fast forward to metaphase II of meiosis."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "During metaphase two of meiosis, each one of these individual chromosomes will basically now align itself once again along the equator and the same segregation process will take place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So the mitotonic spindle will attach itself onto these chromosomes, pulling them apart, and eventually we form these four gamete types as shown in the following diagram."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now notice in each one of these gametes, each one of these gammates, we have a slightly different genetic information and that is because of the process of crossing over."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So when crossing over actually took place, we exchanged genetic information."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Notice that in this case we had uppercase V, uppercase B, and uppercase V uppercase B, okay?"}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But when genetic recombination, when crossing over took place, we have uppercase V, uppercase B, uppercase V, and now we have a lowercase B and so that's exactly what makes this one different than this chromosome right over here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that's exactly why we produce these two gametes."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this gamete is genetically different than this gamete."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Now, if no crossing over actually took place, then these two gametes would be identical because this piece of information would never have been exchanged in the first place."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And if no crossing over took place, this would be identical to this."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "By the same exact reasoning, if we examine this cell right over here when these separate to opposite poles cytokinesis takes place, we form these two gametes and these are genetically different from one another because of this process of crossing over."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So in this case, we had lowercase V, lowercase B, lowercase V, lowercase B and these were identical cystic chromatids."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But now after crossing over, this right over here is lowercase V but this is uppercase B because of crossing over now this is still lowercase B and lowercase V but this chromatid here is no longer identical to this chromatode here a chromatid here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And so that means these two will be different."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And so when they segregate, they produce slightly different gamte."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So this gamut will contain a slightly different genetic information slightly different chromosome than this one right here."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But if no crossing overtook place, we would form two identical chromosomes lowercase B, lowercase V and lowercase B, lowercase V. Instead, because we do have crossing over that takes place, we form one lowercase B, one lowercase V, and the other one is uppercase B, lowercase V. So this is exactly what we mean by the process of crossing over."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "So we see that crossing over allows deploy organisms, such as human beings to basically produce these sex cells, these gamings that have slightly different genetic information than the actual parent, than the parent, or than the female or the male parent."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Because, remember, this chromosome came from the male parent and this chromosome came from the female parent."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "If no genetic recombination in the form of crossing over took place, then the gamuts that we would form at the end, these gamuts here, would be exactly identical to the gametes that came from the parents, the male and the female."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "But because of crossing over, we form these gametes that are slightly different."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "And that means we're going to form individuals."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Our offspring will be genetically unique and genetically different than our own."}, {"title": "Linked Genes, Crossing Over and Genetic Recombination.txt", "text": "Somatic cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Nowadays, many different types of tissues and many different types of organs have been successfully transferred from one individual to a different individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And this process is known as grafting or organ transplant."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, many different examples of successful organ transplants exist."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "For example, we've been able to transplant organs such as our heart, our lungs, our liver, our kidneys, our bone marrow, the ovaries, as well as things like our blood, which we'll focus on in the next lecture."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And the cornea of the eye."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And actually the cornea of the eye is a relatively successful type of grafting process because the cornea represents an immunologically privileged site and that basically decreases the complications that are involved with grafting of the corona."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "In fact, we can successfully graft remove the corona from a cadaver and place it onto a living individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, when we transfer an organ or tissue from one individual to a different individual, in this case that organ or tissue is known as an allograph bud."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "If we're removing a tissue from one individual and moving it onto a different location on that same individual, in this case we call that organ or tissue that is being removed and transferred an autograph."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So auto means we're dealing with that same individual and aloe means we're dealing with two different individuals."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, as you might expect, the process of grafting and organ transplantation is actually a very, very complicated process."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And that's because it deals with a great amount of precision, a great amount of analyzation and a great amount of preparation."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, the primary reason, the primary thing that creates these complications is actually the immune system of that host individual that is accepting that graft or that organ."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's discuss some of the major issues involved with transferring grafts as well as organs from one individual to a different individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's examine graft rejection, let's discuss graft versus host disease and also infections."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And then let's discuss some of the methods that medical professionals actually use to fight these different complications that arise from transplantation."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's begin with graft rejection and let's first recall how our immune system actually works."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So recall that the entire goal of our immune system, the entire goal of wide blood cells is to be able to differentiate between our own host healthy cells and infected cells or pathogens that might make their way into our body."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So our wide blood cells use something called the major histocompatibility complex and self antigens to basically distinguish our whole cells from infected cells or pathogens."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, the problem with grafting or transplantation is when we actually transfer that tissue or that organ, the tissue or the organ on the other individual might have different major histocompatibility complexes and different self antigens."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And if these antigens are not compatible, if there is no match, then what the wide blood cells of that host immune system do is they recognize those other cell antigens of the other individual as pathogenic, as being foreign."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And they mount a defensive response."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "They label those cells for destruction and begin destroying that allograph altogether."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So, once again, when a tissue or organ is transplanted it has a very high chance of being rejected by the host individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Recall that our immune system attacks anything that it recognizes as foreign or pathogenic."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And if the major histocompatibility complex MHC self antigens of the transplanted tissue cells do not match or not compatible with the host cells, then the host immune system will mount a defensive response and destroy that allograph."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And we see that take place in the following diagram."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's suppose this is our host cell."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And the host cell will contain special major histocompatibility complexes on the membrane, as shown in blue."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And it will take some type of protein, some type of self antigen and place it onto that complex, as shown in green."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And the host immune cells, for example, cytotoxic T cells will be able to distinguish this host cell from some type of foreign pathogen as a result of these self antigens present on the MHC protein."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, if we basically transplant a graft, a tissue or an organ that contains cells with a different MHC protein, with a different major histocompatibility complex that contains a different cell antigen, then the host immune cell will label this cell as being pathogenic, as being foreign."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And what will happen is this cell will destroy that graft cell along with that entire allograft."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And what this cytotoxic T cell does specifically is it binds onto this complex and it initiates the release of powerful digestive proteins."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And those proteins drill holes in the membrane of these grass cells and that ultimately lyses and destroys the cell."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So this is the major problem that is involved with the transplantation and grafting process, the actual immune system of that host organism, host individual destroying that transplanted tissue or organ."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, another important complication is actually the opposite of this."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So this is called graft versus host disease or gvhg."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's suppose we're transplanting some type of tissue or organ from one individual to a different individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And this particular organ contains a high concentration of T cells, of white blood cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And one example of such an organ, such a tissue is bone marrow."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So let's suppose we're transformed, we're transferring bone marrow from one individual to a different individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "The problem with this is the bone marrow contains a high concentration of T cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And these T cells, when they're transferred into the host individual, the T cells contain receptors that might not recognize the cell's antigens and the major histocompatibility complexes found on the host cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And what that means is, when the grass cell binds onto the host cell, it will begin to release these enzymes that will destroy the host cells of that host individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So when transplanting tissue that contains a high concentration of white blood cells such as T cells, there is a high probability that the graft T cells will recognize the host cells of that individual as being foreign, as being pathogenic."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And this will begin a defense response in which these T cells will begin attacking and destroying our host cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And this is of particular importance when transplanting things like the bone marrow because bone marrow actually contains a very high concentration of T cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So these are the two major problems, two major complications that accompany grafting an organ transplant."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, another complication that is really no longer a complication because we have ways of dealing with it is infections."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "But this was the problem when organ transplant and grafting was at its beginning."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So the donated tissue or organ may contain dangerous pathogens such as HIV, hepatitis B or hepatitis C, rabies, syphilis and many other different types of diseases and pathogens."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So basically, if we're transplanting an organ that contains HIV into an individual that does not contain HIV that individual will obtain that HIV and will then be HIV positive."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, this was a problem in the beginning but nowadays we have different types of ways of testing for these different types of viruses and pathogenic agents."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And so before the donation or transplantation actually takes place we know what types of pathogenic agents are found in that donated tissue or donated organ."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now the next question is how exactly do we solve these different complications?"}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "What exactly do we do?"}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Well, the best case scenario the best way to actually ensure that the organ or tissue that is transplant that is successfully accepted by that host individual is to actually use the same tissue of that individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now of course this cannot be done always."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "We can, for example, easily transplant a piece of skin from one location to a different locations in our body."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "But obviously we can't transplant things like the heart because we only have a single heart."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Another good case scenario is if we have a twin."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "If we actually have an identical twin this creates very little complications because those two twins will have very similar, if not identical MHC major histor compatibility cells, antigen complexes."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And so when we transplant an organ or tissue from one twin from one of the twins to different twins this will create very little complication and the immune system will accept that organ."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now of course these instances are actually very rare because not always do we have a twin and not always can we actually transplant an organ because we only have one of each organ not including things like our lungs or our kidneys."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, two very common methods, much more common methods than what we just discussed are tissue typing and immunosuppression."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, tissue typing is actually a pretty complicated process so we're not going to go into too much details."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "But what tissue typing basically is it's a process of determining the type of major histocompatibility complexes and a type of self antigens that are found within that host individual."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And then finding the exact match or a very similar match, a compatible match from another individual that contains very similar MHC antigen complexes."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So tissue typing is the process that involves determining the major histocompatibility complex antigens of the host individual and finding a donor that is most compatible that contains the least mismatches."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Another important type of method that is used to basically solve these complications and is probably used virtually on all cases of grafting an organ transplant is immunosuppression."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, immunosuppression deals with using different types of chemical agents that are extracted from other organisms or synthesized in a lab."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And what these chemical agents do is they essentially decrease the ability of our immune system to actually fight off different infections including these grafts and organs that are transplanted into our bodies."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So these chemical agents interfere with the processes of forming white blood cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "For example, they can interfere with the process of protein synthesis or DNA replication and that will greatly hinder the ability of our immune system to actually form any type of white blood cell."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And so that suppresses the immune system and prevents it from actually mounting a defensive attack against that transplanted tissue or organ."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "Now, the major problem with this immunosuppression process is it's actually very dangerous."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So as soon as we suppress our immune system we decrease its ability to find any type of to fight any type of infection."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And that includes a simple infection from the common flu or the common cold."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So because our immune system is suppressed it not only is not capable of fighting that graft but it also can't actually fight off any type of infection."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So people that are immunosuppressed can sometimes die from the common cold or the flu because their immune system is not capable of mounting any type of defense or response."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "On top of that immunosuppressed people are also much more likely to actually develop cancer."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And that's because cells like natural T cells and cytotoxic T cells are the cells that fight off the cancer developing cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And because our system is immunosuppressed that means those cells cannot find those cancer cells."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "And therefore, the cancer cells that come from healthy cells can develop and that can progressively lead to some type of cancer."}, {"title": "Grafting, Organ Transplants and Immunosuppression.txt", "text": "So although this method is actually helpful in fighting off these complications in solving these complications this method is also very dangerous in itself because it depresses our immune system and that can basically lead to an infection or cancer that can ultimately kill that individual."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "The pentose phosphate pathway consists of two different phases."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "We have the oxidative and the nonoxidative phase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now previously we focused on the oxidative phase and we saw that in the oxidative phase, the cells of our body transform a single glucose phosphate molecule into two NADPH molecules and one ribose five phosphate sugar molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now what do our our cells use these two different molecules for?"}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So as we discussed previously, the NADPH molecules are very important reducing agents that exist inside our cells because the cells actually use these molecules to help generate many other biological molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So things like fatty acid molecules, cholesterol molecules, nucleotide molecules, neurotransmitters, all these things require NADPH molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "In addition, the cells also use the NADPH molecules to help detoxify many different types of toxic agents that exist inside our cells."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now what about the ribose phyphosphate molecule?"}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Well, the cells of our body use the ribose phyphosphate to help generate nucleotide based biological molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So anytime the molecule contains a nucleotide, that means it requires ribose phyphosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So things like nucleic acids, so DNA and RNA, ATP molecules, NADH molecules, fad molecules, as well as coenzyme A molecules, all these different things require ribose phyphosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now as it turns out, the majority of the cells of our body most of the time actually require the NADPH much more than they need the ribose phyphosphate molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so what our cells actually do is they take the ribose phyphosphate that is produced via the oxidative phase and they transform that into glycolytic intermediates."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Why?"}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Well, because these glycolytic intermediates can now be transformed into glucose phosphate molecules and these glucose six phosphate can undergo the oxidative phase to produce even more NADPH molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And it turns out that this process here, the transformation of the ribose phyphosphate into these glycolytic intermediates, is the non oxidative phase of the pentose phosphate pathway."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So once again, when the cells need NADPH much more than ribose phyphosphate molecules, the cells can actually transform this pentose sugar, the ribosphy phosphate, into specific glycolytic intermediates via the non oxidative phase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have the oxidative phase and the non oxidative phase and this constitutes the pentos phosphate pathway."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now the non oxidative phase of the pencils phosphate pathway can be broken down into four processes."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have process one, process two, process three, and process four."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So let's begin by focusing on process one."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, in process one, we actually have two steps."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "In the first step, we want to take the ribose phosphosate molecule and transform it into an isomer version, ribulose phosphosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And this is actually the same reaction that we discussed in the previous lecture, except it's in reverse."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so we have the same enzyme as we discussed previously, phosphopentose isomerase that catalyzes this reaction."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, once we form the ribulose phyphosphate, it then undergoes a second reaction which is catalyzed by phosphopentose ephemerase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so what this does is it transforms the ribulose phyphosphate into the zelulose phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And the only difference between these two molecules is the stereochemistry of the third carbon."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So this carbon here and this carbon here, they have a different stereo chemistry."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, why do we need this specific stereo chemistry?"}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Why can't we use this?"}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Well, because the enzyme in the second process of this pathway basically uses only this type of stereochemistry and not this type of stereo chemistry."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we need to form the zelulose as a result of this trans ketilase that we'll talk about in just a moment."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So ultimately, in process one, we want to transform ribose phyphosphate into a zelulos phosphosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And notice we begin with two of them."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have two of these intermediates and we form two of these zelulose phyphosphate products."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, one of these xyulose molecules is used in step two and the other one is used in step four, as we'll see in just a moment."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So let's move on to step number or process two of the pentose phosphate pathway, specifically the non oxidative phase of this pathway."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we take one of these cellulose phyphosphate molecules and we take another ribose phyphosphate molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So so far we actually used three ribose phyphosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So two were used here."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And now the third one we're using in this particular step."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have the enzyme transketilase, which actually requires a cofactor we call Thiamine pyrophosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we'll talk about the mechanism of this enzyme and what this actually does in the next lecture."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "But basically what the transketulase actually does, it takes a two carbon group from the zelulose."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "It takes this entire section, places it onto the ribbon."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So notice both of these are pento sugars, five carbon sugars."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And when we transfer this section onto this molecule, we basically form, we extend that sugar by two carbons and we form a seven carbon sugar known as CETO heptolose seven phosphates."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, if we take away these two carbons from the cellulose, we essentially form a trios, a three carbon sugar."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And that three carbon sugar is known as glycero aldehyde three phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So the products of step two, reaction two of this particular oxidative phase, is the CETO heptulose seven phosphate and the glyceroaldehyde three phosphate and is catalyzed by the transketilase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now in process three of the non oxidative phase, we now take these two products and these two products will act as reactants in process three."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now, the enzyme in this particular case will be different."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "The enzyme here is transaldalase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And what transaldalase does is it takes this entire three carbon section here and transfers it onto this carbon here."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so we transform this molecule into urethrase four phosphates."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we take off three carbons."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so this is a four carbon sugar."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And then we place the three carbons onto this molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we form a six carbon sugar, the fructose six phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And this fructose six phosphate is one of these glycolytic intermediate products."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So this is actually the final product or one of the final products in the non oxidative phase."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now what we want to do in the final step in the final process is we want to take the urethrase for phosphate produced in process three, and we want to take the second zyulose biphosphate that we still have left over from process one."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Remember, we only use one of the two zelulose molecules that we produced in step one in process one."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we use this one right here and now we use the second one in this process four."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "Now the enzyme that catalyzed the process four is the same enzyme that we used here."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so it's no surprise that this same enzyme uses the same substrate molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And what it does is just like in this case, it took off this two carbon component from the cellulose and placed it onto the ribose."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "In this case it once again takes off this two carbon component and places it onto this sugar molecule here."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so we extend this four carbon sugar by two and we form a six carbon sugar we call fructose six phosphate, which is once again a glycolytic intermediate molecule."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And when we cut this one by two carbons, we form the three carbon trios molecule known as gap, the glyceroaldehyde three phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And remember that gap glyceroldehyde three phosphate is also a glycolytic intermediate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we see that if we sum up all these four processes, this is the net reaction that we actually get."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we have to input three ribose phosphate, three ribosphosphate molecules, so two in this step, two in this process and one in this process."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And we essentially get back to fructose six phosphate molecules and a single glyceroaldehyde three phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And so now these are the glycolytic intermediates that can be transformed into glucose six phosphate."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "And that glucosex phosphate can undergo the oxidative phase to form even more NADPH molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So when the cell actually needs the NADPH much more than it actually needs the Ribos phi phosphate, we undergo the non oxidative phase of the pentose phosphate pathway to help us generate even more of these NADPH molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "On top of that, what the non oxidative phase of the pentose phosphate pathway allows us to do is it allows us to actually ingest ribosugars into our body because via this particular pathway we can actually break down the ribosugar into glycolytic intermediates and then those intermediates can used via glycolysis to actually generate high energy ATP molecules."}, {"title": "Nonoxidative Phase of Pentose Phosphate Pathway .txt", "text": "So we see that the link between glycolysis and the pentose phosphate pathway is the non oxidative phase of the pentose phosphate pathway."}, {"title": "Composition of Blood.txt", "text": "Our blood is actually a connective tissue."}, {"title": "Composition of Blood.txt", "text": "And what that means is it consists not only of individual cells, but it also contains an extracellular matrix that is found surrounding those cells."}, {"title": "Composition of Blood.txt", "text": "Now, in order to study the composition of our blood, we can use the process of centrifugation."}, {"title": "Composition of Blood.txt", "text": "So we take a test tube, we place the blood inside that test tube, and we place it inside our centrifuge machine."}, {"title": "Composition of Blood.txt", "text": "And what the machine does is it spins our test tube at very high velocities and that uses that separates the things found inside our blood by density."}, {"title": "Composition of Blood.txt", "text": "And so after this process, we basically see two different layers form."}, {"title": "Composition of Blood.txt", "text": "The bottom layer found at the bottom of the test tube consists of our cells, and the upper portion of the test tube consists of the blood plasma."}, {"title": "Composition of Blood.txt", "text": "So let's begin by discussing what the blood plasma is, what is found inside the blood plasma, and what the function of our blood plasma is."}, {"title": "Composition of Blood.txt", "text": "Now, blood plasma is actually the extracellular matrix that we spoke of earlier, and it makes up about 55% of the volume of our blood."}, {"title": "Composition of Blood.txt", "text": "Now, the blood plasma is a fluidlike substance that consists of many different things."}, {"title": "Composition of Blood.txt", "text": "So let's discuss some of the things that we normally find inside our blood."}, {"title": "Composition of Blood.txt", "text": "So probably the thing that predominates not probably, but definitely the thing that predominates inside our blood is water."}, {"title": "Composition of Blood.txt", "text": "In fact, water is the major solvent of our cells."}, {"title": "Composition of Blood.txt", "text": "And water is also used by the proteolytic enzymes to hydrolyze different types of molecules."}, {"title": "Composition of Blood.txt", "text": "And that's exactly why this makes up as much as 95% of the volume of our blood plasma."}, {"title": "Composition of Blood.txt", "text": "So, number two, we also find different types of proteins, such as, for example, albumin."}, {"title": "Composition of Blood.txt", "text": "Albumin is a protein that carries fatty acids and cholesterol molecules inside the blood plasma."}, {"title": "Composition of Blood.txt", "text": "We also have proteins such as our fibrinogen, which is basically involved in a blood clotting process."}, {"title": "Composition of Blood.txt", "text": "And we have immunoglobulins, which are the antibodies that are used by our immune system."}, {"title": "Composition of Blood.txt", "text": "Number three, we also find nutrients such as amino acids, sugars, as well as fatty acids."}, {"title": "Composition of Blood.txt", "text": "And these are the nutrients that are required by the cell to basically make ATP, make proteins and fats."}, {"title": "Composition of Blood.txt", "text": "Number four, we find a balance of electrolytes."}, {"title": "Composition of Blood.txt", "text": "We have sodium, we have chloride, we have calcium, magnesium, bicarbonate and other ions."}, {"title": "Composition of Blood.txt", "text": "And these are used not only to regulate the PH, but they are also used to actually control the zmodic pressure inside our blood."}, {"title": "Composition of Blood.txt", "text": "Number five, we also find waste products."}, {"title": "Composition of Blood.txt", "text": "So when the cells carry out their processes, they produce waste products such as, for example, urea, lactic acid, and our carbon dioxide."}, {"title": "Composition of Blood.txt", "text": "And these things are released into our blood and they end up in their specific location."}, {"title": "Composition of Blood.txt", "text": "For example, lactic acid ends up in the liver, our carbon dioxide ends up inside our lungs, and urea ends up in our kidneys."}, {"title": "Composition of Blood.txt", "text": "Now, what about number six?"}, {"title": "Composition of Blood.txt", "text": "Hormones."}, {"title": "Composition of Blood.txt", "text": "So hormones are those biological molecules that travel inside our blood from one point to a different point in the body."}, {"title": "Composition of Blood.txt", "text": "And they are basically used to regulate many different types of processes."}, {"title": "Composition of Blood.txt", "text": "Two examples of hormones is ADH, the antidiatic hormone and aldosterone."}, {"title": "Composition of Blood.txt", "text": "So these are the major constituents that are found in the blood plasma."}, {"title": "Composition of Blood.txt", "text": "Now, we can conclude that the blood plasma functions as a fluidlike matrix that is responsible for moving, for transporting different types of substances, nutrients, waste products, minerals, vitamins and so forth, from one point in the body to a different point of the body."}, {"title": "Composition of Blood.txt", "text": "And they are also used to regulate the composition of the nutrients, molecules and ions of the matrix of different cells found inside our body."}, {"title": "Composition of Blood.txt", "text": "Now, what about the cells?"}, {"title": "Composition of Blood.txt", "text": "So, earlier we said that our blood is a connective tissue."}, {"title": "Composition of Blood.txt", "text": "It consists of the matrix known as the blood plasma, and it also contains individual cells."}, {"title": "Composition of Blood.txt", "text": "So the question is, what types of cells are found inside our blood?"}, {"title": "Composition of Blood.txt", "text": "Well, notice that if the blood plasma makes up 55% of the volume of blood, that implies that the remaining 45% makes up our cell."}, {"title": "Composition of Blood.txt", "text": "So the cells make up 45% of the blood volume of our blood."}, {"title": "Composition of Blood.txt", "text": "Now, what types of cells are found inside our blood?"}, {"title": "Composition of Blood.txt", "text": "Well, we have red blood cells, also known as erythrocytes."}, {"title": "Composition of Blood.txt", "text": "We have white blood cells, also known as leukocytes, and we have our thrombocytes, also known as platelets."}, {"title": "Composition of Blood.txt", "text": "And all these three different types of cells arise from the same exact stem cell found in the bone marrow of our bone, known as the hematopoietic stem cell."}, {"title": "Composition of Blood.txt", "text": "So let's briefly discuss the function of each one of these cells and let's begin with the red blood cell, also known as erythrocyte."}, {"title": "Composition of Blood.txt", "text": "Now, recall that oxygen exists in its diatomic form."}, {"title": "Composition of Blood.txt", "text": "So in one oxygen molecule, we have two individual oxygen atoms that are double bonded by nonpolar bond."}, {"title": "Composition of Blood.txt", "text": "And that means oxygen is nonpolar."}, {"title": "Composition of Blood.txt", "text": "Now, because water is the main constituent of blood plasma that makes our blood aqueous."}, {"title": "Composition of Blood.txt", "text": "And that implies that oxygen, because it is non polar, it does not actually easily dissolve in the aqueous blood plasma."}, {"title": "Composition of Blood.txt", "text": "And so what happens, or what needs to happen is when oxygen gets into our lungs, it's the red blood cells that actually pick up that oxygen in the lungs and carry it to the cells of our body that need that oxygen to basically produce ATP for energy."}, {"title": "Composition of Blood.txt", "text": "Now, red blood cells are actually very specialized."}, {"title": "Composition of Blood.txt", "text": "They have very interesting structures, very interesting properties that make them very efficient for carrying oxygen."}, {"title": "Composition of Blood.txt", "text": "So let's discuss what these properties are."}, {"title": "Composition of Blood.txt", "text": "Number one is their shape."}, {"title": "Composition of Blood.txt", "text": "They have a biconcave shape."}, {"title": "Composition of Blood.txt", "text": "And that not only increases the surface area of the red blood cells and makes them very efficient in exchanging oxygen, but it also allows them to actually squeeze and travel through the really tiny capillaries."}, {"title": "Composition of Blood.txt", "text": "So as the red blood cells with the biconcave shape squeeze through the capillaries surrounding our tissues and cells, we basically exchange that oxygen for carbon dioxide."}, {"title": "Composition of Blood.txt", "text": "Now, the next important structure point of our red blood cell is the fact that they do not actually have any organelles."}, {"title": "Composition of Blood.txt", "text": "So they don't have nuclei, they don't have mitochondria or any other organelle, for that matter."}, {"title": "Composition of Blood.txt", "text": "Now, why is that important?"}, {"title": "Composition of Blood.txt", "text": "What is the relevance of that property?"}, {"title": "Composition of Blood.txt", "text": "Well, because they don't have any organelles."}, {"title": "Composition of Blood.txt", "text": "They have a lot of free space inside the red blood cells and that makes them perfect for storing as much oxygen as possible."}, {"title": "Composition of Blood.txt", "text": "Now, the protein that actually carries the oxygen inside the red blood cell is a protein known as hemoglobin."}, {"title": "Composition of Blood.txt", "text": "And hemoglobin can carry up to four different oxygen molecules."}, {"title": "Composition of Blood.txt", "text": "Now, inside a single red blood cell, we have about 280,000,000 of these individual hemoglobin proteins."}, {"title": "Composition of Blood.txt", "text": "And because hemoglobin carries four oxygens, four multiplied by that gives us over 1 billion of these oxygen molecules, is carried in a single red blood cell."}, {"title": "Composition of Blood.txt", "text": "So red blood cells are very, very efficient at their job."}, {"title": "Composition of Blood.txt", "text": "They can carry a lot of these, many of these oxygen molecules."}, {"title": "Composition of Blood.txt", "text": "Now, another important point that I should make is because red blood cells don't actually have any mitochondria, that implies they don't actually use cellular respiration."}, {"title": "Composition of Blood.txt", "text": "So that means they do not use up the oxygen supply that is found within our cell."}, {"title": "Composition of Blood.txt", "text": "And this is another byproduct of the fact that they do not have any organelle."}, {"title": "Composition of Blood.txt", "text": "They are extremely specialized to carry out one purpose, and that is to actually carry those oxygen molecules from one cell to a different cell in our body."}, {"title": "Composition of Blood.txt", "text": "Now, let's move on to leukocytes."}, {"title": "Composition of Blood.txt", "text": "Now, our red blood cells make up the predominant portion of the cells of our blood."}, {"title": "Composition of Blood.txt", "text": "Leukocytes only make up about 1% of the cells of our blood."}, {"title": "Composition of Blood.txt", "text": "But when we have some type of infection, this number can greatly increase."}, {"title": "Composition of Blood.txt", "text": "And this is because leukocytes are actually our immune cells that protect us from bacterial and viral agents."}, {"title": "Composition of Blood.txt", "text": "So we have different types of leukocytes and we'll focus on these different types and their functions."}, {"title": "Composition of Blood.txt", "text": "When we'll discuss our immune system."}, {"title": "Composition of Blood.txt", "text": "For example, we have monocides, we have lymphocytes, and we also have mast cells and other leukocyte types."}, {"title": "Composition of Blood.txt", "text": "Now, let's move on to our Thrombicides, also known as platelets."}, {"title": "Composition of Blood.txt", "text": "Now, the ratio of Thrombocides to red blood cells in our blood is about one to ten."}, {"title": "Composition of Blood.txt", "text": "So we have more of these red blood cells than our platelets."}, {"title": "Composition of Blood.txt", "text": "Now, just like these red blood cells, platelets also do not have any nuclei."}, {"title": "Composition of Blood.txt", "text": "But they are smaller than these red blood cells and they have other organelles."}, {"title": "Composition of Blood.txt", "text": "Now, our platelets actually function in the blood clotting process."}, {"title": "Composition of Blood.txt", "text": "So they travel along our blood vessels until they come to a cut or a hole in the lithium of our blood vessel."}, {"title": "Composition of Blood.txt", "text": "And then they stick to that hole and they initiate a process."}, {"title": "Composition of Blood.txt", "text": "They release chemicals that initiate the blood clotting process."}, {"title": "Composition of Blood.txt", "text": "And we'll discuss this process in much more detail when we'll discuss the immune system and the blood clotting cascade."}, {"title": "Composition of Blood.txt", "text": "So these are the three different types of cells that are found within our blood blood."}, {"title": "Composition of Blood.txt", "text": "And along with these cell types, we also have the blood plasma inside the blood which is basically the extracellular matrix that is found around these cells."}, {"title": "Thyroid Gland.txt", "text": "The next endocrine gland that we're going to focus on in detail is our thyroid gland, or simply our thyroid."}, {"title": "Thyroid Gland.txt", "text": "So let's begin by discussing the location of the thyroid gland in our body."}, {"title": "Thyroid Gland.txt", "text": "So if we examine the front portion of our neck and if we peel off our skin, we're basically going to see our thyroid gland."}, {"title": "Thyroid Gland.txt", "text": "So if we examine and begin with our atom apple so it's this region here, right above the atoms apple, is something known as the thyroid cartilage."}, {"title": "Thyroid Gland.txt", "text": "So we have the atoms apple, we have the thyroid cartilage."}, {"title": "Thyroid Gland.txt", "text": "Above that we have our larynx and then we have a bone known as the hyoid bone."}, {"title": "Thyroid Gland.txt", "text": "Now, below the atoms apples."}, {"title": "Thyroid Gland.txt", "text": "So this section here, this is our thyroid gland, or simply our thyroid, which basically is this orange structure here."}, {"title": "Thyroid Gland.txt", "text": "Now below that is the trachea and on both sides of our windpipe."}, {"title": "Thyroid Gland.txt", "text": "So this entire region is called the windpipe because it actually carries our air into and out of our body."}, {"title": "Thyroid Gland.txt", "text": "On both sides of the windpipe, we have our blood vessels."}, {"title": "Thyroid Gland.txt", "text": "We have the veins known as our internal jugular veins and we also have our arteries known as our common carotid artery."}, {"title": "Thyroid Gland.txt", "text": "We have the right one and we have the left one."}, {"title": "Thyroid Gland.txt", "text": "So essentially what the thyroid gland is, it's an endocrine gland that produces hormones that is located on the front portion of the windpipe and it also extends slightly towards the back."}, {"title": "Thyroid Gland.txt", "text": "Now, there are two types of cells that we're going to discuss in just a moment that are responsible for producing three types of hormones."}, {"title": "Thyroid Gland.txt", "text": "We have T three, also known as the triadothyrene hormone."}, {"title": "Thyroid Gland.txt", "text": "We have the T four, also known as the thyroxine hormone, and we have our calcitonin."}, {"title": "Thyroid Gland.txt", "text": "Now, T three and T four hormones of the thyroid gland are actually controlled and stimulated by a hormone that is produced by our anterior pituitary gland known as the thyroid stimulating hormone or TSH."}, {"title": "Thyroid Gland.txt", "text": "And TSH itself is stimulating controlled by TRH, the thyroid releasing hormone produced by the hypothalamus."}, {"title": "Thyroid Gland.txt", "text": "So we have this positive feedback mechanism that allows us to basically control the production and release of T three and T four."}, {"title": "Thyroid Gland.txt", "text": "And we also actually have a negative feedback mechanism as we'll see in just a moment."}, {"title": "Thyroid Gland.txt", "text": "So let's begin by discussing the triidothyrene hormone T three and the thyroxine hormone, the T four hormone."}, {"title": "Thyroid Gland.txt", "text": "Now, inside our thyroid gland, we have a type of cell known as our follicular cell."}, {"title": "Thyroid Gland.txt", "text": "And this follicular cell is responsible for synthesizing and releasing T three and T four hormones."}, {"title": "Thyroid Gland.txt", "text": "Now, both T three and T four are produced using our tyrosine amino acid."}, {"title": "Thyroid Gland.txt", "text": "T three simply means we have three eyed ions, three eyed atoms."}, {"title": "Thyroid Gland.txt", "text": "Nt four means we have four eyed atoms attached onto that particular hormone."}, {"title": "Thyroid Gland.txt", "text": "Now, T three and T four are both lipid soluble."}, {"title": "Thyroid Gland.txt", "text": "So that means they do not dissolve in water, so they do not dissolve in our blood and they require protein carriers to basically carry them within our bloodstream."}, {"title": "Thyroid Gland.txt", "text": "Now, this also means that T three and T four, because they are lipid soluble, they can easily dissolve across our cell membrane."}, {"title": "Thyroid Gland.txt", "text": "And that means they basically enter the nucleus of our cell that targets out, and they influence our cell on a transcriptional level."}, {"title": "Thyroid Gland.txt", "text": "So they basically affect the different processes in our body, especially protein synthesis."}, {"title": "Thyroid Gland.txt", "text": "So it turns out that T three and T four hormones affect the different types of cells in our body in very similar ways."}, {"title": "Thyroid Gland.txt", "text": "They essentially affect the basal metabolic rate, also known as the resting metabolic rate."}, {"title": "Thyroid Gland.txt", "text": "So this concept basically incorporates all the different processes and reactions that take place in our body in our cells."}, {"title": "Thyroid Gland.txt", "text": "For example, it affects cellular respiration, it affects protein synthesis, and so forth."}, {"title": "Thyroid Gland.txt", "text": "So we see that an increased concentration of T three and T four hormones in our blood actually increases the rate of cellular respiration, increases the rate at which we produce our ATP by using oxygen."}, {"title": "Thyroid Gland.txt", "text": "It also increases the rate of protein synthesis and protein degradation."}, {"title": "Thyroid Gland.txt", "text": "And it also increases the rate at which our heart actually contracts."}, {"title": "Thyroid Gland.txt", "text": "So it influences this basal metabolic rate."}, {"title": "Thyroid Gland.txt", "text": "Now, these hormones are actually also very important in the growth and the development of our organism from the child into an adult."}, {"title": "Thyroid Gland.txt", "text": "Now, we have two important abnormalities that we should be familiar with when we're discussing T three and T four."}, {"title": "Thyroid Gland.txt", "text": "We have something called hypothyroidism, and we have hyperthyroidism."}, {"title": "Thyroid Gland.txt", "text": "So hypo simply means we have an insufficiency of."}, {"title": "Thyroid Gland.txt", "text": "So that means our thyroid gland isn't able to actually produce a sufficient quantity of T three T four for one reason or another."}, {"title": "Thyroid Gland.txt", "text": "And this basically means that the cellular respiration rate will be low."}, {"title": "Thyroid Gland.txt", "text": "So we're not going to have enough energy."}, {"title": "Thyroid Gland.txt", "text": "We're going to feel very lazy."}, {"title": "Thyroid Gland.txt", "text": "We're not going to be that enthusiastic."}, {"title": "Thyroid Gland.txt", "text": "So low levels of these hormones will basically also lead to a gain of weight."}, {"title": "Thyroid Gland.txt", "text": "So we're going to begin to gain weight."}, {"title": "Thyroid Gland.txt", "text": "We're going to basically decrease the respiration rate."}, {"title": "Thyroid Gland.txt", "text": "We're going to decrease our heart rate, among many other things."}, {"title": "Thyroid Gland.txt", "text": "Now, hyperthyroidism is the opposite."}, {"title": "Thyroid Gland.txt", "text": "We basically have an excess of T three T four hormones in our blood."}, {"title": "Thyroid Gland.txt", "text": "So that means our thyroid gland is being over stimulated."}, {"title": "Thyroid Gland.txt", "text": "And one reason why this takes place is a result of some type of tumor on our thyroid gland."}, {"title": "Thyroid Gland.txt", "text": "So if we have too many of these T three T four molecules, we're going to feel very anxious."}, {"title": "Thyroid Gland.txt", "text": "And that's because our body's metabolic rate will increase."}, {"title": "Thyroid Gland.txt", "text": "We're going to basically increase the rate at which we produce our energy."}, {"title": "Thyroid Gland.txt", "text": "That will basically cause us to lose weight."}, {"title": "Thyroid Gland.txt", "text": "It will increase our respiration rate."}, {"title": "Thyroid Gland.txt", "text": "It will increase the rate at which our heart contracts, and so forth."}, {"title": "Thyroid Gland.txt", "text": "Now, earlier we discussed a positive feedback loop."}, {"title": "Thyroid Gland.txt", "text": "So we said that what actually causes the release of T three and T four into the blood is the release of TSH by our interior pituitary gland."}, {"title": "Thyroid Gland.txt", "text": "And what causes this pituitary gland to release TSH is the hypothalamus releasing our TRH."}, {"title": "Thyroid Gland.txt", "text": "So we have a positive feedback loop going this way, a positive feedback loop going this way."}, {"title": "Thyroid Gland.txt", "text": "But when we begin to increase the concentration of T three and T four, that will basically inhibit the release of TRH by the hypothalamus and the release of TSH, the thyroid stimulating hormone, by then to hear a pituitary gland."}, {"title": "Thyroid Gland.txt", "text": "So we have a negative feedback mechanism that basically helps us control the levels of T three and T four in our body."}, {"title": "Thyroid Gland.txt", "text": "So basically, if we have a very low level of T three and T four, that will basically cause the hypothalamus to release TRH, which will cause the anterior pituitary gland to release TSH, which will go on and cause the thyroid to release these two hormones."}, {"title": "Thyroid Gland.txt", "text": "But over time, as the concentration in the blood plasma of T three and T four increases, that will basically affect these two structures via a negative feedback loop, it will cause it will inhibit them from releasing these hormones."}, {"title": "Thyroid Gland.txt", "text": "And so the T three T four levels over time will basically stabilize."}, {"title": "Thyroid Gland.txt", "text": "Now, let's move on to the final type of hormone released by the thyroid gland known as calcitonin."}, {"title": "Thyroid Gland.txt", "text": "Now, we know that the Follicular cells release and produce T three and T four."}, {"title": "Thyroid Gland.txt", "text": "But the power of Follicular cells, also known as the C cells, are the cells that release and produce calcitonin inside our thyroid gland."}, {"title": "Thyroid Gland.txt", "text": "Now, unlike these two hormones, calcitonin is a peptide hormone."}, {"title": "Thyroid Gland.txt", "text": "It's a large peptide."}, {"title": "Thyroid Gland.txt", "text": "And that basically means it's water soluble."}, {"title": "Thyroid Gland.txt", "text": "It can easily dissolve and travel inside our blood, and it binds on to receptor proteins on the plasma membrane of the target cell."}, {"title": "Thyroid Gland.txt", "text": "Now, in the case of T three and T four, their release is controlled by the hypothalamus and by the anterior pituitary gland."}, {"title": "Thyroid Gland.txt", "text": "But the calcitonin is controlled by the levels of calcium inside our blood."}, {"title": "Thyroid Gland.txt", "text": "So if the levels of calcium in the blood is very high, calcitonin will be released by our thyroid gland into the blood."}, {"title": "Thyroid Gland.txt", "text": "And what the calciotonal basically do is it will try to decrease the level of calcium in the blood by three methods."}, {"title": "Thyroid Gland.txt", "text": "The first method is basically it will increase the rate at which the bone absorbs calcium."}, {"title": "Thyroid Gland.txt", "text": "It will decrease the rate of activity of osteoclasts, which are the cells in the bone that basically resorb the bone and release calcium into our blood."}, {"title": "Thyroid Gland.txt", "text": "So it will decrease their activity, but it will increase the activity of osteoblasts, which are those cells in the bone that build the matrix of the bone and absorb the calcium from our blood."}, {"title": "Thyroid Gland.txt", "text": "So by increasing the activity of osteoblast and decreasing the activity of osteoclast inside the bone, the bone basically absorbs the calcium from our blood, thereby decreasing the calcium concentration in our blood."}, {"title": "Thyroid Gland.txt", "text": "Now, the second method by which our calciton basically decreases the calcium concentration inside our blood is by increasing the rate at which our kidneys actually excrete this calcium into our outside environment."}, {"title": "Thyroid Gland.txt", "text": "So it will cause more calcium to be excreted by the kidneys."}, {"title": "Thyroid Gland.txt", "text": "It basically inhibits the activity of certain cells in our kidneys that absorb that calcium."}, {"title": "Thyroid Gland.txt", "text": "And finally, it causes our intestines to basically absorb less calcium."}, {"title": "Thyroid Gland.txt", "text": "And that means the calcium will eventually be excreted into the outside environment."}, {"title": "Thyroid Gland.txt", "text": "So this is our thyroid gland."}, {"title": "Thyroid Gland.txt", "text": "It's a type of endocrine gland that releases and produces three important types of hormones."}, {"title": "Thyroid Gland.txt", "text": "We have T three and T four, which are responsible for controlling the basal metabolic rate."}, {"title": "Thyroid Gland.txt", "text": "It can increase or decrease that rate."}, {"title": "Thyroid Gland.txt", "text": "And our county is basically responsible for controlling the calcium concentration inside our blood."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Before we actually discuss voltagegated and ligandgated ion channels, let's focus on the structure of an ion channel."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And To Generalize The Structure Of An Ion channel, we're Going To Focus On A Specific Type Of ion channel known as The Potassium Ion channel."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So The Potassium ion channel allows the movement Of Potassium Ions across The Membrane, down Their electrochemical, grading From A High Electric chemical Potential to A Low Electric chemical potential."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, the structure of potassium ion channels basically consists of four individual and identical polypeptide chains."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And each one of these subunits, each one of these chains looks like this."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we basically have these three domains."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Three alpha helices one shown in brown, one shown in dark purple, one shown in light purple."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now it's the dark and the light purple alpha helices that we call the membrane spanning alpha helices."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And that's because these are the regions of the protein which are found within that hydrophobic core of the membrane."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "They essentially anchor."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "They attach that entire structure of the protein into that hydrophobic core of the membrane."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so four of these identical polypeptide chains come together to form a tetrimer structure that looks like a cone."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And that's because on one side of that cone we have a larger opening than on the opposing side of that protein."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now we'll see why that's important."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "In just a moment."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "The first question that I basically want to ask is the following what exactly is it about this ion channel that gives it the property we call ion specificity?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So ion specificity is the ability of the ion channel."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "In this case, it's the potassium ion channel to basically move specific ions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "In this case, it's the potassium ions across the cell membrane, while at the same time preventing the movement of all other ions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So the question is, how is this property actually achieved by that potassium ion channel?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And in general, how is it that these ion channels are so specific to types of ions that they move across the cell membrane?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, to answer this question, let's take a look at the following diagram."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So the purple section is basically this tetromer potassium ion channel in a simpler form."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And this is the internal cavity that the potassium ions will actually pass across at the same time."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "That's the same cavity that will block all other ions from actually moving across."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So this is our membrane."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "The outside the cell."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "The inside the cell."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And these orange ions are the Potassium ions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So notice we have a higher concentration on the inside than on the outside."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so these ions will move spontaneously in this direction."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, we also have a bunch of water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And these water molecules basically describe that aqueous environment."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So notice we have an Aqueous environment on the outside and on the inside on top of that, because this portion is wider than this portion of that protein."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So Because We Have A Larger Opening about ten angstroms on the inside side than on the outside side, where it's about three angstroms."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So this internal cavity will have enough space to actually fit those same water molecules that exist on the inside cytoplasmic side of that cell."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, why is that important?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So about two thirds of the central cavity is filled with water, and that makes an aqueous environment."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "But why is that important?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, that's important because these K plus ions, the potassium ions, actually interact with the water molecules to form a more stable structure."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And this interaction creates something known as the Salvation Cage or the Salvation Shell."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So essentially, the full positive charge on these potassium ions interacts with the negatively or the partially negative charges on the oxygen atoms of the water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so the water molecules essentially orient themselves around the potassium to form a cage of water molecules we call the Salvation Cage."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so this Salvation Cage creates an energetically, more stable system and lower in energy because the formation of these bonds essentially releases energy and makes it more stable."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And by the same reasoning, we see that if we break the bonds, that actually requires energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And because two thirds of this internal cavity contains the water, when these potassium ions move into this aqueous environment, they do not lose those salvation cages."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "They do not break those stabilizing interactions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And that's a good thing."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we see that about two thirds of the central cavity is filled with water because of that larger opening and larger amount of space on this side of that protein."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Therefore, as the potassium ions into that cavity, into the inside, because of the presence of water, they do not lose that stabilizing salvation Cage."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "But notice what happens in this particular region."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "This region is very, very small."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "In fact, it's so small and so restricted that the water molecules cannot actually fit into that region because it's only three angstroms wide."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And what that means is if the potassium ion actually wants to make its way into this section and eventually makes its way out of that cell to the other side, it has to actually lose these water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "It has to lose that cage, it has to lose those stabilizing interactions between those water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, we know to lose these interactions, we have to input a certain amount of energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And that process requires energy, but we know this process does not require energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So how is this actually fixed?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "How is this problem actually fixed?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, it turns out that if we zoom in on this section, so let's suppose one of these potassium ions makes its way into this region and it loses these water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So what exactly happens to that potassium ion as it travels through this section?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, within this restricted region of the cavity, we basically have a five amino acid sequence known as a selectivity filter on each side of that potassium ion."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So one on the left side and one on the right side."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we have the sequence of three anion, valine, glycine, tyrosine, and glycine on this side as well as on this side."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And the reason we have these identical sequences is because we have four of these identical polypeptide chains that create this tetrameric structure."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so what happens is one of the functions of the selectivity filter, this sequence of five amino acids, is that they're oriented in such a way so that the Carbonal oxygen atoms, these atoms show the red of these residues."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "These amino acids basically orient themselves in such a way as to form stabilizing directions between the partially negative charges of the oxygen and the false positive charges on those potassium ions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So these interactions shown in green, and those interactions are overall more stabilizing than interaction between the water and the potassium."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So even though we have to input a certain amount of energy for this potassium to actually move into this restricted area and break that salvation cage, we form more stabilizing bonds."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And when these bonds are formed, energy is released."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And the amount of energy that is released in this process is greater than the amount of energy that is used to actually break these bonds."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so the sum of those two values will give us a negative free energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And what that means is this process of the movement of these potassium ions across is an overall spontaneous process."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "It will take place spontaneously because free energy is released into the environment."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, the second function of the selectivity filter, this sequence of five amino acids within this restricted area is to basically give that specific channel its ion specificity."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we see that the selectivity filter also determines the specific nature of that ion channel, its ability to actually move these potassium ions across that membrane."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "The question is why?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, let's begin with the easy case."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Let's suppose that we take an ion that has a greater radius than the potassium."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, if the ion has a greater radius than the potassium, the reason that ion cannot pass across is simply because it's too large."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Its diameter is too large, and it cannot actually move across this three angstrom width."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, what happens if the ion is smaller than potassium?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "That's the slightly more difficult a question to actually answer."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So, for instance, let's compare sodium and potassium."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, Potassium Dionic radius of potassium is about 1.33 angstromes, while the ionic radius of sodium is about 0.95."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so we see that the ionic radius of these potassium ions is about 40% greater than the ionic radius of our sodium ions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Let's suppose this one is sodium."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So if these sodium ions are so much smaller, the question is, why cannot that sodium ion actually pass across that membrane?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "How is it that the potassium ion channel actually blocks the movement of this smaller sodium ion?"}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Well, the answer lies in this salvation cage."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we saw that in the case for potassium, when potassium loses this salvation cage, that requires an input of energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "But because of the size of the potassium, because of it being just the perfect radius, just the perfect size, it can form these intermolecular interactions, which are overall more stable than these intermolecular interactions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so the sum of those two values produces a negative free energy, and this reaction takes place spontaneously."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, in the case of the sodium ions, this is what we basically see."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "The sodium ions form these stabilized interactions with the water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so this is our sodium atom."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "These are the interactions."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "These are the water molecules."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "Now, when the sodium ion moves into this region, what happens is, because its radius is so much smaller than the radius of this potassium, these distances are so much greater, these interactions will be much weaker."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "In fact, these interactions that are formed are not as stable as the interactions that we have here."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so what that means is, on this side, to break this, we have to input a certain amount of energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "But when this is formed, we release a certain amount of energy, but the amount of energy that we release is less than the amount of energy that we need to break these bonds between the water and that sodium."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so, ultimately, we see that because of the small size of the sodium ions, they cannot form stabilizing interactions with amino acids of that selectivity filter."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And what that means is that reaction, the movement of the sodium ion through the potassium ion channel will not be favorable because it will actually require an input of energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "And so the process by which sodium moves across this potassium iron shaw will not take place spontaneously because it will not release a certain amount of free energy."}, {"title": "Ligand-Gated Ion Channels .txt", "text": "So we see that only the potassium ions can actually move across the potassium iron shawn because only the potassium potassium has the proper size, has the proper ionic radius that basically ensures that these interactions formed within this region of that cavity are more stable than interactions between the potassium ions and the water molecules within this salvation cage."}, {"title": "Monohybrid Test Cross.txt", "text": "So now that we know what a punnant square is, let's actually take a look at how we can apply the punant square to help us solve different types of problems in genetics."}, {"title": "Monohybrid Test Cross.txt", "text": "And let's begin by discussing those same two experiments that were conducted by Gregor Mendel which allowed him to basically discover the law of dominance and the existence of dominant traits and recessive traits."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's begin with experiment one."}, {"title": "Monohybrid Test Cross.txt", "text": "Now, in experiment number one, what he did was he took a true breeding tall plant and he mixed it, he crossed it with a true breeding short plant."}, {"title": "Monohybrid Test Cross.txt", "text": "And what that basically means is he took a homozygous dominant plant and he mixed it with a homozygous recessive plant."}, {"title": "Monohybrid Test Cross.txt", "text": "So the phenotype for this plant is tall and the genotype is uppercase T. Uppercase T, where upper case T represents that gene that codes for proteins that expresses the tall height."}, {"title": "Monohybrid Test Cross.txt", "text": "Now, in the case of the homozygous recessive plan, we have a short phenotype and we have a genotype equaling to lowercase T, lowercase T, where lowercase T is the gene that codes for proteins that expresses the short trait and not the toll trait."}, {"title": "Monohybrid Test Cross.txt", "text": "Now, every time he conducted this same experiment, he always found that the f one generation offspring was always tall."}, {"title": "Monohybrid Test Cross.txt", "text": "It was never short."}, {"title": "Monohybrid Test Cross.txt", "text": "The question is, what exactly is the genotype of this f one generation?"}, {"title": "Monohybrid Test Cross.txt", "text": "Well, to determine what the genotype is, we have to determine what all the possibilities of that genotypes are."}, {"title": "Monohybrid Test Cross.txt", "text": "And to do that, we have to apply the punant square."}, {"title": "Monohybrid Test Cross.txt", "text": "Remember, the punant square is the tool that we use in genetics that allows us to determine all the different potential possibilities for the genotype of that particular offspring."}, {"title": "Monohybrid Test Cross.txt", "text": "So we begin with a parent that has uppercase T, uppercase T, and the other parent has lowercase, lowercase T. And they mix, they make their cross and they produce a certain offspring."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's begin with the homozygous dominant, which means we have uppercase uppercase T. And when we produce the gametes, the two T separate into individual cells."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's suppose we have uppercase T and we have uppercase T. Now the other pan has lowercase T, lowercase T. So these two individual genes separate during the process of meiosis to basically form the gametes."}, {"title": "Monohybrid Test Cross.txt", "text": "And so we have gamete one and we have gamete number two."}, {"title": "Monohybrid Test Cross.txt", "text": "So what happens when this mixes with this?"}, {"title": "Monohybrid Test Cross.txt", "text": "Well, we basically form an uppercase T, lowercase T. And so this type of offspring is known as a heterozygous individual."}, {"title": "Monohybrid Test Cross.txt", "text": "It has one dominant and one recessive."}, {"title": "Monohybrid Test Cross.txt", "text": "Now, what will be the phenotype of such an individual?"}, {"title": "Monohybrid Test Cross.txt", "text": "Well, basically as a result of the law of dominance, because uppercase T will mask, it will inhibit the expression lowercase T. In this case, we're going to get a tall and not a short phenotype."}, {"title": "Monohybrid Test Cross.txt", "text": "Now, what will happen when this mixes with this?"}, {"title": "Monohybrid Test Cross.txt", "text": "Well, we basically produce once again, this same type of heterozygous individual."}, {"title": "Monohybrid Test Cross.txt", "text": "In fact, if we examine every single one of these, if this mixes with this, we produce uppercase T, lowercase T, and here we produce upper case T, lowercase T. Remember, because the upper case T is dominant, it always comes before the lowercase T. So we never actually write our genotype in the following way."}, {"title": "Monohybrid Test Cross.txt", "text": "This is an incorrect way to write it because the dominant trait is always placed in front of that recessive trait."}, {"title": "Monohybrid Test Cross.txt", "text": "So what we basically see is 100% of the time the offspring will have a genotype that is equal to uppercase T, lowercase T. And that's precisely why 100% of the time, that offspring will be tall, it will never be short."}, {"title": "Monohybrid Test Cross.txt", "text": "And that's exactly why every time Gregor Mendel actually carried out this experiment, he saw that the offspring always resembled the homozygous dominant parent, the tall parent, and never the homozygous recessive parent, the short parent."}, {"title": "Monohybrid Test Cross.txt", "text": "So 100% of the time we're essentially going to have a heterozygous offspring."}, {"title": "Monohybrid Test Cross.txt", "text": "And that's because this is 25% of the time."}, {"title": "Monohybrid Test Cross.txt", "text": "This is 25% of the time."}, {"title": "Monohybrid Test Cross.txt", "text": "This is 25% of the time, 25%."}, {"title": "Monohybrid Test Cross.txt", "text": "And we add these up and we get 100%."}, {"title": "Monohybrid Test Cross.txt", "text": "Now let's move on to experiment number two."}, {"title": "Monohybrid Test Cross.txt", "text": "So what he did in experiment number two was he took the f one generation that was produced and he basically crossed it with itself."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's suppose we carry out this experiment twice."}, {"title": "Monohybrid Test Cross.txt", "text": "And so he produced two of these plants."}, {"title": "Monohybrid Test Cross.txt", "text": "And so what he did next was he took the f one plant and he crossed it with itself."}, {"title": "Monohybrid Test Cross.txt", "text": "And what that basically means is he crossed two heterozygous offsprings."}, {"title": "Monohybrid Test Cross.txt", "text": "So we have uppercase T, uppercase T for one of the genes and we have a lowercase T and a lowercase T for the other genes."}, {"title": "Monohybrid Test Cross.txt", "text": "And so what this cross is it's a cross between a heterozygous individual and a heterozygous individual for the same exact trait."}, {"title": "Monohybrid Test Cross.txt", "text": "The trade in this case is Hyped."}, {"title": "Monohybrid Test Cross.txt", "text": "And this specific type of test cross is known as a monohybrybrid test cross because we're basically crossing two heterozygous individuals for a given trade for the high trait."}, {"title": "Monohybrid Test Cross.txt", "text": "Now what he found out was that 75% of the time, or about 75% of the time, the individuals were tall, but 25% of the time the individuals were short."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's actually confirm this by using the pundit square."}, {"title": "Monohybrid Test Cross.txt", "text": "So once again, one of the parents is uppercase T, lowercase T. And we know when we form the gametes, the law of segregation tells us that these two genes basically separate into individual cells, into individual gametes."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's suppose this is parent number one."}, {"title": "Monohybrid Test Cross.txt", "text": "And so we have uppercase T here."}, {"title": "Monohybrid Test Cross.txt", "text": "We have lowercase t here."}, {"title": "Monohybrid Test Cross.txt", "text": "And then here we have parent number two."}, {"title": "Monohybrid Test Cross.txt", "text": "So we have lowercase T here and uppercase T here."}, {"title": "Monohybrid Test Cross.txt", "text": "So let's follow the same exact procedures."}, {"title": "Monohybrid Test Cross.txt", "text": "So first step is this crosses with this."}, {"title": "Monohybrid Test Cross.txt", "text": "And if that actually takes place, we produce uppercase T, uppercase T. Now if this crosses with this, we produce uppercase T, lowercase T. How about if this crosses with this?"}, {"title": "Monohybrid Test Cross.txt", "text": "Well, in that case, we produce uppercase T, lowercase T. And finally, if the final case takes place, T T, we have lowercase T, lowercase T. And so what we actually see is 25%."}, {"title": "Monohybrid Test Cross.txt", "text": "So this is 25% of the individuals will be homozygous dominant."}, {"title": "Monohybrid Test Cross.txt", "text": "So we have 25% of these individuals."}, {"title": "Monohybrid Test Cross.txt", "text": "In this case, the plants will be homozygous dominant for that trait."}, {"title": "Monohybrid Test Cross.txt", "text": "Now we have 50% because this is 25% and 25%."}, {"title": "Monohybrid Test Cross.txt", "text": "So 50% of the individuals will actually be heterozygous, just like these plants were the f one generation."}, {"title": "Monohybrid Test Cross.txt", "text": "And by the way, this is the f two generation that is formed."}, {"title": "Monohybrid Test Cross.txt", "text": "So this is the f one generation punant square, and that is the f two generation punant square."}, {"title": "Monohybrid Test Cross.txt", "text": "So we essentially have 25 and 25 that produces 50 heterozygous f two generation."}, {"title": "Monohybrid Test Cross.txt", "text": "And then we have the remaining 25% are actually short, and that's because they're homozygous recessive."}, {"title": "Monohybrid Test Cross.txt", "text": "So we have 25% rhomozygous recessive."}, {"title": "Monohybrid Test Cross.txt", "text": "And so if we tally up these percentages, we see that because of the law of dominance, not only will this have a phenotype of tall, this will also have a tall phenotype, because the uppercase T is dominant over the lower case T. So 25% plus 50% gives us the 75% that was observed by Gregory Mendel when he carried out these experiments."}, {"title": "Monohybrid Test Cross.txt", "text": "And the remaining 25% will have a phenotype that is short because this is lowercase T, lowercase T. And so this is how we can use the pun and square to basically help us solve different types of problems in genetics."}, {"title": "Monohybrid Test Cross.txt", "text": "And we'll look at many more examples in the lectures to come."}, {"title": "Collecting Duct .txt", "text": "The final segment of the nephron is known as the collecting duct."}, {"title": "Collecting Duct .txt", "text": "So, if this is our nephron, then this is our collecting duct."}, {"title": "Collecting Duct .txt", "text": "Now, the collecting duct extends all the way from the cortex of our kidney to the medulla portion of our kidney."}, {"title": "Collecting Duct .txt", "text": "And our collecting duct connects the distal convoluted tubule, this section here, to the ureter that basically extends from our collecting duct and into the urinary bladder, where the urine is actually stored."}, {"title": "Collecting Duct .txt", "text": "So our filter travels from the distal convoluted tubule into and through our collecting duct into the ureter and then into the urinary bladder."}, {"title": "Collecting Duct .txt", "text": "And it is stored inside the urinary bladder until our body actually excretes it to the outside environment."}, {"title": "Collecting Duct .txt", "text": "Now, the question is, what exactly is the function of the collecting duct?"}, {"title": "Collecting Duct .txt", "text": "Well, the collecting duct is involved in reabsorption, and we'll see what it reabsorbs in just a moment."}, {"title": "Collecting Duct .txt", "text": "So, under normal conditions, in the absence of any type of hormone, the collecting duct is impermeable to water."}, {"title": "Collecting Duct .txt", "text": "And that means no water is reabsorbed or secreted into our collecting duct."}, {"title": "Collecting Duct .txt", "text": "However, under normal conditions, it is slightly permeable to sodium ions."}, {"title": "Collecting Duct .txt", "text": "And sodium ions will be reabsorbed by our cells back into the surrounding tissue around our collecting duct, known as the interstituum."}, {"title": "Collecting Duct .txt", "text": "So about 5% of the total sodium ions inside the filtrate will be reabsorbed back into our body in the collecting duct."}, {"title": "Collecting Duct .txt", "text": "Now, as it turns out, the function of our collecting duct is actually controlled by two important types of hormones that we already spoke about."}, {"title": "Collecting Duct .txt", "text": "One of these hormones is ADH, the antidiatic hormone also known as vasopressin."}, {"title": "Collecting Duct .txt", "text": "And the other hormone that controls the functionality of the collecting duct is aldosterone."}, {"title": "Collecting Duct .txt", "text": "So, under dehydrating conditions, that is, when the volume of water inside the blood plasma of our body is low, what happens is our body releases these hormones."}, {"title": "Collecting Duct .txt", "text": "It releases ADH and aldosterone, and these hormones act on our collecting dog to basically make it permeable to water."}, {"title": "Collecting Duct .txt", "text": "Now, the mechanism by which these two hormones actually act are different."}, {"title": "Collecting Duct .txt", "text": "So let's discuss how each one of these hormones affects the functionality of our collecting duct."}, {"title": "Collecting Duct .txt", "text": "And let's begin with ADH."}, {"title": "Collecting Duct .txt", "text": "So, ADH, or antiduretic hormone, essentially stimulates the epithelial cells found along our collecting dust to produce membrane protein channels known as aquaporeans."}, {"title": "Collecting Duct .txt", "text": "And aquaporeans are these specialized types of channels found on the apical side of our membrane that are responsible for actually allowing the movement of water across the membrane."}, {"title": "Collecting Duct .txt", "text": "Now, the question is, in what direction will the water actually flow?"}, {"title": "Collecting Duct .txt", "text": "Will the water flow out of the filtered and into the interstituum, or from the interstituum and back into our lumen of the collecting dug?"}, {"title": "Collecting Duct .txt", "text": "Well, the answer lies in the following idea."}, {"title": "Collecting Duct .txt", "text": "Recall what the function of the loop of Henley was in our discussion on the countercurrent multiplier system and the loop of Henley."}, {"title": "Collecting Duct .txt", "text": "We basically said that what the loop of Henley does is it creates a high concentration of ions of solute ions in the interstituum of aramidoula."}, {"title": "Collecting Duct .txt", "text": "In fact, as we go lower along aramidoula, as we go deeper into aramidoula, the concentration of ions increases."}, {"title": "Collecting Duct .txt", "text": "Now, if we have a higher concentration of ions outside in the surrounding tissue than in the inside of the lumen of our collecting duct, then water will tend to flow from a lower concentration of solute to a higher concentration of solute."}, {"title": "Collecting Duct .txt", "text": "And that's because the sommotic pressure on the outside will be higher."}, {"title": "Collecting Duct .txt", "text": "So once again, ADH stimulates the epithelial cells to produce membrane protein channels known as aquaphorns."}, {"title": "Collecting Duct .txt", "text": "These channels allow the passive transport of water down its gradient to the outside to our interstituent from the filtrate found in the lumen of the collecting duct."}, {"title": "Collecting Duct .txt", "text": "And this is because of the fact that the loop of Henley established this electrochemical gradient."}, {"title": "Collecting Duct .txt", "text": "It concentrated the interstitium so that there is a higher concentration, a higher hypertonicity in the outside than on the inside."}, {"title": "Collecting Duct .txt", "text": "Now, the next question is what exactly is the function of aldosterone?"}, {"title": "Collecting Duct .txt", "text": "So we saw that ADH is responsible for producing these aquaporums, and we'll discuss that in more detail in just a moment."}, {"title": "Collecting Duct .txt", "text": "But what exactly the function of aldosterone?"}, {"title": "Collecting Duct .txt", "text": "Well, aldosterone doesn't actually directly increase the flow of water from our collecting duct."}, {"title": "Collecting Duct .txt", "text": "What it does is it stimulates the production of sodium channels on the apical side of our epithelial cells."}, {"title": "Collecting Duct .txt", "text": "And the particular epithelial cells involved in this process are called principal epithelial cells."}, {"title": "Collecting Duct .txt", "text": "So if we produce more sodium channels on the apical side of the membrane, more sodium ions will be absorbed by the collecting duct."}, {"title": "Collecting Duct .txt", "text": "More sodium ions will travel out of our collecting duct and into our interstituent."}, {"title": "Collecting Duct .txt", "text": "Now, as a result of that, water will basically follow because if we have more sodium ions flowing out, the concentration here will increase, and so water will follow as a result."}, {"title": "Collecting Duct .txt", "text": "And that's exactly what aldo steroid does."}, {"title": "Collecting Duct .txt", "text": "So as sodium moves out of the lumen and into the interstituum, the surrounding tissue around the collecting dug, it also brings water along for the ride."}, {"title": "Collecting Duct .txt", "text": "Now, earlier we said that ADH antidiaretic hormone basically produces more of these aquaporean channels."}, {"title": "Collecting Duct .txt", "text": "The question is, how exactly does this actually take place?"}, {"title": "Collecting Duct .txt", "text": "So let's take a look at diagram A."}, {"title": "Collecting Duct .txt", "text": "In the absence of the ADH hormone, water is impermeable."}, {"title": "Collecting Duct .txt", "text": "So basically, water, these cells are impermeable to water."}, {"title": "Collecting Duct .txt", "text": "So if water tries to basically pass from the apical side to the bacillateral side, it will not be able to pass across."}, {"title": "Collecting Duct .txt", "text": "However, notice what we have inside these cells."}, {"title": "Collecting Duct .txt", "text": "These purple vesicles are known as storage vesicles."}, {"title": "Collecting Duct .txt", "text": "And inside these storage vesicles, we have these aquaporeans."}, {"title": "Collecting Duct .txt", "text": "So, in the absence of ADH, we don't have any of these aquaporeans on the apical membrane."}, {"title": "Collecting Duct .txt", "text": "All these aquaporn channels are found inside these vesicles."}, {"title": "Collecting Duct .txt", "text": "They're stored inside these vesicles."}, {"title": "Collecting Duct .txt", "text": "Now, if we look at diagram B, now we're basically adding our ADH in the presence of ADH antidiauretic hormone stimulates the transfer of these aquaporeans from these storage vesicles and into the membrane on the apical side of the cell."}, {"title": "Collecting Duct .txt", "text": "And now, because we have these aquaporeans, water can easily travel from a low solub concentration inside the lumen to the outside of our cell, on the other side, our surrounding tissue, known as the interstituum."}, {"title": "Collecting Duct .txt", "text": "So this is the method by which ADH acts on our collecting dust and forces it to absorb more water."}, {"title": "Collecting Duct .txt", "text": "So we'll summarize our discussion."}, {"title": "Collecting Duct .txt", "text": "So we see that the collecting duct is actually under the control of these hormones, ADH, as well as our aldosterone."}, {"title": "Collecting Duct .txt", "text": "In the absence of these hormones, the collecting duct is impermeable to water."}, {"title": "Collecting Duct .txt", "text": "And only about 5% of the sodium, total sodium, in the filtrate, is actually absorbed by the collecting duct."}, {"title": "Collecting Duct .txt", "text": "However, when we have the hormone hormones present along this region, these hormones basically stimulate."}, {"title": "Collecting Duct .txt", "text": "They force our collecting duct to become permeable to water."}, {"title": "Collecting Duct .txt", "text": "And as much as 20% of the total water inside the filtrate can actually be absorbed under dehydrating conditions when the blood volume inside our blood plasma is low."}, {"title": "Synaptic Terminal .txt", "text": "Neurons are specialized type of cells that are capable of accepting and sending electrical signals to other cells."}, {"title": "Synaptic Terminal .txt", "text": "And this is the means by which our cells can communicate with one another in a quick and direct fashion."}, {"title": "Synaptic Terminal .txt", "text": "Now, any given neuron accepts an electrical signal on the dendrites and it sends that electrical signal through the cell body and, and into the exxon hill lock."}, {"title": "Synaptic Terminal .txt", "text": "On the exxon hill lock, the action potential is generated and it moves along the axon and until the end of that axon."}, {"title": "Synaptic Terminal .txt", "text": "Now, at the end of each axon, we have extensions, and on the end of each extension, we have a knob like structure that looks like the knob of a door."}, {"title": "Synaptic Terminal .txt", "text": "So this is this structure here."}, {"title": "Synaptic Terminal .txt", "text": "Now, this structure goes by many names."}, {"title": "Synaptic Terminal .txt", "text": "Some of these names include the axon terminal, the synaptic terminal, or the synaptic."}, {"title": "Synaptic Terminal .txt", "text": "Buton so bouton is simply a medical term that refers to a knob like swelling, like the structure shown here."}, {"title": "Synaptic Terminal .txt", "text": "So basically, this entire diagram describes something called the synapse."}, {"title": "Synaptic Terminal .txt", "text": "The synapse includes our neuron that is sending that signal."}, {"title": "Synaptic Terminal .txt", "text": "It includes the space known as our synaptic cleft."}, {"title": "Synaptic Terminal .txt", "text": "And it also includes our cell that is receiving that signal."}, {"title": "Synaptic Terminal .txt", "text": "And basically, this is our system that allows for the transmission of the electrical signal from one cell to the other cell."}, {"title": "Synaptic Terminal .txt", "text": "Now, to describe how the electrical signal is actually passed down from the neuron to some cell, let's focus on a specific type of synapse known as the neuromuscular junction."}, {"title": "Synaptic Terminal .txt", "text": "The neuromuscular junction is a synapse that includes a neuron as well as a muscle cell."}, {"title": "Synaptic Terminal .txt", "text": "So this is our neuron."}, {"title": "Synaptic Terminal .txt", "text": "This is a synaptic terminal of the neuron."}, {"title": "Synaptic Terminal .txt", "text": "So over there is the axon."}, {"title": "Synaptic Terminal .txt", "text": "The axon basically carries our action potential and eventually that action potential comes to our synaptic terminal."}, {"title": "Synaptic Terminal .txt", "text": "Now, the cell that is sending that electrical signal is our presynaptic cell."}, {"title": "Synaptic Terminal .txt", "text": "The cell that is receiving that signal, in this case, it's the muscle cell."}, {"title": "Synaptic Terminal .txt", "text": "This is known as the post synaptic cell."}, {"title": "Synaptic Terminal .txt", "text": "So let's discuss what actually takes place during this process."}, {"title": "Synaptic Terminal .txt", "text": "So, as soon as the action potential comes to our synaptic terminal, it causes the calcium channels on the membrane to open up."}, {"title": "Synaptic Terminal .txt", "text": "As soon as our calcium channels open up, that will cause the influx of calcium ions into the cell."}, {"title": "Synaptic Terminal .txt", "text": "As the calcium ions build up, that will build up the positive charge and that will basically cause it will trigger these synaptic vesicles, synaptic vesicles, to fuse with the membrane of the cell."}, {"title": "Synaptic Terminal .txt", "text": "Now, each one of these synaptic vesicles is carrying hundreds and thousands of neurotransmitters."}, {"title": "Synaptic Terminal .txt", "text": "And in the case of the neuromuscular junction, the neurotransmitter is acetylcholine."}, {"title": "Synaptic Terminal .txt", "text": "So inside each one of these vesicles, we have acetylcholine."}, {"title": "Synaptic Terminal .txt", "text": "And as soon as we have a high concentration of calcium, that will cause these vesicles to undergo an exocytotic process and fuse with the membrane and release these neurotransmitters, ouraceetylcholine."}, {"title": "Synaptic Terminal .txt", "text": "Now, as soon as our acetylcholine are released into the space between these two cells, known as our synaptic cleft, they will begin to travel to the membrane of our postsynaptic cell, our muscle cell."}, {"title": "Synaptic Terminal .txt", "text": "Now, on the membrane of the muscle cell, we have these proteins."}, {"title": "Synaptic Terminal .txt", "text": "These proteins are integral proteins."}, {"title": "Synaptic Terminal .txt", "text": "They're channels."}, {"title": "Synaptic Terminal .txt", "text": "And each one of these protein channels contains a binding side for our acetylcholine."}, {"title": "Synaptic Terminal .txt", "text": "As soon as the acetylcholine binds to our protein on the membrane of the postsynaptic cell, that will cause these channels to open up."}, {"title": "Synaptic Terminal .txt", "text": "And now the sodium ions found on the outside will begin to flow into the cell."}, {"title": "Synaptic Terminal .txt", "text": "As soon as they begin to flow into the cell, that will increase the concentration of our sodium inside the cell, increasing the positive charge, and that will lead to depolarization of the membrane, and that will cause an action potential."}, {"title": "Synaptic Terminal .txt", "text": "Now, the action potential will in turn lead to the contraction of our muscle."}, {"title": "Synaptic Terminal .txt", "text": "So this is exactly what we mean by the transfer of an electrical signal."}, {"title": "Synaptic Terminal .txt", "text": "The electrical signal, in the form of the action potential, is transferred from this synaptic terminal onto the muscle cell, and that ultimately leads to the contraction of our muscle."}, {"title": "Synaptic Terminal .txt", "text": "Now, what exactly happens next?"}, {"title": "Synaptic Terminal .txt", "text": "So our muscle contracts, and let's suppose we want to stop the contraction of the muscle."}, {"title": "Synaptic Terminal .txt", "text": "Now, as long as our acetylcholine molecule is found inside our synaptic cleft, it will continue to bind onto the binding side of these channels."}, {"title": "Synaptic Terminal .txt", "text": "And as long as our acetylcholine binds to these channels, that will continue to create or generate the action potential, which will continue to cause the muscle to contract."}, {"title": "Synaptic Terminal .txt", "text": "So how exactly do we stop the contraction of the muscle?"}, {"title": "Synaptic Terminal .txt", "text": "Well, basically, a special type of enzyme known as acetylcholine esterase goes on and binds onto our acetylcholine that is bound onto our channel."}, {"title": "Synaptic Terminal .txt", "text": "So that is shown in this diagram."}, {"title": "Synaptic Terminal .txt", "text": "So we have the protein channel."}, {"title": "Synaptic Terminal .txt", "text": "We have our acetylcholine bound to the protein channel, and we have the enzyme acetylcholine estherase that bind onto this acetylcholine."}, {"title": "Synaptic Terminal .txt", "text": "And it breaks it down, it divides it."}, {"title": "Synaptic Terminal .txt", "text": "It hydrolyzes aracetal choline into an acetate molecule and into a choline molecule."}, {"title": "Synaptic Terminal .txt", "text": "So we have an acetate, we have the choline."}, {"title": "Synaptic Terminal .txt", "text": "And once we break them down, we inactivate that neurotransmitter."}, {"title": "Synaptic Terminal .txt", "text": "And these two molecules, our choline and acetate, are shuttled."}, {"title": "Synaptic Terminal .txt", "text": "They're transported back into our neuron, into the synaptic terminal of our neuron."}, {"title": "Synaptic Terminal .txt", "text": "And basically, once inside, we can reuse them."}, {"title": "Synaptic Terminal .txt", "text": "We can reuse them to build more acetylcholine molecules for future purposes."}, {"title": "Synaptic Terminal .txt", "text": "And once all these neurotransmitters are broken down, our cell basically stops creating those action potentials."}, {"title": "Synaptic Terminal .txt", "text": "And so the muscle cell will stop contracting."}, {"title": "Synaptic Terminal .txt", "text": "So this is the method by which our electrical signal is transferred from our neuron and onto another cell."}, {"title": "Synaptic Terminal .txt", "text": "And in this particular case, we discuss the synapse between a neuron and a muscle cell known as our neuromuscular junction."}, {"title": "Synaptic Terminal .txt", "text": "So once again, the synapse includes the presynaptic cell, our neuron, as well as the postsynaptic cell, in this case, the muscle cell."}, {"title": "Synaptic Terminal .txt", "text": "As well as everything in between."}, {"title": "Synaptic Terminal .txt", "text": "And that includes our synaptic cleft."}, {"title": "Synaptic Terminal .txt", "text": "So this entire diagram describes our synapse."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Let's suppose that we have the entire genome of some organism, the entire DNA molecule that contains all the different types of genes that are found within that organism."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Now, the question is, if we want to isolate and study a specific type of gene, let's say a single gene within that particular genome, how exactly can we go about doing that?"}, {"title": "Building and Screening Genomic Libraries .txt", "text": "How can we find find that gene, isolate that gene and then make many copies so that we can actually study and experiment with that gene?"}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Well, one way to do it, the common way to do it is to first build a genomic library for that particular genome and then we can use that genomic library to basically screen for that specific gene, to find that gene and then to isolate and make copies of that gene."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So let's begin by discussing how to actually make that genomic library."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So let's begin with step one."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Let's suppose in a single beaker we have a solution that contains that complete genome."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So for simplification purposes, we have a genome in this diagram that only consists of five different genes."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So we have this dark green gene, we have the red gene, light green gene, we have the dark purple gene and the light purple gene."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Now we take restriction enzymes and we add restriction enzymes into that mixture."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And what the restriction enzymes do is they cleave our genome into different fragments and these different fragments will contain the different genes."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So we basically break our genome into these five fragments."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Now, let's suppose that these five fragments all different size, so some are large and some are small."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And what that means is, in the next step, in step two, we can use gel electrophoresis to basically separate the different fragments based on size up to a size value of 15 KB, where KB is kilo basis."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So we run our gelatrophries and those fragments that end up at the bottom are the smallest, while the fragments that end up at the top are the largest."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And each one of these fragments contains some type of gene."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So now we essentially have these five beakers and in each one of these beakers we have a single type of gene."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Now, the problem is we only have one of the genes, but to actually work with them, we have to have many copies of that gene."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so in the next few steps, what we actually want to do is we want to amplify make many copies of each one of these genes."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And one way to do it is to use a plasmid."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "But the way we're going to do it in this lecture is by using a different type of vector, the vector we spoke about previously known as a lambda phage."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Remember, a lambda phage is a bacteriophage that infects bacterial cells such as E. Coli cells."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And we can use the lambda phage to basically infect the bacterial cells and the bacterial cells can then replicate that DNA of interest."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So in step three, we basically take cohesive ends and we add the cohesive ends onto the ends, the edges of these DNA molecules."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So for example, we take this light purple DNA molecule that we isolated in step two, and we add these cohesive ends onto the end of the DNA molecule and then we insert it into a lambda DNA phage molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So we essentially extract a lambda DNA phage molecule from the lambda phage and we cut that molecule with restriction enzymes."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And then we insert that DNA fragment into the lambda DNA phage molecule, the lambda phage DNA molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so this is basically what we produce."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So this orange section is basically part of that lambda phage DNA molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And this molecule has been inserted into that lambda phage molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And then we can follow that with each one of these molecules, we can create the following five recombinant DNA molecules."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And now we can take these recombinant DNA molecules and place them into those lambda phages, the bacteriophages, that are now ready to infect our bacterial cells."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so now we have this army of these unique lambda phages that each contain their own unique recombinant DNA molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so in step five, we can actually take a bacteriophage, we can infect these lambda phase, we can infect those bacterial cells that equalize cells with these different types of lambda phages."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And then essentially those bacterial cells will reproduce and will lice producing many, many copies of these different types of fragment DNA molecules."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so at the end, we essentially have these five beakers."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And in each one of these five beakers, we have many copies of these lambda phages that each contain a specific type of DNA fragment."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "For instance, in this particular, let's call it beaker number one, we have many copies of this lambda phage."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "In this beaker, we have many copies of this lambda phage."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "In the third beaker, we have many copies of this lambda phage and so forth."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "Now the great thing about these lambda phages is they can live on essentially forever, and we can use them at any time to infect other bacterial cells and produce even more copies of that particular DNA fragment."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So once we create that genomic library, by the way, this is what we call a genomic library."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "A genomic library is basically a collection of all the different types of genes found in that particular DNA molecule of that organism."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And for the organism that contains this genome, we have only five genes."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so we have these five beakers that each contain a specific type of gene molecule within that lambda phage."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So in step six now, we actually want to screen that genomic library to find that specific gene of interest."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So once we create the genomic library, we can screen the library to detect that specific gene that we want to isolate and study."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so what we do is we take the petri dish."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And on the petri dish, we basically spot the petri dish with these bacterial cells that are not infected."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And then we infect each one of these spots with each one of these types of lambda phages."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So this lambda phage for this spot is basically infected with this lambda phage, this spot is infected with this lambda phage and so forth."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And the next step, we have to go back into the lab and we synthesize a specific type of DNA probe."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So we create a radioactively labeled DNA probe that has a complementary DNA sequence to that DNA fragment that we're looking for."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so what we do is we add the radioactively labeled DNA probe onto each one of these spots."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And only that spot that contains that DNA fragment that we are looking for will create a hybrid with that radioactively labeled DNA molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And then we can take the results, we can transfer them onto a polymer sheet, and then we can take that polymer sheet and essentially expose it to the process of order radiography."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And this will tell us exactly where that hybrid has formed."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so, for instance, at the antibiotics experiment, we know that within this spot, we have that DNA molecule that we actually want to amplify."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So now we can extract and isolate that DNA molecule."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "We can amplify it, for instance, in a process process known as the polymerase chain reaction."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And now we have many copies of that specific gene of interest."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "And so now we can study it, experimented and do many different types of things with it."}, {"title": "Building and Screening Genomic Libraries .txt", "text": "So this is the process by which we can form genomic libraries and then screen the genomic libraries for specific genes of interest."}, {"title": "Sex Chromosomes.txt", "text": "In human beings, every single one of Aristomatic cells in our body contains 46 individual chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "Now remember, in humans and other deployed organisms, organisms that have a chromosome number of two N, each chromosome in Aristomatic pair contains a homologous chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So since humans contain 46 individual individual chromosomes, that means we have 23 pairs of homologous chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "Now, out of these 23 homologous pairs, 22 pairs are known as autosomal chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "And the other pair, the final pair of chromosomes, is known as the sex chromosome pair."}, {"title": "Sex Chromosomes.txt", "text": "Now, in this lecture, we're going to focus on the sex chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "Now, the first major difference between autosomal chromosomes and sex chromosomes is the following."}, {"title": "Sex Chromosomes.txt", "text": "In autosomal chromosome pairs, the two homologous chromosomes are always the same size and shape."}, {"title": "Sex Chromosomes.txt", "text": "But in the case of sex chromosomes, in females, the two sex chromosomes are the same size and shape."}, {"title": "Sex Chromosomes.txt", "text": "But in males, we have one large sex chromosome and one small sex chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So that means we have two homologous chromosomes that are not the same shape and not the same size."}, {"title": "Sex Chromosomes.txt", "text": "So to see what we mean by that, let's take a look at the following three diagrams."}, {"title": "Sex Chromosomes.txt", "text": "So we have diagram A, diagram B and diagram C. Now, in diagram A, we have an autosomal chromosome pair."}, {"title": "Sex Chromosomes.txt", "text": "So we have this autosom chromosome number one, and it's homologous autosom chromosome number two."}, {"title": "Sex Chromosomes.txt", "text": "So one of these came from the male parent, and the other one came from the female parent."}, {"title": "Sex Chromosomes.txt", "text": "And notice in this pair, these two autosomal chromosomes are the same size and the same shape, and they carry the genes that code for the same exact types of traits."}, {"title": "Sex Chromosomes.txt", "text": "So we have this gene that codes for, let's say, the hair color."}, {"title": "Sex Chromosomes.txt", "text": "And this gene also codes for the hair color, and these are known as alleles."}, {"title": "Sex Chromosomes.txt", "text": "Now, let's move on to diagram B and diagram C. And these two diagrams, we discuss the sex chromosome pair."}, {"title": "Sex Chromosomes.txt", "text": "Now, in females, as I mentioned earlier, we have two individual homologous sex chromosomes that are the same exact size and the same exact shape, and they carry genes that code for similar traits."}, {"title": "Sex Chromosomes.txt", "text": "And these traits, as we'll see in just in a moment, are known as sex link traits or X linked traits."}, {"title": "Sex Chromosomes.txt", "text": "And the reason we call them X linked traits is because this chromosome is known as the X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So in female individuals, both of these sex chromosomes are said to be X chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "So in female individuals, in female humans, there are two X chromosomes that are identical in size and shape and carry genes that code for specific sex linked traits."}, {"title": "Sex Chromosomes.txt", "text": "Now?"}, {"title": "Sex Chromosomes.txt", "text": "What about C?"}, {"title": "Sex Chromosomes.txt", "text": "Well, in C, we describe the situation in male individuals."}, {"title": "Sex Chromosomes.txt", "text": "In males, unlike in females, we only have one X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "And the other sex chromosome is called the Y chromosome."}, {"title": "Sex Chromosomes.txt", "text": "And notice it's much smaller in size and has a slightly different shape than the X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So, in contrast, male individuals have one X chromosome that contains many different types of genes that code for specific sex link traits and it also contains a small Y chromosome that basically has one or several genes that code for maleness."}, {"title": "Sex Chromosomes.txt", "text": "Why is that?"}, {"title": "Sex Chromosomes.txt", "text": "Well, it's because the Y chromosome actually determines what the gender of that particular individual is."}, {"title": "Sex Chromosomes.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Sex Chromosomes.txt", "text": "So, let's suppose we begin inside the male individual and the male individual begins to produce sex cells the gametes known as sperm cells."}, {"title": "Sex Chromosomes.txt", "text": "So this is the precursor sperm cell and because we're dealing with a male individual that means the sex chromosome pair will consist of an X chromosome and a Y chromosome."}, {"title": "Sex Chromosomes.txt", "text": "Now, before meiosis takes place during interface we have to replicate each one of these sex chromosomes so the X chromosome is replicated and so is the Y chromosome replicated."}, {"title": "Sex Chromosomes.txt", "text": "So this is our cell that contains the replicated sex chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "So we have two identical X chromosomes and two identical Y chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "Now, to form our sperm cells, the gametes in this particular male individual meiosis has to take place."}, {"title": "Sex Chromosomes.txt", "text": "And when meiosis takes place, first these two segregate and then these two individual chromosomes segregate at the end, we produce four different possibilities."}, {"title": "Sex Chromosomes.txt", "text": "Now, two of these sperm cells have identical X sex chromosomes the other two have identical Y sex chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "So that means two of the four sperm cells, or 50% of the sperm cells, have the X chromosome and the other 50%, two out of four have the Y chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So basically, we have a 50% chance of producing a sperm cell that is carrying the X sex chromosome and a 50% chance of producing a sperm cell that is carrying the Y sex chromosome."}, {"title": "Sex Chromosomes.txt", "text": "Now, in contrast, if we take a look at this gamete formation process as it takes place in females because females always carry this pair of sex chromosomes so we have X chromosomes in both cases, the only type of Xcel that a female can produce is an X cell that carries the X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "It can never contain a Y chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So female individuals always produce X cells that have X chromosomes."}, {"title": "Sex Chromosomes.txt", "text": "So how do we actually form a male individual?"}, {"title": "Sex Chromosomes.txt", "text": "And how do we actually form a female individual?"}, {"title": "Sex Chromosomes.txt", "text": "Well, to form a female individual, we have to have a sperm cell that carries the X sex chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So we have the sperm cell that is carrying the X chromosome and it combines with the Xcel and the Xcel always carries that X sex chromosome."}, {"title": "Sex Chromosomes.txt", "text": "When they combine, they form a Zygote that contains two X chromosomes and so this will basically be a female."}, {"title": "Sex Chromosomes.txt", "text": "Likewise, to form a male, we have to have the sperm cell that is carrying the Y chromosome as shown here, combined with the Xcel."}, {"title": "Sex Chromosomes.txt", "text": "So this is our Xcel that is also carry or is carrying that X chromosome as in this case because once again, the XL always carries the x chromosome."}, {"title": "Sex Chromosomes.txt", "text": "And so when they combine, we now have this X chromosome and the Y chromosome in the Zygote."}, {"title": "Sex Chromosomes.txt", "text": "And so eventually, this Zygote will develop into a male individual."}, {"title": "Sex Chromosomes.txt", "text": "So we see that because there is a 50% chance of forming a sperm cell that is carrying the X chromosome, so we have 0.5 chance of that taking place, and we have 100% chance of the Xcel forming the X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "So that is equivalent to 1.0."}, {"title": "Sex Chromosomes.txt", "text": "We multiply these two and we see that there is a 0.5 or a 50% chance of forming the female individual."}, {"title": "Sex Chromosomes.txt", "text": "And likewise, we can use the same exact mathematics in this particular case."}, {"title": "Sex Chromosomes.txt", "text": "So 50% chance of the sperm cell carrying the Y chromosome, zero five multiplied by 1.0, and that gives a 0.5 chance or 50%."}, {"title": "Sex Chromosomes.txt", "text": "So we see that forming a female and a male are equally likely events."}, {"title": "Sex Chromosomes.txt", "text": "So this is 50% chance and this is 50% chance."}, {"title": "Sex Chromosomes.txt", "text": "Now, earlier when I mentioned when I introduced the X chromosome, I said that the X chromosome contains many genes that are involved in expressing proteins that basically are important in not only the female individual, but also the male individual."}, {"title": "Sex Chromosomes.txt", "text": "So the X chromosome contains many genes that are necessary for both genders."}, {"title": "Sex Chromosomes.txt", "text": "And that's exactly why both of these individuals, the female and the male, contain X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "In the case of the female, we have two."}, {"title": "Sex Chromosomes.txt", "text": "In the case of the male, we have one."}, {"title": "Sex Chromosomes.txt", "text": "So we have at least one X chromosome in each one of these cases."}, {"title": "Sex Chromosomes.txt", "text": "And that's because it's the X chromosome that carries those necessary genes that are needed for both genders."}, {"title": "Sex Chromosomes.txt", "text": "Now, in contrast, if we look at the Y chromosome, the Y chromosome only usually has one or several genes that are involved for giving that male their maleness."}, {"title": "Sex Chromosomes.txt", "text": "Now, whenever we're looking at genes on the X chromosome, those genes on the X chromosome are known as sex linked genes or X linked genes."}, {"title": "Sex Chromosomes.txt", "text": "And that's because these are the genes that express proteins that are necessary for the different types of traits that exist in males as well as females."}, {"title": "Sex Chromosomes.txt", "text": "So let's take a look at the female and then let's take a look at the male."}, {"title": "Sex Chromosomes.txt", "text": "So we know that in the female, the two types of sex chromosomes are the X chromosome and the X chromosome."}, {"title": "Sex Chromosomes.txt", "text": "Now, we know that a gene can either be dominant or a gene can be recessive."}, {"title": "Sex Chromosomes.txt", "text": "Now, if the gene is dominant, we usually describe the gene with an uppercase letter."}, {"title": "Sex Chromosomes.txt", "text": "If the gene is recessive, we usually describe it with a lowercase letter."}, {"title": "Sex Chromosomes.txt", "text": "Now, what are the different possibilities of a female?"}, {"title": "Sex Chromosomes.txt", "text": "Well, a female can be either homozygous dominant, and this is the case when we have, let's say, an uppercase B and an upper case B gene."}, {"title": "Sex Chromosomes.txt", "text": "So what's one example of a gene that is found on the X chromosome?"}, {"title": "Sex Chromosomes.txt", "text": "Well, our gene that basically codes for color blindness."}, {"title": "Sex Chromosomes.txt", "text": "So an uppercase B basically means the individual will not be color blind."}, {"title": "Sex Chromosomes.txt", "text": "And in this particular case, if we suppose, let's suppose that the brown gene shown here is the gene that codes for color blindness."}, {"title": "Sex Chromosomes.txt", "text": "Uppercase B means that's the dominant gene and the individual will not be colorblind."}, {"title": "Sex Chromosomes.txt", "text": "And so because both of these are upper case B's, we have homozygous dominant."}, {"title": "Sex Chromosomes.txt", "text": "Now, likewise, we can also be homozygous recessive."}, {"title": "Sex Chromosomes.txt", "text": "And in this particular case, we have lowercase B, lower case B."}, {"title": "Sex Chromosomes.txt", "text": "And in this particular case, the individual will be colorblind because we have two recessive genes."}, {"title": "Sex Chromosomes.txt", "text": "Now, we can also be heterozygous."}, {"title": "Sex Chromosomes.txt", "text": "And that means one of them could be upper case B, the other one could be lower case B."}, {"title": "Sex Chromosomes.txt", "text": "In this particular case, the individual, the female individual will not be colorblind because the dominant basically inhibits the expression of that recessive gene."}, {"title": "Sex Chromosomes.txt", "text": "Now, in the case of male, the only thing that we can have is hemiscigus."}, {"title": "Sex Chromosomes.txt", "text": "And what hemisigus means is we only have one gene and not a pair of genes."}, {"title": "Sex Chromosomes.txt", "text": "So in this case, we have a pair of alleles."}, {"title": "Sex Chromosomes.txt", "text": "But in this case, we do not have a pair of alleles because our male only contains one X."}, {"title": "Sex Chromosomes.txt", "text": "And it's the X chromosome that carries those sex link genes."}, {"title": "Sex Chromosomes.txt", "text": "So if our individual is uppercase B, that means they won't be colorblind, but if they're lowercase B, they will be colorblind."}, {"title": "Sex Chromosomes.txt", "text": "And this type of scenario is called hemisiagus."}, {"title": "Sex Chromosomes.txt", "text": "Hemisiagus means we only have one of the X chromosomes and not two."}, {"title": "Sex Chromosomes.txt", "text": "And so we only have one of these sex link genes and not two, as we have in the female case."}, {"title": "Sex Chromosomes.txt", "text": "Now, the last thing that I'd like to briefly talk about is the inactivation of the X chromosome in female individuals."}, {"title": "Sex Chromosomes.txt", "text": "So it turns out that in female individuals, in female somatic cells, one of the chromosomes, one of the X chromosomes is actually inactivated and we produce this structure known as the bar body."}, {"title": "Sex Chromosomes.txt", "text": "So in female somatic cells, one of the X chromosomes is typically inactivated by transforming that active X chromosome into an inactive X chromosome we call the bar body."}, {"title": "Sex Chromosomes.txt", "text": "Now, which one of the two sex X chromosomes are transformed into the bar body is random."}, {"title": "Sex Chromosomes.txt", "text": "And what that means is it's random which one of these will transform into the X body."}, {"title": "Sex Chromosomes.txt", "text": "So in about 50% of the somatic cells, this chromosome is transformed into the bar body and becomes inactive."}, {"title": "Sex Chromosomes.txt", "text": "But in the other 50% of the somatic cells, it's this chromosome that is transformed into the bar body."}, {"title": "Proteolytic Activation .txt", "text": "The next mechanism of enzyme regulation that we're going to focus on is known as proteolytic activation or proteolytic cleavage or sometimes known as proteolysis."}, {"title": "Proteolytic Activation .txt", "text": "Now what exactly is this process of proteolysis?"}, {"title": "Proteolytic Activation .txt", "text": "Well, sometimes our cell produce enzymes initially in their inactive form and these inactive enzymes, precursor enzymes, are known as proenzymes or zymogens."}, {"title": "Proteolytic Activation .txt", "text": "And we'll see many different examples in just a moment."}, {"title": "Proteolytic Activation .txt", "text": "Now to actually activate these enzymes we have to basically cleave the enzymes as specific peptide bonds."}, {"title": "Proteolytic Activation .txt", "text": "So sometimes we cleave one peptide bond, sometimes we cleave many peptide bonds, but the end result is the same exact when our enzymeogen undergoes proteolytic activation, proteolytic cleavage, by some type of protease we basically produce the fully functional form of that enzyme."}, {"title": "Proteolytic Activation .txt", "text": "Now when we discussed the process of phosphorylation we said that only those enzymes and proteins that are found inside our cells can actually be controlled via the process of phosphorylation."}, {"title": "Proteolytic Activation .txt", "text": "And that's because phosphorylation actually requires the presence of ATP."}, {"title": "Proteolytic Activation .txt", "text": "And ATP molecules are found abundantly only inside our cells."}, {"title": "Proteolytic Activation .txt", "text": "So that means phosphorylation can control only those enzymes and proteins which exist inside our cells."}, {"title": "Proteolytic Activation .txt", "text": "On the other hand, unlike phosphorylation, proteolytic activation does not require ATP."}, {"title": "Proteolytic Activation .txt", "text": "And what that means those enzymes and proteins which are found outside our cells in the extracellular environment can readily undergo the process of proteolytic activation."}, {"title": "Proteolytic Activation .txt", "text": "Now unlike allosteric regulation and covalent modifications such as phosphorylation, which can take place many times on any given enzyme, when a zymogen undergoes proteolytic activation it will only undergo this process once in the lifetime of that enzyme."}, {"title": "Proteolytic Activation .txt", "text": "So once again, proteolytic activation does not require ATP, adenosine, triphosphate and so it can readily take place outside the cells."}, {"title": "Proteolytic Activation .txt", "text": "In addition, enzymatic proteolysis only occurs once in the lifetime of that enzyme."}, {"title": "Proteolytic Activation .txt", "text": "Now the next question I want to explore is what are some examples of enzymes, biological proteins found inside our body that utilize the process of proteolytic activation?"}, {"title": "Proteolytic Activation .txt", "text": "So I've listed six different categories, six different types of enzymes."}, {"title": "Proteolytic Activation .txt", "text": "So category one and two we're going to focus on in much more detail in the next several lectures."}, {"title": "Proteolytic Activation .txt", "text": "And three to six, we're going to focus briefly only in this lecture."}, {"title": "Proteolytic Activation .txt", "text": "So let's begin with one digestive enzyme."}, {"title": "Proteolytic Activation .txt", "text": "So whenever we ingest different types of food particles, we ingest these macromolecules."}, {"title": "Proteolytic Activation .txt", "text": "So proteins, carbohydrates, lipids, and it's the function of these digestive enzymes to basically break down these large macromolecules into smaller food particles that can be ingested by the individual cells."}, {"title": "Proteolytic Activation .txt", "text": "And these digestive enzymes are initially created in their zymogen form."}, {"title": "Proteolytic Activation .txt", "text": "And that's important because we don't want the digestive enzymes to be activated at all times."}, {"title": "Proteolytic Activation .txt", "text": "We only want to activate these digestive enzymes when we're actually digesting, when we actually eat the food."}, {"title": "Proteolytic Activation .txt", "text": "So we have these two organs, we have the pancreas in the stomach that basically synthesize a variety of different types of zymogens."}, {"title": "Proteolytic Activation .txt", "text": "And to activate these zymogens we have to undergo the process of proteolytic cleavage, proteolytic activation."}, {"title": "Proteolytic Activation .txt", "text": "And only then when we activate these zymogens can these enzymes actually function and digest, break down all the different types of macromolecules that we ingest into our body."}, {"title": "Proteolytic Activation .txt", "text": "Now, some examples of digestive enzymes in their zymogen form are listed on the board."}, {"title": "Proteolytic Activation .txt", "text": "So we have trypsinogen, which is the zymogen form of trypsin."}, {"title": "Proteolytic Activation .txt", "text": "We have chymatrypsinogen, which is the zymogen form of chimetryptin."}, {"title": "Proteolytic Activation .txt", "text": "We have pepsinogen, we have prolastase and we have pro carboxy peptidase."}, {"title": "Proteolytic Activation .txt", "text": "And again, we'll talk about these in much more detail in the next two or three lectures."}, {"title": "Proteolytic Activation .txt", "text": "Now let's move on to the blood clotting enzyme."}, {"title": "Proteolytic Activation .txt", "text": "So inside our body we have the process we call the blood clot cascade."}, {"title": "Proteolytic Activation .txt", "text": "And what this basically involves is the proteolytic activation of many different types of zymogens into many different types of active enzymes which basically help us produce those proteins which are involved in creating the clog, when, for example, there's some type of trauma to blood vessel inside our body."}, {"title": "Proteolytic Activation .txt", "text": "So when we experience trauma or some type of cut to the blood vessels, our body initiates a response that involves a cascade of proteolytic cleavages that ultimately produces enzymes and proteins which are responsible for basically sealing off that cut in that trauma area."}, {"title": "Proteolytic Activation .txt", "text": "Now, one example that we're going to look at in the next several electrodes is prothrombin."}, {"title": "Proteolytic Activation .txt", "text": "This is a very important zymogen that is activated into the thrombin which basically needed to produce those fibrin molecules that essentially form that clock."}, {"title": "Proteolytic Activation .txt", "text": "Now let's discuss three, four, five and six."}, {"title": "Proteolytic Activation .txt", "text": "So we have hormonal enzymes, we have a process known as apatosis or program cell death."}, {"title": "Proteolytic Activation .txt", "text": "We have a very important fibrous protein that is found in bone and skin."}, {"title": "Proteolytic Activation .txt", "text": "Basically, that is a component of the extracellular environment known as collagen."}, {"title": "Proteolytic Activation .txt", "text": "And then we're going to briefly look at developmental and remodeling processes."}, {"title": "Proteolytic Activation .txt", "text": "So number three, there are many hormones inside our body that are examples of zymogens."}, {"title": "Proteolytic Activation .txt", "text": "And these Zionigens must be activated via proteolytic activation."}, {"title": "Proteolytic Activation .txt", "text": "And these hormones are known as pro hormones."}, {"title": "Proteolytic Activation .txt", "text": "So one example of such a hormone that is activated via proteolytic activation is insulin."}, {"title": "Proteolytic Activation .txt", "text": "So many hormones are synthesized in their zymogen form and must be activated via the process of proteolytic cleavage."}, {"title": "Proteolytic Activation .txt", "text": "And one common example is insulin."}, {"title": "Proteolytic Activation .txt", "text": "And this is the hormone that is basically used to regulate the glucose level, the sugar level in our blood."}, {"title": "Proteolytic Activation .txt", "text": "So our cells first synthesize insulin in the prepro insulin form."}, {"title": "Proteolytic Activation .txt", "text": "And prepro insulin must undergo a single proteolytic cleavage at a single site to basically produce proinsulin."}, {"title": "Proteolytic Activation .txt", "text": "But proinsulin is not yet a fully functional enzyme."}, {"title": "Proteolytic Activation .txt", "text": "Proinsulin then undergoes two proteolytic cleavages to essentially form the active form known as insulin."}, {"title": "Proteolytic Activation .txt", "text": "And only then can insulin actually listed its response."}, {"title": "Proteolytic Activation .txt", "text": "Number four, the process of epitosis."}, {"title": "Proteolytic Activation .txt", "text": "And we spoke about this process in detail when we discussed biology."}, {"title": "Proteolytic Activation .txt", "text": "So we said that epitosis is known as programmed cell death."}, {"title": "Proteolytic Activation .txt", "text": "This is basically when a set of special enzymes initiate the process of cell death."}, {"title": "Proteolytic Activation .txt", "text": "Now why would we ever want to actually kill off our cells?"}, {"title": "Proteolytic Activation .txt", "text": "Well one reason is if our cell is infected by some type of pathogen, if we have an infected cell we don't want that infected cell to infect other healthy cells."}, {"title": "Proteolytic Activation .txt", "text": "And so we want to kill off that cell."}, {"title": "Proteolytic Activation .txt", "text": "And this is the process that helps us basically kill off that cell."}, {"title": "Proteolytic Activation .txt", "text": "Also when the embryo is developing sometimes we actually want to kill off certain cells in a certain area."}, {"title": "Proteolytic Activation .txt", "text": "For instance when we develop the fingers and the toes to actually develop these digits we have to destroy the cells in between these areas to basically go from this to this."}, {"title": "Proteolytic Activation .txt", "text": "And this process is a result of epitosis."}, {"title": "Proteolytic Activation .txt", "text": "So our cells synthesize these zymogens we call procast spaces and these procast spaces undergo proteolytic activation to form their active form cast spaces."}, {"title": "Proteolytic Activation .txt", "text": "And the cast spaces are these enzymes responsible for activating the process of apatosis."}, {"title": "Proteolytic Activation .txt", "text": "And again we want to undergo aptosis in one of two instances if we have infested cells or if we want to stimulate the proper embryological development in that developing embryo."}, {"title": "Proteolytic Activation .txt", "text": "Now let's move on to five and six."}, {"title": "Proteolytic Activation .txt", "text": "So the most common type of fibrous protein that is found inside our body for example it's found in bone, it's found in skin and it's generally found in the areas surrounding our cells."}, {"title": "Proteolytic Activation .txt", "text": "So the extracellular environment, this fibrous protein as you might know is collagen."}, {"title": "Proteolytic Activation .txt", "text": "But collagen must be activated from its pro enzyme form from its zymogen form and the Xymogen form is known as pro collagen."}, {"title": "Proteolytic Activation .txt", "text": "In fact this leads us directly into six."}, {"title": "Proteolytic Activation .txt", "text": "We have another enzyme known as collagenase which is actually responsible for activating the pro collagen into collagen."}, {"title": "Proteolytic Activation .txt", "text": "And so collagenase is the enzyme that catalyzes the cleavage of peptide bonds in collagen."}, {"title": "Proteolytic Activation .txt", "text": "And this can either actually activate that collagen molecule or it can break down that collagen molecule and destroy that collagen structure."}, {"title": "Proteolytic Activation .txt", "text": "And this process is important in remodeling of the extracellular environment as well as the development of the embryo."}, {"title": "Proteolytic Activation .txt", "text": "So collagenase can be used to activate collagen as well as break down collagen during the process of embryological development as well as the remodeling of the extracellular environment."}, {"title": "Proteolytic Activation .txt", "text": "And just like collagen exists in a zymogen form we call pro collagen, collagenase also exists in a zymogen form called procologenase."}, {"title": "Proteolytic Activation .txt", "text": "So we have all these different types of enzymes found inside our bodies which depend on proteolytic activation to actually be activated and to exist in their fully functional form."}, {"title": "Proteolytic Activation .txt", "text": "And in the next several lectures we're going to focus on digestive enzymes as well as blood clotting enzymes."}, {"title": "Watson-Crick Model of DNA.txt", "text": "In the 1950s."}, {"title": "Watson-Crick Model of DNA.txt", "text": "There are four individuals involved in uncovering and discovering what the structure of DNA molecules was."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And these four individuals include Maurice Wilkins, rosalind Franklin, james Watson, and Francis Crick."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now what these four individuals essentially did is they were able to develop and study xray diffraction patterns of DNA five fibers."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And from these x ray diffraction photographs they were able to deduce the following four points about DNA molecules."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Point A if we examine any DNA molecule, the DNA molecule consists of two individual strands of nucleic acid."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So we have two polynucleotide chains in a single DNA molecules and these two chains essentially run in an antiparallel fashion and they wind around a common access."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And this can be described by the following diagram."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So this is one strand, this is the five end of the strand and this is the three end of the strand and it runs along our common axis in the following direction from the top to the bottom."}, {"title": "Watson-Crick Model of DNA.txt", "text": "The second polynucleotide chain is this chain here and it runs in the opposite direction."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So it essentially winds around the comet axis and it runs from the bottom to the top."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So we have the five end here and the three end here for the first chain and the three end here and the five end here for that second chain."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And so in this particular case, let's imagine that the axis of rotation basically lies along our Y axis and these two strands essentially curl around, they coil around our common axis."}, {"title": "Watson-Crick Model of DNA.txt", "text": "This is point number one."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So a single DNA molecule consists of two individual nucleic acid chains that wind about a common axis and these two polynucleotide chains run in opposite directions."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So although they are parallel, they run in opposite directions."}, {"title": "Watson-Crick Model of DNA.txt", "text": "B, the backbone of."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So if we examine the following diagram, these are the backbones and these are the nitrogenous bases."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And remember, in our study on the backbone we said that a backbone consists of these repeating units of sugar phosphate groups."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So we have sugar phosphate, sugar phosphate, sugar phosphate, and that runs along the entire backbone."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And in the diagram these arrows are basically our backbone."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now what they were able to show is that the backbone is found on the outside portion, on the exterior portion of that DNA molecule and that's because these phosphate groups found on a backbone contain negative charges and they are stabilized by the aqueous environment that contains polar water molecules."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And we'll examine that in much more detail in the next several electros."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now if the backbone is found on the exterior, then the interior, the inside of that double helix essentially contains the nitrogenous bases."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So if we examine on the inside portion of our molecule, we have these nitrogenous bases, which are relatively non polar, while on the outside we have the actual strand, we have the backbone that contains the sugar and phosphate groups, and these are found on the outside."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Point number three."}, {"title": "Watson-Crick Model of DNA.txt", "text": "These bases are essentially perpendicular with respect to the common axis."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So, once again, if this is the common axis, then these bases are essentially like so if this is the common axis, the bases are at a 90 degree angle with respect to this common axis."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And this allows for the stacking of the bases on top of one another."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, if we examine any one of these base pairs, so let's say this base pair and this base pair, the distance between any two base pairs is given to be 3.4 angstromes, or equivalently 0.3 nm."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, what they were also able to show is that in a single turn of a DNA molecule, there is a distance of 34 angstromes."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And if we divide this quantity into this, we get a value of ten."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So 34 angstroms divided by 3.4 angstroms gives us ten."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And what that means is there are ten bases in every single turn of that DNA molecule."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So what do we mean by turn?"}, {"title": "Watson-Crick Model of DNA.txt", "text": "Well, let's begin on this point on our DNA molecule, on this strand."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And when the strand basically makes a 360 degree turn, that is what we mean by single turn."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And in that 360 degree turn, there are ten bases."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And that means every time we go from one base to another, there's an angle change in 36 degrees, because 36 divided by ten gives us 36 degrees."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So every single time we go from, let's say, this base pair down to this base pair, the DNA turns by 36 degrees."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And when we go down ten of these base pairs, our degree measure is 36 times ten or 360 degrees."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, the final observation they are able to deduce following these X ray diffraction patterns is the fact that the entire diameter of this DNA molecule is 20 angstroms."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, what about the base pair?"}, {"title": "Watson-Crick Model of DNA.txt", "text": "So how exactly do these base pairs actually stack within the interior portion of our DNA molecule?"}, {"title": "Watson-Crick Model of DNA.txt", "text": "Well, they are able to basically show that one purine always bonds to a single Pyridine and the other purine always binds to the other Pyridine."}, {"title": "Watson-Crick Model of DNA.txt", "text": "In DNA molecules, they are able to show that our guanine bonds with cytosine and adenine binds with thiamine."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And these are the interactions that basically exist between our bases."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So we have guanine forms three hydrogen bonds with cytosine."}, {"title": "Watson-Crick Model of DNA.txt", "text": "This is one, two, three, and adenine forms only two of these hydrogen bonds."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And what that basically means is if our DNA molecule contains a higher amount of guanine cytosine bases compared to adenithiamine, that means our DNA molecule will be more stable, because this base pair contains three H bonds, but this base pair only contains two H bonds."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, the final thing that I'd like to briefly talk about is what actually holds and stabilizes that double helix structure."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Well, number one are these hydrogen bonds that exist between our base pair."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So this is base pair number one, base pair number two, base pair number three, and so forth."}, {"title": "Watson-Crick Model of DNA.txt", "text": "The red molecules are the guanine, the blue molecules are the cytosine."}, {"title": "Watson-Crick Model of DNA.txt", "text": "The green molecules are the adenine, and the orange molecules are the thymine."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And because they essentially are located adjacent with respect to one another, we have these hydrogen bonds shown in purple."}, {"title": "Watson-Crick Model of DNA.txt", "text": "Now, because we have a distance of 3.4 angstromes between any base pair, and because this distance corresponds to Vander valve forces, that means we have a bunch of London dispersion interaction taking place between our bases."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So these bases are basically stacked on top of one another."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And because this distance of 3.4 angstroms is the perfect distance for London dispersion forces, that means we also have these Vandervile forces holding our bases together and contributing to the overall structure of the DNA molecule."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And finally, we also have the hydrophobic effect and the hydrophobic interaction."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So remember, inside the nucleus of ourselves, we have an aqueous environment that consists of the water molecule."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And because water is polar, what that means is this DNA molecule exists in a polar environment."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And that's exactly why the backbone, which contains the polar phosphate groups, essentially lie on the outside, and these relatively non polar bases essentially cluster on the inside."}, {"title": "Watson-Crick Model of DNA.txt", "text": "And because of this hydrophobic effect, these bases are able to cluster very well on the inside and they create the stacking effect and that leads to these Vandervile forces and these hydrogen bonds."}, {"title": "Watson-Crick Model of DNA.txt", "text": "So this is the double helix structure of the DNA molecule that we also call the Watson Crick model of DNA."}, {"title": "Western Blotting .txt", "text": "Another method that we can use in biochemistry to help us locate a specific protein that we want to study is Western blotting."}, {"title": "Western Blotting .txt", "text": "And just like in the Elizabeth methods, western blotting also utilizes antibodies."}, {"title": "Western Blotting .txt", "text": "So the entire point in a western blot is to form a specific antibody that can bind onto that protein that we want to locate."}, {"title": "Western Blotting .txt", "text": "And when this this process of binding takes place, it somehow allows us to visualize where that protein is, as we'll see in just a moment."}, {"title": "Western Blotting .txt", "text": "So let's begin by supposing."}, {"title": "Western Blotting .txt", "text": "We have a sample of proteins."}, {"title": "Western Blotting .txt", "text": "Now, where did the sample actually come from?"}, {"title": "Western Blotting .txt", "text": "So suppose we have a collection of cells, and inside the cells we have proteins."}, {"title": "Western Blotting .txt", "text": "And the protein that we want to actually locate is found within the cells."}, {"title": "Western Blotting .txt", "text": "So the way that we're going to isolate the proteins from inside the cells is by fractionating our cells and then placing that fraction into a differential centrifuge machine."}, {"title": "Western Blotting .txt", "text": "And then as a result of centrifugation, we're going to basically isolate the proteins found inside our cell."}, {"title": "Western Blotting .txt", "text": "Now, once we isolate the protein sample, we take the sample of proteins and place it into a gel electrophoresis setup."}, {"title": "Western Blotting .txt", "text": "So we use SDS polyacrylamide gel electrophoresis and that allows us to use an electric field to separate the proteins based on their size."}, {"title": "Western Blotting .txt", "text": "So this is what we get following our gel electrophoresis experiment."}, {"title": "Western Blotting .txt", "text": "And so this band represents those proteins that are the largest in size."}, {"title": "Western Blotting .txt", "text": "And this band represents the proteins that are the smallest in size."}, {"title": "Western Blotting .txt", "text": "Remember, in SDS polyacrylamide gelatrophrases, these proteins move as a result of charge, as a result of being inside an electric field."}, {"title": "Western Blotting .txt", "text": "And the largest proteins move the slowest because they have the greatest resistance."}, {"title": "Western Blotting .txt", "text": "Now, once we form the setup, we also basically want to form the monoclonal antibody that is specific for that protein that we want to study."}, {"title": "Western Blotting .txt", "text": "And that protein that we want to study, we call the antigen."}, {"title": "Western Blotting .txt", "text": "So we synthesize this monoclonal antibody, we call the primary antibody that can bind to that antigen, the protein that we actually want to locate."}, {"title": "Western Blotting .txt", "text": "Now, once we form the monoclonal antibody and once we run gelatrophrases, we then transfer that separated protein sample onto a polymer sheet."}, {"title": "Western Blotting .txt", "text": "And this step is basically done to make it easier for us to work with our separated protein mixture."}, {"title": "Western Blotting .txt", "text": "Now, the next step is to take this polymer sheet and we mix it with this antibody that we form in step one."}, {"title": "Western Blotting .txt", "text": "And once we mix these two mixtures, this antibody, the primary antibody, it will basically bind onto the proteins found in one of these bands because one of these bands will contain that antigen that is specific for this protein."}, {"title": "Western Blotting .txt", "text": "And so let's suppose it's the second band from the top that contains the proteins that we want to study."}, {"title": "Western Blotting .txt", "text": "And so this antigen or this antibody will bind to the antigen, the protein found in the second band."}, {"title": "Western Blotting .txt", "text": "So the monochrome antibody is added onto the polymer sheet containing the separated protein mixture and it only binds onto the antigen, onto the protein that we actually are interested in."}, {"title": "Western Blotting .txt", "text": "Now, in step number five, we synthesize yet another antibody and now we synthesize an antibody that is radioactively labeled."}, {"title": "Western Blotting .txt", "text": "And what that allows us to do in the final step is to visualize exactly where that protein is."}, {"title": "Western Blotting .txt", "text": "Now, the antibody that we want to synthesize the second time around, this antibody in step number five is known as the secondary antibody."}, {"title": "Western Blotting .txt", "text": "And the secondary antibody is made so that it binds onto that primary antibody that we form in step one."}, {"title": "Western Blotting .txt", "text": "So once we form this secondary radioactively labeled antibody, we then mix this mixture of antibody with our polymer sheet that contains that antigen that is bound to the primary antibody."}, {"title": "Western Blotting .txt", "text": "And what happens is, because this was formed to bind onto this blue primary antibody, this complex is formed."}, {"title": "Western Blotting .txt", "text": "So the polymer sheet containing the antibody antigen complex is now exposed to a solution containing the radioactively labeled antibody."}, {"title": "Western Blotting .txt", "text": "So we take the green mixture of antibodies."}, {"title": "Western Blotting .txt", "text": "We reacted with the polymer sheet that contains the blue antibody bound onto the protein found on this second band."}, {"title": "Western Blotting .txt", "text": "Now, the radioactive antibody will only bind to this band and not the other bands because only this second band contains this protein, the antibody bound onto the antigen because this was built specifically to bind onto this primary blue antibody."}, {"title": "Western Blotting .txt", "text": "Now, in the final step, we basically take an Xray film."}, {"title": "Western Blotting .txt", "text": "We expose it to Xrays."}, {"title": "Western Blotting .txt", "text": "And what that allows us to do is allows us to visualize exactly where this radioactively labeled antibody has bound to."}, {"title": "Western Blotting .txt", "text": "And because it is bound to the protein found on the second band and none of these other bands contain this one bound to them, that means only the second band will appear dark on an Xray film."}, {"title": "Western Blotting .txt", "text": "And that allows us to exactly pinpoint where that protein is, the protein that we want to study."}, {"title": "Western Blotting .txt", "text": "And now we can take the protein and isolate the protein from this particular location on that Xray film."}, {"title": "Law of Dominance .txt", "text": "Gregor Mendel was an Austrian monk who in his spare time conducted many different types of scientific experiments by breeding pea plants."}, {"title": "Law of Dominance .txt", "text": "And unlike the breeders that came before him gregor Mendel actually quantified his results."}, {"title": "Law of Dominance .txt", "text": "So what that means is he not only wrote down his results but he also made many mathematical calculations."}, {"title": "Law of Dominance .txt", "text": "And it's that mathematical analysis that allowed him to correctly predict the many different types of phenomenon that we know of today."}, {"title": "Law of Dominance .txt", "text": "In fact, it's the work of Gregor Mendel that paved the way to modern day genetics."}, {"title": "Law of Dominance .txt", "text": "And that's precisely why we consider Gregor Mendel to be the father or the founder of modern day genetics."}, {"title": "Law of Dominance .txt", "text": "Now, why did he actually work with pea plants?"}, {"title": "Law of Dominance .txt", "text": "What makes pea plants so special?"}, {"title": "Law of Dominance .txt", "text": "Well, it turns out that the traits of these pea plants are highly variable."}, {"title": "Law of Dominance .txt", "text": "Now, what do we mean by a highly variable trait?"}, {"title": "Law of Dominance .txt", "text": "Well, let's consider the following example."}, {"title": "Law of Dominance .txt", "text": "Let's examine a trait in humans we call the eye color."}, {"title": "Law of Dominance .txt", "text": "Now, we know that the colors of our eyes varies from one individual to another individual."}, {"title": "Law of Dominance .txt", "text": "Someone might have hazel eyes another person might have blue eyes or green eyes or gray eyes or brown eyes."}, {"title": "Law of Dominance .txt", "text": "So we have many different types of variations for that particular trait and that's precisely what makes that trait highly variable in humans."}, {"title": "Law of Dominance .txt", "text": "And in the same analogous way, these pea plants also contain traits that vary from one plant to another plant and thus they're highly variable."}, {"title": "Law of Dominance .txt", "text": "Now, what traits did he actually study?"}, {"title": "Law of Dominance .txt", "text": "Well, some of these traits are listed on the board."}, {"title": "Law of Dominance .txt", "text": "So he examined, for example, the height of the pea plant and we have two types of height."}, {"title": "Law of Dominance .txt", "text": "We have tall and we have short pea plants."}, {"title": "Law of Dominance .txt", "text": "He also studied the color of the seeds."}, {"title": "Law of Dominance .txt", "text": "We have yellow seeds and we have green seeds."}, {"title": "Law of Dominance .txt", "text": "He also studied the color of the ponds in which those seeds were in."}, {"title": "Law of Dominance .txt", "text": "So we have yellow ponds and green plants and green ponds."}, {"title": "Law of Dominance .txt", "text": "He also examined the shape of the seeds."}, {"title": "Law of Dominance .txt", "text": "We have round seeds we have wrinkled seeds he examined the shape of the ponds we have inflated ponds and we have constricted pods and he examined the color of that seed coat that is around that actual seed and we have white and we have gray seed coats."}, {"title": "Law of Dominance .txt", "text": "So he basically took many of these pea plants and he conducted many different types of experiments."}, {"title": "Law of Dominance .txt", "text": "And two of these experiments are shown on the board and it's these two experiments that eventually led the way to the principle of dominance as we'll see in just a moment."}, {"title": "Law of Dominance .txt", "text": "Now, before he actually conducted these two experiments and many experiments like it he spent several years trying to develop a type or a line of pea plants known as the true breeding line of pea plants."}, {"title": "Law of Dominance .txt", "text": "Now, what exactly do we mean by a true breed?"}, {"title": "Law of Dominance .txt", "text": "Well, a true breed is a type of plant that if you made it with itself it will produce that same trait over and over, generation after generation."}, {"title": "Law of Dominance .txt", "text": "So to see an example, let's consider the following case."}, {"title": "Law of Dominance .txt", "text": "Let's suppose we have a male individual who is true breed for the color blue."}, {"title": "Law of Dominance .txt", "text": "So their eyes are blue and they're true breed for that color."}, {"title": "Law of Dominance .txt", "text": "And we take a female who is also true breed for that blue eye color."}, {"title": "Law of Dominance .txt", "text": "Now, if they mate, they will produce an offspring who also has the color blue."}, {"title": "Law of Dominance .txt", "text": "And no matter how many times we try to mate them, we will always get that same result."}, {"title": "Law of Dominance .txt", "text": "So that is what we mean by a true breeding plan."}, {"title": "Law of Dominance .txt", "text": "A true breeding plan for any one of these trades listed below will produce only that trade generation after generation."}, {"title": "Law of Dominance .txt", "text": "Now, let's actually take a look at one of the first experiments that he conducted."}, {"title": "Law of Dominance .txt", "text": "So experiment number one in that experiment, mendel basically made it, he crossed two different true breeding plants for opposite or contrasting traits."}, {"title": "Law of Dominance .txt", "text": "So what do we mean by that?"}, {"title": "Law of Dominance .txt", "text": "Well, let's choose any one of these traits."}, {"title": "Law of Dominance .txt", "text": "Let's suppose we choose the high trait."}, {"title": "Law of Dominance .txt", "text": "What he did was he took a true breeding for the tall trade and he made it a true breeding plant for the short trade."}, {"title": "Law of Dominance .txt", "text": "So this is basically what he did."}, {"title": "Law of Dominance .txt", "text": "We have a true breeding tall plan with a true breeding short plant."}, {"title": "Law of Dominance .txt", "text": "And then he examined what he produced and he did this many different times with all of these traits and he basically studied the result."}, {"title": "Law of Dominance .txt", "text": "Now, this generation initial generation is known as the parental generation or the p generation."}, {"title": "Law of Dominance .txt", "text": "And this first offspring is known as the first filial generation or simply the f one generation."}, {"title": "Law of Dominance .txt", "text": "Now, what exactly did he see every time he conducted this experiment?"}, {"title": "Law of Dominance .txt", "text": "Well, what he saw is he found that the offspring plant, the f one generation that was produced was either one of these two."}, {"title": "Law of Dominance .txt", "text": "And in the case of this height experiment, this offspring was always the tall offspring."}, {"title": "Law of Dominance .txt", "text": "So it was never the short, it was always the tall."}, {"title": "Law of Dominance .txt", "text": "And likewise, when he conducted each of these cases, he saw that it was always one and not the other one."}, {"title": "Law of Dominance .txt", "text": "So the question is what exactly happened to that short trade that came from this?"}, {"title": "Law of Dominance .txt", "text": "Was the short trade actually lost in the process of mating, in the process of crossing?"}, {"title": "Law of Dominance .txt", "text": "Well, to answer this question whether or not the short trade was lost in this offspring, he conducted a second experiment."}, {"title": "Law of Dominance .txt", "text": "He said what if I take this f one generation and I made it with itself with another f one generation in the following manner?"}, {"title": "Law of Dominance .txt", "text": "So let's suppose I conduct this experiment twice."}, {"title": "Law of Dominance .txt", "text": "I produce two of these f one offspring and I made them to produce the f two generation offspring."}, {"title": "Law of Dominance .txt", "text": "What exactly will I see?"}, {"title": "Law of Dominance .txt", "text": "And let's suppose I do this 1000 times."}, {"title": "Law of Dominance .txt", "text": "Well, what happened is he saw that about 75% of the time the offspring, the f two offspring were tall, but 25% of the time the offspring were actually short."}, {"title": "Law of Dominance .txt", "text": "So about 750 of those offspring out of a thousand were tall and 250 were short."}, {"title": "Law of Dominance .txt", "text": "Now, what exactly does this tell us about that trade that came from this short plant?"}, {"title": "Law of Dominance .txt", "text": "It tells us that the trade was not lost even though the f one generation was always tall."}, {"title": "Law of Dominance .txt", "text": "We see that because we see the short offspring in the f two generation that trade must not be lost."}, {"title": "Law of Dominance .txt", "text": "It must still exist within that plant because it reappears in this f two generation."}, {"title": "Law of Dominance .txt", "text": "So Gregor Mendel concluded that because the short trade reappeared in the second f two generation, that trade for the short plant was not lost during that mating process, during that crossing process."}, {"title": "Law of Dominance .txt", "text": "And this led directly into the principle of dominance."}, {"title": "Law of Dominance .txt", "text": "So Gregor Mendel argued that each trait in a given plant is controlled by two hereditary factors."}, {"title": "Law of Dominance .txt", "text": "And nowadays we know that these hereditary factors are actually the genes that are found on our DNA."}, {"title": "Law of Dominance .txt", "text": "So remember, a gene is simply a sequence of nucleotides that are found within a DNA section."}, {"title": "Law of Dominance .txt", "text": "And these genes basically code for a specific type of trait, for a specific type of protein that expresses that given trait."}, {"title": "Law of Dominance .txt", "text": "So each one of these plants basically contains two of these hereditary factors."}, {"title": "Law of Dominance .txt", "text": "So let's express this mating process by using these hereditary factors to see exactly what we mean."}, {"title": "Law of Dominance .txt", "text": "So we begin with a true breeding tall plan."}, {"title": "Law of Dominance .txt", "text": "And what that means is both of these hereditary factors express the toll trait."}, {"title": "Law of Dominance .txt", "text": "And so to represent the toll trade, let's use uppercase T. And to represent the short trait, let's use lowercase C. So a true breeding toll plant is uppercase T uppercase T while the true breeding shore plant is lowercase T. Lowercase T. Because both of these hereditary factors which we now know to be genes must represent the trait for that shore plant."}, {"title": "Law of Dominance .txt", "text": "Now, when we combine these two individuals, when we combine these two plants, we get the offspring, the f one generation that contains one gene, one hereditary factor that came from one parent and the other one came from the other parent."}, {"title": "Law of Dominance .txt", "text": "So upper case T, lowercase T. Now, no matter how many times he conducted this experiment, he always got a tall offspring."}, {"title": "Law of Dominance .txt", "text": "So what that means is even though that lowercase T is inside that offspring, only the uppercase T is actually expressed."}, {"title": "Law of Dominance .txt", "text": "And so what that implies is that uppercase T is dominant over the lowercase T, which is recessive."}, {"title": "Law of Dominance .txt", "text": "And by dominant means that uppercase T inhibits that lowercase T from expressing that short trait."}, {"title": "Law of Dominance .txt", "text": "So in the f one generation offspring, the hereditary factor of the tall pair and uppercase t seemed to mask or inhibit the expression of the hereditary factor that came from that short parent lowercase t. And in such a case, we say that the tall hereditary fact, the upper case t is dominant over that lowercase t, the short one, which is said to be recessive."}, {"title": "Law of Dominance .txt", "text": "And this is precisely what the principle of dominance is."}, {"title": "Law of Dominance .txt", "text": "So the principle of dominance, which stems from these types of experiments done by Gregor Mendel, basically states that in some situations we see that there is a certain gene that is dominant over another gene."}, {"title": "Law of Dominance .txt", "text": "And in this case, it's the uppercase T. It's the trade for the tall plant that was dominant over the trade for that short plant, lowercase T. So uppercase T was the trade that block the expression of that lowercase T. And that is what we mean by the principle of dominance."}, {"title": "ATCase Allosteric Regulation.txt", "text": "The first enzyme regulation mechanism that we're going to focus on will be allosteric regulation."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And to demonstrate how this is actually used and how it works inside ourselves, let's take a look at a specific type of allosteric enzyme known as aspersate transcarbomoly."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So in this lecture and the next several lectures, we're going to focus on how this enzyme actually works and how it is regulated."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So let's begin by discussing the reaction that this enzyme actually catalyzes."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So that the reaction is shown on the board."}, {"title": "ATCase Allosteric Regulation.txt", "text": "We have carboyl phosphate that reacts with aspartate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So these are the two substrate molecules to the aspartate transcarbomolase and this catalyzes the conversion of these molecules into these two products."}, {"title": "ATCase Allosteric Regulation.txt", "text": "We have orthophosphate and we also have the N carbomoyl aspartates."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now the first question you might be thinking is what's the big deal with this reaction?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "What is the physiological significance of this reaction inside our body?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "Well, as it turns out, this reaction is actually the first step in the very long biological synthesis of nitrogenous basis perimedine bases."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And the perimedines are actually used to produce the perimedine based nucleotide triphosphates, for instance, the citadine triphosphates or simply CTP."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So the ultimate result of this reaction is the production of this CTP molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so this can be seen in the following reaction pathway."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So we have the carbomol phosphate reacts with the aspartate in the presence of this enzyme to produce the Nicarbomoyl aspartate as well as that orthophosphate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And then these products react many many times to ultimately form that citadine triphosphate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And these nucleuside triphosphates are basically used to produce to build DNA molecules inside our body."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So this reaction is a pretty big deal."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now the question is how do we know that this enzyme is in fact an allosteric enzyme?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "How do we know that there exists a biological molecule inside our body that is used to basically control the activity of this enzyme?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "Well, the first evidence that this is an allosteric enzyme came from early studies that basically showed that the rate of formation of this and carbon as pertain depends on the concentration of this final product, the CTP."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And this is described in the following graph."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So we have the Y axis is the rate of formation of the M carbon oil aspartate and the x axis is the concentration of this final product in this reaction here, the CTP, the citadine triphosphate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So what this curve basically shows us, what the blue curve tells us is when inside our cells we have a low concentration of citadine triphosphate, the rate of formation of this intermediate will be relatively high."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so what that implies is the activity of the atcase that aspartate transcarbomolase will also be high."}, {"title": "ATCase Allosteric Regulation.txt", "text": "But as we increase the concentration of CTP, as we produce more and more CTP and in fact, once our cells concentration of CTP is plantful, we're going to see that somewhere here."}, {"title": "ATCase Allosteric Regulation.txt", "text": "If we look at the rate of formation of this molecule, it will be much lower than in this particular case."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so what that implies is as the concentration of CTP increases, it somehow goes back to this reaction here and affects the activity of this atcase because ultimately it's the atcase that controls the rate of this reaction of the production of this intermediate and carbon oil aspartate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now, the question is where exactly does the CTP molecule actually bind to on the atcase?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "Well, can the CTP bind onto the active side of this enzyme?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "The only way to bind onto the active side is if the CTP actually resembles has the same structure as either aspartate or carbon oil phosphate."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And we know that the structure of this looks nothing like the structure of either of these two substrates."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so what that means is for CTP to actually inhibit the activity of atcase it must bind onto some other side other than the active side."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And those sites, as we said previously, are known as allosteric sites, regulatory sites."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So we see that in this biological synthesis of CTP, it's the end product."}, {"title": "ATCase Allosteric Regulation.txt", "text": "It's the CTP itself that goes back to the beginning, to the first step in the reaction and inhibits the activity of this aspartate transcarbolase."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And we know from basic biology that this type of pathway is known as the negative feedback loop or negative feedback inhibition."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And this CTP molecule is known as an allosteric inhibitor of this enzyme."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that's how we know that this enzyme is controlled allosterically inside our cells."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So once again, these results suggest that the end product of the atcase initiative reaction must bind onto and inhibit the activity of that aspartate transcarbomolase."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And this is known as negative feedback inhibition."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now, since the structure of the CTP, the citadine triphosphate, is nothing like the structure of these substrate molecules, that means this molecule does not bind to the active side, but it binds to some other regulatory site known as the allosteric site."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And because it inhibits the activity of that enzyme, we call the CTP an allosteric inhibitor to this enzyme here."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So we see that as low concentrations of the citadine triphosphate in our cells there is not enough CTP to actually bind onto the atcase."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so the activity of atcase will be high and the rate of production of the N carbon oil aspartate will also be high."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And this is shown in the following curve."}, {"title": "ATCase Allosteric Regulation.txt", "text": "At low concentrations of CTP somewhere here, the rate of production will be high somewhere here."}, {"title": "ATCase Allosteric Regulation.txt", "text": "But as we increase the concentration of CTP, the rate will drop."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that's because now we have ample amount of CTP and some of them will go back and bind onto this enzyme, basically inhibit that enzyme."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that decreases the rate of production of this intermediate molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that makes sense because if we have abundant amounts of CTP we do not want to waste energy and produce this intermediate molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so that's exactly why we limit the production of n carbon oil aspartate by controlling the activity of this enzyme alospa."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now, before we actually go into our discussion of the structure of this enzyme, the final thing that I'd like to focus on in this lecture is the fact that aspartate transcarbomolase observes cooperative behavior."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, like most allosteric enzymes, atcase actually exhibits cooperativity."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so what that means is the binding to one side affects the binding affinity of the other sides on that same enzyme."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And if we graph the relationship between the rate at which we produce this product molecule, the ncarbon oil as pertain with respect to the concentration of the substrate, the aspartate, as shown in this diagram, we're going to see not the typical Michaela SmithIn curve, but we're going to see the sigmoidal s shape curve."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that's because this enzyme and allosteric enzymes in general, observe cooperative behavior."}, {"title": "ATCase Allosteric Regulation.txt", "text": "Now, what do we mean by cooperative behavior?"}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, let's think back to hemoglobin."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, when we discussed hemoglobin, we discussed what it means for an enzyme or a protein to behave in a cooperative fashion."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, in our discussion on hemoglobin, we said that hemoglobin behaves cooperatively because it consists of different subunits."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so it has different active sites."}, {"title": "ATCase Allosteric Regulation.txt", "text": "It has more than one active side."}, {"title": "ATCase Allosteric Regulation.txt", "text": "It has more than one side to which the oxygen actually binds to."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so because of that, every time an oxygen binds onto one of the sites, it basically creates a conformational change in the structure of that enzyme."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And that induces it increases the affinity of the other sites for that same substrate, for that oxygen molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so what that implies is the reason ATCAs exhibits cooperative behavior is because it consists of multiple subunits, and those subunits must have additional active sites."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And so when one of those active sites Is filled with the substrate molecules, such as the aspartate, the other active sites become much more likely to actually bind to that substrate molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "That's why we have this sigmoil curve."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, this cooperative behavior implies that atcase must consist of multiple subunits and hence multiple active sites."}, {"title": "ATCase Allosteric Regulation.txt", "text": "It has multiple active sites."}, {"title": "ATCase Allosteric Regulation.txt", "text": "As a substrate binds onto one of those active sites, it changes the affinity of the other active sites for that substrate molecule."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And this is due to the interaction between the different subunits."}, {"title": "ATCase Allosteric Regulation.txt", "text": "And we'll discuss much more why this actually takes place and how they interact with one another when we discuss the structure of this enzyme."}, {"title": "ATCase Allosteric Regulation.txt", "text": "So, in the next lecture, we're going to focus on the structure, the threedimensional shape, and the subunits that are found inside the aspartate, transcarbolase, or atcase allosteric enzyme."}, {"title": "Autoimmunity.txt", "text": "Our immune system displays something known as immunological tolerance."}, {"title": "Autoimmunity.txt", "text": "So our wide blood cells of our immune system are naturally immunologically tolerant to the healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "And what that means is these wide blood cells will not attack the healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "Why is that?"}, {"title": "Autoimmunity.txt", "text": "Well, because our healthy cells produce induced proteins called self antigens and they display these self antigens on special protein complexes found on the membrane of those healthy cells and they display these antigens to wide blood cells."}, {"title": "Autoimmunity.txt", "text": "So when a wide blood cell sees a self antigen on a healthy cell, it will not attack that healthy cell."}, {"title": "Autoimmunity.txt", "text": "So under normal and healthy conditions, our immune system has no problem distinguishing between these self antigens found on healthy cells and pathogenic antigens found on infected cells or on invading pathogens such as bacterial cells."}, {"title": "Autoimmunity.txt", "text": "However, in certain cases and in certain individuals, our immune system can actually lose its natural immunological tolerance to the healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "And what that means is our immune system can no longer distinguish or differentiate between self antigens of healthy cells and pathogenic antigens."}, {"title": "Autoimmunity.txt", "text": "And at this point, the white blood cells will begin to attack not only the pathogens and infected cells, but also the healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "And this condition in which our immune system loses its natural immunological tolerance to our healthy cells is known as autoimmunity or autoimmune disease."}, {"title": "Autoimmunity.txt", "text": "Now, what are some examples of autoimmune diseases?"}, {"title": "Autoimmunity.txt", "text": "Well, multiple sclerosis is one."}, {"title": "Autoimmunity.txt", "text": "Rheumatoid arthritis is a second one."}, {"title": "Autoimmunity.txt", "text": "Diabetes type one is a third one."}, {"title": "Autoimmunity.txt", "text": "And we also have myosthenia gravis, which we'll focus on briefly in this lecture."}, {"title": "Autoimmunity.txt", "text": "So what exactly is myosthenia gravis?"}, {"title": "Autoimmunity.txt", "text": "Well, this is an autoimmune disease of our body that affects our skeletal tissue."}, {"title": "Autoimmunity.txt", "text": "So basically, our body begins to produce an antibody that it normally shouldn't."}, {"title": "Autoimmunity.txt", "text": "And when this antibody is produced, it begins to circulate inside our blood and it binds onto acetylcholine receptors found between the motor neurons of our nervous system and our muscle tissue, skeletal muscle tissue."}, {"title": "Autoimmunity.txt", "text": "And by binding onto these acetylcholine receptors it blocks the action potential, our electrical signal from actually moving from the nervous system to our skeletal muscle."}, {"title": "Autoimmunity.txt", "text": "And this decreases our ability to actually voluntarily control our contraction of skeletal muscle."}, {"title": "Autoimmunity.txt", "text": "And this can lead to many problems because for example, as we know, the process of breathing involves the diaphragm and the diaphragm is in fact a skeletal muscle."}, {"title": "Autoimmunity.txt", "text": "So in a person that has myosthenia gravis, if they begin to exercise very vigorously, they will have problems breathing because this autoimmune disease affects the weight of ability that we actually contract our skeletal muscle."}, {"title": "Autoimmunity.txt", "text": "Now, although this topic of autoimmunity is heavily researched, we still actually do not quite understand how autoimmunity actually takes place."}, {"title": "Autoimmunity.txt", "text": "But we do have some idea."}, {"title": "Autoimmunity.txt", "text": "So some possibilities that basically that cause autoimmunity might be a genetic mutation on our DNA in a section that codes for some type of important component of our immune system."}, {"title": "Autoimmunity.txt", "text": "For example, the major histocompatibility complex as we'll see in just a moment."}, {"title": "Autoimmunity.txt", "text": "Another fact that that might lead to autoimmunity are infections that we experience as a result of some type of pathogens."}, {"title": "Autoimmunity.txt", "text": "And we'll see what that is in just a moment."}, {"title": "Autoimmunity.txt", "text": "Another factor might be damage to immunologically privileged sites and we'll see what that means in just a moment."}, {"title": "Autoimmunity.txt", "text": "So let's begin with gene mutations."}, {"title": "Autoimmunity.txt", "text": "So earlier we discussed these self antigens and the fact that our immune cells, white blood cells can distinguish between our healthy cells and non healthy cells by these self antigens."}, {"title": "Autoimmunity.txt", "text": "And we said the self antigens must be displayed on special protein complexes on the membrane of the healthy cells."}, {"title": "Autoimmunity.txt", "text": "And these protein complexes are known as major histocompatibility complexes or simply MHC."}, {"title": "Autoimmunity.txt", "text": "Now, these protein complexes must be coded by some type of section within our DNA."}, {"title": "Autoimmunity.txt", "text": "But what happens if there is a mutation within that section of our genetic code?"}, {"title": "Autoimmunity.txt", "text": "That means we no longer have the ability, this cell no longer has the ability to produce this MHC complex that is needed to actually display the self antigen."}, {"title": "Autoimmunity.txt", "text": "And in this particular case, our white blood cells."}, {"title": "Autoimmunity.txt", "text": "When they approach this otherwise healthy cell they will not notice those self antigens because the self antigens will not be able to bind onto the membrane because of the missing major histocompatibility complex."}, {"title": "Autoimmunity.txt", "text": "And therefore the wide blood cells will begin to attack these otherwise normal cells."}, {"title": "Autoimmunity.txt", "text": "So a genetic predisposition is believed to be one possible cause of autoimmunity."}, {"title": "Autoimmunity.txt", "text": "Research indicates that autoimmunity runs in the family or may run in the family and may be passed down to offspring from parent."}, {"title": "Autoimmunity.txt", "text": "Now, genetic mutations, for example in the DNA that codes for MHC membrane proteins may lead to autoimmunity as we just discussed."}, {"title": "Autoimmunity.txt", "text": "Now let's move on to factor number two that might lead to autoimmunity infections by pathogen."}, {"title": "Autoimmunity.txt", "text": "So let's suppose some type of pathogen infects our body and infects a cell."}, {"title": "Autoimmunity.txt", "text": "So here we have an infected cell."}, {"title": "Autoimmunity.txt", "text": "Now, what the infected cell will do is it will take a certain antigen that came from that pathogen and it will display it on this MHC protein complex."}, {"title": "Autoimmunity.txt", "text": "So the major histocompatibility complex as shown."}, {"title": "Autoimmunity.txt", "text": "Now, in some cases the pathogenic antigen that is displayed on our membrane that came from that pathogen might resemble some other self antigen that is found on healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "So we have two healthy cells in some place in our body."}, {"title": "Autoimmunity.txt", "text": "And notice that these green cell antigens which are normally seen by the white blood cells as normal resemble the pathogenic antigen."}, {"title": "Autoimmunity.txt", "text": "Now, when our adaptive immune system begins producing plasma cells and these plasma cells begin to produce these antibodies that can bind to this pathogenic antigen these antibodies will not only bind to the pathogenic antigen but because of the resemblance between these two antigens our antigen and self antigen."}, {"title": "Autoimmunity.txt", "text": "These antibodies will also begin to bind on the self antigens of our normal, healthy cells."}, {"title": "Autoimmunity.txt", "text": "And once that binding takes place these antibodies will essentially label these healthy cells for destruction by our wide blood cells."}, {"title": "Autoimmunity.txt", "text": "For instance, an example of such an infection is streptococcal infections that take place, for example, in our throat."}, {"title": "Autoimmunity.txt", "text": "So for instance, streptococcal infections can produce antigens that have similar epitopes compared to self antigens found in our heart."}, {"title": "Autoimmunity.txt", "text": "This can lead to a condition an autoimmune disease known as Rheumatic heart disease."}, {"title": "Autoimmunity.txt", "text": "Now, an epitope is basically a special sequence on that antigen that binds onto our antibody."}, {"title": "Autoimmunity.txt", "text": "So when an individual is infected by a pathogen that pathogen may contain or produce antigens that resemble the self antigens of the healthy cells of our body."}, {"title": "Autoimmunity.txt", "text": "When the pathogenic antigens induced the immune system to produce antibodies the antibodies not only bind on the pathogenic antigen but because of the resemblance they also bind onto our self antigens."}, {"title": "Autoimmunity.txt", "text": "In this particular case, the streptococcal infection produces antibodies that not only bind to that pathogen but also to the cells of our heart."}, {"title": "Autoimmunity.txt", "text": "So we have gene mutations as well as pathogenic infections that can lead to autoimmunity."}, {"title": "Autoimmunity.txt", "text": "Now, what about the third factor?"}, {"title": "Autoimmunity.txt", "text": "What exactly is an immunologically privileged site?"}, {"title": "Autoimmunity.txt", "text": "Well, there are certain locations in our body that do not have any lymph vessels or do not have any blood vessels."}, {"title": "Autoimmunity.txt", "text": "And what that means is why blood cells have no way of actually getting to these locations."}, {"title": "Autoimmunity.txt", "text": "And what that implies is because the wide blood cells cannot get to these immunologically privileged sites then the self antigens found on the cells of these immunologically privileged sites basically are not recognized by the white blood cells."}, {"title": "Autoimmunity.txt", "text": "So certain places of our body are out of reach to the majority of our white blood cells because they contain virtually no blood vessels or no lymph vessels."}, {"title": "Autoimmunity.txt", "text": "And two examples are our cornea in the eye as well as our brain."}, {"title": "Autoimmunity.txt", "text": "So when some type of physical damage takes place on these immunologically privileged sites for example, somebody punches us in the eye the self antigens might actually get somehow into our blood system or into our lymph system."}, {"title": "Autoimmunity.txt", "text": "And when these self antigens begin to circulate inside our blood because the white blood cells have never actually encountered these self antigens they will see them as pathogenic antigens and they will begin to produce plasma cells that produce antibodies that bind to these self antigens and destroy those self antigens."}, {"title": "Autoimmunity.txt", "text": "And what will happen is these wide blood cells and antibodies will move into the eye and will begin to destroy not only this eye that experience that physical damage but also the other eye because the other eye contains those same types of self antigens."}, {"title": "Autoimmunity.txt", "text": "So these are the three different factors that can lead to autoimmune diseases."}, {"title": "Autoimmunity.txt", "text": "So we have immutations along our DNA that codes for special types of things like the major histocompatibility complex that is involved in helping our white blood cells distinguish between healthy cells and our pathogens."}, {"title": "Autoimmunity.txt", "text": "Now, viral or some type of bacterial infections can also lead to autoimmunity scan damage to to our immunologically privileged sites."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So since when the subject let's discuss how exercise in cancer actually affects glycolysis and glucose transporters."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And let's begin by discussing exercise."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So let's suppose we begin to run and initially we're running slowly."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And what that implies is the skeleton muscle cells will be able to get that oxygen and the oxygen will go around all the different types of skeleton muscle cells."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so to basically meet the high demand of ATP molecules, these skeleton muscles will essentially begin the process of glycolysis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "They will increase the rate of glycolysis which produces ATP and Pyruvate molecules."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now Pyruvate under aerobic conditions will go into the mitochondria and the citric acid cycle will take place."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And that will not only generate many more ATP molecules, but perhaps even more importantly, it will regenerate those NAD plus coenzymes that are essentially used up in step six of glycolysis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So remember, in glycolysis, in step six we essentially use up NAD plus coenzymes."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And the process of glycolysis itself does not actually regenerate these NAD plus coenzymes."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And if we don't regenerate the NAD plus coenzymes because we have a limited supply of these coenzymes in our cells, glycolysis will essentially end very quickly."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so under aerobic conditions, we use the citric acid cycle to regenerate those NAD plus molecules."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now let's suppose we switch from a slow jog to a very fast run."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So now we're essentially sprinting."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "What will begin to happen now?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Well, what will happen is the cells will basically experience Hypoxia."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And Hypoxia is defined as the state of our cells in which we don't have enough oxygen to actually go around all the cells."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so we have oxygen deficiency."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, if the cells don't have enough oxygen, they basically cannot regenerate those energy plus molecules in the citric acid cycle."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And that's why they switch to an anaerobic cycle we call lactic acid fermentation."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And lactic acid fermentation is actually able to produce those NAD plus molecules."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And that means glycolysis can actually continue and produce those ATP molecules."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, the problem with this process is it's only a temporary solution."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Why?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Well, because as lactic acid takes place, or as lactic acid fermentation takes place, it produces lactic acid."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And the lactic acid basically dissociates into H plus ions and lactate ions."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And what that means is those H plus ions, as they build up, they will increase the acidity of that environment found within and outside of these cells."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And that will basically or that can cause damage and harm to the cells of our body."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so what happens is the buildup of the H plus ions essentially inhibits the activity of the third enzyme, phosphor Fructacion age, which essentially catalyzes the most important step, the commitment step of glycolysis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And if this enzyme is inhibited, that causes the inhibition of hexokinase and that essentially causes the process of glycolysis to stop."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so we're not going to be able to actually spring for very long for this exact reason?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Because Glycolysis stops and our skeletal muscle tissue will not be able to get the ATP molecules that they actually need to continue the process of running."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, this is especially important for those skeleton muscle cells which are found far away from the blood vessels."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Why?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Well, because the blood vessels are the conduits that bring those glucose molecules to the cells and these cells essentially uptake the glucose molecules by using these glucose transporters and the glucose is then broken down into ATP and Pyruvate via Glycolysis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So we see that lactic acid fermentation will be especially active in those muscle cells that lie far away from blood vessels."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And although lactic acid fermentation will solve the problem of the ATP production temporarily, it's not a very good solution in the long term because it actually causes the deactivation, the inhibition of the process of Glycolysis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, we know that over time, if we continue to exercise on a daily basis, we're going to basically build up endurance, we're going to be able to sprint for longer, we're going to be able to run quicker."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "The question is why?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Well, the partial answer is the following because our cells begin to respond and they respond by producing a factor known as Hypoxia inducing transcription factor which is HIF One."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, what exactly is the function of the Hypoxia inducing transcription factor?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So as the name implies, what it does is it essentially affects transcription, it essentially affects the expression of specific genes."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, what genes with this transcription factor actually affect?"}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Well, it's the genes that code for proteins and enzymes involved in actually breaking down that glucose and uptaking the glucose into the cell."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So things like glucose transporters and enzymes involved in Glycolysis are actually stimulated."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So we see that this sector stimulates the expression of genes that code for the Glycolytic enzymes as well as the glucose transporters that we find along the membrane of that cell."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So here we have the summary of the process of Glycolysis and we have ten steps."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And so we have ten different enzymes and seven of these enzymes are affected by that hypoxy inducing factor one, hypoxia inducing transcription factor one."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So Hexacinase, phosphor, fructacinase and pyruvate kinase, the three most important enzymes because they're actually involved in catalyzing."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "The Irreversible steps are essentially all stimulated as well as Algalase gap dehydrogenase where Gap stands for glycero, aldehyde three phosphate phosphaglyceride kinase as well as enolase."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So all these seven enzymes are essentially produced at a much higher rate and that means Glycolysis will be much more effective and much more efficient eventually if we continue to exercise on a daily basis."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "On top of that, we also express many more glucose transporters, specifically the Glute One and the Glute three."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And what that does is it basically ensures that these cells that do lie next to these blood vessels are actually able to uptake those glucose molecules from the lumen of the blood vessels much more quickly and much more effectively."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, what this doesn't fix is the problem that we have."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So the fact that some of these skeletal muscle cells are found far away from blood vessels."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So that problem is actually fixed by this same hisIF one molecule because it stimulates the vascular and the file growth fact, the VEGF, to basically stimulate the growth of those blood vessels so that these blood vessels can actually permeate into these hard to reach places that we find these skeleton muscles in."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So again, if we continually exercise, we have some type of anaerobic exercise that stimulates the release of the HIF One molecule, the Hypoxia inducing transcription factor one that basically stimulates the expression of the genes that code for proteins and enzymes involved in the process of glycolysis and also code for glucose transporters."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "On top of that, it also stimulates the VEGF molecule to basically go on and stimulate the growth of those blood vessels and that ultimately increases our endurance and allows us to basically carry out that process much more effectively and much more efficiently."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Now, exercise, as it turns out, is not the only process that uses this particular type of mechanism."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "Another very important and very dangerous thing that uses this mechanism is cancer."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So cancer or cancer cells are these abnormal cells that essentially grow very quickly and very rapidly."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So they divide very quickly."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And what that means is they have to have a very high supply of ATP to actually live and continue dividing and growing."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And cancer cells to basically determine that they have these blood vessels to basically ensure that they have these blood vessels next to them at all times so that they can receive the supply of glucose and then use that glucose in the highly effective process of glycolysis to produce those ATP molecules which allow them to actually grow and divide quickly."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "They also use this same mechanism."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "They release the Hypoxiainducing transcription factor that stimulates not only the expression of these enzymes and glucose transporters but also stimulates the growth of those blood vessels which can permeate into that tumor and around that tumor and that ensures that the tumor actually survives and those cancer cells actually survive and grow."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So cancer cells use the same mechanism to actually increase the rate of tumor growth."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So cancer cells depend on glucose for rapid growth and division."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "And this can be especially problematic for those cells down far away from blood vessels because again, the blood vessels actually bring those glucose molecules to those cells in the first place."}, {"title": "Effect of Exercise and Cancer on Glycolysis .txt", "text": "So therefore, to actually adapt and to be able to actually survive under these Hypoxic conditions they use the HIF One factor and the veg factor to basically help keep the high energy demand and to allow for rapid growth and rapid proliferation of those cancer of sales."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Digestive enzymes are not the only enzymes inside our body that must be activated via the process of proteolytic cleavage."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Another set of enzymes found inside our body that are also activated via the process of proteolytic cleavage are the enzymes involved in creating blood clots."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And the process by which we create blood clots is known as the blood clotting cascade."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So let's suppose we have some type of trauma inside our blood vessel, and so the endothelium of that blood vessel basically ruptures."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We have a cut in our blood vessel."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now, what begins to happen is two different processes, two different pathways begin to take place."}, {"title": "Activation of Coagulation Cascade .txt", "text": "One of these pathways is a quick process and the other pathway is a bit slower."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have the extrinsic pathway, that's the quick one, and we have the slightly slower one, that's the intrinsic pathway."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So in the extrinsic path and what happens is as a result of that cut in the blood vessel, we have a glycoprotein found in the membrane of that blood vessel that is exposed."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And that membrane glycoprotein, the integral glycoprotein, is known as tissue factor or TF."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So all the molecules in this diagram that are purple, they're simple proteins, and in this case, this is a glycoprotein."}, {"title": "Activation of Coagulation Cascade .txt", "text": "The blue molecules are Zymogen."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So basically enzymes in their inactive form, and the red molecules are the active form of enzyme."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So purple molecules are proteins, they're not enzymes."}, {"title": "Activation of Coagulation Cascade .txt", "text": "The blue molecules are the zymogen form of the enzyme and the red molecules are the active form of that enzyme."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So once we have the rupture, we have the exposure of the tissue factor."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And basically, once the TF is exposed to the blood plasma, we have this molecule that is activated."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So Zymogen Seven is activated into its active form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And then this enzyme number Seven, basically binds onto the tissue factor to form an active complex, which then goes on and basically activates Zymogen Ten into its active form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this is basically the extrinsic pathway."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And the entire purpose of this extrinsic pathway is to basically create a quick response and activate this important protein, enzyme Ten, because it's enzyme Ten, after combining with another protein Five, that basically activates prothrombin into Thrombin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And then it's Thrombin that is used to actually form the blood clots that are used to seal off that particular rupture in the blood vessel."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now, at the same exact time, to amplify, to greatly increase the number of X that we activate, we also have the other pathway, the intrinsic pathway."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so in the intrinsic pathway, what happens is as a result of the exposure of the collagen found in the extracellular environment outside that blood vessel, so basically, as a result of that cut in the blood vessel, we basically create a cascade of events."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We have these activation events taking place."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We have Xiaomogen Twelve activating to its enzyme Twelve, and enzyme Twelve activates Eleven into its active form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Eleven, then activates nine."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Into its active form, which combines with protein Eight to basically activate the same x, the same enzyme, ten xiaomogen ten, that we have in this case."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so these two pathways basically converge to form the single pathway we commonly call the final common pathway, or simply the common pathway."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so as a result of these two different pathways, we have the amplification, the increase in the number of ActiveX active ten enzymes that we form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so we ultimately amplify the number of prothrombin that we activate into Thrombon."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And once again, Thrombin then activates an enzyme known as fibrinogen into Fibrin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And it's the fibrin that ultimately forms our blood clots, which basically looks something like this."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And we'll see exactly what that is in just a moment."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we see that the blood clot cascade is actually a pretty complicated cascade."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And actually it involves even more molecules than shown on the board."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And what it also has is many different types of positive feedback loops."}, {"title": "Activation of Coagulation Cascade .txt", "text": "For instance, what Thrombin actually does is it not only activates fibrinogen into fibrin, as we'll discuss in detail in just a moment, thrombin also creates many different positive feedback loops."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So it actually moves on to many of these zymogens and it further activates those zymogens into their active form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And what these different positive feedback loops do is they further amplify the number of Thrombon that we actually form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So that what happens is as soon as we have that rupture, we form many of these blood clots very quickly and very effectively, so that none of that blood plasma actually leaks out into the extracellular environment found outside that blood vessel that we can actually seal off that rupture very quickly and very effectively."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So once again, when blood vessels experience trauma and rupture, our body uses over a dozen different enzymes and proteins to create a cascade of events that ultimately forms blood clots that are used to seal off that particular cut in that blood vessel."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And again, we have these blue molecules, these are the zymogen enzymes."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Then we have the red ones, those are the active form of that zymogen."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And the purple molecules, these molecules are basically proteins."}, {"title": "Activation of Coagulation Cascade .txt", "text": "They're not enzymes."}, {"title": "Activation of Coagulation Cascade .txt", "text": "They're proteins involved in actually assisting this cascade of events."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have the extrinsic and intrinsic pathway, which basically work together to amplify the number of protein or enzyme x that we produce, which ultimately then follows the final common pathway."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So the extrinsic and intrinsic pathways basically converge into the final common pathway that ultimately forms and activates Thrombin, which then goes on to activate Fibrinogen into fibrin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So blood clots are formed via series of zymogen activations."}, {"title": "Activation of Coagulation Cascade .txt", "text": "This cascade consists of the extrinsic and the intrinsic pathways that work together to amplify the activation of an important seren protease known as Thrombin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And Thrombin is that serum protease that is needed to actually proteolytically activate fibrinogen, which then basically forms these aggregates we call fibrin molecules, which consist of this meshlike network that is used to actually seal off that particular clot."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So that particular cut and these are known as blood clots."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now in addition, what we don't show is these many different types of positive feedback loops that we also have in this particular cascade."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And as I mentioned earlier, for instance we have Throb and that creates many different types of positive loops and so it goes back to many of these zymogens and it basically activates the zymogens even further so that ultimately we amplify the number of blood clots that we form at the end."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So in addition Throbbin creates many positive feedback loops that further amplifies the formation of the blood clots."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now as we see we have many examples of zymogen."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have this is a zymogen, this is a zymogen, these are zymogens and so forth."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now the Zymogen that we actually studied very well is this zymogen here."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this is the xiaomogen that we're going to study."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We're going to see how Thrombin a seren protease basically activates fibrinogen proteolytically into fiber and fibrin basically looks something like this."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So let's discuss the process by which Thrombin actually activates fibrinogen."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this is basically the structure of a single fibrinogen molecule."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Notice we have many different sections."}, {"title": "Activation of Coagulation Cascade .txt", "text": "In fact we have six chains."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Two of these chains consist of the purple A and lowercase alpha."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Two of these chains consist of the blue B and the beta chain, the orange one and two of these are our gamma."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So the green ones so we have these green, those are the gamma we have, these are the orange ones, those are the beta."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We have these light blue ones, those are the BS."}, {"title": "Activation of Coagulation Cascade .txt", "text": "We have these purple uppercase A's and then we have these red lowercase alphas."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so we have many different chains found in a single fibringen molecule."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this molecule is in its inactive form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "This is the zymogen form of this molecule."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now what exactly does Thrombin actually do?"}, {"title": "Activation of Coagulation Cascade .txt", "text": "So the entire goal of the extrinsic pathway and the intrinsic pathway is to basically amplify and activate this protein X, protein Ten."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And the enzyme Ten basically combines with five to go on and form Thrombin from the Xymogen form prothrombin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now Thrombin is actually a serine protease and it will activate this fibrinogen molecule pro Eelytically."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And what it does is it cleaves at four different locations."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So what are these four locations?"}, {"title": "Activation of Coagulation Cascade .txt", "text": "So right here, right here, right here and right here and this is shown in the following diagram."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So essentially the active Thrombon goes on and cleaves at these four locations."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And what that does is it completely removes these two B chains and these two A chains and these four individual chains once they are removed we call them fibrinopeptides."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so we remove these four fibrino peptides and what we form is, is a single active fibrom monomer."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this is basically what it looks like."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we remove these four chains and we form the following active fibrin monomer."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So monomer simply means we have a single fibrin molecule in its active form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So Thrombin is a serum protease that uses proteolytic activation to activate fibrinogen."}, {"title": "Activation of Coagulation Cascade .txt", "text": "This molecule and the way that it activates it is by cleaving at four different sites on that molecule and by cleaving at these four different sites we basically remove four different peptides."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And these four peptides are shown here."}, {"title": "Activation of Coagulation Cascade .txt", "text": "These are known as fibrino peptides and what we ultimately form is a fibrin monomer that consists of these three different subunits."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So alpha, B and gamma."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And we have twice the number of these."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So these are the two of our so that should actually be not a B but a beta."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So this should be a beta."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have two of these orange betas, we have two of these green gammas and then we have these red alphas and we basically removed these purple A's and those blue BS."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Now once we form the fiber and monomer, what exactly happens next?"}, {"title": "Activation of Coagulation Cascade .txt", "text": "Well by cleaving and removing these two sections, and these two sections we basically expose a very important section of that fibrin molecule."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And because we expose that section of our fibrin it activates that fibrin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so one fibrin monomer will basically go on and interact with another fibrin monomer."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And this process will continue until we basically form this very long meshlike structure and aggregate we call the fibrin or simply the blood clot."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And this is basically what it looks like."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So the proteolytic cleavage of fibrinogen exposes regions of the structure that can interact with other fibrin monomers."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Therefore fibrin monomers spontaneously aggregate to form long fibers structures called fibrin."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have the aggregation of these fibrin monomers because now these sections here are basically exposed and these sections found on the alpha unit, the red one can basically interact and fit into these holes found on the green structures, those gamma units."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so this is basically what we form."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have these red structures found on the alpha that interact with the blue hole, the green structures, the holes found in the green structures, those gamma structures."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And so we form this mesh like structure, this meshlike network of fiber monomers and we call this entire structure fiber or blood clots."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And these blood clots can basically aggregate right across that rupture and that seals off that rupture."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have the polymerization of fiber monomers that forms blood clots that can seal off the ruptures that form as a result of that trauma."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we see that not only digestive enzymes are activated via the process of proteolytic cleavage, these enzymes that are part of the blood clot cascade are also activated via the process of proteolytic cleavage."}, {"title": "Activation of Coagulation Cascade .txt", "text": "And we see that proteolytic activation is a very dominant mechanism here because essentially the majority of all these different zymogens are activated via the process of proteolytic cleavage."}, {"title": "Activation of Coagulation Cascade .txt", "text": "So we have these zymogens, the blue ones here, these Zion's here, as well as the main Zion, the Prothrombin, which basically is activates the Thrombin and then goes on to activate the fibringen into fibrin, which ultimately forms those."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Blood clots, those meshlike networks of fibrin monomers that essentially seal off and prevent the leaking of the blood plasma from within that blood vessel and into the extracellular environment found around that blood vessel."}, {"title": "Activation of Coagulation Cascade .txt", "text": "Song."}, {"title": "Triglycerides .txt", "text": "Our cells use fatty acids for a variety of different reasons."}, {"title": "Triglycerides .txt", "text": "But one important reason is to actually store energy."}, {"title": "Triglycerides .txt", "text": "So fatty acids are fuel molecules, and our cells store fatty acids in a form we call triglycerides or triathoglycerides."}, {"title": "Triglycerides .txt", "text": "And this is what a triathoglycerol actually looks like."}, {"title": "Triglycerides .txt", "text": "So we have three fatty acids, one, two, three, shown in blue, which which are basically attached onto this connecting molecule, this scaffolding molecule we call a glycerol."}, {"title": "Triglycerides .txt", "text": "And together, this is what we call triathloglycerol or triglycerides."}, {"title": "Triglycerides .txt", "text": "Now, inside our body, we essentially store potential energy in three types of macromolecules."}, {"title": "Triglycerides .txt", "text": "So we have glycogen, which is a carbohydrate, we have proteins and we have triglycerides."}, {"title": "Triglycerides .txt", "text": "And notice, based on these numbers, much more energy is actually stored in triglycerides than in proteins, glycogen or glucose."}, {"title": "Triglycerides .txt", "text": "Only about 170 kilojoules are stored in glucose and 2500 kilojoules are stored in glycogen."}, {"title": "Triglycerides .txt", "text": "In fact, these two quantities will last us about 24 hours."}, {"title": "Triglycerides .txt", "text": "So, whereas carbohydrate storages are used up after about 24 hours so a day, fat storage can actually help sustain the processes of our cells in our body for several weeks."}, {"title": "Triglycerides .txt", "text": "And that's because it makes up the predominant portion of the total energy that is readily available to the cells of our body."}, {"title": "Triglycerides .txt", "text": "So we have 420,000 kilojoules of energy that is stored in triglyceride."}, {"title": "Triglycerides .txt", "text": "So what that basically means is when we run out of these two storages of energy, our body will begin to break down the triglycerides to form the high energy ATP molecules."}, {"title": "Triglycerides .txt", "text": "And that will last us several weeks."}, {"title": "Triglycerides .txt", "text": "And after we run out of our triglyceride storages, that's when our body begins to actually break down the protein, the muscles of our body, for energy."}, {"title": "Triglycerides .txt", "text": "Now, the question is, what makes triglycerides so special?"}, {"title": "Triglycerides .txt", "text": "Why is it that our cells actually choose to store the predominant amount of energy within our fat molecules, the triglycerides, and not within, for instance, the glycogen?"}, {"title": "Triglycerides .txt", "text": "Well, these two properties make glyceroaldehyde such a highly concentrated storage of energy."}, {"title": "Triglycerides .txt", "text": "So number one is their highly reduced molecules and number two is their anhydrous."}, {"title": "Triglycerides .txt", "text": "Now, what do we mean by highly reduced?"}, {"title": "Triglycerides .txt", "text": "Well, essentially, we have removed lots of electrons from the triglycerides."}, {"title": "Triglycerides .txt", "text": "We have removed lots of electrons from the fatty acids."}, {"title": "Triglycerides .txt", "text": "And that's important because we can actually break down the triglycerides via oxidation many, many times to produce a large number of molecules that we can then use to help generate those ATP energy molecules."}, {"title": "Triglycerides .txt", "text": "The second reason is the fact that it's anhydrous."}, {"title": "Triglycerides .txt", "text": "And what that basically means is it's free of water."}, {"title": "Triglycerides .txt", "text": "We don't have hydroxyl groups attached onto the fatty acids like we do, for instance, in glycogen."}, {"title": "Triglycerides .txt", "text": "And what that means is water molecules will not tend to associate with fatty acid chains."}, {"title": "Triglycerides .txt", "text": "And what that means is the fatty acids will be a much more concentrated form of energy storage than glycogen."}, {"title": "Triglycerides .txt", "text": "In fact, for 1 gram of glycogen, there are about 2 grams of water that associates with that gram of glycogen."}, {"title": "Triglycerides .txt", "text": "Why?"}, {"title": "Triglycerides .txt", "text": "Well, because glycogen, which consists of glucose monomers, contains many hydroxyl groups and those hydroxyl groups are polar and so they attract water."}, {"title": "Triglycerides .txt", "text": "And so what that means is glycogen is not a very concentrated form of energy storage like triglycerides are."}, {"title": "Triglycerides .txt", "text": "So we see that the fact that triglycerides are highly reduced and anhydrous dismiss triglycerides, highly compact and highly concentrated stores of metabolic cell energy."}, {"title": "Triglycerides .txt", "text": "So the complete oxidation of fatty acids yields about 38 kilojoules of gram that we oxidize."}, {"title": "Triglycerides .txt", "text": "And if we compare that to oxidizing, carbohydrates or proteins, this only yields about 17 kilojoules per gram that we actually oxidized."}, {"title": "Triglycerides .txt", "text": "So we're able to actually store much more energy in these fatty acids."}, {"title": "Triglycerides .txt", "text": "And when we break down these triglycerides, we can also actually form many more high energy ATP molecules."}, {"title": "Triglycerides .txt", "text": "Now, within our body, we have different types of cells that can actually store fatty acids."}, {"title": "Triglycerides .txt", "text": "But there are two most important cells because these are the cells that store the predominant number of fat molecules."}, {"title": "Triglycerides .txt", "text": "And this includes our fat cells, also known as adipose cells, as well as muscle cells."}, {"title": "Triglycerides .txt", "text": "Now, these adipose cells, fat cells are specialized in the sense that they store most of these triglycerides within their cytoplasm."}, {"title": "Triglycerides .txt", "text": "And these triglycerides basically aggregate together to form these large fat globules inside the cytoplasm."}, {"title": "Triglycerides .txt", "text": "And these fat globules actually make up the majority of the volume of these fat cells."}, {"title": "Triglycerides .txt", "text": "Now, muscle cells can also store these triglycerides."}, {"title": "Triglycerides .txt", "text": "And muscle cells store these triglycerides predominantly if you actually use them for energy production, for ATP production."}, {"title": "Triglycerides .txt", "text": "Now, let's briefly discuss digestion, absorption and transport of triglyceride."}, {"title": "Triglycerides .txt", "text": "So the majority of the fat that we actually ingest into our body in our diet basically are these triglycerides."}, {"title": "Triglycerides .txt", "text": "Now, triglycerides, as we said earlier, are insoluble in water because they're nonpoll."}, {"title": "Triglycerides .txt", "text": "Remember, they're anhydrous."}, {"title": "Triglycerides .txt", "text": "And what that basically means is when we ingest these triglycerides into our body, when the triglycerides make their way into the lumen of our small intestine, because the lumen is an aqueous environment, it consists of water, what that means is these triglycerides will begin to aggregate together to basically form these large fat globules."}, {"title": "Triglycerides .txt", "text": "Now, our pancreas secretes special enzymes, proteolytic enzymes known as lipases."}, {"title": "Triglycerides .txt", "text": "And these lipases are actually responsible for cleaving these after bonds that exist within triassoglyceral."}, {"title": "Triglycerides .txt", "text": "So we have lipases which can act on these bonds."}, {"title": "Triglycerides .txt", "text": "And when they cleave, let's say, this bond and this bond, we basically form this monoacalcerol and two fatty acids."}, {"title": "Triglycerides .txt", "text": "And once we form these molecules, only then can these molecules actually be absorbed by the cells found in our small intestine."}, {"title": "Triglycerides .txt", "text": "So our small intestine doesn't actually or the cells of the small intestine doesn't actually absorb the triathylglycerides."}, {"title": "Triglycerides .txt", "text": "Instead, it absorbs these types of molecules, the constituents, the fatty acids and the monoastylglycerol."}, {"title": "Triglycerides .txt", "text": "Now, the problem is, because of the fact that this is a non polar molecule and our aluminum is predominantly an aqueous environment, we form these large fat globules."}, {"title": "Triglycerides .txt", "text": "And the lipase enzymes can't actually get to the majority of these triglycerides because they exist at the center of the fat globules."}, {"title": "Triglycerides .txt", "text": "And so our liver basically uses cholesterol molecules to help build bile salts."}, {"title": "Triglycerides .txt", "text": "And the bile salts are actually stored in our gallbladder and released into the small intestine."}, {"title": "Triglycerides .txt", "text": "And once the bile salts actually make their way into the small intestine, what the bile salts do is they begin to emulsify and break down those fat globules into smaller constituents."}, {"title": "Triglycerides .txt", "text": "And what these biosalts are, are they're essentially these anciopathic molecules that can associate not only with the aqueous environment in the lumens of the small intestine, but also with these fat globules."}, {"title": "Triglycerides .txt", "text": "And that's exactly what allows them to actually emulsify and break down these fat globules."}, {"title": "Triglycerides .txt", "text": "And once it breaks them down to the fat globules, then the live places can actually begin to act on the individual triathyl glycerols and that can break them down to these two constituents, which then can be absorbed by the cells found in the lumen of our small intestine."}, {"title": "Triglycerides .txt", "text": "So in the lumen, we basically have these aggregates of triathlolyceros, the fat globules, when our gold bladder basically secretes the bile salts, that helps emulsify them into triglyceride, triglycerides or triathloglycerides."}, {"title": "Triglycerides .txt", "text": "And then the triglycerides are acted, or the lipases act on these triglycerides, breaks them down into fatty acids and monoacoglycerides."}, {"title": "Triglycerides .txt", "text": "And then those are absorbed by the cells found in the small intestine."}, {"title": "Triglycerides .txt", "text": "And once these fatty acids and mono acid glycerols actually make their way to the cell into the cytoplasm, they are then used to resent as the triglycerides."}, {"title": "Triglycerides .txt", "text": "Why?"}, {"title": "Triglycerides .txt", "text": "Well, because these actually need to make their way to the target cells, the fat cells and the muscle cells."}, {"title": "Triglycerides .txt", "text": "And so triglycerides, before actually making their way into the lymph system of our body, they are placed into these carrier molecules, carrier particles known as Kylin microns."}, {"title": "Triglycerides .txt", "text": "Now, a chylam micron basically consists of proteins, cholesterol molecules, phospholipid molecules, fat soluble vitamins and other molecules."}, {"title": "Triglycerides .txt", "text": "But the predominant portion of these chylam microns are triglycerides."}, {"title": "Triglycerides .txt", "text": "In fact, triglycerides make up about 90% of the portion of the Kylim micron."}, {"title": "Triglycerides .txt", "text": "Now, once we form these Kylan microns, they then move into the limb system and then they travel into the blood plasma."}, {"title": "Triglycerides .txt", "text": "And once inside the blood plasma, these Kylim microns move onto the membranes of target cells."}, {"title": "Triglycerides .txt", "text": "So cells like adipose cells, fat cells or muscle cells."}, {"title": "Triglycerides .txt", "text": "And once they attach onto the membrane, they once again are broken down back into the fatty acid and monoacoglycerols."}, {"title": "Triglycerides .txt", "text": "And then those are absorbed by that particular cell."}, {"title": "Triglycerides .txt", "text": "And so, if we're talking about fat cells, once these are ingested into the cell, they are then converted back into triglycerides."}, {"title": "Triglycerides .txt", "text": "And then those triglycerides begin to basically aggregate together to form these large aggregate molecules known as fat globules."}, {"title": "Triglycerides .txt", "text": "So we see that the takeaway lesson from this particular lecture is the fact that these triglycerides are very, very specialized in the sense that they're very highly concentrated forms of energy storage compared to glycogen and protein."}, {"title": "Triglycerides .txt", "text": "We're able to actually store much more potential energy within the fat molecules, the triglycerides, than the proteins or carbohydrate molecules."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "In the previous several lectures, we discussed what an action potential is and we discussed what a muscle contraction is."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So basically, we said that an action potential causes a muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "We also discussed the graph of an action potential that takes place in skeletal muscles and that take place in cardiac muscles."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "Now, what we're going to emphasize is in this lecture is the fact that an action potential is not the same thing as a muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So oftentimes when students are learning about these two concepts, they forget that these two concepts are different, but they are connected."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So an action potential is an electrical signal that is usually generated in the nervous system of our body."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And that electrical signal travels to a particular muscle cell and it causes that particular muscle cell to basically contract."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So although these two concepts are related, they are not the same thing."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So let's begin by discussing the action potential and the muscle contraction of skeletal muscles."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And then let's take a look at cardiac muscles."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So to contract, or to contract any skeletal muscle, our action potential, our electrical signal, must be generated in the central nervous system of our body."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So the brain or the spinal cord."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And once we generate this action potential, it then travels through the axon of the motor neuron and eventually it ends up on the cell membrane of the skeletal muscle cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And once it ends up on the cell membrane of that skeletal muscle cell, it generates its own action potential."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And this action potential inside the cell ultimately leads to a set of processes that cause the contraction of that muscle."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So to see what we mean, let's take a look at the following graph."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So, the y axis is the membrane voltage."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So as we go up, we basically make it more positive."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "It increases in size, while the x axis is the time."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So as we go along the x axis, the time increases."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And this is given in milliseconds."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So we have 100 milliseconds, 200 milliseconds, 300 milliseconds, and so forth."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So the blue graph is the action potential as it is generated on the membrane of that skeletal muscle cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And the red graph, e, is the graph that describes our muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And notice what we see from this diagram."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "We see that the muscle contraction takes place after the action potential actually occurred."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So basically, we have the cell membrane of that skeletal muscle."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "It depolarizes once it receives the signal from the nervous system."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And by depolarizing, it basically creates this kind of peak in our action potential."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So it generates this action potential."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So we have depolarization, then we have repolarization and we have hyperpolarization."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And only then does our muscle contraction actually begin to take place."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So with respect to our red curve, with respect to the muscle contraction, this section is known as the late 10th period because this is when our action potential is actually taking place."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "When the action potential is taking place, that basically leads to the sarcoplasm reticulum of the skeleton muscle cell to open up, open its calcium channels, and release the calcium ions into the cytoplasm of that cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And that takes time."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So, as the action potential is taking place, during this latent period of the muscle contraction, we basically have the increase in concentration of the calcium inside the cytoplasm."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And once the concentration increases to a very high value, basically when this time elapses, then only then do we have our contraction actually taking place."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So, in skeletal muscle, the action potential leads to the opening of the calcium channels on the sarcoplasm reticulum."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And as the calcium ions begin to flow into our sinoplasm, that increases the concentration."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And only when the concentration is high enough, when this time actually passed, does the muscle contraction actually take place, because only then do we have enough calcium to actually bind to the actin of our thin filament and initiate that contraction between the thin filament and the thick filament inside the sarconer of our muscle cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So this is our description of the skeletal muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So this is known as the latent period."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "This is when our calcium concentration increases."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "This is known as the contraction period, and this is known as our relaxation period."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So now let's move on to our cardiac muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So remember, the action potential of skeletal muscles looks like this."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "But the action potential for cardiac muscle looks like this, because we have this extended period known as our plateau phase."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So basically, in this case, our comparison between the graph or the action potential on the membrane and the muscle contraction looks something like this, which is slightly different."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "We see that the muscle actually begins to contract before our action potential has finished."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So basically, when we're somewhere in between our plateau phase, that's when our muscle contraction basically almost reaches the highest portion."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So about when we reach this point here does our muscle contraction actually begin to take place."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And this is important in our heart, because the heart must actually create a single, forceful and steady muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So that means we need to have this extended period to actually depolarize the adjacent muscle cells inside our heart."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So in cardiac muscle cells, the action potential also causes the release of calcium ions into the cytoplasm of the cardiac myoside, the cardiac muscle cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And this ultimately causes the contraction of the sarcombers and the contraction of the muscle as a whole."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "Now, in both cases, the muscle contraction takes place sometime after the action potential has been initiated, has been generated on the cell membrane."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "In this case, the muscle contraction takes place after the action potential took place."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "In this case, we have our action potential generated."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And then somewhere in between, we have the initiation of the muscle contraction."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So this is because before the muscle contraction actually takes place, we have to increase the concentration of our calcium ions inside the cytoplasm of that cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And that means we have to wait a little time period."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "We have to wait a little for that calcium concentration to actually build up."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "And what causes that build up of calcium ions is the action potential itself."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So the action potential must take place to open up those voltage gated calcium channels so that the calcium can rush into the cytoplasm the cell."}, {"title": "Action Potential vs. Muscle Construction Graphs.txt", "text": "So that's exactly why the muscle contraction takes place after the action potential has been generated."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Inside our body and inside our cells, we have a great variety of different types of proteins."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now, let's suppose we want to study a specific type of protein."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "The question is, how do we get a hold of that protein of interest?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Because inside our body, any given protein always exists in a mixture of all different types of proteins and all different types of biological molecules."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So if we have a sample, if we have a solution of proteins, how do we know the protein that we want to study is in that mixture in the first place?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And if that protein is in that mixture, how do we purify that sample and isolate that protein among all different types of proteins found in that mixture?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Well, to answer question number one, to basically determine whether or not our protein is present in that sample, we have to conduct a protein assay."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now, what is a protein assay?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Well, a protein assay is some type of test."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "It's some type of procedure that allows us to identify the presence of that specific protein of interest based on some type of specific property or some type of specific functionality of that protein."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And we'll see exactly what that means in just a moment."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So if we obtain a positive test result to our essay, then what that means is that protein of interest is present in that sample."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "If we get a negative result, that means the protein is not present in that sample and we have to go out and get a new sample that does contain that protein."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So whenever we're conducting some type of assay there are two questions we have to ask ourselves."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Question number one is, is the protein present in our sample?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And the way that we answer the question is by measuring the protein activity or if we're dealing with an enzyme, which is usually the case, we measure the enzyme activity of that protein and we'll see exactly how that's done in just a moment."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And the second question is, if that protein is present and we can measure the enzyme activity, what is the concentration of that protein?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "What is the amount of protein found inside that sample?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So once we know the enzyme activity and the concentration of that protein that are sampled, we can then calculate the specific activity."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And during our purification process, when we're isolating that specific protein we can use the specific activity value to basically determine how pure our sample actually is."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So we conduct our protein acid and we know that the protein is found inside our sample."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And then we begin carrying out the purification processes."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And during these processes, this is when we use the specific activity value, as we'll see in just a moment."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So in the next lecture, we're going to focus on the different types of processes that we can use to basically purify our sample."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "In this lecture, we're going to focus on measuring enzyme activity."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "When we conduct our protein assay."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So to demonstrate how we can measure enzyme activity, let's actually focus on a specific type of enzyme found ourselves known as lactate dehydrogenase."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So lactate dehydrogenase is a biological catalyst that basically converts lactate into Pyruvate."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "In the process, we reduce NAD plus into NADH."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So this is the oxidized version of nicotine amide adenine dinucleotide."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And this is the reduced version of nicotine amy adenine dinucleotide."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So in our body, lactate is transformed into Pyruvate by using lactate dehydrogenase."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "In the process, we reduce nicotine amide adenine dinucleotide."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now, Pyruvate NADH are basically used to basically form ATP molecules, the energy molecules used by our cells."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now the question is, how do we measure the activity of this enzyme?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So we can measure the activity of this enzyme indirectly by measuring how much of the product is actually formed."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So our choice is we can either measure Pyruvate or we can measure NADH."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So let's focus on NADH."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "But before we actually measure NADH, we have to know some type of specific property of NADH that NAD plus doesn't actually have."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Well, one major difference between NAD plus and NADH is the fact that NADH can actually absorb a specific type of light with a specific type of wavelength."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So NADH can absorb light that has a wavelength of 340 nm."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So basically, if we have some type of solution that contains these two reactants and we place our sample of enzymes into that solution, and if this enzyme is present in that mixture, then what happens is if we begin measuring how much light is absorbed where the light has this specific wavelength value."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "If the absorbedance increases over time, then that means is we produce more of this product because this product is able to absorb more of that light."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So once again, one property of reduced nicotine amide adenine dinucleotide, NADH, is that it has the ability to absorb light of a specific wavelength, 340 nm."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Therefore, we can monitor the activity of the enzyme indirectly by examining how much light is absorbed by that solution."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And this is shown in the following diagram."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So in this diagram, these red dots are basically the NAD plus molecules, and these blue figures are the lactate."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So we take this solution and we add the enzyme sample into our solution."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And if one of the enzymes in that sample is lactate dehydrogenase, then these blue figures will be converted into these purple Pyruvate molecules."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "In the process, the red NAD plus molecules will be converted to the green NADH molecules."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And as this process is taking place, we're measuring how much light is being absorbed."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And if that is increasing, then we know that our enzyme is present because only this enzyme can catalyze this reaction."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "If nothing took place, if we measured no absorbance of light, then that means that enzyme is not present in our mixture."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So what exactly is the enzyme activity?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Well, the enzyme activity is the number of moles of products that are produced."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "In this case, the moles of NADH produced per the time that we're basically studying."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So the time can be a minute, it can be five minutes and so forth."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So the enzyme activity is the moles of product divided by the time."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now, once we know the enzyme activity, we can then calculate what our concentration of that protein is and once we know what the enzyme activity and the concentration of that protein, that enzyme, in this case lactate dehydrogenase we can then calculate the specific activity, because the specific activity is the ratio of the enzyme activity to the concentration of that protein."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So enzyme activity divided by amount of enzyme."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So what exactly is this value?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Well, the value tells us the moles of product produced over some time period per amount of enzyme found inside that particular sample."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now what this can be used for is when we actually know."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So following the assay, when we know that inside our sample we have our protein, we can then begin the purification process."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And during the purification process we can continually calculate the specific activity value."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And if the specific activity value is increasing then what that means is our sample is getting pure and pure."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And eventually if we have a sample in which we only have that enzyme, the lactate dehydrogenase, at this particular point we're going to reach a maximum value for that specific activity and this will no longer increase."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "The slope will be zero, it will be a straight line."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So we can see that this value, which is calculated by knowing this and the concentration can be used to basically determine if our sample is in fact pure."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Now, in the next lecture, we're actually going to discuss how we purify our sample by beginning with our cell."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "Because if we want to study this particular enzyme, that enzyme, it's found in the cell."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "So the first question is before we even conduct our essay, how do we actually isolate the lactate dehydrogenase from that cell?"}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "What we have there is a process known as differential centrifugation."}, {"title": "Enzyme Assay, Enzyme Activity and Specific Activity.txt", "text": "And we'll discuss exactly what that means in the next lecture."}, {"title": "Introduction to Carbohydrates .txt", "text": "In nature, we have four major classes of biomolecules and so far we discussed two of these four major classes."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we focused on proteins and euclicic acids."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now we're going to move on and discuss the third class of biomolecules we call carbohydrates, or simply sugars."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, in nature, the organism use sugars for a variety of different ways."}, {"title": "Introduction to Carbohydrates .txt", "text": "And in this lecture, we're going to briefly discuss four different different roles that sugars actually play."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, there are many different types of sugar molecules, but the major sugar molecule that we use inside our body is glucose."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, where does glucose, and then generally, where do sugar molecules actually come from?"}, {"title": "Introduction to Carbohydrates .txt", "text": "Well, sugar molecules are produced by plants."}, {"title": "Introduction to Carbohydrates .txt", "text": "And plants basically capture that energy that is stored in light that comes from the sun and it transforms that energy into the chemical bonds within the sugar molecule."}, {"title": "Introduction to Carbohydrates .txt", "text": "So what happens is in the sun we have all these different nuclear reactions which take place and produce they release energy."}, {"title": "Introduction to Carbohydrates .txt", "text": "And that energy is then stored in electromagnetic waves which propagate through space."}, {"title": "Introduction to Carbohydrates .txt", "text": "And some of this electromagnetic radiation eventually makes its way to the Earth and to the plants on Earth."}, {"title": "Introduction to Carbohydrates .txt", "text": "And so what these plants do is they take the carbon dioxide in the atmosphere, that's the carbon source."}, {"title": "Introduction to Carbohydrates .txt", "text": "And then they take the water found in the soil and they use the energy stored in light."}, {"title": "Introduction to Carbohydrates .txt", "text": "They combine these two reactants to produce these products."}, {"title": "Introduction to Carbohydrates .txt", "text": "So the sugar molecule, as well as oxygen that we then breathe and use on the electron transport chain in the process of aerobic cellular respiration."}, {"title": "Introduction to Carbohydrates .txt", "text": "So essentially, when we ingest these carbohydrates, which are produced by plants, for instance, when we ingest bread products or pasta products and so forth, we essentially ingest carbohydrates which are derived and produced by plants."}, {"title": "Introduction to Carbohydrates .txt", "text": "And so once we ingest these carbohydrates, our body breaks down these carbohydrates into their individual monomer sugars."}, {"title": "Introduction to Carbohydrates .txt", "text": "And if this monomer sugar is not a glucose molecule, we typically transform that into a glucose molecule because it's the glucose that we use in the process of glycolysis and aerobic cellular respiration to basically produce the high energy ATP molecules that we use inside our body."}, {"title": "Introduction to Carbohydrates .txt", "text": "And if we already have too many of these ATP molecules, if we have enough, the glucose can be stored in the form of glycogen for later use."}, {"title": "Introduction to Carbohydrates .txt", "text": "So ultimately, what happens is that energy that is produced in the nuclear reactions is basically stored in these chemical bonds within these sugar molecules."}, {"title": "Introduction to Carbohydrates .txt", "text": "And when we ingest these sugar molecules, we essentially take that same energy that came from the sun and store it in the ATP molecules and use those ATP molecules to carry out all the different types of processes that take place inside our cells."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we see that the first role that sugars play is basically energy storage and fuel source."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we use these sugars to basically carry out different types of reactions by using these ATP molecules that ultimately came from the glycolysis process, the breakdown of glucose."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, the second role that sugars play is actually being present in nucleic acids such as RNA and DNA molecule."}, {"title": "Introduction to Carbohydrates .txt", "text": "In fact, ATP adenosine triphosphate itself contains a ribose sugar."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we have these RNA DNA molecules, which are nucleic acids."}, {"title": "Introduction to Carbohydrates .txt", "text": "And what that means is they basically play the role of storing genetic information and passing genetic information down from one individual to the offspring."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, these RNA and DNA molecules basically contain sugar components."}, {"title": "Introduction to Carbohydrates .txt", "text": "In the case of RNA, we have the ribosugh."}, {"title": "Introduction to Carbohydrates .txt", "text": "In the case of DNA we have the deoxyribose sugar."}, {"title": "Introduction to Carbohydrates .txt", "text": "And deoxy simply means on the second carbon, we don't have a hydroxyl group."}, {"title": "Introduction to Carbohydrates .txt", "text": "So if we take a look at the following molecule so if this base is, let's say, adenine, then this molecule would be that ATP molecule that we spoke of earlier."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we have the triphosphate group, we have that nitrogenous base and these two groups are essentially connected to one another as a result of this sugar."}, {"title": "Introduction to Carbohydrates .txt", "text": "So this is a ribosugar that bridges these two molecules."}, {"title": "Introduction to Carbohydrates .txt", "text": "And every single RNA molecule basically contains this group here, this unit."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, the next function of sugars, the next role that sugar is actually playing organisms and this includes inside our own bodies is using sugars to basically modify lipids and proteins."}, {"title": "Introduction to Carbohydrates .txt", "text": "And we'll discuss this in much more detail in the next several lectures."}, {"title": "Introduction to Carbohydrates .txt", "text": "So basically we can diversify the capabilities and the functionality of proteins and lipids by basically attaching sugar components onto these macromolecules."}, {"title": "Introduction to Carbohydrates .txt", "text": "So by combining sugars and proteins and sugars and lipids and so forth, we can basically increase the capabilities of these molecules."}, {"title": "Introduction to Carbohydrates .txt", "text": "For instance, we already spoke about an important glycoprotein when we discussed the coagulation cascade."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we discussed the tissue factor."}, {"title": "Introduction to Carbohydrates .txt", "text": "So we said that the tissue factor is basically a glycoprotein."}, {"title": "Introduction to Carbohydrates .txt", "text": "So this is shown in green and this is, let's say, the cell membrane of some endothelial cell found in the blood vessel."}, {"title": "Introduction to Carbohydrates .txt", "text": "So what this tissue factor does is it's actually a glycoprotein that basically interacts with other molecules, namely factor seven, to form a dimer complex."}, {"title": "Introduction to Carbohydrates .txt", "text": "And this glycoprotein, this tissue fact, is actually used to initiate the blood clot and cascade, the formation of the blood clot."}, {"title": "Introduction to Carbohydrates .txt", "text": "More specifically, it initiates the extrinsic pathway of that coagulation cascade."}, {"title": "Introduction to Carbohydrates .txt", "text": "And we have many, many, many different types of examples of ways in which we can actually modify proteins as well as lipids and thereby diversify their function, thereby increase their capabilities and functionality."}, {"title": "Introduction to Carbohydrates .txt", "text": "Now, the final thing I'd like to mention about sugar molecules is that in plants as well as in bacterial cells, sugars actually make up."}, {"title": "Introduction to Carbohydrates .txt", "text": "The components, are components of cell walls."}, {"title": "Introduction to Carbohydrates .txt", "text": "And cell walls are very important, important because they serve very, very important functions."}, {"title": "Introduction to Carbohydrates .txt", "text": "So they basically protect the sound."}, {"title": "Introduction to Carbohydrates .txt", "text": "They also give the cell structure."}, {"title": "Introduction to Carbohydrates .txt", "text": "They act in communication and also in transport."}, {"title": "Introduction to Carbohydrates .txt", "text": "And we'll discuss this in much more detail when we'll focus on plants in the process of photosynthesis."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, when we discussed the oxygen binding curve for hemoglobin, we actually didn't mention a very important fact about that curve."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So the oxygen binding curve for hemoglobin that we spoke about previously was actually the curve for hemoglobin when it is present inside red blood cells."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So why is that important?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Well, it turns out that if we isolate and peer purify the hemoglobin and then we examine the oxygen binding curve for pure hemoglobin, there will be a tremendous difference between the binding curve for the pure hemoglobin and the binding curve for that hemoglobin found inside red blood cells."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, the oxygen binding curve of hemoglobin inside red blood cells differs considerably from the pure hemoglobin curve, as we can see from the following graph."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, in the graph, the y axis is the fractional saturation of hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "It ranges from zero to one."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And the x axis is the concentration of oxygen in the surroundings given to us in partial pressures."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So basically, we have millimeters of mercury, and the range is from zero to about 100."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, the black curve describes the oxygen binding curve for pure hemoglobin when we essentially isolate it out of the red blood cells, while the blue curve describes the binding curve of hemoglobin as it is present inside red blood cells."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And notice that the blue curve is shifted to the right with respect to that black curve."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "The question is why?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So let's talk about how much of the hemoglobin actually unloads when it goes from the lungs to the exercising tissue in two cases, to see the difference between these two cases."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So let's begin inside the lungs."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, inside the lungs, the partial pressure is about 100 mercury, and so the x value is 100."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And if we find the corresponding y value on these two curves, we get the same value of about zero point 98."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So inside the lungs, 98% of these two types of hemoglobin, the pure hemoglobin and the hemoglobin found in red blood cells, 98% of that hemoglobin is saturated with oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, what happens when we go down to our exercising tissues where the partial pressure drops to about 20 mercury?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, here is where we see that tremendous difference."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "If we find the corresponding y value for the black curve, the pure hemoglobin, the value is around 0.9."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that means 90% of the hemoglobin, the pure hemoglobin will be saturated with oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And so that means a difference of 98 -90."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Or 8% of that oxygen will be unloaded to the tissues."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, if we compare to the hemoglobin as it is present inside red blood cells."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "The corresponding y value is around zero point 32 so that means 98 -32 gives us 66%."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So 66% of that hemoglobin will unload and release the oxygen into the cells found inside that exercising tissue."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this is a big difference between the pure hemoglobin case."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So what that means for some reason, the hemoglobin, when it's present inside red blood cells, the affinity for oxygen decreases."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that is precisely what allows the hemoglobin to unload so much oxygen to the tissues, to the tissues and cells of that exercising area."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So once again, in red blood cells, hemoglobin is able to unload 66% of the oxygen when going from the lungs to the exercising tissue."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "While if we compare the pure hemoglobin, we see that pure hemoglobin only unloads 8% of that oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "The question is, why is there this difference?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "What accounts for this difference in the first place inside the red blood cells?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Why is it that inside the red blood cells, the affinity of hemoglobin for oxygen is so much lower than in the pure hemoglobin case?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Well, the answer lies in this molecule here."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "The molecule is known as two three BPG or two three biphosphoglycerate."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "This is a naturally occurring molecule that is found inside our cells."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "It is an intermediate in the process of glycolysis."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, notice one thing about this two, three BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "It contains many negative charges."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So we have 12345 negative charges."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that will be very important in just a moment."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So it turns out that it's the 23 BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "That creates this rightward shift in the oxygen binding curve."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "This molecule is precisely why this curve shifts to this blue curve as shown in the following diagram."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So this molecule is an allosteric effector of hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "What that means is it binds onto a location that is different than where oxygen binds to, and it creates some type of change in the function in the affinity of that hemoglobin molecule for oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, before we discuss where that molecule actually binds to, let's recall one important fact about deoxyhemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, deoxy hemoglobin exists in the T state, in the ten state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And one fact about the T state is it's very unstable."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So in the absence of the two three BPG molecule, there is a pocket, there is this space that is formed at the center of the deoxy hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And inside that space, there is electrostatic repulsion that takes place between the amino acids on the beta one and the beta two subunits."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So this is the hemoglobin, this is the beta one, beta two, and these are the alpha subunits."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And if we examine at the corners of these two beta subunits, there are these residues that carry positive charges."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And these positive charges basically repel one another."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this destabilizes the T state of that deoxy hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, what does this actually mean physiologically?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Well, if the T state is destabilized, there's only one thing that the deoxy hemoglobin molecule can do."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So if this is very unstable, then that will shift the equilibrium towards the product side, where the product side is the Rstate."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And the Rstate is the structure of that hemoglobin that is very likely to actually bind oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So what that means physiologically, in the absence of the two three BPG molecule as a result of the electrostatic repulsion that takes place inside the center of that hemoglobin that drives the hemoglobin towards the R state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And it's the R state that becomes very likely to bind oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that's exactly why the pure hemoglobin has a very high affinity for oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that's exactly why the black curve is to the left with respect to that blue curve."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, what happens in the presence of two, three BPG?"}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Well, two, three BPG is a relatively small molecule that contains many negative charges."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this molecule is small enough to actually fit inside that positively charged pocket found at the center of the deoxy hemoglobin in the T state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And by going into that pocket, the negative charges of this two three PPG can interact with the positive charges of the residues found on the beta one and the beta two subunits."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And if we zoom in on this interaction so this black molecule is the two, three BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "If we zoom in on this molecule, this is what we get."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So this is histidine 141 Lysine 82 and histidine two."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "These are the three residues that contain the positive charges found on the beta one subunits located at the center of the hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And these are the three residues, HistoGene two Lysine 82 and HistoGene 143 that are found on the beta two subunits."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So the number basically describes its position along that sequence, along the polypeptide sequence."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So all these six residues contain positive charges and those positive charges form these electrostatic interactions with the negative charges on the two three BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this decreases the overall net charge in this area and that stabilizes the deoxy hemoglobin and it stabilizes the T state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And by stabilizing the T state, that drives the equilibrium back towards the T state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And now the T state can exist by itself without binding to that oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And what that means is that basically shifts the entire curve toward the right side and then decreases the affinity of the hemoglobin for oxygen because now the T state can exist because it is more stable than in the absence of that 23 BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So once again, the T state of hemoglobin in its pure form is highly unstable because it contains a pocket with positive charges at the center of that tetrimer where the positive charges come from these six amino acids found on these opposing beta subunits."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So this instability pushes the equilibrium towards the R state, towards the right side."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And physiologically, what this means is pure hemoglobin, in the absence of two three BPG would bind oxygen way too strongly with a very high affinity because it would exist predominantly in the R state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that's precisely why the curve is found towards the left side with respect to the blue curve because as we shift the curve towards the left side, that increases the affinity of that molecule hemoglobin towards oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, in our red blood cells, we have this molecule, 23 BPG that can bind into that pocket because it's a small enough, and b contains the negative charges."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And by interacting with the positive charges, we decrease the overall charge in that center area, and that stabilizes the t state of the deoxy hemoglobin and drives the equilibrium back towards the t state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that decreases the affinity of the hemoglobin for oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that shifts the entire curve towards the right side."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So from this black curve to this blue curve."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And so we see that inside our red blood cells, we have this allosteric effector, the two three BPG molecule that binds onto a location other than the heme group."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So it binds towards the center."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And the entire purpose of it is to basically stabilize the t state, make the t state more stable and lower in energy, and that drives the curve towards the right side, decreasing the affinity of hemoglobin for oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And what that means mathematically is much more of that hemoglobin will actually be able to unload and release the oxygen towards to the cells of our exercising tissue, as seen in the following calculation."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So 66% compared to only 8% in the case of pure hemoglobin when we don't have the two three BPG."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So, in the presence of two, three BPG, the two three BPG binds to the pocket, and it stabilizes the t state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "Now, when we increase the concentration of oxygen, for example, when the deoxy hemoglobin in the t state with a two, three BPG returns from those tissues back to the lungs, the concentration of oxygen increases."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And as the concentration of oxygen increases, the oxygen begins to slowly bind onto the heme groups of these different polypeptides in the hemoglobin molecule."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And as oxygen begins to bind to the heme groups, that basically creates a conformational change."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So these two dimers basically begin to rotate 50 degree, 15 degrees with respect to one another."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that conformational change basically collapses this inner pocket, and it squeezes the two three BPG molecule right out of the center of the hemoglobin."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And once the two three BPG is squeezed out of that pocket, that shifts our equilibrium back to the right side, the r state."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that makes the heme groups much more likely to bind oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that's a very important idea, because when the deoxyhemoglobin returns back to the lungs, we want that hemoglobin to be able to easily bind to oxygen with a high affinity."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And that's exactly what we see actually happen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "So when oxygen begins to bind to the heme groups in the lungs, the center pocket collapses, and that squeezes the two three BPG allosteric effector out of that pocket."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this drives the hemoglobin into the relaxed state, and it makes it much more likely to actually bind that oxygen."}, {"title": "Effect of 2,3-BPG on Hemoglobin .txt", "text": "And this cycle basically repeats itself as the hemoglobin moves from the lungs to the tissues and back to the lungs."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "Episode phosphate molecules."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "So we see that in either case, we can basically form this glucose molecule from the Pyruvate."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "Oh, and by the way, we actually need to use two pyruvate molecules to actually form a single glucose."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "So technically, all these steps up until this step here basically requires using two different molecules."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "So we have two molecules here, two molecules here, two molecules here, two molecules here, as well as two molecules here."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "And then these two molecules combine to basically form this sugar molecule and so forth."}, {"title": "Gluconeogenesis Steps 3-10 Part II .txt", "text": "So all these steps are basically multiplied by two."}, {"title": "Overview of Glycolysis Part II .txt", "text": "We have two pyruvates, two ATPs, two Nadhs, two H pluses, and two H, two zeros."}, {"title": "Overview of Glycolysis Part II .txt", "text": "And the amount of energy that is released is negative 96.2 kilojoules per mole."}, {"title": "Overview of Glycolysis Part II .txt", "text": "So we see that when glucose is broken down in the process of glycolysis, this is actually an overall exergonic reaction under physiological conditions, conditions that exist inside ourselves."}, {"title": "Glucagon Signal Pathway .txt", "text": "Inside our body, we have two types of cells which are predominantly responsible for actually storing and breaking down glycogen."}, {"title": "Glucagon Signal Pathway .txt", "text": "So these cells are the skeleton muscle cells and the liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, skeleton muscle cells are responsible for creating and generating voluntary motion."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so when skeleton muscle cells break down glycogen into glucose, they use that glucose to basically produce, reduce the ATP molecules, the energy molecules needed to create voluntary motion."}, {"title": "Glucagon Signal Pathway .txt", "text": "On the other hand, liver cells are responsible for actually maintaining and regulating the proper blood glucose levels in our body."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so when liver cells actually break down glycogen into glucose, they can release that glucose into the blood and that helps our body maintain the correct level of glucose in our cardiovascular system."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, what I'd like to discuss in this lecture is what ultimately is the signal that initiates the breakdown of glycogen in our liver cells as well as in our skeletal muscle cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "So let's begin by focusing on liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "So there are two important types of hormones that play a role in actually signaling the breakdown of glycogen in liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "And these hormones are glucagon and epinephrine."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, glucagon plays a much greater role in liver cells than epinephrine, but in skeleton muscle cells, it's epinephrine that actually initiates the breakdown of glycogen."}, {"title": "Glucagon Signal Pathway .txt", "text": "So let's imagine that our body is undergoing starvation."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so what that means is in our blood plasma we have a relatively low concentration of glucose."}, {"title": "Glucagon Signal Pathway .txt", "text": "And to basically increase the level of glucose, the liver cells have to begin breaking down the glycogen into glucose and release that glucose into the blood plasma."}, {"title": "Glucagon Signal Pathway .txt", "text": "So how exactly does this process actually take place?"}, {"title": "Glucagon Signal Pathway .txt", "text": "This is what we call the glucagon signal transduction pathway."}, {"title": "Glucagon Signal Pathway .txt", "text": "So let's take a look at the following diagram which basically outlines this complicated process."}, {"title": "Glucagon Signal Pathway .txt", "text": "So, we begin in the alpha cells of the pancreas."}, {"title": "Glucagon Signal Pathway .txt", "text": "The alpha cells of the pancreas basically produce this peptide hormone we call glucagon."}, {"title": "Glucagon Signal Pathway .txt", "text": "And once glucagon makes its way into the bloodstream, it then travels onto the membrane of liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "On the membrane of liver cells is a receptor, a seven transmembrane receptor, seven TM receptor known as the glucagon receptor."}, {"title": "Glucagon Signal Pathway .txt", "text": "And glucagon binds onto this side of this glucagon receptor, shown in orange."}, {"title": "Glucagon Signal Pathway .txt", "text": "And once the binding takes place, that initiates a process on the other side of this seven TM receptor protein."}, {"title": "Glucagon Signal Pathway .txt", "text": "So on the other side, we have this g protein that contains a GDP bound to it."}, {"title": "Glucagon Signal Pathway .txt", "text": "When the GDP is bound to it, it is inactive."}, {"title": "Glucagon Signal Pathway .txt", "text": "But upon the binding of glucagon, the GDP is expelled and a GTP enters this pocket."}, {"title": "Glucagon Signal Pathway .txt", "text": "And once the GTP is bound, it activates the g protein, causes it to actually dissociate from this orange glucagon receptor."}, {"title": "Glucagon Signal Pathway .txt", "text": "And once this g protein dissociates, it moves on onto adenylate cyclist."}, {"title": "Glucagon Signal Pathway .txt", "text": "And what it does is it stimulates adenylit cyclase and enzyme to basically begin the catalyzation the transformation of ATP molecules into cyclic amp molecules."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, cyclic Amp molecules are secondary messengers whereas the Glucagon hormones are primary messengers in this Glucagon signal transduction pathway."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so what cyclic Amp molecules do is they move on and bind onto the inactive version of PKA."}, {"title": "Glucagon Signal Pathway .txt", "text": "So blue means inactive and red means active."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, when cyclic and P bind onto the regulatory sides of PKA, they cause the dissociation of those regulatory sites from the catalytic sites from those catalytic subunits and that activates those catalytic subunits."}, {"title": "Glucagon Signal Pathway .txt", "text": "So once this process takes place, that activates PKA protein kinase A."}, {"title": "Glucagon Signal Pathway .txt", "text": "And remember that protein kinase A is capable of actually phosphorylating and thereby activating many other target proteins."}, {"title": "Glucagon Signal Pathway .txt", "text": "And in this particular stigma transduction pathway, the target protein is phosphorolase kinase."}, {"title": "Glucagon Signal Pathway .txt", "text": "So remember from a previous discussion that phosphorase kinase must be activated by two different factors."}, {"title": "Glucagon Signal Pathway .txt", "text": "One is phosphorylation and the other one is calcium."}, {"title": "Glucagon Signal Pathway .txt", "text": "So let's focus on the phosphorylation for just a moment."}, {"title": "Glucagon Signal Pathway .txt", "text": "So we have PKA, which is activated by the binding of cyclic Amp, goes on and activates phosphorylase kinase."}, {"title": "Glucagon Signal Pathway .txt", "text": "And what phosphorase kinase does is it goes on and activates Glycogen phosphorase."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, Glycogen phosphorase is that enzyme that initiates step one of Glycogen breakdown."}, {"title": "Glucagon Signal Pathway .txt", "text": "So ultimately, we see that the signal, the primary messenger molecule that initiates Glycogen breakdown in the liver cells is in fact leukagon."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, what about epinephrine?"}, {"title": "Glucagon Signal Pathway .txt", "text": "Epinephrine also actually plays an important role, but a smaller role in liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "Epinephrine binds to beta adrenergic receptors as well as alpha adrenergic receptors."}, {"title": "Glucagon Signal Pathway .txt", "text": "When it binds to the beta adrenergic receptor it basically follows a similar pathway to the pathway outlined here."}, {"title": "Glucagon Signal Pathway .txt", "text": "But when epinephrine, which is, by the way, a tyrosine based hormone, when epinephrine actually binds onto the alpha adrenergic receptor, what it does is initiates the phosphonosatide cascade."}, {"title": "Glucagon Signal Pathway .txt", "text": "And what that cascade actually does is it basically stimulates the release of calcium ions that are stored inside the lumen of the endoplasm reticulum of these liver cells."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so we have the influx of these calcium ions into the cytoplasm of the liver cell."}, {"title": "Glucagon Signal Pathway .txt", "text": "And remember from our discussion on phosphoralase kinase that the calcium ions actually bind onto the delta units of phosphorace kinase."}, {"title": "Glucagon Signal Pathway .txt", "text": "And so on top of phosphorelating the phosphorylase kinase to actually activate this enzyme the calcium ions also have to bind to the phosphorylase kinase."}, {"title": "Glucagon Signal Pathway .txt", "text": "So we see that Glucagon actually stimulates PKA to phosphorylate the phosphorylase kinase while the epinephrine helps release the calcium ions which are also needed to actually activate the phosphorylase kinase."}, {"title": "Glucagon Signal Pathway .txt", "text": "And together this causes the activation of the phosphoralase kinase that is needed to ultimately begin the process of Glycogen breakdown inside the liver cells of our body."}, {"title": "Glucagon Signal Pathway .txt", "text": "Now, for skeletal muscle cells, it's epinephrine that basically stimulates the breakdown of Glycogen and the ultimate generation duration of ATP from the glucose molecules."}, {"title": "Glucagon Signal Pathway .txt", "text": "And this allows the skeleton muscles to actually generate voluntary motion."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So let's suppose you have a double stranded DNA molecule and in that double strand DNA molecule is a gene that you want to study."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now, before you can study that gene, you have to make many copies of that gene so that once you have many copies at your disposal, you can carry out a variety of different types of experiments with that particular gene of interest."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now, if you don't know what the sequence of nucleotides in that gene is, but if you do know where that gene is found, if you do know what the flanking sequence is, what the sequence surrounding that gene is, how exactly can you make many copies of just that gene found inside that DNA molecule?"}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Well, in biochemistry there's a process known as the polymerase chain reaction or PCR that allows us to do just that."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So the polymerase chain reaction is a very effective method by which we can actually amplify make many copies of a single DNA segment."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And it's very useful because it allows us a very quick way to make millions or even billions of copies of a single DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "It also allows us to make copies of a gene or DNA segment that is relatively long, about 10,000 nucleotides in length."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And it also allows us to make the copies without actually knowing what the sequence of nucleotides in that gene is, as long as we know what the flanking sequence is."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we have to know what the flanking sequence is because we have to build DNA primers for the DNA replication process, as we'll see in just a moment."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So what do we mean by a flanking sequence?"}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So let's take a look at the following double transit DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Let's suppose you're given this molecule and this is the gene that we actually want to amplify."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So it begins here and ends here."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now we don't know what the sequence of nucleotides in this target sequences, the target sequence of the sequence we want to amplify, but we do know where that DNA segment is found."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We do know what the flanking sequences, the flanking sequence are."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Basically these sequences found on both sides of that gene of interest."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So the flanking sequence is a segment of DNA that we do not want to replicate, but that we know the sequence of nucleotides because we have to know what the sequence within these sections here, because we're going to build the DNA primers that can essentially hybridize with those flanking regions."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Because the DNA polymerase that is used in the polymerase chain reaction needs the primus to actually synthesize the DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So PCR requires that we know the flanking sequence of nucleotides surrounding that target DNA segment."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We need this sequence to produce DNA primers needed for replication."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now let's actually take a look at the process of polymerase chain reaction."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We can essentially break this process down into three steps or three stages."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we have step number one, step number two and step number three."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And these three steps basically compose one cycle of the polymerase chain reaction."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And as we'll see at the end, we can conduct many cycles to produce as many DNA copies as we want to."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So let's begin with step number one."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now the entire point in this reaction is to basically use a special type of DNA polymerase molecule to basically replicate our DNA."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now, to begin the process of replication, the double stranded DNA molecule must actually separate."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we have to break the hydrogen bonds."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now what's one way to break the hydrogen bonds between the bases?"}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Well, one way to break the bonds is to heat our solution that contains that double stranded DNA."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So if we heat our solution with that double stranded DNA molecule of interest to a temperature of 95 degrees Celsius for about 15 seconds, then that's just enough time to basically break all those bonds between our two strands and separate our two strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now the next process is we want to actually anneal those DNA primers that we form."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So in a laboratory, because we know what the flanking sequence is, we can basically build the DNA primers that will bind onto the three end of our DNA strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So that is shown in the following diagram."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So step two is annealing of the DNA primers, the heated DNA solution."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now it's cooled to a temperature of about 54 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And that's just the right temperature for those DNA primers to actually anneal and hybridize with the three ends of those DNA strands that are now single strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And notice these two strands of DNA will not form the hydrogen bonds because now we're going to have many of these DNA primers floating around and in between our two DNA strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So the lower temperature will allow for the hybridization between the primers and the DNA and one DNA primer anneals to the three end of each one of these DNA strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "The reason we have the Anneal at the three end?"}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Because the DNA polymerase, as we'll see in step three, always reads that DNA molecule beginning at the three end and moving towards the five end because it synthesizes from the five end to the three N. So this green primer is the primer that Anneales to the three end of this trend."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And the blue DNA primer is the primer that anneales to the three end of the other DNA molecule as shown in that diagram."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And finally in step three, what we have to do is we have to use a special DNA polymerase that is heat resistant and we can obtain this DNA polymerase from prokaryotic cells that live in hot springs."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Because in hot springs the temperature is high, it's about in the."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So if we use this special heat resistant DNA polymerase, we place it into our mixture and we bump the temperature back up to about 72 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "This is the optimal temperature for this special heat resistant thermosilic DNA polymerase that is called TAC DNA."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now, what the polymerase does, like any polymerase, it uses those primers, it begins at the primers and it moves from the five to the three end to basically synthesize and replicate that DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So that is shown in the following diagram."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So, once again, step three."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "The cooled solution at 54 degrees Celsius is heated to a temperature of 72 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "This is the optimal temperature for the thermophilic."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So thermo is heat filling, is loving, so, heat loving DNA polymerase called taq."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So, tag DNA polymerase."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "The polymerase begins DNA synthesis on the primers and elongates in a five to three direction on both ends."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And this is shown in the following diagram."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So the DNA polymerase attaches onto this five prime primer and it moves along this direction, synthesizing the complementary strand to this DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And likewise, another DNA polymerase attaches onto this side and moves in this direction, synthesizing the complementary strand to this DNA strand here."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And so after one cycle of PCR, we have two copies of that DNA molecule."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Now, the great thing about PCR is we don't have to do anything else to repeat the cycle."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "All we have to do is simply change the temperature back to 95 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So once we complete cycle one, we're essentially in this stage."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And the next step is if we want to repeat the cycle again, we increase the temperature back to 95 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "What will happen is these two strands."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So now we have two strands, we have two double helices of these DNA molecules."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We increase the temperature so that they essentially separate."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Then we drop the temperature to 54 degrees Celsius."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We still have the primers in solution."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "Those primers will essentially hybridize with the proper ends, and then we increase the temperature back to 72 degrees Celsius so that that's the temperature where DNA polymerase can begin its replication process."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And once again, after cycle two completes, we essentially have four copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we begin with a single copy."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "After one cycle, we have two copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "After two cycles, we have four copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "After three cycles, we're going to have eight copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And the general equation that describes how many copies of DNA we can theoretically produce after N number of cycles is two to the power of N. So this gives us the number of copies of DNA after N number of cycles."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And we can see after 20 cycles, we're going to have over 1 million copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "After 30 cycles, we're going to have over 1 billion of these copies."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And we begin with a single DNA molecule whose DNA sequence we did not actually know."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And that's the great thing about the polymerase chain reaction."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we can make many, many copies over a very short period of time and we don't even have to know what that sequence of that DNA segment is."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And we can carry the entire process out in a single beaker."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "We don't have to even put anything in."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "All we have to do is we have to initially combine all these ingredients."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "So we basically need the primers, we need that DNA strand, we need the four types of deoxy nucleotide, five prime, triphosphates, and we need the DNA polymerase."}, {"title": "Amplifying DNA with Polymerase Chain Reaction .txt", "text": "And as long as we keep on changing the temperature back and forth, we're going to repeat the cycle many, many times and eventually form many copies of that DNA segment that we want to study."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Aspertain transcarbomoulase or simply atcase is an allosteric enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And like most allosteric enzymes, it displays Cooperativity."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So in this lecture, I'd like to focus on the cooperative nature of atcase and then discuss two allosteric effectors to this enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So we're going to focus on citadine triphosphate CTP and adenosine triphosphate state ATP."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, let's begin by discussing the quotinary structure of this enzyme and how its coronary structure actually affects the likelihood that the substrate will bind onto the active signs."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, when the concentration of the substrate molecule is low inside the cell, the entire coordinary structure of the enzyme exists predominantly in the T state, the ten state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So what do we mean by the ten states?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Well, in the ten state of this enzyme, the two catalytic primers and these are the orange structures in this diagram are basically found in close proximity with respect to one another, and they create a very compact and very constrained structure."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so what that means is the active sites in these catalytic triumphs are going to have a low affinity for that substrate molecules."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so at low substrate concentrations, the substrate molecules are not going to be likely to be bound to those active sites."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so that will create a low catalytic rate, a low catalytic activity."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, when we begin to increase the substrate concentration inside the cells of our body, the substrate molecules will begin to bind onto the active side."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So let's suppose one substrate molecule binds onto one of the active sides of this enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And once the binding takes place, what that does is it shifts the equilibrium of this entire equation slightly to the right side, from the T state to that r state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so as we increase the concentration of the substrate, even more of those substrate molecules begin to bind onto the active sites."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And eventually, that shifts the entire curve to the right side."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And at a very high substrate concentration inside our cells, the entire curve will be shifted."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "This way, this error will be very, very small."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so this enzyme will exist predominantly in the r state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, what do we mean by the r state?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Well, the r state is also known as the relaxed state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And that's because these two orange catalytic trimers have now moved far apart."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "They rotated, and so they created this relaxed structure."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And in this structure, the active sites have a high affinity for the substrate molecule."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so what that means is the rate of activity of this enzyme when the enzyme's quadinary structure is in the r state will be much higher than compared to that T state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And that's exactly why, at high concentration of substrate, the activity of that enzyme will be high because it exists in that r state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So what's actually taking place is upon the binding of the substrate molecules into the active sides."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "The active sides found on the different catalytic trimers basically begin to interact with one another and they cooperate with one another."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And that's exactly what shifts entire curve from one side of the equation to the other side of the equation."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And this is what we know as the cooperative behavior of Alphaic enzymes such as aspartate transcarbomolase."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And this mechanism can be described by using the concerted model which we actually use to describe the behavior of hemoglobin molecules."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So based on this model, the activity of this aspartate transcarbomolase is all or nothing."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "It either exists in the T state in which this enzyme is inactive or it exists in the r state in which the enzyme is fully active."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And it's the concentration of the substrate inside the cell that ultimately determines where the equilibrium will actually lie."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And a high substrate concentration, the enzymes coronary structure will exist in the r state while at low substrate concentrations the enzymes coronary structure will exist in the T state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, if we take a look at the following diagram, we have three different curves."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So the y axis is the rate of product formation for this enzyme catalyzed reaction and the x axis is the concentration of that substrate molecule."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, at low concentration of the substrate molecule, we're going to exist predominantly in the T state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And it's this green curve that describes the Michaela's mental curve for this particular enzyme, for this particular coronary structure."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so notice at some particular substrate concentration the rate of activity will be low and that's because the active sites of the enzyme have a low affinity for that enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "But as we begin to increase the concentration of that substrate, that begins to shift the entire curve into the r state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And once we transform the quaternary structure from the tense to the relaxed state, the blue curve is the curve that basically begins to describe that quarterinary behavior."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so according to this blue curve at the same substrate concentration, we see that the rate of activity is much higher."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So the green curve describes the Michael's mental curve for the 10th state, the blue curve describes for the relaxed state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And if we combine these two curves we obtain the actual black curve that describes the S shaped, the Sigmoidal curve for this allosteric enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And this is what we know as the concerted model."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "We have the all or nothing behavior in which we either exist in the T state in which the enzyme is inactivated or the art state in which the enzyme is fully active and basically carries out that particular catalytic reaction."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, what about the two types of allosteric effectors that our cells actually use to basically control and regulate the activity of this enzyme?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So let's begin by focusing on CTP."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So remember, this enzyme catalyzes the first step in the biosynthetic process of CTP citadine triphosphate."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And it's the CTP that basically creates a negative feedback loop that goes back and binds onto the Alastairic sites found on these red regulatory chains."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And by binding onto these red regulatory chains, it decreases and inhibits the activity of that enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "The question is, how does this actually take place?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Well, upon the binding of CTP to the red regulatory chains, what it does is it stabilizes the T state of that enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So it lowers the energy of that T state, it makes it more stable."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So as these brown CTP molecules bind onto each one of these regulatory chains, as shown here, it stabilizes the energy of this T state, makes it much more stable, and that shifts the equilibrium from the R state into the T state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so what that means is when CTP actually binds onto the regulatory chains, these CTP molecules make it more difficult for the substrate to actually bind onto the active sides and transform this coronary structure from the T state into the R state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so in this manner, our cells use these CTP molecules to actually regulate the behavior of this enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So when we have a high concentration of CTP, we don't want to produce any more CTP."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And so the cell uses the CTP in a negative feedback loop to basically inhibit the activity of this enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, the second type of allosteric effector of this enzyme is actually ATP adenosine triphosphate."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "In fact, adenosine triphosphate, just like CTP, also binds onto that same regulatory chain, these red chains."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "But unlike CTP, when ATP binds onto these regulatory chains, it actually increases the rate of activity of this enzyme and increases the rate of activity of the enzyme by displacing the CTP molecule from that regulatory chain and shifting the entire curve from the T state to that R state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So Adamosine triphostate, or ATP, is also now a steric effector of atcase."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "It binds to the same side on the regulatory chain, but it actually increases the activity of that ATCA."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So at high concentration of ATP, the ATP will displace the CTP from the regulatory side on those regulatory chains, and that will shift the equilibrium from the T state to the R state and make the active sites much more likely to actually bind and convert that substrate molecule into the final product, the CTP."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, the question is, what is the physiological significance of this effect?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Why exactly does a high concentration of ATP activate this enzyme in the first place?"}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Well, for two reasons."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "First of all, if we have a high concentration of ATP, that means we have plenty of energy inside our cells."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And that implies if we have plenty of energy, we can easily use that energy to actually synthesize these nucleuside triphosphates, such as ATP, by using this enzyme right here."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, the second reason why a high ATP concentration basically stimulates this enzyme to carry out its process is because of the following reasoning."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So at a high concentration of ATP, when we have many ATP molecules inside our cells, that means we can use the ATP molecules to actually synthesize nucleocide triphosphates or RNA and DNA molecules."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "But to actually synthesize these nucleic acids, we not only need the ATP, we also need other nucleotide triphosphates, specifically perimedidine nucleocide triphosphates such as CTP."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And if we have a high amount of ATP, that usually means we have an unequal distribution of the perimeterine to purine nucleocide triphosphates."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And to equalize this distribution of nucleotide triphosphates perimeterine to purine nucleotide triphosphates, we have to carry out this reaction to actually increase the amount of CTP, the perimedidine nucleocide triphosphate that is found inside our cell."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So physiologically, a high ATP concentration means that there is an unequal distribution of the nucleocide triphosphates, the purine to perimeidine nucleocide triphosphates, and therefore, the cell tends to equalize this distribution by producing more perimedine nucleotide triphosphates, such as CTT."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "So we basically conclude that the reason this enzyme displays Cooperativity is because the individual subunits of this enzyme actually interact with one another."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "And by binding of the substrate molecule, we essentially shift the equilibrium from the T state to the R state."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Now, in order to regulate the activity of this enzyme inside our cells, in order to actually turn on or turn off the activity of the cell of this enzyme, our cells use these two regulatory effectors."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "CTP and ATP bind to the same regulatory chains."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "Those allosteric sites found on these red regulatory chains, but they have opposite effects."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "CTP creates a negative feedback loop that basically decreases the activity, inhibits the activity of this enzyme."}, {"title": "Cooperatively and Allosteric Effectors of ATCase .txt", "text": "But ATP binds and displaces the CTP out of that regulatory chain, and it actually increases the activity of the enzyme by shifting the equilibrium from the 10th state to that more active R state."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we know that ourselves can actually break down fatty acids to form ATP molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And this process is known as beta oxidation."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So within the matrix of our mitochondria, activated fatty acid molecules are completely oxidized to form acetyl coenzyme A molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And these acetyl coenzyme A molecules can then be used to actually generate high energy ATP molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, the question that I'd like to discuss in this lecture is the following."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "How many ATP molecules can the cells of our body actually generate when they completely oxidize and break down fatty acids?"}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, the answer to this question actually varies and it depends on the length of that hydrocarbon chain within that particular fatty acid."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And so as our example, we're going to use the most common fatty acid that we find in humans known as palmitic acid."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And palmitic acid contains 16 carbons within that particular hydrocarbon chain."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now remember that each time a fatty acid undergoes a beta oxidation process, we shorten that fatty acid by two carbon atoms."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And so what that means is because we have 16 carbon atoms within palmitic acid, more specifically, within the activated version of palmitic acid we call palmitoyl coenzyme A, then that means a total of seven cycles of beta oxidation will basically cleave the molecule and break it down into acetyl coenzyme A units."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And to see exactly why seven, let's take a look at the following diagram."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we begin with our activated version of palmitic acid, palmitoil coenzyme A, and we have 1234 all the way to 16 carbon atoms within that hydrocarbon chain."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, after six cycles of beta oxidation, we basically release six acetyl coenzyme A molecules and we have a molecule left over that contains four carbon atoms."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have the C, four keto acyl coenzyme A."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, if this molecule undergoes one more beta oxidation, then we produce these two identical acetylcoenzine A molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And so that's why we need six plus one more."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So seven cycles of beta oxidation to produce a total of six, seven and eight acetyl coenzyme A molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, acetylco enzyme A molecules are not the only energy bearing molecules that are produced within the beta oxidation process."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "We also generate one NADH molecule and one Fadh, two molecule every time the beta oxidation process actually takes place."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So recall that each cycle of beta oxidation uses up one water molecule, one Fad, one NAD plus, and one Co enzyme A."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "In the process, we generate one Fadh, two, one NADH, and one H plus ion."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So that basically means if we sum up all these seven reactions, this is the net reaction that we're going to get."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we incorporate, we input one palmitol coenzyme A, seven Fad molecules, seven NAD plus molecules, seven water molecules, and seven coenzyme A molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And what happens is we essentially form."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have 6788 acetyl coenzyme A molecules, seven Sadh, two seven nadhs, and seven H plus ions."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So this is a total number of molecules that we form after seven cycles of beta oxidation."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now the next question is how many ATP molecules can we actually form from?"}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "These molecules form here."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So let's begin with Fadh two and NADH molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "These two molecules, once we form them in the beta oxidation process, they move on onto the electron transport chain."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And remember from our previous discussion that we said a single Fadh two molecule generates about 1.5 ATP molecules while a single NADH molecule generates 2.5 ATP molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, what about the acetyl coenzyme A molecule?"}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Well, the acetyl coenzyme A molecules, once they're formed in the beta oxidation process, they are incorporated into the citric acid cycle."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And remember that a single acetyl coenzyme A molecule that is fed into the citric acid cycle generates three NADH molecules, one Fadh two molecule and one GTP molecule."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, because we have eight acetyl coenzyme A molecule molecules going into the citric acid cycle, we generate a total of eight multiplied by each one of these two coefficients."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have 24 nadhs, eight Fadh twos and eight GTP molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, the GTP are basically transformed into ATP aviativity of a specific type of enzyme found inside our cells."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And these two molecules basically end up on the electron transport chain."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So let's tally up the total number of molecules produced."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have seven Fadh twos here, and we have eight multiplied by one."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So eight fadh twos here."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So seven plus eight, that gives us 15 Fadh two molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "We have eight multiplied by three."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So 24 plus seven, that gives us 31 NADH molecules and we also have the eight GTPs."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now recall in our discussion on the activation of fatty acids, we said that two ATP molecules are actually used up when we transform palmitic acid into its activated form, palmitoyle coenzyme A."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we also actually use up two ATP molecules when we activate the fatty acid."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have to take that into account when we actually sum up our results."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So how many ATP molecules are generated when 31 of these nadhs are actually oxidized along the electron transport chain?"}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "So we have 31 NADH molecules multiplied by 2.5 ATP per NADH molecule."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "That gives us 77.5 ATP molecules."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "Now, 15 multiplied by 1.5 gives us 22.58 multiplied by one because we have a one to one conversion from GTP to ATP, that gives us eight."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And we also use up two ATP molecules during the activation process, so we have to subtract the two."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And so we have 108 minus two."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "And that gives us a net total of 106."}, {"title": "ATP yield in Fatty acid oxidation.txt", "text": "ATP molecules are actually generated when the most common type of fatty acid in humans, palmitic acid, is completely oxidized into its constituents within the matrix of the mitochondria of our cells."}, {"title": "Amplification of Blood Clotting .txt", "text": "Whenever a rupture takes place in a blood vessel of our body it creates a leaking of blood."}, {"title": "Amplification of Blood Clotting .txt", "text": "Some of that blood begins to leak out of the blood vessel and into the tissue of our capillaries."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, if this condition is not repaired, if the blood vessel is not sealed off in some way or form, too much blood can actually leak out of that blood vessel."}, {"title": "Amplification of Blood Clotting .txt", "text": "And that can lead to the opening of our capillaries."}, {"title": "Amplification of Blood Clotting .txt", "text": "And that can lead to the collection of blood, the pooling of blood in those capillaries, which eventually causes the individual to go into shock."}, {"title": "Amplification of Blood Clotting .txt", "text": "That decreases the blood pressure of that individual and the individual can ultimately die."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, as a result of this reasoning we might assume that blood ruptures would be a constant life threatening situation if it wasn't for our body's ability to actually repair and seal off the ruptures in a very effective and very efficient way by using the blood clot and cascade."}, {"title": "Amplification of Blood Clotting .txt", "text": "And one reason why the blood clot and cascade is so effective and so efficient is because it allows a very quick way to produce a great number of blood clots that can aggregate and collect and form a mesh like structure that keeps a watertight seal across that blood vessel and that prevents the movement of blood across that rupture."}, {"title": "Amplification of Blood Clotting .txt", "text": "So this amplification and magnification of blood clots in the blood clot cascade is achieved by using multiple different pathways."}, {"title": "Amplification of Blood Clotting .txt", "text": "So we have the intrinsic pathway and we have the extrinsic pathway and it's also achieved by using positive feedback loops."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, what is a positive feedback loop?"}, {"title": "Amplification of Blood Clotting .txt", "text": "Well, in a certain pathway in a certain reaction pathway we have many intermediates."}, {"title": "Amplification of Blood Clotting .txt", "text": "And what a positive feedback is it's when one of those intermediates down that reaction pathway returns back to some initial molecule and activates it and promotes its activation so that ultimately we produce even more of the final product in this case, even more of our blood clot."}, {"title": "Amplification of Blood Clotting .txt", "text": "So recall that DCE is our blood clotting cascade."}, {"title": "Amplification of Blood Clotting .txt", "text": "So our extrinsic pathway is shown with the black arrows."}, {"title": "Amplification of Blood Clotting .txt", "text": "The intrinsic pathway is shown with the blue arrows and when these two pathways converge they form the final common pathway and that is shown in red."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, the positive feedback loops are shown in green."}, {"title": "Amplification of Blood Clotting .txt", "text": "So let's begin with those."}, {"title": "Amplification of Blood Clotting .txt", "text": "So we know that the entire purpose of the intrinsic and the extrinsic pathway is to produce this complex the dimer protein complex we call prothrombinase."}, {"title": "Amplification of Blood Clotting .txt", "text": "And that's because it's prothrombinase that ultimately activates prothrombin into thrombin."}, {"title": "Amplification of Blood Clotting .txt", "text": "And it's thrombin that essentially activates fibrinogen to form fiber and that's the protein fiber that aggregates to form those blood clots."}, {"title": "Amplification of Blood Clotting .txt", "text": "So the entire point of the intrinsic and extrinsic pathway is to form these two components to basically form this dimer that consists of the two subbutants factor ten and factor five, we call prothrombinase."}, {"title": "Amplification of Blood Clotting .txt", "text": "So notice that when we actually form thrombin thrombin not only activates fibrinogen into fibrin and calls upon platelets and aggregates factor 13 that is needed to form the covalent bonds between the fibrin molecules."}, {"title": "Amplification of Blood Clotting .txt", "text": "But Thrombin actually goes back to the beginning of this entire pathway and activates three different types of factors."}, {"title": "Amplification of Blood Clotting .txt", "text": "It activates factor eleven, it activates factor eight and it activates factor five."}, {"title": "Amplification of Blood Clotting .txt", "text": "And this process amplifies, it produces even more of these dimer complexes that are needed to produce these blood clots."}, {"title": "Amplification of Blood Clotting .txt", "text": "So Thrombin goes on to factor eleven, it takes the inactive form and it activates it."}, {"title": "Amplification of Blood Clotting .txt", "text": "And what factor eleven does is it goes to activate factor nine and that ultimately creates more of these dimers as shown in this diagram."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, Thrombin also activates factor eight."}, {"title": "Amplification of Blood Clotting .txt", "text": "And factor eight essentially circulates in our blood and it attaches to this VWF factor, which basically stands for a Von Villebrand factor."}, {"title": "Amplification of Blood Clotting .txt", "text": "And the Von Villabrant factor is a protein that attaches to factor eight and stabilizes its structure, then attaches to factor nine."}, {"title": "Amplification of Blood Clotting .txt", "text": "And this complex essentially goes on and activates the formation of prothrombinase."}, {"title": "Amplification of Blood Clotting .txt", "text": "So Thrombone activates this complex, it activates factor eleven and it also directly activates factor five."}, {"title": "Amplification of Blood Clotting .txt", "text": "It causes it to bind onto factor ten."}, {"title": "Amplification of Blood Clotting .txt", "text": "And so once again forming prothrombinase."}, {"title": "Amplification of Blood Clotting .txt", "text": "And all these three positive feedback loops essentially carry out the same exact function to form more of these prothrombinase molecules which eventually form more of Thrombin."}, {"title": "Amplification of Blood Clotting .txt", "text": "And that ultimately forms more blood clots that are needed to actually seal off that rupture that took place inside our blood vessel."}, {"title": "Amplification of Blood Clotting .txt", "text": "So these are the three positive feedback loops that you have to be familiar with during the process of blood clotting."}, {"title": "Amplification of Blood Clotting .txt", "text": "Now, on top of these positive feedback loops, we also have other pathways that essentially also amplify and magnify the number of blood clots that we actually form."}, {"title": "Amplification of Blood Clotting .txt", "text": "So notice in this blood clot cascade, we don't directly go from this factor to this."}, {"title": "Amplification of Blood Clotting .txt", "text": "Well, we do go from this to this because the formation of this dimer, that CF seven dimer, directly affects the formation of prothrombinase."}, {"title": "Amplification of Blood Clotting .txt", "text": "But we also have these other pathways."}, {"title": "Amplification of Blood Clotting .txt", "text": "And what these all other pathways do is once again, they form more of these prothrombinases and these ultimately form more of our blood clots."}, {"title": "Amplification of Blood Clotting .txt", "text": "So if we look at factor eleven, factor eleven, which is activated by factor twelve, goes on to activate nine, which ultimately forms more of these dimer protein complexes."}, {"title": "Amplification of Blood Clotting .txt", "text": "So factor eleven is used to amplify the amount of factor nine form, which ultimately forms more active factor ten proteins and that forms more of these complexes leading to this final pathway that creates more blood clots."}, {"title": "Amplification of Blood Clotting .txt", "text": "And if we also look at the TF seven complex, we have this direct mechanism by which direct pathway by which we form more of these dimers."}, {"title": "Amplification of Blood Clotting .txt", "text": "But also this TF seven complex creates more of these active factor nine."}, {"title": "Amplification of Blood Clotting .txt", "text": "And these active factor nine basically also amplified the amount of these dimers form."}, {"title": "Amplification of Blood Clotting .txt", "text": "So we have a very complex and very extensive pathway, different pathways involved and the ultimate goal of these pathways is to create all these different routes by which we can form as many blood clots as possible."}, {"title": "Amplification of Blood Clotting .txt", "text": "So one good analogy is if you're trying to fill a bathtub with water, instead of using one faucet, you could use two faucets to speed up the process."}, {"title": "Amplification of Blood Clotting .txt", "text": "Better yet, if you somehow have access to three faucets, four faucets, it would create a much quicker process."}, {"title": "Amplification of Blood Clotting .txt", "text": "And this is exactly what is done with the blood clot and cascade."}, {"title": "Amplification of Blood Clotting .txt", "text": "Imagine having thousands of different faucets that are used to fill that same bathtub."}, {"title": "Amplification of Blood Clotting .txt", "text": "We're going to carry out the process at a much quicker rate than if we had a single direct pathway to that fibrin that forms the blood clots."}, {"title": "Amplification of Blood Clotting .txt", "text": "Instead of having that one faucet, we have many of the different faucets that all carry out the same function to altin produce as much blood clots as possible to basically seal off that rupture and prevent the individual from going into shock."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Osmotic and hydrostatic pressure are two different types of fluid pressures which are responsible for allowing the movement of fluid from one location to a different location within some given region of space."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, let's begin by describing what osmotic pressure is."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "But before we actually define what asthmaic pressure is we have to discuss something called osmotic potential as well as osmosis."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So let's suppose we have the following object, a marker."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, anytime we take a mass, for example, the marker, and we let go, we know that mass, the marker will always move from a higher gravitational potential to a lower gravitational potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So objects naturally move down their gravitational potential gradient from a high potential to a low potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, in the same analogous way, if we take a water molecule, the water molecule will always move down its water potential gradient, also known as the zmodic potential gradient."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So water naturally moves from a high osmotic potential to a low asthmatic potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, when an object, a mass, is on the ground, we define the ground to be a zero potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And in the same exact way, we give pure water a value of zero asthmonic potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So pure water is arbitrarily assigned an Astronic potential of zero."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, if we take the pure water and now we add some type of additional solute molecule, for example, sodium ions, then we decrease the sommotic potential of that non pure water."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So now it becomes more negative."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So pure water is given a potential of zero."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "But anytime we take pure water and we add our solute molecules, now we're decreasing the sommotic potential, we're making it more negative."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, let's suppose we have the following system."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So we have a closed container, as shown."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "On the left side, we have pure water."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "On the right side, we have water as well as our additional solute molecules."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So these green molecules are solute molecules, for example, our sodium ions."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, separating the left side from the right side is a semipermeable membrane."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And the semipermeable membrane has small pores that allows the movement of water molecules but does not allow the movement of these solute molecules."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So the green dots cannot actually move across the semipermeable membrane."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "But the water molecules not shown can actually move across the semipermeable membrane."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, from this discussion above, we know pure water has a potential, an osmotic potential of zero."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "But this water that contains the solute molecules has a smaller, a more negative osmotic potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So we have a high osmotic potential, a low osmotic potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And what that means is water will begin to naturally move down its osmotic potential gradient from the left side to the right side in the same analogous way that the marker will move down its gravitational potential gradient."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So once again, suppose the left side only contains pure water while the right side contains water."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Along with some solute molecules shown in green."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "The two sides are separated by a semipermeable membrane that only allows water to move across."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, since pure water has an asthmatic pressure and an osmotic potential of zero, but the right side has a more negative osmotic potential, so it's smaller osmotic potential."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Water will naturally flow from the left side to the right side, down the osmotic potential gradient."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, we can rephrase this."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "We can say that water moves from a low solute concentration, the left side, to a higher solid concentration, the right side."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So this is known as osmosis."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So osmosis is the process by which water naturally flows from a high osmotic potential or low solid concentration to a low osmotic potential or a high solid concentration."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And this is described by the following diagram."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So, water tends to move from a high osmotic potential, the left side, which is also the low solub concentration, and it moves to the low osmotic potential or the high solub concentration, the right side."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So it always naturally moves from this side to this side."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And this is known as osmosis."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Osmosis is the process by which water naturally moves down its osmotic potential gradient."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, the next question is what exactly is osmotic pressure?"}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Because osmotic pressure has to do with the process of osmosis."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So now let's suppose we take the same exact situation."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And now we place an impermeable membrane, for example, our hand."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "We place the hand in front of the semipermeable membrane."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So now the hand acts as the impermeable barrier."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "What will happen next?"}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Well, as the water tries to move across this barrier, because we have an impermeable barrier, our hand, the water, will not be able to move across."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And that's because our hand, the impermeable barrier, actually creates a pressure that prevents that osmosis from taking place."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And that's exactly what osmotic pressure is."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Osmotic pressure is the pressure that needs to be applied to actually prevent osmosis from actually taking place."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So if we block the semipermeable membrane with some type of impermeable barrier, for example, our hand, we will be applying a pressure that will ultimately stop osmosis from taking place."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So the pressure that must be applied to stop the natural flow of water down its osmotic potential gradient is called osmotic pressure."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So notice that the water tries to move this way, but our osmotic pressure points in the opposite direction because what it does is it ultimately stops the water from actually moving across this membrane."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, what about hydrostatic pressure?"}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "What exactly is hydrostatic pressure?"}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Well, hydrostatic pressure is slightly easier to actually explain because hydrostatic pressure is nothing more than fluid pressure."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So whenever a liquid actually travels through some type of conduit, through some type of pipe, the individual liquid molecules actually collide with the walls of that conduit with the walls of that pipe."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Now, when each individual liquid molecule collides with the wall, it exerts a force."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And if we sum up all the individual forces that the liquid molecules exert and divided by the surface area of the wall of the conduit on which those forces actually act on, then we obtain the fluid pressure, also known as hydrostatic pressure."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So, if we have any fluid moving along the following conduit, then the liquid molecules exert a force on the walls of that conduit, as shown in this diagram."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "And if we take the sum of all these forces, if we find the net force due to all the liquid molecules and divided by the surface area of the wall of the conduit on which those forces act on, then we get the hydrostatic pressure."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So notice these two pressures are not exactly the same thing."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "Osmotic pressure is simply the pressure we have to apply to prevent osmosis from actually taking place, to prevent the water from moving down its osmotic potential gradient."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "But hydrostatic pressure is the pressure that is a result of that movement of the fluid, the liquid, along some given conduit."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "It's the pressure that is created by the molecules on the walls of that conduit."}, {"title": "Osmosis Osmotic pressure and Hydrostatic Pressure .txt", "text": "So this is the difference between osmotic pressure and hydrogen hydrostatic pressure."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Suppose we have a solution, and in that solution we have some type of polypeptide."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And the polypeptide exists in its fully functional threedimensional tertiary state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, if we increase the temperature of our solution or if we add some type of denaturing chemical agent, what will begin to happen is that protein will begin to unfold."}, {"title": "Cooperatively of Protein Folding .txt", "text": "It will begin to lose its tertiary structure, followed by the secondary structure, and eventually it will denature and form a non functional, biologically inactive protein."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, at the same time, if we remove that denaturing chemical agent or if we decrease the temperature back to normal, what will happen is that denatured form of the polypeptide will basically begin to refold and eventually will fold into the fully active native state of that protein."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, we know that this happens because it's the primary structure, it's that specific sequence of amino acids in that polypeptide that actually determines what that final three dimensional structure of that protein actually is."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the protein easily is able to go from that non functional denatural state to the fully functional native state because it's the primary structure that determines the tertiary structure of that protein."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, the question we want to focus on in this lecture is how exactly does the folding or unfolding process actually take place?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "How exactly does the protein unfold from the native state into that denatured state?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "Or how does a protein fold from a denatured state and to that fully functional threedimensional state?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "So, let's begin by taking a look at the following graph."}, {"title": "Cooperatively of Protein Folding .txt", "text": "What the graph basically describes is the percentage of the proteins that are denatured versus the conditions that the protein is actually under."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So as we go from left to right along the x axis, we either increase our temperature of the solution or we increase the amount of chemical denaturing agent that is found within that mixture."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So when no chemical agents are found in the solution and the temperature is normal, 0% of the proteins are denatured, and all the proteins essentially exist in their fully functional threedimensional folded native states."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, as we begin to increase our temperature or as we begin to increase the amount of chemical agent, what begins to happen?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "Well, initially nothing really happens."}, {"title": "Cooperatively of Protein Folding .txt", "text": "A small amount of the protein begins to unfold."}, {"title": "Cooperatively of Protein Folding .txt", "text": "But as we approach this section, we see a sharp increase in the percentage of the protein that have denatured."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Eventually we basically reach this point where all the protein exists in their fully unfolded denatured state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the curve that we get is a sigmoidal curve."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we have a sharp transition from the folded to the unfolded."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And we can also look at the graph going the other way."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So as we decrease the temperature, as we return it back to normal, or we remove those chemical agents, we see a sharp transition from the denatured to that fully folded active state of that protein."}, {"title": "Cooperatively of Protein Folding .txt", "text": "The question is, why exactly does this actually happen?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "Well, it happens because of the cooperative nature of protein folding and unfolding."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So what do we mean by protein folding?"}, {"title": "Cooperatively of Protein Folding .txt", "text": "Cooperativity well, let's suppose we're going from this state to this state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we essentially bump up our temperature."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And once we increase our temperature, what begins to happen is a certain segment of that protein begins to become unstable."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And some of those bonds holding that segment together begin to break."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, as that segment and that localized region on that protein becomes unstable because it is connected to other segments of that protein, it disrupts these interactions with the other segments, and that causes those other segments to basically break down as well."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we have one segment breaking down causes, let's say, a second segment to also break down."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And that second segment, by breaking down, causes a third segment in close proximity to also break down."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these different segments of the protein structure, as they begin to break down, they cooperate with one another to basically unfold that entire protein structure."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so eventually, because of this cooperative nature, we have this really sharp rise in the amount of protein that are denatured."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Likewise, we can also look at it in the other way."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Let's suppose we're going from this to this state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we decrease the temperature of our solution."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So as we decrease the temperature, a certain segment of that protein in its denatured state becomes to stabilize."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And because of that, it begins to interact with some segment."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And as those segments interact, they stimulate other segments to stabilize themselves and to interact."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so eventually, this cooperativity of these different segments and the protein caused the folding process to basically take place quickly, as shown by the following sharp rise in our curve."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the curve describes how most proteins in our body fold or unfold."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And notice that the curve shows that the majority of proteins transition sharply from the unfolded to the unfolded state and vice versa."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And this is because of the cooperative nature of proteins."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So proteins fold and unfold cooperatively."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So let's take a look at the following diagram to see exactly what we mean."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And actually, this diagram also tells us something else."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So let's begin in our native state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we begin essentially in this condition when all the proteins exist in their native state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, as we begin to increase the temperature of our solution, that begins to destabilize some section of that particular protein molecule."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So let's suppose initially we begin to destabilize all these bonds found in here."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So remember, this is the tertiary structure of our protein."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And in the tertiary structure, we have these amino acids that are found far away from one another in that polypeptide that are interacting."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we have a bunch of these secondary structures."}, {"title": "Cooperatively of Protein Folding .txt", "text": "We have these alphaloo, or we have these alpha helixes, and we have the beta pleated sheets."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so the amino acids found on this beta pleated sheet interact with amino acids found on this beta pleated sheet."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these bonds are part of the tertiary structure of our polypeptide."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So let's suppose for argument's sake that initially by increasing the temperature, we destabilize this segment of our DNA."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So initially we begin to break down these bonds, these non covalent interactions, so that eventually we go from the native state to intermediate state A, where all of these bonds are essentially broken down."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, in the process, by breaking down these bonds here, we change the shape of our molecule and we cause other bonds to begin to break as well."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So other segments of that protein molecule begin to break down as well."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So for example, these bonds here are affected and so they break down as well."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these bonds begin to break down."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So in this particular case, we begin to break down our tertiary state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these are our secondary states, as shown in the following diagram."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the secondary structures, so this is intermediate state A."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we continue to increase our temperature."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And as we continually destabilize the different segments of our protein, those segments destabilize other segments."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So as these move apart, these begin to move apart."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these interactions begin to break, these interactions begin to break."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so eventually we form intermediate state B, in which all these bonds between these beta sheets and these beta sheets eventually break, and the bonds between the beta sheets and these alpha helixes break as well."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so intermediate state B describes only the secondary structures involved."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So we have these four beta pleated sheets and these three alpha helices."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now eventually, as we continue to increase our temperature, the hydrogen bonds that hold all these secondary structures will also break."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so these different secondary structures will eventually break down denature until we form a single long polypeptide in its linear state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So now we only have the primary structure."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so notice as we go from the native state to our denatured state, these interactions take place cooperatively."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And not only that, but we also go through these intermediate states."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so what that means is during the folding or unfolding process, going this way is unfolding, going this way in reverse, is folding."}, {"title": "Cooperatively of Protein Folding .txt", "text": "During either process, proteins follow a partly defined pathway that consists of these intermediate states."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so what we see in this particular case, we have two intermediate states, but we could also have five intermediate states, ten intermediate states and so forth."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And what these intermediate states basically describe is that is they describe energy states."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So what that means is when a protein folds or unfolds, it doesn't actually follow a precisely defined pathway, but it follows a partially defined pathway."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And what that means is when the protein, let's say, unfolds, it goes from a very stable native state into a less stable state that has its own energy into a higher energy state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So this is even less stable than this and finally into this final state that is less stable than either one of these states."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And so when the protein either folds or unfolds, it does so cooperatively."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And that's why we have the Sigmoidal curve."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And not only that, but it has to pass through these intermediate structures to actually get to that final structure."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So when we go between these two structures, the native state, the three dimensional functional state and our denatural state, that protein must actually follow these different intermediate structures."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, an important point must be emphasized."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So let's suppose we take the protein and we denature it once."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the first time around, it goes through this specific structure A, this specific structure B, and then it ends up in its denatured state."}, {"title": "Cooperatively of Protein Folding .txt", "text": "Now, let's suppose we reform this same native protein and now we denature it once again."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the second time around, that protein will not go through a molecule that looks exactly like B and it will not go through a molecule that looks exactly like A."}, {"title": "Cooperatively of Protein Folding .txt", "text": "But what it will follow is a pathway that is similar in energy."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the second time around, when this same protein will denature, it will create an intermediate A that resembles this molecule in terms of its energy."}, {"title": "Cooperatively of Protein Folding .txt", "text": "And then it will find this state that also resembles this in terms of its energy value."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So what that means is when a protein folds or unfolds, it follows a partially defined pathway."}, {"title": "Cooperatively of Protein Folding .txt", "text": "So the pathway isn't exactly defined."}, {"title": "Cooperatively of Protein Folding .txt", "text": "It's not the same every time, but it's partially the same in the sense that the protein has to go through these different energy values to get from this low energy, thermodynamically stated state to the higher and energy, thermodynamically unstable state."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Although the cells of our body can use all sorts of different types of signal transduction pathways to initiate cellular processes that ultimately create some type of physiological effect, all these signal transduction pathways have four important properties in common."}, {"title": "Common Properties of Signal Pathways .txt", "text": "They share four important principles."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And to demonstrate what these principles are, I'd like to focus in on the four different types of pathways pathways that we discussed so far."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in our discussions, we discussed epinephrine signaling, insulin signaling, EGF signaling, and we also looked at the phosphonosatide cascade."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So what exactly are the four factors that these four pathways actually have in common?"}, {"title": "Common Properties of Signal Pathways .txt", "text": "Well, fact number one is they all use protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Fact number two is they all use secondary messenger molecules."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Fact number three is or property number three is they all depend on specific interactions between proteins and other molecules to basically stimulate that process."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And number four is they all have to be terminated once they are actually complete, once they carry out their specific type of physiological effect."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So to demonstrate why this is actually true, let's take a look and summarize the four different pathways that we discussed so far."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And let's begin by discussing what types of protein kinases are used by the four different types of pathways that we discussed up to this point."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So let's begin with the epinephrine signaling pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So remember, in our discussion of the epinephrine signaling pathway, we focused on the physiological effect of running away from an animal."}, {"title": "Common Properties of Signal Pathways .txt", "text": "We set a bear."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And so we said that a kinase is used in this particular pathway, namely protein kinase A."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Protein kinase A is activated by a secondary messenger molecule that we'll talk about in a moment, cyclic amp."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And once the protein kinase A is activated, it goes on to activate affected molecules."}, {"title": "Common Properties of Signal Pathways .txt", "text": "For instance, enzymes which carry out the breakdown of Glycogen into glucose."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And then the glucose can be used by these, let's say, skeleton muscle cells to basically produce ATP molecules which themselves are used to basically contract the skeleton muscle."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And once the skeleton muscle contracts, that is precisely what allows us to basically run away from that animal, from that bear."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So carry out that particular type of physiological effect."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, what about the phosphorosotide cascade?"}, {"title": "Common Properties of Signal Pathways .txt", "text": "What types of kinases are used in this case?"}, {"title": "Common Properties of Signal Pathways .txt", "text": "Well, in our discussion we focused on two different types of kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "We discussed protein kinasea and Cammodulen, so calm dependent protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And we said in this particular cascade and we used the physiological effect of decreasing or increasing blood pressure."}, {"title": "Common Properties of Signal Pathways .txt", "text": "We said that these two types of kinases are basically crucial for allowing that smooth muscle in the cardiovascular system to actually contract."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And so what these do is they stimulate the breakdown of Glycogen and they stimulate the contraction of those smooth muscles which also depend on ATP to basically contract."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, in the case of insulin signaling, we said that insulin signaling is basically used once we ingest a carbohydrate rich meal."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So once we ingest all these carbohydrates, the glucose concentration in our blood plasma increases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And we want to use the insulin signaling pathway to basically allow the uptake of the glucose into the cells and then allow the transformation of glucose into Glycogen."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And so that's exactly what insulin signaling pathway actually does."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And to accomplish this, we basically use four important types of kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So the receptor cell that binds insulin actually contains a tyrosine protein kinase that is needed to initiate this entire process."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Then we have a lipid kinase that is necessary to basically transform Pip two into Pip three."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And that lipid kinase is known as phosphoinosatide three kinase."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Then we have the Pip three dependent protein kinase which is used to basically activate protein kinase B, also known as AKT."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And what protein kinase B does is it basically stimulates the movement of glucose transporters into the membrane of our cells, for instance, skeletal muscle cells."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And then these skeleton muscle cells can essentially uptake the glucose molecules and transform the glucose molecules into Glycogen as a result of the activity of these protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, in the EGF signaling pathway we discussed four different types of protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So just like in the case of insulin here, the EGF receptor also contains a tyrosine protein kinase that is needed to actually initiate that signaling pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And then we also examined three other examples of kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we spoke about rats which were actually needed to activate mex, and then the mechs are needed to activate hercs."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And these irks are protein kinases that move into the cell, into the nucleus of our cell, and inside the nucleus, they essentially activate these transcription factors which increase the rate of expression of genes and that ultimately allows the cell to produce many proteins that ultimately allow the cell to grow and divide, which is what the physiological effect is in this particular case."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So when we spoke about this pathway we said that the physiological effect might be, for instance, actually sealing off that cut that we might experience on the epidermal cells of our skin."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we see that a protein kinases are used by all four pathways that we discuss, and this implies that they play a crucial role in this signal transduction pathway and actually carrying out that particular type of physiological effect."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, secondary messengers are also used by each one of these four different types of pathways."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And we said that all these signal pathways use these secondary messengers to basically amplify that initial signal."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So these secondary messengers are intracellular agents, they could be molecules or ions whose concentration can be greatly amplified, thereby amplifying the overall signal that was initially taken up by that cell."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So these secondary messengers typically act on proteins or enzymes that play crucial roles in the signal transduction pathways."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And so in our discussion, these are the secondary messengers that we discussed, except in this particular case, we actually didn't discuss how calcium or cyclic Amp is used by this pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So let's begin with Epinephrine signaling."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in Epinephrine signaling, we said that once a specific protein, the G alpha protein, binds until adenolate cyclists."}, {"title": "Common Properties of Signal Pathways .txt", "text": "It stimulates Adenon cyclists to transform ATP into C amp."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And Camp is that secondary messenger used by the Epinephrine signaling."}, {"title": "Common Properties of Signal Pathways .txt", "text": "What it does is it binds into protein kinase A and it activates protein kinase A."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, for the case of the phosphoride, so that's actually spelled incorrectly."}, {"title": "Common Properties of Signal Pathways .txt", "text": "But let's imagine that's phosphoride cascade."}, {"title": "Common Properties of Signal Pathways .txt", "text": "We discussed three different types of secondary mastery molecules."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we looked at IP Three, we looked at Dag, and we also looked at calcium."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we said that IP Three has to bind onto a calcium channel in the Er membrane to allow the calcium to move into the cytoplasm."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And then the calcium, with the help of dad, must bind onto a special protein we call protein kinased and that activates protein kinase C. On top of that, calcium also actually goes on to bind to calm modulin to form the calcium calmodulent complex, which then which then goes on to activate those calamodulin dependent protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "In the case of insulin signaling, we discussed how for the Pip Three dependent protein to actually begin to actually be able to activate protein kinase B, that Pip Three dependent protein kinase must actually bind Pip Three."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And the Pip Three itself is actually produced by the phosphorusotide three kinase."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, in our discussion of EGF signaling, we actually did not examine these two secondary messengers, but these are in fact secondary messengers that stimulate the EGF signaling pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So calcium as well as cyclic adenosine monophosphate."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, let's move on to property number three that all these four have in common."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And that's the fact that all of these different pathways depend on the correct interaction between protein molecules and other molecules in that pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So within any signal transduction pathway, proteins interact with other molecules."}, {"title": "Common Properties of Signal Pathways .txt", "text": "These other molecules can be proteins or they can be lipids or they can be secondary menstrual molecules such as the calcium ions."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And these interactions basically stimulate and pass down the information needed to ultimately stimulate the cellular processes that lead to some particular type of physiological effect."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in the case of this pathway, physiological effect might be running away in the case of this pathway."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we might regulate the blood pressure in this pathway, we actually want to uptake that glucose and transform the glucose into Glycogen."}, {"title": "Common Properties of Signal Pathways .txt", "text": "In this pathway, we actually want to repair certain types of damages to the Epidermal cells or the Epithelial cells."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, many of these pathways have different types of interactions."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in this particular case, I've listed a single interaction that exists in each one of these pathways."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in the case of Epinephrine, we said that the activated G alpha protein must go on and bind to adenylate cyclists to actually transform those ATP molecules into cyclic Amp molecules, which then go on and activate protein kinasea."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So in epinephrine signaling, the ALPHAG protein must interact with adenos cyclists for that pathway to actually continue."}, {"title": "Common Properties of Signal Pathways .txt", "text": "In the case of the phosphoric cascade, we saw that the IP three has to bind onto a specific ligand gated calcium on channel on the Er membrane to actually allow the movement of the calcium from the Er lumen and into the cytoplasm."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And only then can protein kinase C and the calmodulatenant protein kinase actually be activated."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, in the case of insulin signaling, we said that the IRS one must bind onto that insulin receptor to actually act as an adaptive protein to allow the attachment of the phosphor nosetie three kinase, that specific type of lipid kinase that is needed to actually transform the pip two into the pip three molecule that we mentioned right over here."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And finally, in the EGF signaling pathway, we said that the GRB two must be able to bind and attach onto that EGF receptor to actually act as the adaptive protein and allow the attachment of the SOS."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And only then can the SOS actually activate that Rasp protein which goes on to activate raft, which then goes on to activate the mex and the IRCS and so forth."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So interactions play very important roles in these signal transduction pathways."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And finally, we have termination."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So all these pathways, even though they're very important in actually carrying out some type of physiological effect, they must be regulated and controlled correctly."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Because if they are not regulated and controlled correctly, if they're not shut down at the proper times, they can cause damage to our body."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And as we'll see in the next lecture, they can actually lead to cancer."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, what are some common ways by which these pathways are actually shut down?"}, {"title": "Common Properties of Signal Pathways .txt", "text": "Well, one way is for the primary messenger to actually dissociate from the side of that particular receptor."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And we examined this particular method when we discussed epinephrine signaling."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So epinephrine can actually dissociate from its side and that can basically stop that process from taking place."}, {"title": "Common Properties of Signal Pathways .txt", "text": "We also discussed the fact that G protein so in the case of epinephrine signaling and also in the case of the EGF signaling, there are G proteins that contain GPA's activity."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And what that means is they actually have a built in timer that allows it to deactivate the process after some time has passed."}, {"title": "Common Properties of Signal Pathways .txt", "text": "And we also discussed phosphatase."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So many of these pathways, actually all the pathways depend on protein kinases."}, {"title": "Common Properties of Signal Pathways .txt", "text": "Now, the protein kinases actually activate molecules by phosphorylation and to reverse this process to deactivate that target molecule by removing vasal sporal group, we depend on phosphatases to carry out that process."}, {"title": "Common Properties of Signal Pathways .txt", "text": "So we see that these are the three common mechanisms that are used by these different signal transduction pathways to basically terminate or turn off the activity of that signal transduction pathway."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So now that we know what a pedigree is and how we can analyze it to discover the way that our traits for certain types of diseases are passed down from one generation to another, let's take a look at the following pedigree and try to determine how the color blindness trait is passed down from one generation to another."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's take a look at the following pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have generation number one that consists of these four individuals."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Generation number two, that consists of these four individuals, and generation number three, that consists of these five individuals."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, the uncolored shape basically means we're dealing with an individual that has a normal phenotype, and that individual is a non carrier."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "The colored shape basically means we're dealing with an individual that exhibits color blindness."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "They have the phenotype for color blindness, while half colored means they have the normal phenotype, but they are a carrier."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, what do we mean by a carrier?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Well, that means we're dealing with a heterozygous individual."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And what that implies is our inheritance for that particular disease must be recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "The question remains, is it autosomal recessive or is it sex link recessive?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So that's what we basically want to discover."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "That's what we want to determine in this lecture."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's begin by trying to determine which one of those it is."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's begin by assuming that we're dealing with an autosomal recessive mode of inheritance."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So remember, the way that we carry out these pedigrees is by beginning is by assuming something."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And then with that assumption, we have to check the consistency of that particular pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "That is, is this consistent with the information that is given to us in this pedigree?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So what do we mean by autosomal recessive?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's suppose the gene we're talking about is color blindness."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And let's designate color blindness with the gene given by letter B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So the dominant gene is given by uppercase B, and the recessive gene is given by lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's take a look at our pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Or actually, let's just kind of denote these as this is our dominant gene and this is our recessive gene that basically codes four color blindness."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So it's the recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Okay, so let's move on to generation one."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "In generation one, we have one couple and a second couple."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "If we look at the first couple, we have a male that is uncoolored."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And what that means is they have normal vision."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "They are not a carrier."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that means their genotype must be uppercase B. Uppercase B, on the other hand, this female is fully colored, and that means they must be homozygous recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So lowercase b lower case B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, what happens when we make these two individuals?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have an individual that is given by uppercase uppercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And so the gametes produced by this individual, the sperm cells produced are uppercase B and uppercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Likewise, the Xcels produced by this individual a, lowercase B, lowercase upper B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So if we carry out this pun and square, we basically get uppercase B, lowercase B, uppercase B, lowercase B, uppercase B, lower case B, uppercase, lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we see that all the possibilities are exactly the same."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So what that means is our offspring for this particular mating process must be heterozygous."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, is that information consistent with the pedigree information that we have on the board?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this one is basically uppercase B, lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "But this one, according to our pedigree, must be lowercase B, lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that is inconsistent with this information here because what this punnant square tells us is 100% of the offspring, be it male or female, must be heterozygous."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So they must be half colored."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "In this case, this one is half colored, but this one is fully colored."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that means our genetic inheritance cannot be autosomal recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So it cannot be this."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we know that it can't be this."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, let's do the same exact thing, but let's assume that it is."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Well, if it's not autosomal, it must be sex linked recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's confirm that it is in fact sex linked recessive, that the color blindness gene is sex link recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now, what do we mean by sex link recessive?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "What that means is the colorblindest gene is always located and only located on the X chromosome, never the Y."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have X uppercase B basically means our normal color vision gene."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "We have X lowercase B is the color blindness gene, right?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And then we have the why?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Well, the Y is simply the Y chromosome that determines the maleness of that particular individual."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "It doesn't actually carry that particular trait for that disease."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's carry out the same exact process."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "But now we don't use these B's."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "We use the X and the BS."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So once again, this individual here, a male, is uncolored."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And what that means is the genotype must be X uppercase by Y."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And this individual, a female, is fully colored."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And what that means is they will be colorblind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that is only true when both of those X chromosomes contain that color blind as gene."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have x lowercase b. X lowercase b."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "In this particular case, we have a male in the village of that is color blindlind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And so we have X lowercase B, and Y in this case, we have an uncooled."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that means we have normal vision."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have normal genes on both of those X chromosomes."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So x Uppercase B x Uppercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's begin by carrying out this particular Punnett square."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's just isolate this case."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's begin with right over here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have X uppercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And then we have A. Y are the male gametes, x lowercase B, x lowercase B for the female XL's female gametes."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And so if we carry out this punant square, we get X uppercase BX, lowercase B, x uppercase BX lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "We have x uppercase b y, and x lowercase by."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Okay, so these here are our females and these here are our males."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So notice that both males."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So 100% of the males produced from this crossing process right here will be fully colorblind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And what that means is just like this one here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So what that means is this information is consistent with this square right over here because we are given a male that is fully colorblind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have x lowercase by and that is consistent with this punitive square."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "That tells us 100% of the males produced from that mating process will basically be color blindly."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now what this row tells us is 100% of our females will be the carrier for this particular trait."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So they will have normal phenotype, but they will be half colored, they will be heterozygous as is given to us by this particular pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this pedigree information is consistent with the fact that it's sex link recessive."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Let's confirm the same thing about this crossing here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So now we're crossing this male individual."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have the sperm cells are x lowercase by and then we have x uppercase b, x uppercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Okay, so we have x uppercase B, we have x lowercase B, we have x uppercase b, x lowercase B, we have x uppercase b y, and we have x uppercase by."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this tells us a slightly different case than in this particular scenario."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So now 100% of our males are going to be normal for that color vision and that's exactly what is told by this particular square."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this square, because it's not colored, means it must be x uppercades by."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that's exactly what we get from this particular Punnett square."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Now what the female so the female information given by this Punnett square basically tells us that all of them are once again heterozygous."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "They are normal phenotype, but they are carriers."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So it's x uppercase b, x lowercase B, and that's consistent with this information."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Finally, to fully show that our trade is sex link recessive, we have to ensure that when this individual mates with this individual, these are all possible."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So let's take this individual here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have the sperm cells are x lowercase by and then we have x uppercase B, and then x lowercase B."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this here is our opponent square."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we have x uppercase BX lowercase b, we have x lowercase BX lowercase b, we have x uppercase by and we have x lowercase by."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So what this information tells us is it tells us that the female so this can either be heterozygous for that particular trade, so it can either have a normal phenotype but be a carrier, which is consistent with this right over here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this individual, this female child is in fact the carrier, but they have a normal phenotype, they have normal vision."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "The other square for the female basically tells us that they're colorblind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Both of those traits are lowercase bees, and that is consistent with this individual right over here."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "What about the male?"}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "Well, for the male, we either have a color block or we have normal vision."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And that's exactly what this information tells us."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So this right over here is normal."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So x uppercase by, and these two are basically colorblind."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So x lowercase b y and x lowercase by."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "So we see that by making the assumption that our trait, in this case, it's our colorblind trait, by making the assumption it's sex link recessive, we are able to basically use the information given to us in the pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And we were able to correlate this information with information that was obtained from these pundits square experiments."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "That is, this information given to us from the sex link recessive assumption was consistent with the pedigree information that we began with."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And initially we saw that it couldn't be autosomal recessive because the information given to us from this pound square was not consistent with information given to us in this section of our pedigree."}, {"title": "Pedigree Analysis of Sex Linked Recessive Traits .txt", "text": "And this is how you carry out the pedigree analysis experiments in genetics."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Oxygen is not the only molecule that can bind onto the heme group of hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Another molecule that can bind to the same exact group on hemoglobin is carbon monoxide."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And in fact, carbon monoxide is about 250 times as likely to actually bind to hemoglobin than oxygen."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And what that means is when we we have oxygen, carbon monoxide, and hemoglobin present in the same mixture, carbon monoxide will have no problem out competing the oxygen for that heme group on hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "On top of that, when carbon monoxide actually binds onto hemoglobin, because of its very high affinity, it's very difficult to actually displace and release the carbon monoxide from hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, the question is, how exactly does the binding of carbon monoxide onto hemoglobin affect the oxygen hemoglobin dissociation curve?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So, to see what the effect is, let's take a look at the following diagram."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So, as always, the Y axis is the percentage saturation of hemoglobin inside our blood plasma, and it ranges from zero to 100%."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, the x axis is the partial pressure of oxygen inside our tissues given to us in millimeters of mercury."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So it ranges from zero to 100."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, the blue curve describes the normal oxygen hemoglobin dissociation curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "That is, it describes a situation when we have no carbon monoxide present inside our blood plasma."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "On the other hand, the red curve describes a situation when we do have carbon monoxide present inside the blood plasma."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "In fact, it describes a particular situation where 50% of the hemoglobin is occupied by carbon monoxide."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And whenever carbon monoxide bind onto hemoglobin, we call the hemoglobin carboxy hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, the question is, what exactly can we tell from this curve?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Well, first thing we can see is if we examine this side of the curve, the red curve is bound to the left of the normal blue curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And what that means is, by binding to our hemoglobin, what carbon monoxide does is it creates a leftward shift in our curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "The question is, why does this actually take place?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And what physiological consequence does this actually have on the tissues of our body?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Well, basically, when carbon monoxide binds onto the heme group of hemoglobin, it makes the other empty heme groups much more likely to actually bind oxygen molecules."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So, by binding to our hemoglobin, carbon monoxide makes or increases the affinity of hemoglobin to oxygen."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And that's exactly what creates this leftward shift in the first place."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So, due to the higher affinity of carboxy hemoglobin to oxygen, it will make it much less likely that the hemoglobin will actually release the oxygen to the tissues and cells that are exercising in our body."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Therefore, even though we'll have plenty of oxygen present in the atmosphere and inside our blood plasma, because carboxy hemoglobin binds oxygen so much more strongly than in the normal case, much less of the oxygen will actually arrive at the tissues of our body."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And this condition that can ultimately lead to suffocation is known as carbon monoxide poisoning."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, the other effect that the binding of carbon monoxide has on hemoglobin curve is the following."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Notice that the blue curve is found much higher than the red curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "We see that there is a drop in our curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "The question is why?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Why does this take place, and what effect does it have on our tissues?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Well, basically, once carbon monoxide actually binds onto one of the heme groups of hemoglobin, it decreases the amount of oxygen that the hemoglobin can actually bind."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "For example, if a given hemoglobin molecule is bound to two carbon monoxide, that means only two oxygen can actually bind onto the hemoglobin versus the four oxygen in the normal case."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So what this does is it decreases the oxygen carrying capacity of the hemoglobin inside our blood plasma, and that's why we have the drop in this curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And that means, because we have a decrease in oxygen carrying capacity, once again, less oxygen will be ultimately delivered to the tissues of our body."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So, two effects are in place."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "We have a drop in the curve, which is a result of the actual binding of the Co to our hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "It decreases the oxygen carrying capacity."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And effect number two is we have a leftward shift in the curve."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And this means that carboxy hemoglobin decreases the affinity or increases the affinity of hemoglobin to oxygen."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And that means oxygen will be held much more tightly by the hemoglobin, and less of it will be released and unloaded to the tissues of our body."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So we conclude that although our body actually does produce a very tiny amount of carbon monoxide, and carbon monoxide does have a certain beneficial effect in our body, because our body naturally produces such a small quantity of hemoglobin, our blood contains about 0 mercury of carbon monoxide."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "That means our carbon monoxide or natural levels of carbon monoxide inside our blood plasma have no adverse effects on hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "However, other processes that take place outside of our body, for example, the production of car exhaust or the process of smoking these processes produce much more carbon monoxide."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And if we are exposed to even a small amount of carbon monoxide that comes from these processes, it can ultimately lead to the condition of carbon monoxide poisoning."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Now, how exactly would one treat carbon monoxide poisoning?"}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "Well, recall that carbon monoxide and oxygen bind to the same exact location on hemoglobin, and they bind reversibly."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And what that means is carbon monoxide is actually a competitive inhibitor of oxygen."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "So recall that in competitive inhibition, by increasing the concentration of the substrate, in this case the oxygen, we can actually cause the oxygen to outcompete the carbon monoxide for that position on the heme group of heat hemoglobin."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "And so, by increasing the amount of oxygen inside our blood, we can actually treat the carbon monoxide poisoning."}, {"title": "Carbon Monoxide and Hemoglobin.txt", "text": "In fact, that's exactly how it is treated by doctors."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So, as we already know, the citric acid cycle is super important to our cells, because the cells not only use the citric acid cycle to actually generate those NADH molecules which are then used by the electron transport chain."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "To create the high energy ATP molecules."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "But the TCA cycle, the citric acid cycle is also used to actually produce the building blocks that that are used by ourselves."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And this is summarized in this diagram."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So Pyruvate is transformed into acetyl coenzyme A-V-A Pyruvate decreboxylation and then vanacetal coenzyme A is fed into the TCA cycle, the citric acid cycle."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And in this cycle we not only use vatacetylcoenzyme A to form the ATP molecules v oxidative phosphorylation, but some of the intermediate molecules of the TCA cycle are also actually used to form many building blocks used by the cells of our body."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "For instance, citrate molecules via specific type of pathway that we're going to focus on in a future lecture, can be used to synthesize fats fatty acid molecules."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Alpha key to glutarate another intermediate of the TCA cycle can be used to form glutamate amino acids and other amino acids and we can also actually form purine nitrogenous bases."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Succinctoenzyme A, a third intermediate of the citric acid cycle, can be used to form heme groups and porphyrine groups."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So remember, these groups are used by enzymes such as hemoglobin and myoglobin."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And we also have oxyloacetate that can actually be used in gluconeogenesis to form glucose molecules."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And on top of that, we can also use oxalo acetate to form other amino acids and purity nitrogenous bases as well as pyrimidine nitrogenous bases."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So the point is, this is the center of metabolism."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "All the fuel molecules that we use to break down into ATP, this is where the fuel molecules end up."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "On top of that, we can use these intermediates of the citric acid cycle to basically produce many different types of amino acids and bases and glucose molecules as well as other important groups used by the enzymes and proteins of Arabani."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Now, what I'd like to focus on in this lecture briefly is the following idea."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Because the citric acid cycle is so important, we have to make sure that the concentrations, the levels of these intermediate molecules is actually kept in check."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So the concentration, the level of these molecules cannot actually drop below a certain value because if it does, the citric acid cycle will not actually take place."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And so I'd like to focus on a specific type of process that allows us to actually regenerate and replenish the concentration of oxalo acetate, which in turn allows us to actually replenish the concentration of all these other intermediates."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So remember, because this is a cyclic process, because we begin with oxyloacetate and then go back to that oxyloacetate, what that means is by replenishing the concentration of oxyloacetate, we in turn replenish the concentration of all the other intermediate molecules that are needed to produce all these different types of building blocks, as well as the NADH molecules which are needed to form ATP along the electron transport chain."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So what is this process that allows us to actually replenish the oxyloacetate concentration?"}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Well, it's a process that we actually discussed when we discussed gluconeogenesis."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So remember now discussion on gluconeogenesis."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "In gluconeogenesis, the first step in that process is to transform the Pyruvate molecule into oxyloacetate and the enzyme that catalyzes this step is Pyruvate carboxylase."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So Pyruvate carboxylase essentially attaches a carbon dioxide molecule onto that Pyruvate to form oxyloacetate."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "In the process we essentially break down an ATP to drive this process in this direction."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So we see that by attaching a carbon dioxide onto the Pyruvate, we are able to form the oxalo acetate."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And that allows us to keep to maintain a specific minimal level concentration of the oxalo acetate within the citric acid cycle, which in turn allows us to maintain a specific level of the other intermediates and that allows all these important processes to continue taking place inside our cells."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So for the citric acid cycle to keep up with the energy demands of the cell and the demands of producing all these different types of biological building blocks, the concentrations of the intermediate molecules within the TCA cycle must be regulated."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So we must maintain a minimal level of those intermediates."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So when our cells, for instance, deplete the concentration of oxalo acetate by, for instance, producing all these different types of building blocks, we essentially want to replenish the concentration via specific type of reaction that is catalyzed by Pyruvate carboxylate."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So in this step, we attach a CO2 molecule onto Pyruvate to form the four carbon molecule known as oxalo acetate."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "In the process, we hydrolyze an ATP by using water to basically drive the synthesis of this molecule in this general direction."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So when we have plenty of ATP molecules inside our body, because if our energy value is low we have a relatively high concentration of ATP, under these conditions the oxyloacetate will be transformed into a variety of products."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Well, because we're not going to need to use the oxyloacetate to actually generate those NADH molecules, to use the NADH molecules to produce ATP via the electron transport chain."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And so instead of using the oxylacetate to produce ATP, we're going to use the oxalo acetate to generate all these different types of biological molecules such as glucose specific amino acids, pure and bases and pyramididine bases."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "Now, if we have low energy charge values in a cell, if we have a relatively low amount of ATP in such cases we do want to actually form those ATP molecules, the NADH molecules and in turn the ATP molecules."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "And so under these conditions the Pyruvate will be used to replenish the concentration of oxalo acetate so that they can be used, the oxalo acetate can be used to actually synthesize those NADH molecules that can then be used by the electron transport chain to generate those ATP."}, {"title": "Replenishing Oxaloacetate in Citric Acid Cycle .txt", "text": "So in the next series of lectures, we're going to move on and focus on the electron transport chain and oxidative correlation."}, {"title": "Epithelial Tissue.txt", "text": "There are four major types of tissues found in the human organism."}, {"title": "Epithelial Tissue.txt", "text": "We have connective tissue, muscle tissue, nervous tissue, and we also have a tissue that is found in our digestive system and exciratory system known as the epithelial tissue or simply the epithelium."}, {"title": "Epithelial Tissue.txt", "text": "Now, epithelium consists of specialized types of cells known as the epithelial cells cells."}, {"title": "Epithelial Tissue.txt", "text": "And these cells come in different forms and different shapes as we'll see in just a moment."}, {"title": "Epithelial Tissue.txt", "text": "Now, first, let's define what the function and the purpose of the epithelial tissue is."}, {"title": "Epithelial Tissue.txt", "text": "So the epithelial tissue has three important functions."}, {"title": "Epithelial Tissue.txt", "text": "Firstly, it functions in protection."}, {"title": "Epithelial Tissue.txt", "text": "It protects the cells found underneath our epithelial layer from things like toxins, UV radiation, acidity and many other things."}, {"title": "Epithelial Tissue.txt", "text": "It acts to basically exchange the nutrients and the waste products between the cells found beneath our epithelial layer and our body cavity."}, {"title": "Epithelial Tissue.txt", "text": "And three, it basically synthesizes and secretes special types of molecules such as proteolytic, enzymes, sweat, mucus, as well as many other things."}, {"title": "Epithelial Tissue.txt", "text": "Now, epithelial cells which constitute the epithelial tissue come in three different shapes."}, {"title": "Epithelial Tissue.txt", "text": "So we have our cuboidal, columnar and squamous."}, {"title": "Epithelial Tissue.txt", "text": "Now, cuboidal simply means that the shape of our epithelial cell is of a cube."}, {"title": "Epithelial Tissue.txt", "text": "Our columnar simply means we have these rectangular like columns and C squamous simply means our cells are very flat so they look something like this."}, {"title": "Epithelial Tissue.txt", "text": "Now, these cells can basically organize themselves to form our epithelial tissue or the epithelium."}, {"title": "Epithelial Tissue.txt", "text": "And epithelium can be organized in three different ways."}, {"title": "Epithelial Tissue.txt", "text": "We can have simple epithelium, we can have stratified epithelium and we can also have something known as pseudostratified epithelium and we'll see what that means in just a moment."}, {"title": "Epithelial Tissue.txt", "text": "First, let's discuss simple and stratified epithelium."}, {"title": "Epithelial Tissue.txt", "text": "Now, a simple epithelium means that we have a single layer of cells across the entire basement membrane and we'll see what the basement membrane is in just a moment."}, {"title": "Epithelial Tissue.txt", "text": "And simple epithelium is usually found in that region of our digestive system that requires secretion and or absorption."}, {"title": "Epithelial Tissue.txt", "text": "On the other hand, stratified epithelium simply means we have many layers of our epithelial cells stacked on top of one another and this type of epithelium is usually found in those regions that is exposed to a continual amount of mechanical and chemical stress."}, {"title": "Epithelial Tissue.txt", "text": "And we'll see what that means in the next several lectures."}, {"title": "Epithelial Tissue.txt", "text": "So a third type of epithelium is known as pseudostratified epithelium."}, {"title": "Epithelial Tissue.txt", "text": "And this basically means that our layer of cells looks like it's multilayer, but it actually consists of a single layer of cells."}, {"title": "Epithelial Tissue.txt", "text": "So basically, this is an example of pseudostratified epithelium."}, {"title": "Epithelial Tissue.txt", "text": "So pseudostratified epithelium contains an arrangement of cells and arrangements of nuclei that resembles the typical arrangement found in stratified epithelium, but it actually consists of a single layer."}, {"title": "Epithelial Tissue.txt", "text": "So let's move on to our structure."}, {"title": "Epithelial Tissue.txt", "text": "Let's discuss the several components that we need to know in terms of our epithelial cells and epithelium."}, {"title": "Epithelial Tissue.txt", "text": "So we have this collection of cells that let's suppose it's found inside our stomach or inside our small intestine."}, {"title": "Epithelial Tissue.txt", "text": "So we have these epithelial cells that basically form a single layer."}, {"title": "Epithelial Tissue.txt", "text": "So this is a simple epithelium."}, {"title": "Epithelial Tissue.txt", "text": "And because the shape of these cells is that of a rectangle, that means these are columbnar cells."}, {"title": "Epithelial Tissue.txt", "text": "So we have a simple columnar epithelium."}, {"title": "Epithelial Tissue.txt", "text": "Now, this side is our lumen side."}, {"title": "Epithelial Tissue.txt", "text": "This is the cavity of our organ."}, {"title": "Epithelial Tissue.txt", "text": "For example, it's the cavity of the stomach or it's the cavity of our small intestine."}, {"title": "Epithelial Tissue.txt", "text": "Now, the side of our cells that faces our lumen side is known as the apical side."}, {"title": "Epithelial Tissue.txt", "text": "But the other side that faces our basement membrane is known as the basil lateral side or simply the basal side."}, {"title": "Epithelial Tissue.txt", "text": "So we have this basal side that is attached to our basement membrane."}, {"title": "Epithelial Tissue.txt", "text": "And the basement membrane simply is a matrix that consists of specialized proteins and other molecules whose function is to basically act as a base for these cells."}, {"title": "Epithelial Tissue.txt", "text": "So the basement membrane provides an attachment point for these epithelial cells."}, {"title": "Epithelial Tissue.txt", "text": "And below the basement membrane, we have some sort of connective tissue."}, {"title": "Epithelial Tissue.txt", "text": "So we have these blood vessels, we have our capillaries, we have these veins that basically provide the nutrients to these cells and also take away the waste products that are secreted by these cells."}, {"title": "Epithelial Tissue.txt", "text": "So the side of the cell that points towards the lumen side, the cavity, is known as the apical side, while the side attached to our basement membrane, it's called the basil lateral side."}, {"title": "Epithelial Tissue.txt", "text": "Now, the basement membrane is also sometimes known as the basal lamina or the basal membrane."}, {"title": "Epithelial Tissue.txt", "text": "Now, this basement membrane acts as an attachment point for the cells."}, {"title": "Epithelial Tissue.txt", "text": "It holds those cells together and it consists of specialized proteins such as, for example, collagen."}, {"title": "Epithelial Tissue.txt", "text": "Now, epithelial cells, as we mentioned earlier, are found in our digestive system as well as in many other places of our body."}, {"title": "Epithelial Tissue.txt", "text": "For example, our skin."}, {"title": "Epithelial Tissue.txt", "text": "Now, the stomach, the small and large intestines all consists of layers of these specialized epithelial cells."}, {"title": "Epithelial Tissue.txt", "text": "And these epithelial cells not only protect our internal cells and organs, but they also secrete as well as absorb many different types of nutrients, nutrients into our body."}, {"title": "Epithelial Tissue.txt", "text": "And we'll see how this actually takes place in the next several lectures when we focus on the stomach, the small intestine, as well as the large intestine."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Inside our body we have these specialized cells known as adipose cells that function to basically store fatty acids in their triglyceride form."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So if we look within a cytoplasm of these adipose cells, we'll find these large structures known as fat globules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And these fat globules consist entirely of individual triglyceride molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, we know the cells of our body can actually actually use these triglyceride molecules to help generate ATP molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "But how exactly does this process actually take place?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So as we'll see in just a moment, the utilization of these triglycerides to actually help us generate these high energy ATP molecules involves three different steps, three different stages."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So in stage one, these triglycerides are actually broken down and mobilized into their fatty acid and glycerol form."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Once that takes place, the fatty acids are released into the bloodstream and the bloodstream carries these molecules of fatty acids to their target cell."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Once the fatty acid makes its way into the cytoplasm of that target cell, that's when stage B actually takes place."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And in stage B, these fatty acids are activated, they're made more reactive and then they're transported into the matrix of the mitochondria."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And that's when stage C begins."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "In stage C, those fatty acids are broken down in the matrix of the mitochondria into acetyl coenzyme A molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And these acetyl coenzyme A molecules can be fed into the citric acid cycle to help us generate the high energy ATP molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, in this lecture, what I'd like to focus on is stage A."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So the breakdown of the mobilization of these triglycerides into fatty acids and glycerol molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And this takes place within these adipose cells, fat cells of our body."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So let's suppose that we just woke up and after waking up, we basically want to go for a run or a swim."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So we want to carry out some type of exercise."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, overnight, what happened was the cells of our body used up their supply of glucose and glycogen."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And so as soon as we go for that morning run or swim, our cells will depend on triglycerides to actually form the ATP molecules that are needed to carry out those particular cell processes."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And so the question is, what actually initiates the breakdown and the mobilization of triglycerides within our fat cell in this circumstance?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Well, basically specific types of hormones."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So we have hormones such as glucagon and epinephrine that can initiate the breakdown of the mobilization of triglycerides."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So we have some type of primary messenger molecule."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So it can be glucagon or it can be epinephrine that binds onto a specific seven transmembrane protein receptor found on the membrane of adipose cells."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once it actually binds, it creates a conformational change in that seven TM structure and that causes structural changes in the g protein."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And what that does is it releases the GDP and it basically accepts the GTP."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once the GTP binds onto that g protein and activates the protein and the protein then travels and binds onto another membrane molecule known as adenylate cyclist."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And what this enzyme basically does is, upon the binding, it is activated."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Upon the binding of the g protein, it is activated, and it begins the conversion of ATP molecules into cyclic Amp molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And the cyclic Amp is a secondary messenger in this particular cyclical transduction pathway."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, the cyclic Amp molecules then move on to target protein."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So PKA molecules protein kinase A."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So cyclic Amp binds onto the regulatory units of the PKA."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "That causes the dissociation of the catalytic units from the PKA, and that activates the PKA."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once the PKA is actually activated, protein kinase A goes on to phosphorylate and activate two important types of enzymes involved in the breakdown and the mobilization of triglyceride."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So what are these important enzymes?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Well, one of them is known as parolipin A, and the other set of enzymes are known as hormone sensitive lipases."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So these two enzymes work together to basically help break down these triglycerides into fatty acids and glycerol molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "More specifically, the paralypinate basically binds onto the fat globules found in the cytoplasm of adipose cells, and they stimulate the remodeling and the restructuring of these fat globules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "What that does is it exposes the ester bonds of the triglycerides."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And now the hormone sensitive lipases, such as triglyceride lipase, essentially bind onto those exposed ester bonds and begin cleaving breaking hydrolyzing those triglyceride ester bonds."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And so, ultimately, we transform the triglycerides into the individual, free floating fatty acids and the glycerol molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once that takes place, these two molecules in their mobilized form, are now released into the bloodstream."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, once inside the bloodstream, what happens next?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Well, glycerol molecules contain one to three hydroxyl groups, and that makes them polar molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And because our blood plasma consists predominantly of water, that means glycerol will be soluble in the blood plasma, and so it will not actually require any type of protein carrier to transport it within the blood plasma."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, glycerol molecules ultimately end up in liver cells, and we'll discuss exactly what happens to the glycerol molecules in just a moment."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "But first, let's actually look at these fatty acids."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, fatty acids contain this relatively long hydrocarbon chain, the R group, and that makes fatty acids insoluble in water."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And so they will not be able to actually dissolve in our blood plasma."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And unlike glycerol molecules, fatty acids will require a protein transported molecule."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And this molecule is known as serum albumin."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So serum albumin actually binds fatty acids in the blood plasma, and it carries those fatty acids to the target cell."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And in the example that I gave before, the target cell that the fatty acids are carried to are the skeleton muscle cells that help us carry out the different types of voluntary motions."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now, what happens to the glycerol?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Well, the glycerol, as I said earlier, moves into liver cells."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once inside the cytoplasm of liver cells."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "An enzyme known as glycerol kinase traps that glycerol inside that liver cell and it traps it by giving it a negative charge."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So it actually takes off a phosphoryl group from an ATP, places it onto the oxygen of glycerol, forms an ATP, as well as the l isomer of glycerol three phosphate."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And this traps the glycerol inside that particular liver cell."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now what happens next is that glycerol three phosphate is transformed into dihydroxy acid zone phosphate by the enzyme glycerol phosphate dehydrogenase and it also actually reduces the NAD plus and generates NADH."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So this is essentially an oxidation reaction where the glycerol three phosphate is oxidized into the dihydroxy acetone phosphate."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And once we form this, it is then transformed into the deisomer of glycero aldehyde three phosphate."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "And recall that glyceroaldehyde three phosphate is an intermediate of both the glycolytic pathway glycolysis as well as glucooneogenesis."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now the fate of this glyceroaldehyde three phosphate basically depends on the conditions of the body and the liver cell."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So essentially if we need to generate ATP molecules within a liver cell, then the glycero aldehyde three phosphate can basically undergo glycolysis."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "We can form Pyruvate and that can help us generate ATP molecules."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "On the other hand, if the liver cells have to maintain, let's say, increase the blood glucose levels in our body, then the glyceroaldehyde three phosphate can undergo gluconeogenesis and form the glucose molecule and the glucose can be released into the blood plasma of our body to help regulate and maintain the proper glucose levels of the body."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "So we see that the glycerol that is formed from the breakdown of the triglycerides ultimately ends up in the liver cell and it can be used by the liver cell to basically help maintain the correct blood glucose levels and also also help generate ATP molecules needed by that liver cell."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Now what happens to the fatty acids?"}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "Well, this is what I'd like to focus on in the next lecture."}, {"title": "Mobilization of Triglycerides in Adipose Cells .txt", "text": "In the next lecture we're going to discuss how these fatty acids are activated within the target cell and then transported into the matrix of the mitochondria of that target cell."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Previously, we focused on pyruvate carboxylation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So what we basically said is once Glycolysis takes place in the cytoplasm and we form the Peruvate molecules under aerobic conditions, when we have plenty of oxygen in the cell, the pyruvate molecules will then move into the matrix of the mitochondrion."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And once inside the matrix, before the pyruvate molecules can actually enter the citric acid cycle, they must be activated."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And the way that we activate the pyruvate molecule is by removing a carbon dioxide and taking the remaining two carbon components of the pyruvate, known as the CETO group, and placing it onto a carrier molecule known as coenzyme A COA."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So at the end of pyruvate decarboxylation that takes place in the matrix of the mitochondria, we form the CETO coenzyme A complex."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, this activates the molecule and allows it to actually enter the citric acid cycle."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So we see that pyruvate decarboxylation actually is the connection."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It's the link between Glycolysis and the citric acid cycle of aerobic cell respiration."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So pyruvate carboxylation connects or links Glycolysis to aerobic cell respiration by creating the Cecil coenzyme A molecule that can readily enter the first step of the citric acid cycle."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so in this lecture, I'd like to begin our discussion on the first step of the citric acid cycle."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So what exactly is the first step?"}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Well, once we form the cetil coenzyme A complex, it goes into the citric acid cycle and undergoes step one."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And in step one, the ultimate goal is to combine the Cetal group of the cetil coenzyme A, the two carbon component, onto a four carbon component, a four carbon molecule found in the matrix of the mitochondria known as oxyloacetate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this is the same oxyloacetate that we saw when we discussed Gluconeogenesis."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So the four carbon molecule oxyloacetate is ultimately combined with this two carbon component, the CETL group of acetyl coenzyme A, to form a six carbon molecule 123456, known as citrate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, citrate is the conjugate base of citric acid and citric acid is an example of a tricarboxylic acid."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And that's why the citric acid cycle is also sometimes known as the TCA cycle, tricarboxylic acid cycle."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And of course, we also regenerate the coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And the coenzyme A can now be reused in the process of pyruvate carboxylation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, as we can see from the following overall reaction, step one of the citric acid cycle is actually a multi step process."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It consists of two different steps."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And both of these steps are essentially catalyzed by an enzyme known as citrate synthase."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And as the name applies, as the name implies, we essentially synthesize the citrate molecule beginning with these two reactant molecules."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So these are the substrate molecules to the citrate synthase."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, step number one is actually an Aldol condensation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And we'll look at the details of this step in just a moment."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And in step one, we form a citral coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, the citral coenzyme A is actually very high in energy."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Well, because of this thyouester bond that connects the carbon and the sulfur."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So this is a very high energy bond."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And in step two, once we undergo the condensation reaction we'll undergo a hydrolysis reaction in which a water molecule will be used in the enzymes active site to actually cleave the high energy bond forming these two products the citrac molecule and the coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this step essentially releases energy and this is a step that drives this entire step one of the citric acid cycle."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So once again, the first step produces a citro coenzyme A complex which contains the six carbon component attached onto the coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "This reaction is what we call an Aldo condensation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "The second step releases the coenzyme a component to form the citrate molecule as well as this individual coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this is a hydrolysis reaction which we use a water to actually cleave this bond."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so the oxygen essentially attaches itself onto this carbon here to form this group shown here."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, it's the second step of this overall process that drives the overall equilibrium of this process to the product side so that we can basically form the citrate molecules effectively and efficiently."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And that's because the cleavage of this high energy bond is actually a very beneficial process because we don't want to have this high thio esther bond, this high in energy thio ester bond."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So in this lecture, I'd like to focus on step one or actually the first process of step one."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So the Aldol condensation reaction because this step is much more complicated than the simple hydrolysis step."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So before we look at the reaction mechanism what actually takes place in the active side of the enzyme, let's discuss briefly this citrate synthase enzyme."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So citrate synthase, the enzyme that catalyzes step one of the citric acid cycle is actually a dimer enzyme."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It consists of two identical subunits and one of these subunits is shown on the board."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Basically, we have two of these subunits that essentially interact with one another to form the citrate synthes."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now let's take a look at this subunit."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And actually the subunit contains three types of domains or actually two types of domains but overall three domains."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So we have one domain here, then we have an intermediate domain and another domain here."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And these domains are essentially identical but they're different to this middle domain."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And we see that we have active sites found right over here, right next to this domain and here right next to this domain."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And interestingly, what happens is these two molecules don't actually bind to the active side together."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It's the oxalo acetate that binds into the active side of that enzyme."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Well, because initially in its open confirmation the enzyme the citrate synthase only contains an active pocket, an active side for the binding of oxalo acetate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It does not yet contain a pocket that can bind the seeds of coenzyme a."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So what we see happening first is the oxyloacetate molecule."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "The four carbon molecules shown here binds into the active side."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And once it binds into the active side, it creates conformational changes."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So it causes these two domains to basically rotate inward."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So going this way and when that rotation takes place, it does several important things."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Number one is it seals off the active side."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Well, it doesn't actually seal off the active side entirely."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Why?"}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Well, because this molecule has to enter that particular active side."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And we'll see that in this step, as we'll see in just a moment, this actually creates that entire sealing process, whereas seal off that active side completely."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So we go from the open confirmation to the closed confirmation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And what this also does is upon the binding of the oxalo acetate to the active side of the citrate sentase, it creates an additional binding site in that active side that can now bind the CETO coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So we see that once the oxyloacetate binds to the active side, it creates conformational changes that induces the opening of a binding site, the creation of a binding site that can bind the CETO coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And what it also does is it basically shifts the catalytic residues in the actuide in their proper orientation, which can basically begin this aldol condensation step."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So once again, the enzyme first binds the oxalo acetate into the active side, which causes the conformational changes in the structure."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "As shown here, we essentially go from an open confirmation to a closed confirmation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "But it's not entirely closed because we still have to be able to fit the Cetal coenzyme A so that they actually can interact with one another to form the citral coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And once the citral coenzyme A is formed, as we'll see in just a moment, only then do we have a complete closure of these active sites."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So once this conformational change takes place, it also creates a binding site for acetylco enzyme A and shifts the catalytic residues in the active side of the enzyme into their proper orientation and position so that the catalysis reaction can actually take place."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So to summarize how this process of aldole condensation, basically the first process, step one of the citric acid cycle actually takes place, let's take a look at three of these three diagrams, beginning with diagram number one."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, in diagram number one, we have the active side of our enzyme and there are three different types of residues that basically catalyze this process."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "We have histidine 274, we have histidine 320, and we also have Aspartate 375."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, this here is basically the Cecil coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this here is the oxalo acetate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So let's suppose the oxalo acetate binds into the active side that induces a conformational change that then allows that acetyl coenzymen to bind into the active side."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so now we have this diagram."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So in step one, what takes place is we ultimately want to form an enol intermediate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And remember, the enol form of this molecule contains a hydroxyl group here and a double bond between this carbon and this carbon."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So remember from organic chemistry that whenever we have an aldol condensation reaction, we essentially have an enorm intermediate molecule."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so, to essentially stimulate the formation of this enormous molecule that will act as a nucleophile that will help form the citrull coenzyme A, we see that these enzymes, or I should say these catalytic residues of the enzyme, actually help with this process."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So HistoGene 274 uses the hydrogen ion attached onto this nitrogen."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "It donates that H ion onto the oxygen of this carbonyl group shown here."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And what that does is it weakens this double bond between the carbon and the oxygen at the same time as pertain 375 basically acts as a base and it takes away the H ion from the methyl group shown here."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And by taking away the H ion, it allows this sigma bond to basically go on and form a pi bond, displacing these two electrons, allowing those two electrons to take that H ion."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so we see that these two catalytic residues essentially allow the formation of the enormity, the double bond that will act as a nucleophile in the next step, as we'll see in just a moment."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So in one we have histidine 274, shown here in the acticide, is used to give the carbonyl oxygen that H plus ion."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this stimulates the removal of a hydrogen ion from the methyl group by aspertain 375."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So together, these residues act on this acetyl coenzyme A and allows the formation of that enol intermediate molecule that now contains that pi bond between these two carbons of the acetyl group."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, let's move on to four and five."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So now, before this ENL intermediate can actually act as a nucleophile, we have to convert this oxyloacetate into a good electrophile."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Because remember, anytime we have a nucleophilic attack, we have an electrophile that is actually being attacked."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Now, in this form here, the oxyloacetate is not a good enough electrophile."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so what happens is now we have histidine 320 that donates its H ion onto this oxygen of the carbonyl group of the oxalo acetate."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And this basically weakens the pi bond, it forms a carbocation intermediate and that converts this poor electrophile into a much better electrophile."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so now, because this is a very good electrophile, this pi bond of this ENL can act as a nucleophile and attack the carbon nucleophilically to form that connection between this acetyl group and this citrate molecule."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so, in the next step, we are able to actually form that citral Co enzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And once we form the citrus coenzyme A, that induces even more conformational changes that completely seal off these active sites."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And by sealing off the active side, that basically prevents different types of competing reactions from actually taking place."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "So we see that in part four, the H plus ion of histidine 320 is given to the carbonyl group of the oxyloacetate, creating the strong, the good electrophile."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "Next, the pi bond of the ENL can act as a nuclear while taking the carbon of this oxylace, forming that intermediate, that citral coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And once the citral coenzyme A is actually formed, that induces even more conformational change that essentially closes off and seals off the active side of the enzyme completely."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so now we have this microenvironment within the active side of the enzyme that basically means all different types of substrate molecules are found in closed proximity and they're found in the proper orientation."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And that means this reaction basically can continue onwards."}, {"title": "Step 1 of Citric Acid Cycle .txt", "text": "And so once we form this citrate once we form the citral coenzyme A intermediate, the phosphorus."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Hemoglobin consists of four individual polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "We have the alpha one and alpha two chains which are identical with respect to one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And we also have the beta one and the beta two chains, which are also identical with respect to one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And in each one of these polypeptide chains, we have this rat structure."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And these red structures are the heme groups."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "They contain the iron and the protoporphy that are responsible for binding diatomic oxygen."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And because one hein group binds 01:02 molecule, one hemoglobin molecule can bind in total a maximum of four diatomic oxygen molecules."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, usually, instead of picturing our hemoglobin as consisting of four individual chains, we look at the hemoglobin as consisting of two individual dimers."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "One of these dimers is the alpha one, beta one dimer, and the other dimer is the alpha two beta two dimer."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Remember, a dimer is simply a molecule that consists of two polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, because alpha one and because alpha one and alpha two are identical and beta one and beta two are identical, we see that alpha one beta one dimer is identical to alpha two, beta two dimer."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And we'll see in just a moment why we break it down into these two dimers instead of breaking it down into four individual polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, let's begin by recalling some information about hemoglobin that we learned previously."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So we said the fact that the oxygen binding curve for hemoglobin is sigmoidal basically implies that hemoglobin behaves in a cooperative fashion."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And what that means is the different heme groups actually interact with one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So as one of the heme group becomes occupied with oxygen, it causes the other heme groups to increase their affinity for oxygen."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And likewise, when one of the heme groups releases the oxygen, the other occupied heme groups become much more likely to unload and release that oxygen."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So this is what we mean by the cooperative nature and the cooperative behavior of hemoglobin molecules."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, once again, what this implies is that the heme groups, the four heme groups in hemoglobin somehow interact with one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "They cooperate with one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "But if we examine the structure of hemoglobin, we'll see that the four different hemoglobin molecule, the four different heme groups, these red structures within each polypeptide chain are actually separated by a certain distance."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And what that implies is the heme groups do not actually interact with one another in a direct fashion."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And as we'll see in just a moment, even though the heme groups do not interact with one directly, the surfaces between the polypeptide chains do interact with one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And more specifically, it's the surface to surface interaction between the two dimers in this hemoglobin that actually causes that cooperative behavior of hemoglobin."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So to see how that takes place, let's take a look at the following diagram."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So, in this diagram to the left, we have the alpha helix of one of the polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this alpha helix is attached to this heme group."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So remember, the heme group shown here consists of the organic component that is known as the protoporphrine."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And it also contains that inorganic metal atom, that iron atom."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, the iron atom is attached to the proximal HistoGene amino acid that is attached to this polypeptide chain."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And notice that because the oxygen is not attached to our iron atom, that iron atom is found below the plane of that protoporphine."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Because when it's not balanced as an oxygen, the iron is simply too large of an atom."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "It contains a large electron density."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, this green structure is simply the surface of the adjacent polypeptide subunit."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And notice there's a certain distance between these two subunits and they interact in a certain way."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, what happens when oxygen actually binds onto the iron of this heme group?"}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So because of the electronegative character of oxygen, when diatomic oxygen shown here actually binds onto this heme group, more specifically, onto the iron of that heme group, it pulls away some of that electron density from that hein group, it pulls away some of that electron density from that iron atom."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And because some of the electrons move away from that iron atom, it decreases the electron density and the size of that iron atom."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And now, because the iron atom is smaller, it is able to move into the plane, into the center of the plane of that protoporphy and as shown in the following diagram."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So as the diatomic oxygen binds onto the iron, it pulls the iron inward into the center of the proteporphine molecule."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And because the iron, which is this purple molecule here, is attached to that proximal histidine, it also pulls on that proximal histidine."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this in turn pulls on this entire alpha helix of that polypeptide chain."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And so when the binding takes place, there is a change in surface to surface interaction between these two adjacent polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Notice the distance here and the distance here basically changes."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this changes the electrostatic interaction between these two polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And it's this surface to surface interaction change that causes the cooperative behavior between the different polypeptide chains and the different heme groups found inside that polypeptide chain."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So once again, as oxygen binds onto the heme group, as shown in the following diagram, it decreases the size of that iron atom, pulling it into the plane of the proteporphinen."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And since the iron atom is attached onto the proximal histidine, it pulls on that proximal histidine."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And that in turn pulls and shifts that entire polypeptide chain as shown in this diagram."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So this shift causes a conformational change in the surface to surface interaction between the adjacent subunits."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this is precisely what leads to the cooperative behavior of the hemoglobin molecule."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, if we examine the structure, the quarterly structure of the deoxy hemoglobin, deoxy hemoglobin is simply the hemoglobin molecule in which the four heme groups are unoccupied."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "The quarterinary structure of deoxy hemoglobin is very constrained because the interactions are not very good."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And so because of this constrained nature of deoxyhemoglobin, we call that state the 10th state or simply the t state."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So the coronary structure of deoxy hemoglobin is quite constrained."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And for this reason, deoxy hemoglobin is said to exist in the t state where t stands for tense."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, when oxygen begins to bind onto the heme group, it creates this conformational change and it causes this change in the interaction between the surfaces of the different polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And what this does is it lifts that constraint, it relaxes that tertiary, it relaxes that quarterly structure of that hemoglobin molecule."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And that's precisely why when all the four heme groups become occupied with oxygen because of the relaxed state of that coronary structure of the hemoglobin, we call this state the r state, where r stands for relaxed."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So we see that on the other hand, even though deoxy hemoglobin is quite constrained and exists in the t state, oxymoglobin contains a much more relaxed conformation due to the interactions between the surfaces of the polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this is called the r state or the relaxed state."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Now, earlier I said that instead of looking at this hemoglobin molecule as consisting of four polypeptide chains, typically we examine the hemoglobin molecule as if it consists of two dimers the alpha one, beta one, and the alpha two beta two."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Why is that?"}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "Well, that's because when our molecule goes from the 10th state, the deoxyhemoglobin state to the relaxed state, that oxymoglobin state, the two alpha beta dimers rotate 15 degrees with respect to one another."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this rotation is what causes this cooperative behavior of that hemoglobin molecule."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "This rotation is what causes that shift to take place from the 10th state to that relaxed state."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So when hemoglobin is oxygenated, one of the AlphaBeta dimers rotates 15 degrees with respect to the second AlphaBeta dimer."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this shift leads to the cooperative behavior of hemoglobin."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "So we conclude that when we have the deoxyhemoglobin and one of the unoccupied heme groups begins to bind an oxygen molecule, it induces a conformational change from the t state to that relaxed state."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And by inducing this change, there's a change in the surface to surface interaction between the polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And this is precisely what causes that cooperative behavior of the different heme groups found in each one of these polypeptide chains."}, {"title": "T-state and R-state of Hemoglobin.txt", "text": "And that's exactly why when one oxygen binds onto one of the heme groups, that conformational change causes the other heme groups to increase their affinity for binding oxygen."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So let's summarize the functions of the different hormones involved in the menstrual cycle."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And before we begin let's make two important distinctions."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Let's divide the menstrual cycle into two phases."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So we have the before ovulation, the pre ovulatory phase and we have the after ovulation phase, the post ovulatory phase."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And the reason we have to make this decision distinction is because the different hormones involved in the menstrual cycle have slightly different functions in these two phases as we'll see in just a moment."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So let's begin in the before ovulation phase."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Before ovulation simply means it's before that secondary follicle actually ruptures and before it releases that secondary oxide into the fallopian tube."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now recall that there are three important organs involved in the menstrual cycle."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "We have the hypothalamus and the interior pituitary gland found in the brain and we have the ovary found in the pelvic region of that female individual."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now the hypothalamus releases a special type of hormone known as the gonadotropin releasing hormone or GnRH."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And what GnRH does is it moves down to the anterior pituitary gland and it stimulates that gland to produce two important hormones the luteinizing hormone and a follicle stimulating hormone."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So the more GnRH we have in our bloodstream the more of these two hormones we're going to have in our bloodstream."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now both LH and FSH move down to the ovaries and stimulate the development of the follicle inside the ovaries but they do it in two different ways as we'll see in just a moment."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So let's take a look at our developing follicle."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "The developing follicle actually consists of several important components."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "We have the actual developing oicide the developing ex cell shown in red."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "We also have the nutritious fluid shown in green."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And we have two different types of cells."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "The dark purple cells are the granolosis cells and the light purple cells are the Fegus cells and these two cells have different functions."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now the follicle stimulating hormone actually stimulates the differentiation and the proliferation of the granulosa cells while the luteinizing hormone stimulates differentiation and the proliferation of these FECA cells."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And what these two cells do is they work together to form a hormone known as estrogen."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So theca cells use cholesterol to form androgens and then they release those androgens and give the androgens to granulosa cells."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And the granalosa cells contain a special enzyme that is capable of transforming the androgens produced by FECA cells into estrogen."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now once they produce estrogen the estrogen basically does several things."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Firstly, it initiates the thickening of the lining of the uterus."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "It basically thickens the endometrium in preparation for a potential implantation by a zygote if fertilization actually takes place."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And what estrogen also does is it goes up to the hypothalamus and via a positive feedback loop it stimulates more GnRH to actually be released."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And because we have more going onotrop and releasing hormone in the blood system we have more LH and FSH because this positively stimulates the interior pituitary gland."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now, the estrogen also actually directly affects the interior pituitary gland and as a result it releases more LH and FSH into our blood."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So we see that more estrogen means more LH and FSH."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "In fact, it's the increase in estrogen that creates that surge in LH that actually causes Ovulation to take place in the first place."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So these are the hormones and their functions before Ovulation."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So let's suppose we have that surge in LH and Ovulation actually takes place."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "What happens next?"}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Well, we still have the gonadoshop releasing hormone that is produced by the hypothalamus and it still stimulates the interior pituitary gland to continue to produce LH as well as FSH."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now, what LH does post Ovulation is it actually forces the remaining component of the follicle to mature into the corpus luteum to produce the corpus luteum."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And the Lutonizing hormone stimulates the corpus luteum to produce not only estrogen but another type of hormone known as progesterone."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now, estrogen initiates the thickening of the endometrium but progesterone actually maintains that thickening process."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "What it also does is it basically inhibits the contraction of the muscle found inside the uterus and it also inhibits the production of secondary follicles."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now notice what it does to the hypothalamus and to the interior pituitary gland, the progesterone as well as the estrogen that is produced by the corpus luteum."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now, instead of creating a positive feedback loop as it did before Ovulation post Ovulation these two hormones create a negative feedback loop."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So they basically cause the hypothalamus to release less GnRH."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And so because we have less of this we're going to have less LH and FSH stimulation and these also directly affect the interior pituitary gland."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So that means once again we'll have less LH and less FSH actually form."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Now, what exactly is the result of that?"}, {"title": "Hormones in Menstrual Cycle.txt", "text": "Well, because of this negative feedback loop we'll have less Lewinizing hormone present in the blood."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And because the corpus luteum means the luteinizing hormone to actually exist because we have less luteinizing hormone we'll have our corpus lute eventually deteriorate into the corpus albicans."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "And so what that means is because we have less of this we'll eventually form less progesterone and that basically ends the cycle, the menstrual cycle and it causes the process of menstruation to take place as long as no fertilization actually occurs."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So we see that progesterone and estrogen in the post Ovulation stage actually cause the process of menstruation and that ends the menstrual cycle and cause the cycle to basically repeat itself."}, {"title": "Hormones in Menstrual Cycle.txt", "text": "So these are the hormones involved in the menstrual cycle and we see that their functions are slightly different before Ovulation and after Ovulation actually takes place."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "In the next several lectures we're going to focus on a biochemical process that takes place within the cytoplasm of our cells as well as within all other organisms."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And this pathway is the pentose phosphate pathway."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now the pentose phosphate pathway is very important for several reasons."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Number one, what it does is it gives our cells away to basically produce a very important reducing agent that is used in many different types of pathways and reactions within our cells."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And this reducing agent is known as NADPH, which stands for nicotine amide adenine Dinucleotide phosphate."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now NADPH is not the same thing as NADH."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "NADH is the molecule that is used along the electron transport chain."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So the electron transport chain oxidizes the NADH molecules and uses that to generate ATP molecules."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "On the other hand, NADPH is actually used as a reducing agent in many different types of biological processes."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "What are these biological processes?"}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Well, for instance, fatty acid biosynthesis, nucleotide biosynthesis, cholesterol, bisynthesis, neurotransmitter biosynthesis, as well as many different types of detoxification processes as we'll discuss in future lectures."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now, what's the difference between NADH and NADPH in terms of their structure?"}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Well, the only difference is if we examine the second carbon hydroxyl group on one of the ribose units on the NADPH molecule it will be phosphorylated and in the case of NADH it is not phosphorylated."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So if we take a look at this diagram we'll see what we mean."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So we have one of the ribose units and a second ribose unit on this ribose unit on the second carbon."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So this is carbon 1234 and five on this second carbon the hydroxyl group is actually phosphorylated and that's the difference between NADH and NADPH."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now the pentosphosate pathway also has several other important roles."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Number two is it actually provides our cells, our body, a way to break down five carbon sugars that we ingest from our diet."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So it provides a way to break down pencil sugars obtained from the diet."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "It also provides us a way to synthesize pento sugars, for instance, ribo sugars that we commonly use to synthesize other important biochemical molecules such as DNA molecules, RNA molecules, coenzyme A molecules, ATP molecules, NADH molecules, as well as fad molecules."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And the final important role of the pentose phosphate pathway is that it allows us a synthesis and the breakdown of the less common four carbon and seven carbon sugars."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now, as we'll discuss in much more detail in the lectures to come, we can break down the pentosphosphate pathway into two phases or two stages."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "The first phase is known as the oxidation phase or the oxidative phase."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "In this phase, what we basically do is we essentially oxidize glucose molecules."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "More specifically, we oxidized glucose phosphate molecules into ribose five phosphate molecules."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "In the process we also generate those that reducing agent, the NADPH molecules."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So this is the reaction that takes place in the oxidative phase."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So we have glucose six phosphate we have two NADP plus molecules and an H two O molecule."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "On the reactant side, on the product side, we produce a ribose phyphosphate."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "We generate the NADPH molecules, the reducing agents that can be used in a variety of biphynthetic processes as discussed in that section."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And we also generate carbon dioxide."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So we see that in the first phase, the oxidative phase, the cell breaks down glucose into a five carbon sugar, a pento sugar and also releases a carbon dioxide and generates the much needed NADPH."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "Now, in the second stage, in the second phase, that's the non oxidative phase."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And what happens is we have three carbon, four carbon, five carbon, six carbon and seven carbon sugars are interconverted from one to the other."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And if we have an excess of five carbon sugars what this pathway does is it basically transforms the five carbon sugars into intermediates that can be part of the glycolytic pathway."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "And we'll discuss that in much more detail in the lectures to come."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "So ultimately, the pentose phosphate pathway gives our body a way to actually digest."}, {"title": "Introduction to Pentose Phosphate Pathway.txt", "text": "They'll break down as well as synthesize five carbon sugars and it also gives us a way to actually create these reducing ages molecules, NADPH molecules which are needed in many different types of biosynthetic processes that take place within our cells."}, {"title": "Pedigree Analysis.txt", "text": "A pedigree is a tool that is used by geneticists that helps them discover the way that a trait for some disease is passed down from one generation to another generation."}, {"title": "Pedigree Analysis.txt", "text": "Now, by analyzing a pedigree like the one shown on the board, geneticists can basically discover two important things about that trade for disease."}, {"title": "Pedigree Analysis.txt", "text": "Number one, they can basically uncover the the mode of trait inheritance."}, {"title": "Pedigree Analysis.txt", "text": "So is the trait for a disease recessive or is it dominant?"}, {"title": "Pedigree Analysis.txt", "text": "They can also uncover whether or not that trait is found on the sex chromosome, the X chromosome, or if it's found on an autosome."}, {"title": "Pedigree Analysis.txt", "text": "So let's focus in on the following pedigree and let's describe the different components of a pedigree."}, {"title": "Pedigree Analysis.txt", "text": "So beginning with the shapes."}, {"title": "Pedigree Analysis.txt", "text": "So we have two types of shapes."}, {"title": "Pedigree Analysis.txt", "text": "We have squares and we have circles."}, {"title": "Pedigree Analysis.txt", "text": "Now, the squares describe a male individual and the circles describe a female individual."}, {"title": "Pedigree Analysis.txt", "text": "We also have colored squares and circles, and we have uncoloured squares and circles."}, {"title": "Pedigree Analysis.txt", "text": "Now, a colored shape basically describes an individual that has the phenotype for that particular disease and expresses that disease, while the uncooled individual, the uncolored shape, describes individual that does not show that particular phenotype for that particular disease, so they are not affected by that disease."}, {"title": "Pedigree Analysis.txt", "text": "Now, all these individuals, all these shapes found along the same road describe all the individuals that belong to the same exact generation."}, {"title": "Pedigree Analysis.txt", "text": "So, for example, individual one, two, three and four belong to, let's say the P generation."}, {"title": "Pedigree Analysis.txt", "text": "Individuals 56789 belong to the F one generation and individuals ten, 1112 and 13 belong to the F two generation."}, {"title": "Pedigree Analysis.txt", "text": "Now, said another way, if we belong to this generation here, then these are our parents."}, {"title": "Pedigree Analysis.txt", "text": "These are the siblings of our parents and these are our grandparents."}, {"title": "Pedigree Analysis.txt", "text": "Now, we also have these lines."}, {"title": "Pedigree Analysis.txt", "text": "What exactly the lines actually describe?"}, {"title": "Pedigree Analysis.txt", "text": "Well, the lines describe the relationship between the different individuals of our family."}, {"title": "Pedigree Analysis.txt", "text": "Remember, the pedigree describes the ancestry of our family."}, {"title": "Pedigree Analysis.txt", "text": "So basically, if we look at individual one and individual two, what this line describes is the fact that this is a married couple and they have three children, five, six and seven, which are all normal with respect to the phenotype."}, {"title": "Pedigree Analysis.txt", "text": "Now, this is couple number two."}, {"title": "Pedigree Analysis.txt", "text": "So we have three and four, basically mates."}, {"title": "Pedigree Analysis.txt", "text": "They produce child eight and child nine."}, {"title": "Pedigree Analysis.txt", "text": "So this is our mother that has a normal phenotype."}, {"title": "Pedigree Analysis.txt", "text": "This is our father that has the normal phenotype, and they have four children."}, {"title": "Pedigree Analysis.txt", "text": "So if this is you, then these are your siblings."}, {"title": "Pedigree Analysis.txt", "text": "So we have a normal and abnormal phenotype for the male."}, {"title": "Pedigree Analysis.txt", "text": "We have a normal phenotype for the female and an abnormal phenotype for that female."}, {"title": "Pedigree Analysis.txt", "text": "So this will express that particular disease."}, {"title": "Pedigree Analysis.txt", "text": "Now, sometimes we're also going to see shapes, either a circle or a square that are half filled, that are half colored."}, {"title": "Pedigree Analysis.txt", "text": "And whenever we see a shape that is half filled, what that means is we're dealing with a recessive trait for that particular disease."}, {"title": "Pedigree Analysis.txt", "text": "So if the disease in question is recessive, then the way that we describe heterozygous individuals for that particular trait is by using the following symbol for a woman and a square, a half filled square for a man."}, {"title": "Pedigree Analysis.txt", "text": "So this describes a heterozygous female individual that contains a dominant upper case and a recessive lowercase."}, {"title": "Pedigree Analysis.txt", "text": "So let's suppose B is our gene."}, {"title": "Pedigree Analysis.txt", "text": "So this is a heterozygous individual."}, {"title": "Pedigree Analysis.txt", "text": "And this phenotype will be normal because the upper case B is dominant over the lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "But this individual is said to be a carrier of that disease because they have that lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "So individual has normal phenotype, but is a carrier of that particular gene."}, {"title": "Pedigree Analysis.txt", "text": "Now, in this particular case, as you'll see many times, I haven't actually included this symbolism."}, {"title": "Pedigree Analysis.txt", "text": "And that's simply because sometimes when you're looking at pedigrees, this will not be used."}, {"title": "Pedigree Analysis.txt", "text": "So to see how we can analyze a pedigree, let's take a look at the following example."}, {"title": "Pedigree Analysis.txt", "text": "Let's suppose that this pedigree describes the Albinism gene or the Albinism disease."}, {"title": "Pedigree Analysis.txt", "text": "And our goal is to basically answer these two questions."}, {"title": "Pedigree Analysis.txt", "text": "So is the disease recessive or dominant?"}, {"title": "Pedigree Analysis.txt", "text": "Is it autosomal or is it X length?"}, {"title": "Pedigree Analysis.txt", "text": "So the way that we solve these problems is we solve them by beginning by assuming a certain statement to be true."}, {"title": "Pedigree Analysis.txt", "text": "So let's begin."}, {"title": "Pedigree Analysis.txt", "text": "Our first assumption is that the gene or the disease is sex linked and it is recessive."}, {"title": "Pedigree Analysis.txt", "text": "So we begin by making this assumption, by assuming that it's true."}, {"title": "Pedigree Analysis.txt", "text": "And then we check the pedigree to see if that actually works."}, {"title": "Pedigree Analysis.txt", "text": "If that assumption works."}, {"title": "Pedigree Analysis.txt", "text": "So we're assuming that our Albinism disease is sex link recessive."}, {"title": "Pedigree Analysis.txt", "text": "What that means is, because this is a female individual, we have two X chromosomes."}, {"title": "Pedigree Analysis.txt", "text": "And both of those X chromosomes must carry the recessive gene to produce a phenotype that is expressed."}, {"title": "Pedigree Analysis.txt", "text": "So this individual is Xbxb and this individual is X lowercase by because we're dealing with a male."}, {"title": "Pedigree Analysis.txt", "text": "Now this individual must be X uppercase B and Y lowerc or just Y, because if this was lowercase B, this would be an abnormal individual that expresses that disease."}, {"title": "Pedigree Analysis.txt", "text": "So now, by assuming that these are the genotypes of these two individuals, let's see what we produce for our offspring."}, {"title": "Pedigree Analysis.txt", "text": "So let's use the punant square."}, {"title": "Pedigree Analysis.txt", "text": "So we have our male individual, the gametes of the male individual."}, {"title": "Pedigree Analysis.txt", "text": "And now we have the gametes of the female individual."}, {"title": "Pedigree Analysis.txt", "text": "So we have this pun and square right over here."}, {"title": "Pedigree Analysis.txt", "text": "So we produce X, uppercase BX, lowercase BX."}, {"title": "Pedigree Analysis.txt", "text": "This should be XY x lowercase by x uppercase B, x lowercase BX, lowercase B and Y."}, {"title": "Pedigree Analysis.txt", "text": "So notice what we see."}, {"title": "Pedigree Analysis.txt", "text": "We see that if we produce a female, both females must be heterozygous."}, {"title": "Pedigree Analysis.txt", "text": "But if we produce a male, the male must express the phenotype for that disease because in both cases, they have the lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And this is not consistent."}, {"title": "Pedigree Analysis.txt", "text": "It does not work with the pedigree that we have because this individual, which is a male, has a normal phenotype."}, {"title": "Pedigree Analysis.txt", "text": "And we see that by making this assumption that is impossible."}, {"title": "Pedigree Analysis.txt", "text": "And so what that means is this initial assumption that our disease is sex link recessive does not actually work."}, {"title": "Pedigree Analysis.txt", "text": "So now we eliminated the fact that our disease is sex link recessive, so it cannot be sex link recessive."}, {"title": "Pedigree Analysis.txt", "text": "Now let's now assume that it is."}, {"title": "Pedigree Analysis.txt", "text": "So let's see, assumption number two is it is autosomal recessive."}, {"title": "Pedigree Analysis.txt", "text": "Let's see if that actually works out."}, {"title": "Pedigree Analysis.txt", "text": "So autosomal recessive and what that basically means is the only time that we express a disease phenotype, a phenotype that expresses that disease is when both of those autosomes contain a gene that is recessive."}, {"title": "Pedigree Analysis.txt", "text": "And so this female individual must be lowercase B lowercase B, and this male must be lowercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "Now what about these two individuals?"}, {"title": "Pedigree Analysis.txt", "text": "Well, they can either be uppercase B uppercase B, or they can be uppercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "So we have two different possibilities and we can test both of these possibilities to see if they actually work."}, {"title": "Pedigree Analysis.txt", "text": "Let's begin by assuming that this individual has this genotype and this individual also has that genotype."}, {"title": "Pedigree Analysis.txt", "text": "So in this particular case we can carry out our punish square."}, {"title": "Pedigree Analysis.txt", "text": "So we basically produce b lowercase b b lowercase b b lowercase b b lowercase b So that means all these individuals, including this one, number seven, is uppercase B, lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And the same thing is true here."}, {"title": "Pedigree Analysis.txt", "text": "This one is upper case B, lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And notice that this is consistent with this data because our heterozygous individual will not express that phenotype."}, {"title": "Pedigree Analysis.txt", "text": "So this is the phenotype or the genotype of these two individuals."}, {"title": "Pedigree Analysis.txt", "text": "Now for this to actually work, we have to continue the process and see that these possibilities, these phenotypes, actually work out."}, {"title": "Pedigree Analysis.txt", "text": "So let's cross these two heterozygous individuals."}, {"title": "Pedigree Analysis.txt", "text": "So we have upper case B, lowercase B, uppercase B, lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "We produce uppercase b, uppercase b, uppercase b, lowercase b, uppercase b, lowercase b and uppercase b."}, {"title": "Pedigree Analysis.txt", "text": "Or uppercase, I should say lowercase b, lowercase b."}, {"title": "Pedigree Analysis.txt", "text": "So this also is consistent because we have this possibility that one of the offspring will have a phenotype that expresses that particular disease."}, {"title": "Pedigree Analysis.txt", "text": "So that must mean this individual is lowercase B, lower case B."}, {"title": "Pedigree Analysis.txt", "text": "So we can conclude that by making the assumption that our disease albinism is autosomal recessive, this actually is consistent with the pedigree that was provided to us."}, {"title": "Pedigree Analysis.txt", "text": "Now we can also carry out the same exact process and by assuming that instead of being BBB, it can be, for example, b lowercase B B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "If we carry out this same experiment, we'll see that this data is also consistent with that."}, {"title": "Pedigree Analysis.txt", "text": "So all we have to do is change this to lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And so now we change around our opponent square, we get B lowercase B, lowercase B, lowercase B, lowercase B, lowercase B, lowercase B, and we see that this individual can also be B or uppercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "So that works as well."}, {"title": "Pedigree Analysis.txt", "text": "Now, we can try other examples as well."}, {"title": "Pedigree Analysis.txt", "text": "So by trying out this, we see that it works."}, {"title": "Pedigree Analysis.txt", "text": "So that means our disease must be this."}, {"title": "Pedigree Analysis.txt", "text": "But we can also try, for example, autosomal dominant, okay?"}, {"title": "Pedigree Analysis.txt", "text": "And we can basically determine if that actually works out."}, {"title": "Pedigree Analysis.txt", "text": "Now, if it's autosomal dominant, that means there are two possibilities of expressing Ara phenotype, where either uppercase B uppercase B, or where uppercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And if we begin by assuming it's autosomal dominant, what that means is this individual here must either be uppercase B, uppercase B or uppercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "But this individual must be lowercase B lowercase B if we're assuming it's autosomal dominant."}, {"title": "Pedigree Analysis.txt", "text": "So remember, these two genotypes will express that phenotype for that disease, right?"}, {"title": "Pedigree Analysis.txt", "text": "So we have disease phenotype, but only lowercase B. Lowercase B in this particular case will not express that phenotype."}, {"title": "Pedigree Analysis.txt", "text": "So that's why these are our phenotypes."}, {"title": "Pedigree Analysis.txt", "text": "And the same thing is true here."}, {"title": "Pedigree Analysis.txt", "text": "Uppercase B, uppercase B or uppercase B?"}, {"title": "Pedigree Analysis.txt", "text": "Lowercase B and BB."}, {"title": "Pedigree Analysis.txt", "text": "So now, if we carry out this same experiment, what do we see?"}, {"title": "Pedigree Analysis.txt", "text": "Well, let's suppose it's upper case B and this."}, {"title": "Pedigree Analysis.txt", "text": "So we see that if it was uppercase B, uppercase B, lowercase B, lowercase B, all of these must be uppercase B, lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And what that means is all of these must actually express that disease for the phenotype, for that disease, which is not true, which is not consistent with this pedigree, because all these have normal phenotype."}, {"title": "Pedigree Analysis.txt", "text": "Now, if we assume that this individual is this here, what we get is we get BB."}, {"title": "Pedigree Analysis.txt", "text": "And so we see that we have BB."}, {"title": "Pedigree Analysis.txt", "text": "BB, okay?"}, {"title": "Pedigree Analysis.txt", "text": "So in this case, it does work out, because what that means is all these individuals must be lowercase B, lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "But the same thing must be true here as well."}, {"title": "Pedigree Analysis.txt", "text": "What this must mean is this individual is this, this individual is this in order to get lowercase B lowercase B."}, {"title": "Pedigree Analysis.txt", "text": "And if these two individual mates, if these two individuals mates, the only type of offspring they produce is lowercase B lowercase B, which is inconsistent with this one here, because this must be either uppercase B lowercase B, or uppercase B, uppercase B, which is not possible if we're assuming autosomal dominance."}, {"title": "Pedigree Analysis.txt", "text": "So this is how we use the pedigree, how we can actually analyze the pedigree to basically help us answer these two questions and to help us determine how a given trade for some particular disease is actually passed down from one generation to another generation."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Thus far in our discussion on DNA replication we discussed the process by which our doublestranded DNA molecule must unwind itself before replication actually takes place."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And we said that a special type of protein known as DNA helicase must bind to the origin of replication on the doublestranded DNA and this helps break the a hydrogen bonds that exist between our adjacent nitrogenous bases on our adjacent nucleotides."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And this therefore unwinds and unzips our double stranded DNA and exposes the single stranded DNA molecule."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So basically our DNA helicase binds to the origin of replication and as it moves it breaks the hydrogen bond and it unwinds our single stranded DNA molecules."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And after we expose these sections another type of enzyme known as single stranded DNA proteins or simply SSB proteins bind to those exposed regions and they allow, they keep the two single strands from reassociating and reforming the hydrogen bonds."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So these single stranded binding proteins are shown in green in this diagram."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So once that takes place another enzyme known as DNA gyrase binds onto our double stranded DNA and it basically creates or introduces negative super coils and this decreases the stress that is involved with the process of unwinding."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Now once we actually unwind our double stranded DNA molecule and we expose these single stranded DNA regions another type of molecule known as primates which is basically an RNA polymerase creates primers or RNA primers."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Remember, an RNA primer is basically a sequence of nucleotides that are needed for DNA polymerase to bind and to begin the synthesis of our daughter strands."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Now, how exactly does DNA polymerase actually synthesize our daughter strand?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Well, basically DNA polymerase acts as a catalyst."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "It catalyzes the formation of our phosphol digester bonds."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So it takes the nucleotides that are found in the environment so these are free nucleotides and attaches these nucleotides together via phosphol diaster bonds or phosphol diaster linkages."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "In the process."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Every time we form a phosphodia linkage by using the DNA polymerase we release a pyrophosphate into the environment and this basically drives the process of DNA replication."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Now DNA polymerase can only read the parent strand in the three to five direction and this implies that it can only synthesize the new daughter DNA molecule in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we have the DNA helicase that binds at the origin of replication."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Eventually it moves a certain distance and it ends up at the location known as the fork of replication."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "The fork of replication is basically the location of our DNA helicase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we can imagine that DNA helicase moves in the left directions towards the left along the x axis we have the DNA gyrase that basically induces those negative super coils that decreases the stress involved with unwinding."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And we have the SSB proteins, the single stranded binding proteins that basically act to make sure that those two single strands do not reassociate with one another."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And once we unwind, what happens is the DNA polymerase shown in red basically binds onto our single stranded DNA molecules and it creates those phosphodia ester bonds by combining, by attaching our nucleotides together."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So first we form the RNA primer by using our primase enzyme and this is shown in purple."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And then we basically create those other nucleotides by using our RNA polymerase or DNA polymerase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And notice that for the case of the parent strand that runs from the three to the five direction, the DNA polymerase basically creates the nucleotides begin with the five and ending with the three end."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we see that DNA polymerase has no problem synthesizing our daughter's strand on the parent molecule that runs three to five."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "However, what happens in this case for the parent strand that begins with the five and ends with the three?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "If our DNA polymerase attaches to this side it must synthesize in the three to five direction and that is not allowed."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Remember, the DNA polymerase can only synthesize in the five to three direction, it cannot synthesize from the three to five direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we see that this strand that is formed by using the three to five parent strand is known as the leading strand."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And it's known as the leading strand because it is synthesized continuously without much problem."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "However, how exactly does the DNA polymerase actually synthesize the other parent strand that runs from the five to the three directions?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So let's take a look at the following diagram and let's determine how this actually takes place."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So let's begin with our parent strand that runs from the three to the five direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we can imagine that DNA helicase attaches to the origin of replication."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "It moves a certain distance and it unwinds our double stranded DNA."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So first we have the primates that lays down the RNA primer."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So let's suppose we have our RNA primer as shown and then what happens?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Our DNA polymerase basically continuously forms our nucleotide piece by piece."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we form the following continuous strand and notice the formation actually takes place in the same exact direction as the movement of our helicase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So the helicase, this enzyme moves to the left along our x axis and the replication also takes place in the same direction towards the left, along our x axis."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So because this is the three end, this end of the new daughter new strand is our five end and this is the three end."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And this makes sense because our DNA polymerase can only synthesize in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "But what about this case?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "What happens here?"}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Notice the same thing cannot happen here because if that happened, because this is the five end, the first nucleotide must be the three end and our DNA polymerase cannot synthesize in the three to five end."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So instead what happens is we use our primates and the primates, instead of forming only one RNA primer we form many RNA primers."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we form as many RNA primers as we can."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So once we form the RNA primer, as our DNA polymerase moves this way, we see that our nucleotides are basically formed in the backward direction going this way."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So as our DNA polymerase moves this way along our parent strand that runs from the three to five, the one that runs from the five to three, it takes place in the opposite direction going this way."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we form backwards with respect to the movement of our helicas."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we basically form going this way."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "This goes here, this goes here, this goes here and this goes here."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So this is known as the lagging strand because it lags behind the leading strand."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So the leading strand is formed continuously and our DNA polymerase moves in the same direction as the motion of the fork, as the motion of our helicase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "But for the lagging strand our direction of the DNA polymerase is backwards, it's reversed."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And this is important because it basically ensures that the DNA polymerase forms in the five to three directions."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So for the lagging strand so let's designate it using our red color."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "This end is the five end and this end is the three end."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So we see going this way we form the five to three end and this we form the five to three end."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And that makes sense because DNA polymerase can only form the new strands in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And each one of these individual fragments, individual pieces, are known as the okasagi fragments."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So once again for the leading strand, for this strand here, the DNA polymerase uses the primer to initiate replication."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So this purple section is the primer."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Our DNA polymerase bind onto our primer and it moves along this fashion, along this direction in a continuous fashion, adding the nucleotide continuously piece by piece in the forward direction in the same direction as the movement of this DNA helicase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "But to synthesize the other strand known as the lagging strand, primates creates many RNA primers as far as possible down our parent strand that runs in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And then DNA polymerase works backwards with respect to direction of the movement of this replication fork."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So the replication fork moves this way, this is synthesized this way, but this is synthesized in the opposite direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And we see that the DNA helicase basically reads the parent strand in the allowed three to five direction and it forms the lagging strand in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So therefore the polymerase forms the lagging strand in a piece wise fashion."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So piece by piece in a discontinuous manner and each one of these pieces is known as the Okasagi fragments."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Now, this process is important because it basically ensures two important things."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Firstly, as our helicase moves this way we see that the DNA polymerase is able to actually form the leading strand and our lagging strand at about the same exact time."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And this type of process also ensures that the DNA polymerase creates both of these strands in the five to three direction."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So, going this way, we synthesize in a five to three fashion."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And going backwards, we also synthesize in the five to three fashion, which is the only way by which DNA polymerase actually synthesizes our new daughter DNA strands."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "Now, once we actually form all these Okasagi fragments, once we form the lagging strand, we have to connect those lagging strands."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And the way we connect those strands is we remove these purple primers and we replace them with the proper nucleotides."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And we connect the nucleotides by forming the phosphor disaster bonds."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "And the enzyme that basically does this is known as DNA ligase."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So once the Okasagi fragments are formed, an enzyme called DNA ligase connects the Okasagi fragments by creating phosphodia ester linkages between our adjacent Okasagi fragments."}, {"title": "DNA Replication: Leading and Lagging Strand .txt", "text": "So this is the process by which DNA is replicated."}, {"title": "Glycolysis .txt", "text": "Glycolysis is a series of reactions that ultimately transforms glucose into energy molecules known as ATP that are used by the cell."}, {"title": "Glycolysis .txt", "text": "Now, the net result of glycolysis is the formation of two pyruvate molecules, two ATP molecules, two NADH molecules, two water molecules and two hydrogen ions."}, {"title": "Glycolysis .txt", "text": "Now, glycolysis is an anaerobic process and that means it does not require oxygen to actually take place."}, {"title": "Glycolysis .txt", "text": "And that's why glycolysis is used by all different types of cells, including prokaryotic and eukaryotic cells."}, {"title": "Glycolysis .txt", "text": "Now, glycolysis can be divided into three stages."}, {"title": "Glycolysis .txt", "text": "We have stage one, stage Two and stage three."}, {"title": "Glycolysis .txt", "text": "Now, in stage one, we actually use energy."}, {"title": "Glycolysis .txt", "text": "So the entire purpose of stage one is to prepare the glucose molecule for a breakdown."}, {"title": "Glycolysis .txt", "text": "So in stage one, we trap that glucose inside the cell and we transform our low energy glucose into a high energy glucose."}, {"title": "Glycolysis .txt", "text": "And then in Stage two, we use that unstable high energy glucose and we break it down into two molecules."}, {"title": "Glycolysis .txt", "text": "And then we use those two molecules that we broke down in stage two in stage three and we use those molecules, we harvest the energy within those molecules and we produce the ATP molecules in stage three."}, {"title": "Glycolysis .txt", "text": "So let's begin by looking at the details of stage one."}, {"title": "Glycolysis .txt", "text": "So in Stage one, we take the glucose, we transport that glucose across the cell membrane into the cytoplasm of the cell."}, {"title": "Glycolysis .txt", "text": "And then we use an enzyme known as Hexokinase to basically transform a glucose into glucose six phosphates."}, {"title": "Glycolysis .txt", "text": "So we use an ATP molecule, we take a phosphate group from the ATP molecule and transfer it onto our glucose."}, {"title": "Glycolysis .txt", "text": "So we form glucose six phosphate."}, {"title": "Glycolysis .txt", "text": "Now, there are two reasons why we have to phosphorylate our glucose, why we have to add that phosphate group."}, {"title": "Glycolysis .txt", "text": "One of the reasons is because we want to trap that glucose inside the cytoplasm."}, {"title": "Glycolysis .txt", "text": "We want to keep that glucose from exiting our cell."}, {"title": "Glycolysis .txt", "text": "And by adding this negatively charged phosphate group, we basically keep that glucose inside the cytoplasm because it no longer is capable of being transported across our cell membrane."}, {"title": "Glycolysis .txt", "text": "So once our glucose is transformed into glucose phosphate, it stays within the cytoplasm of that cell."}, {"title": "Glycolysis .txt", "text": "The second reason why we have to phosphorylate our glucose is to transform the glucose from the low energy stable form into a less stable form."}, {"title": "Glycolysis .txt", "text": "So we destabilize the glucose by adding the phosphate group."}, {"title": "Glycolysis .txt", "text": "So we create this negatively charged group on the glucose and then destabilizes our molecule and that will help us break down the molecule in stage two."}, {"title": "Glycolysis .txt", "text": "So step two of stage one involves transforming the six membered sugar glucose into the five membered isomer, the fructose."}, {"title": "Glycolysis .txt", "text": "So we use an enzyme known as phosphorlucose isomerase and we basically transform glucose six phosphate into fructose six phosphate."}, {"title": "Glycolysis .txt", "text": "So step two does not require energy."}, {"title": "Glycolysis .txt", "text": "And in step three, we take the fructose six phosphate and we use an enzyme known as phosphor fructose kinase."}, {"title": "Glycolysis .txt", "text": "We use an ATP molecule and transfer a second phosphate group onto that fructose."}, {"title": "Glycolysis .txt", "text": "So fructose 116 biphosphate is formed that contains one two high energy phosphate groups."}, {"title": "Glycolysis .txt", "text": "And we also utilize that ATP molecule."}, {"title": "Glycolysis .txt", "text": "So this is a very unstable molecule compared to our glucose."}, {"title": "Glycolysis .txt", "text": "And that's exactly why in stage two we can now break down this unstable molecule as we'll see in just a moment."}, {"title": "Glycolysis .txt", "text": "Now, step three is actually very important stage one because it's our committing step."}, {"title": "Glycolysis .txt", "text": "So once we undergo step three, our glucose molecule actually commits to our glycolysis pathway."}, {"title": "Glycolysis .txt", "text": "So for example, if we move back to this molecule, the glucose six phosphate, the glucose six phosphate does not necessarily have to actually go on to produce the fructose 116 biphosphate."}, {"title": "Glycolysis .txt", "text": "If we have plenty amounts of energy inside the cell, the glucose six phosphate can then be stored as glycogen."}, {"title": "Glycolysis .txt", "text": "Now, if we don't have that much energy in a cell, then the glucose six phosphate will go on to form the fructose six phosphate, which will go on to form the fructose one six biphosphate."}, {"title": "Glycolysis .txt", "text": "But once this step takes place, that glucose is fully committed to Aragly Colesis pathway."}, {"title": "Glycolysis .txt", "text": "That is, there is no turning back."}, {"title": "Glycolysis .txt", "text": "So once we form the high energy fructose 116 biphosphate, we move on to stage two."}, {"title": "Glycolysis .txt", "text": "In stage two, the entire purpose of stage two is to basically take the high energy molecule and break it down into two, three carbon molecules."}, {"title": "Glycolysis .txt", "text": "So by using an enzyme known as aldalase, so we basically transform the fructose 116 biphosphate into the dihydroxy acetone phosphate, this molecule and the glycerol aldehy three phosphate, also known as PGAL, which looks something like this."}, {"title": "Glycolysis .txt", "text": "Now, in stage three, we actually need to use the PGAL."}, {"title": "Glycolysis .txt", "text": "So in stage two, the second step, the fifth step is to take the dihydroxy acetone phosphate and transform it into the PGAL by using an enzyme known as trio's phosphate, osamrase."}, {"title": "Glycolysis .txt", "text": "So in stage two, we basically do not use any energy and the entire goal is to produce two PGAL molecules."}, {"title": "Glycolysis .txt", "text": "And finally, let's move on to step three, or stage three."}, {"title": "Glycolysis .txt", "text": "So stage three itself involves five individual steps, and this is the process where we produce our ATP molecules as well as the water molecules and our NADH molecules."}, {"title": "Glycolysis .txt", "text": "So let's begin with stage three."}, {"title": "Glycolysis .txt", "text": "And we begin with the PGAL molecule that we form in stage two."}, {"title": "Glycolysis .txt", "text": "So we take the PGAL and we basically reacted with a special type of enzyme known as glyceroaldehyde three phosphate dehydrogenates."}, {"title": "Glycolysis .txt", "text": "And this enzyme basically uses an NAD cofactor as well as API, which is our phosphate, and it produces the one three biphosphoglyceride."}, {"title": "Glycolysis .txt", "text": "So basically, we reduce the NAD plus into NADH by taking this H from the PGAL and transferring onto the NAD."}, {"title": "Glycolysis .txt", "text": "And then we take that phosphate and we add it onto this carbon."}, {"title": "Glycolysis .txt", "text": "So the entire step of, the entire purpose of step six is to basically reduce our NAD and oxidize this PGAL."}, {"title": "Glycolysis .txt", "text": "And so basically we add a second phosphate group and we create a destabilized molecule."}, {"title": "Glycolysis .txt", "text": "Now this one three biphosoglycerate is also known as one three BPG."}, {"title": "Glycolysis .txt", "text": "And then we take the one three BPG and we actually mix it with ADP as well as an enzyme known as phosphaglycerate kinase."}, {"title": "Glycolysis .txt", "text": "And we transfer this phosphate group onto the ADP to produce our first ATP molecule as well as the three phosphorglycerate which also contains this phosphate group."}, {"title": "Glycolysis .txt", "text": "Now in step eight we take this and we transform it into this molecule to phosphoglycerate by using an enzyme known as phosphoglycerate mutase."}, {"title": "Glycolysis .txt", "text": "And what we do is we transfer this phosphate onto this section as shown, and then in step nine we have an elimination step taking place."}, {"title": "Glycolysis .txt", "text": "So we basically we add an H onto this oxygen, onto this oxygen and then we basically kick off that water molecule that is produced as a result."}, {"title": "Glycolysis .txt", "text": "So in step nine we basically have a condensation reaction taking place, we produce the water and the phosphoenopyruvate."}, {"title": "Glycolysis .txt", "text": "And finally in the last step, in step ten, we also produce an ATP molecule by transferring the phosphate onto the ATP."}, {"title": "Glycolysis .txt", "text": "And the final step, the final product is our Pyruvate molecule and the enzyme involved in step ten is known as the Pyruvate kinase."}, {"title": "Glycolysis .txt", "text": "So the final product of stage three and Glycolysis is Pyruvate."}, {"title": "Glycolysis .txt", "text": "Now notice in stage three, in step six we produce one NADH."}, {"title": "Glycolysis .txt", "text": "In step seven and ten we produce one ATP each."}, {"title": "Glycolysis .txt", "text": "And in step nine we produce a single H 20."}, {"title": "Glycolysis .txt", "text": "Now this only shows one PGAL reacting, but in stage two we produce two."}, {"title": "Glycolysis .txt", "text": "So that means stage three takes place twice and we form two nadhs, we form four ATPs and we form two H 20 molecules."}, {"title": "Glycolysis .txt", "text": "So now let's count up all the reactants and all our products."}, {"title": "Glycolysis .txt", "text": "So the reactants are basically the glucose."}, {"title": "Glycolysis .txt", "text": "So we also have two ATP molecules, one and two that have to be utilized."}, {"title": "Glycolysis .txt", "text": "We have four ATP molecules, so we have one, two, and because it takes place twice, we have four ADP molecules."}, {"title": "Glycolysis .txt", "text": "We have one because it takes place twice, we have two PiS phosphates, we have two NAD pluses because this takes place twice."}, {"title": "Glycolysis .txt", "text": "And we have two H pluses, which I haven't shown in these steps."}, {"title": "Glycolysis .txt", "text": "And the products are two pyruvates."}, {"title": "Glycolysis .txt", "text": "Once again, because this takes place twice, we have four ATPs."}, {"title": "Glycolysis .txt", "text": "So basically 1234, because it occurs twice."}, {"title": "Glycolysis .txt", "text": "Two nadhs, we have two H, two O's, we have four H pluses."}, {"title": "Glycolysis .txt", "text": "Once again, I haven't specified where those were formed."}, {"title": "Glycolysis .txt", "text": "And we have the two ADPs."}, {"title": "Glycolysis .txt", "text": "So now if we cancel out some things, so basically we have four HS here, two H's here, that crosses out, this becomes a two."}, {"title": "Glycolysis .txt", "text": "We have two ATPs, we have four ATPs, this crosses out, this crosses out, this becomes a two."}, {"title": "Glycolysis .txt", "text": "And we have the four ADPs here, the two ADPs here, these cross out, this becomes a two."}, {"title": "Glycolysis .txt", "text": "So the net reaction of Glycolysis is as follows."}, {"title": "Glycolysis .txt", "text": "We have a glucose."}, {"title": "Glycolysis .txt", "text": "We have two ADPs, two phosphates and two NAD pluses on the reactant side."}, {"title": "Glycolysis .txt", "text": "And we produce the net result are two pyruvates, two ATPs, two Nadhs, two water molecules and two H plus ions."}, {"title": "Glycolysis .txt", "text": "So basically stage one of Glycolysis requires two ATP molecules and we produce our two ADPs."}, {"title": "Glycolysis .txt", "text": "In stage two we take the high energy fructose, one six biphosphate and we break that down into essentially two PGAL and no energy is actually used up or produced."}, {"title": "Glycolysis .txt", "text": "And in stage three, this is where we produce our ATP molecules."}, {"title": "Glycolysis .txt", "text": "So we produce a total of four ATP molecules, two Nadhs, two water molecules."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "In our discussion on the properties of enzymes, we mentioned one very important property of enzymes, namely the ability of the enzyme to catalyze the biological reactions that take place inside our body and inside our cells."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, what that ultimately means is enzymes speed up the rate at which chemical reactions take place."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, by speeding up a chemical reaction reaction enzymes essentially decrease the time that is needed for that particular chemical reaction to actually reach equilibrium."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, this is a very important thing to remember about enzymes."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Enzymes decrease the time that is needed to reach equilibrium."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "But enzymes do not actually change the equilibrium itself."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "They do not change the energy of the product and reactants, nor they actually change the amount of product or reactants that is formed at equilibrium."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So to see what we mean, let's take a look at the following energy diagram."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So, let's suppose we have a hypothetical elementary single step reaction in which the reactants are these and the products are these."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So on the reactant side, we have a bond between A and B, and C exist by itself."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "On the product side, we now have a bond between B and C, and A exist by itself."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, based on the following energy diagram so the y axis is the Gibbs free energy and the x axis is the reaction progress."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So we go from reactants to products."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Notice that if we compare the y coordinate value of the products to the y coordinate value of the reactants, this is lower in energy than this."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And what that means is if we take the free energy of the products and we subtract it from the free energy of the reactants, we get a negative value."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And what that means is free energy will be produced, will be released."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "When this reaction takes place, the delta g is negative."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And so that implies this reaction is exergonic, it is spontaneous."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And as long as we have enough energy to overcome the activation barrier, this quantity here the reactants will spontaneously and naturally form these products because they are lower in energy and therefore more stable."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So once again, enzymes do not affect the free energy value of the products, nor will they affect the free energy value of the reactants."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And since the energy value of the product and reactants will not be effective, that means the delta g, the difference between this and this will not be affected as well."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, because it's the energy of the product and reactants."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And specifically, it's the difference between the energy of the product and reactants that determines the concentrations of products and reactants that will exist at equilibrium."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Because the enzymes do not affect the energy values of the products and reactants, they will not affect the concentration of the products and reactants that will exist at equilibrium."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So once again, we know that enzymes do not affect the free energy of the reactants and products."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "This implies that they will not change the equilibrium of the reaction."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "That is the same concentration of products and reactants will be formed in the presence as in the absence of the enzyme."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So this is the case where we have our uncatalyzed reaction."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "But if we add an enzyme the energy value of the reactants and products will not actually change."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, if the thermodynamics of the products and reactants is not changed by an enzyme, what is actually changed?"}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Well, recall that the kinetics of the chemical reaction is determined by the energy of the transition state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And the transition state is this transient molecule, transient stage that exists between the reactants and our products."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, what exactly will the transition state look like when we go from the reactants to the products?"}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Well, we have a single elementary, a single step elementary reaction in which on the reactants side we have a bond between A and B."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And on the product side, we have a bond between B and C. And what that implies is to actually go from the reactants to the products, we have to break the bond between A and B and we have to form the bond between B and C. So in that transition stage, what we're going to see is a bond breaking between A and B."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So B will begin to move away from A and because the electron density will basically move away, that bond between A and B will begin to break."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that can be described by using a dashed line."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So this dashed line between A and B basically moves."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "B is moving away and the bar and that bond is being broken."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "On the other hand, because B is approaching C, the electron densities of these two atoms or molecules is overlapping."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And so we begin to form that bond."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So we have a partially formed bond here and a partially broken bond here."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And because the electron densities aren't overlapping very well, that will increase the energy of the transition state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "In fact, according to the diagram, the energy of the transition state represents the highest possible free energy value on the following curve."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And so if we are to actually mark down on the curve where that transition state actually is this highest, most peak on the curve, the apex represents that transition state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So we can basically write that this is in fact that transition state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "It represents the highest, the maximum energy value in that particular chemical reaction."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And this Daggert symbol describes the energy state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So to calculate the free energy value of the transition stage, of that molecule, of that chemical reaction, we simply take this Y coordinate value and we subtract the energy of the reactants."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So the energy of the transition state minus the energy of the reactants gives us this quantity known as the free energy of activation or simply the activation energy, the activation barrier of this particular chemical reaction."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, what happens is when the enzyme actually takes in these molecules."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So we have the enzyme in the enzyme."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "We have this special location in that enzyme that we're going to discuss in much more detail in the next lecture."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "But this special location in the enzyme is known as the active side."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And it's the active side that creates a microenvironment and binds to these molecules here."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So these reactants will move into the active side of that enzyme, creating the enzyme substrate complex."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And what the enzyme actually does inside that active side is it stabilizes this partially broken bond and this partially formed bond."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And by stabilizing these partially broken or formed bonds, it lowers the energy of activation."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "It stabilizes the transition state, lowering that free energy of activation."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And if we lower that free energy of activation, we increase the rate at which that reaction takes place."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So, once again, enzymes bind specific substrates on regions called active sites to form the enzyme substrate complex."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "By binding substrates in the active sites, enzymes stabilize the energy of the transition state, which in turn stimulates the breakage of the old bonds and the formation of the new bonds to form that product molecule, as shown in this particular diagram."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So if we look at the following diagram once more, when we go from the uncannyyzed to the catalyzed case, we see that the energy of the products or reactants is not changed."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "This energy is the same as this energy value, and this energy is the same as this energy."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So the change in Gibbs free energy between our products and reactants is not changed."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "What is changed is the energy between the transition state and the reactants."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So here we see that there's a stabilization of the transition state and a lowering in energy."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that means the difference between the energy of this transition state and the reactants will be smaller in this case than in this case."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And this is precisely what makes that reaction actually go quicker."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So by adding an enzyme, or we decrease the time it takes for equilibrium to actually establish."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "But once equilibrium is actually established, the same concentrations of products and reactants are formed in the catalyzed case as that uncategalyzed case."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, let's discuss something called the maximum velocity of enzymes."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So the maximum velocity of enzymes basically describes the maximum activity at which the enzyme will actually operate."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So let's suppose in our mixture, we have a total of 100 enzymes, and each one of these enzymes will have its own active site."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "Now, if we add 50 substrate molecules, that only 50 enzymes will contain active sites that are filled."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that means our entire mixture, because only half of the enzymes are filled, the entire activity of all the enzymes will be half of its maximum value."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "But if we continue adding substrate molecules so that we add, let's say, 100 substrate molecules, then all the active sites and all the enzymes will be filled."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that means the entire activity of our mixture of enzymes will be at a maximum velocity."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that's exactly what this graph actually represents."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So the Y axis is the enzyme activity, also called the enzyme velocity."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And the X axis is the substrate concentration."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So basically, this dashed line represents the maximum velocity at which that enzyme or the mixture of enzymes will actually operate."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And notice we have this line and this curve will never actually cross this line."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "It will never actually go higher than the line because if we have, for example, 100 enzymes, we only have 100 possible active sites."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So even if we have, let's say, 200 substrate molecules because we have an excess of substrate molecules and only 100 active sites, we have a maximum activity at which only 100 active sites at a time can actually be filled."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So as we increase our substrate concentration, we see that the enzyme activity increases up to a certain value known as the maximum enzyme activity or maximum enzyme velocity."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So we see that at a constant concentration of enzyme, the enzyme activity will continue to rise until a certain maximum value is reached, known as the maximum velocity."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And the maximum velocity represents the condition in which all the active sites this should be active, not activate."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So let's change that."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So all the active sites so all the active sites are filled with appropriate substrate."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So that basically represents the condition in which if, let's say, we have 1000 enzymes, each enzyme has one active site, if we have 1000 substrate molecules, then all the active sites will be filled."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And that is the point at which that enzyme is operating at a maximum enzyme velocity, at a maximum enzyme activity."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "So in the next lecture, we're going to focus on how that active side actually stabilizes that transition state."}, {"title": "Enzymes Stabilize Transition State .txt", "text": "And we're going to focus much more on what that active side actually does and how it binds to its appropriate substrate molecule."}, {"title": "Meiosis I .txt", "text": "In the next two lectures, we're going to begin our discussion on a type of sexual reproduction process that takes place in eukaryotic cells known as meiosis."}, {"title": "Meiosis I .txt", "text": "Now, when we discussed mitosis, we said that mitosis is a cell division process that somatic cells undergo."}, {"title": "Meiosis I .txt", "text": "So somatic cells are the eukaryotic cells that divide via mitosis."}, {"title": "Meiosis I .txt", "text": "Now, those eukaryotic cells that divide via meiosis are known as gametocides."}, {"title": "Meiosis I .txt", "text": "So gametocides divide via meiosis, and somatic cells divide via mitosis."}, {"title": "Meiosis I .txt", "text": "Now, both of these processes are a type of cell division."}, {"title": "Meiosis I .txt", "text": "The question is, what exactly is the major difference between mitosis and meiosis?"}, {"title": "Meiosis I .txt", "text": "So in mitosis, our somatic cell divides into two genetically identical cells that are diploid."}, {"title": "Meiosis I .txt", "text": "And that means the chromosome number does not actually change."}, {"title": "Meiosis I .txt", "text": "If we begin with 46 chromosomes, we're going to end up with cells that contain 46 chromosomes."}, {"title": "Meiosis I .txt", "text": "However, in the process of meiosis, our gamethocide divides into four genetically different haploid cells."}, {"title": "Meiosis I .txt", "text": "And that means if we begin with 46 chromosomes, the chromosome number will be divided by two."}, {"title": "Meiosis I .txt", "text": "So we're going to end up with cells with Taploid cells that contain only 23 chromosomes."}, {"title": "Meiosis I .txt", "text": "Now, in humans, our male gametocide is known as a spermatocide, while our female gametoside is known as the oocyte."}, {"title": "Meiosis I .txt", "text": "Now, before meiosis actually takes place, and before the cell divides via meiosis, the cell undergoes a process known as interface, which is similar to the interface that takes place in somatic cells before they divide via mitosis."}, {"title": "Meiosis I .txt", "text": "Now, during interface, we have a phase known as the S phase."}, {"title": "Meiosis I .txt", "text": "And during the S phase of interface, we have the DNA that is replicated."}, {"title": "Meiosis I .txt", "text": "And in humans, where we have 46 chromosomes, all 46 chromosomes, or 23 pairs of homologous chromosomes, are basically replicated during the process of S phase in interface."}, {"title": "Meiosis I .txt", "text": "So our DNA is actually replicated before meiosis actually takes place in the same way that the DNA is replicated before mitosis takes place."}, {"title": "Meiosis I .txt", "text": "Now, what exactly do we mean by this replication process?"}, {"title": "Meiosis I .txt", "text": "Let's take a look at the following diagram."}, {"title": "Meiosis I .txt", "text": "So, let's take one of these 23 pairs as shown in the following diagram."}, {"title": "Meiosis I .txt", "text": "So this is our pair of homologous chromosome."}, {"title": "Meiosis I .txt", "text": "So we have homologous chromosome one and homologous chromosome two."}, {"title": "Meiosis I .txt", "text": "Now, these two chromosomes are genetically different from one another."}, {"title": "Meiosis I .txt", "text": "One of these chromosomes, let's say the purple one, came from the male, and the other one, let's say the brown one, came from the female parent."}, {"title": "Meiosis I .txt", "text": "So these are genetically different, but they are homologous."}, {"title": "Meiosis I .txt", "text": "And what that means is both of these chromosomes carry genes that code for the same exact trait."}, {"title": "Meiosis I .txt", "text": "So what that means is let's suppose that the purple chromosome contains the gene that codes for the hair color."}, {"title": "Meiosis I .txt", "text": "That means the brown one will also contain the gene that codes for the hair color."}, {"title": "Meiosis I .txt", "text": "That's exactly why these are homologous."}, {"title": "Meiosis I .txt", "text": "So during S phase of interface, before meiosis actually takes place, we replicate each one of these individual chromosomes."}, {"title": "Meiosis I .txt", "text": "So we replicate the purple one and we produce this, and we replicate the brown one, and we produce this."}, {"title": "Meiosis I .txt", "text": "Now, this is identical with respect to this, and that's exactly why we call them cystochromatids."}, {"title": "Meiosis I .txt", "text": "So these two cystochromatids are identical with respect to one another."}, {"title": "Meiosis I .txt", "text": "Now, on this chromosome, we also have two identical cystochromatids."}, {"title": "Meiosis I .txt", "text": "And these two chromosomes, just like these two individual chromosomes, are said to be homologous with respect to one another."}, {"title": "Meiosis I .txt", "text": "So we basically double the number of chromatids, but the number of pairs remains the same."}, {"title": "Meiosis I .txt", "text": "We have one pair and one pair here, but we have four chromatids here and only two chromatids here."}, {"title": "Meiosis I .txt", "text": "So that means during s phase, we double the number of chromatids."}, {"title": "Meiosis I .txt", "text": "Now, once our gametocides actually undergo the process of sphase, those gametocides are known as primary gametosides."}, {"title": "Meiosis I .txt", "text": "So our male gametocides are known as primary spermatocides, while our female gametocides are known as primary oocytes."}, {"title": "Meiosis I .txt", "text": "Now, before the female organism, before the female human is actually born, all the oocytes basically become primary gametocytes or primary oocytes."}, {"title": "Meiosis I .txt", "text": "And we and we'll talk more about that when we'll discuss the process of sexual reproduction."}, {"title": "Meiosis I .txt", "text": "Now, let's actually get into the process of meiosis."}, {"title": "Meiosis I .txt", "text": "Now, as we said, meiosis is the process by which a single cell, a single gametocide, divides into four genetically different haploid cells."}, {"title": "Meiosis I .txt", "text": "Now, we can divide the process of meiosis into two stages."}, {"title": "Meiosis I .txt", "text": "We have meiosis one and meiosis two."}, {"title": "Meiosis I .txt", "text": "In this lecture, we're going to focus only on meiosis one."}, {"title": "Meiosis I .txt", "text": "In the next lecture, we're going to discuss the process of meiosis two."}, {"title": "Meiosis I .txt", "text": "Now, just like mitosis can be divided into four stages, meiosis one can be divided into four individual stages."}, {"title": "Meiosis I .txt", "text": "We have ProPhase one, metaphase one."}, {"title": "Meiosis I .txt", "text": "We have anaphase one, and telephase one."}, {"title": "Meiosis I .txt", "text": "So let's take a look at each one of these individual phases and describe what takes place in each one of the phases."}, {"title": "Meiosis I .txt", "text": "And let's begin with ProPhase one of meiosis."}, {"title": "Meiosis I .txt", "text": "Now, ProPhase one of meiosis is somewhat similar to ProPhase of mitosis in that in ProPhase one of meiosis, we have the two centrioles that begin to move to opposite ends."}, {"title": "Meiosis I .txt", "text": "And as they begin to move to opposite ends, they begin to synthesize our mitotonic spindle apparatus, and they begin to synthesize the spindle fibers, which begin to grow and move into the nucleus of our cell."}, {"title": "Meiosis I .txt", "text": "Now, at the same exact time, the chromatin condenses into the chromosomes and the nuclear membrane, as well as our nucleolus, begins to disappear."}, {"title": "Meiosis I .txt", "text": "And that's exactly what allows our spindle fibers to make its way into the nucleus area of our cell."}, {"title": "Meiosis I .txt", "text": "Now, the major difference between ProPhase one of meiosis and ProPhase of mitosis is the following."}, {"title": "Meiosis I .txt", "text": "So the major process that takes place within ProPhase one is a type of genetic recombination process known as crossing over."}, {"title": "Meiosis I .txt", "text": "And we'll see what crossing over is in just a moment."}, {"title": "Meiosis I .txt", "text": "Now, before crossing over actually takes place, our two homologous pairs of chromosomes actually have to find one another and basically orient themselves side by side, and then that allows crossing over to actually take place."}, {"title": "Meiosis I .txt", "text": "So before crossing over takes place, homologous pairs must find each other and move side by side with respect to each other."}, {"title": "Meiosis I .txt", "text": "And this pairing, this movement of the homologous chromosomes next to one another, is known as synapses."}, {"title": "Meiosis I .txt", "text": "And this is shown in the following diagram."}, {"title": "Meiosis I .txt", "text": "So the first step of synapses is the following."}, {"title": "Meiosis I .txt", "text": "These two homologous pairs of chromosomes that we spoke of earlier actually have to find each other and move side by side."}, {"title": "Meiosis I .txt", "text": "And then when they move side by side, these chromatids of these two chromosomes have to overlap."}, {"title": "Meiosis I .txt", "text": "They have to intertwine, as shown in the following diagram."}, {"title": "Meiosis I .txt", "text": "So during the process of synapses, the point at which our two chromatids intertwine, or overlap, is known as our chiasma."}, {"title": "Meiosis I .txt", "text": "And in this diagram, the chiasma is basically this point here."}, {"title": "Meiosis I .txt", "text": "It's the point at which our two chromatids, this chromatid and this chromatid, basically overlap."}, {"title": "Meiosis I .txt", "text": "Now, because we have four individual chromatids, we have one chromatid, two, three chromatid, four."}, {"title": "Meiosis I .txt", "text": "This entire structure is known as a tetrid."}, {"title": "Meiosis I .txt", "text": "So basically, the tetrid refers to the orientation of these individual four chromatids that are very close with respect to one another."}, {"title": "Meiosis I .txt", "text": "Now, once synapses actually takes place and we form our chiasma, then crossing over actually takes place."}, {"title": "Meiosis I .txt", "text": "So crossing over is a type of genetic recombination process in which we have the exchange of genetic information from this chromatid and this chromatid."}, {"title": "Meiosis I .txt", "text": "So basically, crossing over produces two new recombinant chromosomes, as shown in the following diagram."}, {"title": "Meiosis I .txt", "text": "So this section ends up on this chromatid, and this section ends up on or this section ends up on this chromatid to form the following two recombinant chromosomes."}, {"title": "Meiosis I .txt", "text": "So crossing over produces our two recombinant chromosomes."}, {"title": "Meiosis I .txt", "text": "And notice that each one of the chromatids on the chromosomes are genetically different from one another."}, {"title": "Meiosis I .txt", "text": "So this chromos or this chromatid is different than this chromatid, and this chromatid is different than this one, and it's different than this one."}, {"title": "Meiosis I .txt", "text": "So each one of these chromatids have their own unique genetic information, and that's exactly what our recombinant genetic recombination actually does."}, {"title": "Meiosis I .txt", "text": "So this is the major process that takes place in ProPhase one that differentiates ProPhase one from ProPhase of mitosis."}, {"title": "Meiosis I .txt", "text": "Now let's move on to metaphase one of meiosis."}, {"title": "Meiosis I .txt", "text": "So during metaphase one, the spindle fibers actually attach themselves to the kinetic or region of each one of these tetrids."}, {"title": "Meiosis I .txt", "text": "And what these spindle fibers basically do is they align the tetris along the center along the equatorial line of Aracel, as shown in the following diagram."}, {"title": "Meiosis I .txt", "text": "So let's suppose Aracel contained only six pairs of homologous chromosomes."}, {"title": "Meiosis I .txt", "text": "So that means we're going to have three tetrades, as shown in the following diagram, that are aligned along the center."}, {"title": "Meiosis I .txt", "text": "Notice that metaphase one is not exactly the same as metaphase of mitosis."}, {"title": "Meiosis I .txt", "text": "In metaphase of mitosis, we actually align these individual chromosomes along our equator."}, {"title": "Meiosis I .txt", "text": "So in metaphase of meiosis, we would have six of these align along our equator."}, {"title": "Meiosis I .txt", "text": "But in metaphase one of meiosis, we only have three because we form these tetrids and these tetrids are basically aligned along our equator."}, {"title": "Meiosis I .txt", "text": "So we have 23 tetris that are basically aligned along the equator, and together we have 23 times two or 46 chromosomes."}, {"title": "Meiosis I .txt", "text": "Now let's move on to anaphase one of meiosis."}, {"title": "Meiosis I .txt", "text": "In anaphase, we have the process of disjunction."}, {"title": "Meiosis I .txt", "text": "And disjunction basically means our spindle fibers begin to pull on our chromosomes and we separate our chromosomes."}, {"title": "Meiosis I .txt", "text": "So these three chromosomes begin to go onto the left side and these other three begin to move to the right side."}, {"title": "Meiosis I .txt", "text": "So we separate our tetras."}, {"title": "Meiosis I .txt", "text": "So during anaphase one, this junction occurs, that is, the chromosome pair in the tetra are separated two opposite poles."}, {"title": "Meiosis I .txt", "text": "Now, notice one important point."}, {"title": "Meiosis I .txt", "text": "So let's take a look at this tetrid here."}, {"title": "Meiosis I .txt", "text": "So this chromatid and this chromatid are basically the same chromatid that we began with in this diagram before the S phase actually took place."}, {"title": "Meiosis I .txt", "text": "So these are the two original homologous chromosomes where one came from the mother and one came from the father."}, {"title": "Meiosis I .txt", "text": "And notice what happens in the process of anaphase."}, {"title": "Meiosis I .txt", "text": "So our chromosome that came from the father is separated from the chromosome that came from the mother."}, {"title": "Meiosis I .txt", "text": "And this means that our genes that are homologous, that code for the same type of traits, are separated during the process of anaphase."}, {"title": "Meiosis I .txt", "text": "And this is known as the law of segregation."}, {"title": "Meiosis I .txt", "text": "So notice that the original maternal and paternal homologous pair are separated."}, {"title": "Meiosis I .txt", "text": "So this is separated from this, this is separated from this, and this green one is separated from this orange one."}, {"title": "Meiosis I .txt", "text": "This process is absolutely random, and that basically means this can end up on this side or it can end up on this side."}, {"title": "Meiosis I .txt", "text": "Now, this process is random, so either one can end up on either side and this process of segregating our alleles our genes that code for similar traits that came from the female and the male parent this segregation process is known as the law of segregation and we'll talk more about the law of segregation when we'll get into genetics."}, {"title": "Meiosis I .txt", "text": "Now, let's move on to the process known as telephase one."}, {"title": "Meiosis I .txt", "text": "So following anaphase one of Meiosis, we have telephase one of Meiosis."}, {"title": "Meiosis I .txt", "text": "So during telephase one, the nuclear membrane begins to reform around each set of chromosomes."}, {"title": "Meiosis I .txt", "text": "So we form two nuclei on the left side of the cell and the right side of the cell."}, {"title": "Meiosis I .txt", "text": "At the same time, the nucleolus basically reforms, our spindles begin to basically deteriorate and what also happens is our nuclear membrane begins to basically separate into two and the cytoplasm also begins to divide."}, {"title": "Meiosis I .txt", "text": "So cytokinesis begins to take place."}, {"title": "Meiosis I .txt", "text": "Now, once the cell actually divides, one of the cells will have this information and the other cell will have this information and notice our initial cell had 123456 chromosomes and after this division, each cell will have one, two, three chromosomes."}, {"title": "Meiosis I .txt", "text": "And one, two, three chromosomes."}, {"title": "Meiosis I .txt", "text": "So during telephase one, we have our nuclear division that basically transforms our diploid cell into a haploid cell."}, {"title": "Meiosis I .txt", "text": "So in humans, we begin with 46 chromosomes."}, {"title": "Meiosis I .txt", "text": "And when telephase one takes place, we're going to end up with a haploid number of chromosomes."}, {"title": "Meiosis I .txt", "text": "And that's exactly why telephase one of meiosis is also known as the reduction division, because it reduces the chromosome number from 46 to 23 chromosomes."}, {"title": "Meiosis I .txt", "text": "So this is the process known as meiosis one."}, {"title": "Meiosis I .txt", "text": "Next is meiosis two, and we're going to focus on meiosis two in the next lecture."}, {"title": "Calcium and Calmodulin .txt", "text": "Calcium ions are these very important minerals that exist essentially in every single cell of our body."}, {"title": "Calcium and Calmodulin .txt", "text": "And calcium ions play many different roles."}, {"title": "Calcium and Calmodulin .txt", "text": "They have many different functions."}, {"title": "Calcium and Calmodulin .txt", "text": "And one of the functions of calcium ions is it actually acts as a secondary messenger molecule in signal transduction pathway."}, {"title": "Calcium and Calmodulin .txt", "text": "So, for instance, as we discussed previously, when we examined the a phosphor nosetide signal transduction pathway, we saw that calcium played a very important role."}, {"title": "Calcium and Calmodulin .txt", "text": "It acted as a secondary messenger molecule."}, {"title": "Calcium and Calmodulin .txt", "text": "And the cell used the calcium to basically stimulate different types of proteins."}, {"title": "Calcium and Calmodulin .txt", "text": "The question is, what is it about calcium that actually makes these calcium ions such prevalent and good intracellular secondary messengers?"}, {"title": "Calcium and Calmodulin .txt", "text": "Well, there are two facts, two things about calcium that makes them so prevalent."}, {"title": "Calcium and Calmodulin .txt", "text": "Number one is our cells can actually easily detect even the smallest changes in calcium mine concentrations inside the cell in a cytoplasm."}, {"title": "Calcium and Calmodulin .txt", "text": "And number two is calcium mines can actually form very strong interactions with proteins."}, {"title": "Calcium and Calmodulin .txt", "text": "And we'll see why that's important and what that does in just a moment."}, {"title": "Calcium and Calmodulin .txt", "text": "So let's focus on number one."}, {"title": "Calcium and Calmodulin .txt", "text": "The smallest changes in cytoplasmic calcium ion concentration can be detected by the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "So let's take a look at the following diagram."}, {"title": "Calcium and Calmodulin .txt", "text": "We have the outside of the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "We have the plasma membrane of the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "We have the cytoplasm of the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "And this is the membrane of the er."}, {"title": "Calcium and Calmodulin .txt", "text": "So this is the inside of the endoplasm reticulum, the lumen of the endoplasm reticulum."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, the first thing we should notice is if we compare the concentration of calcium ions on the inside the cytoplasm to, let's say, the outside or even the lumen, we'll see that inside the cytoplasm, we have a very low concentration of calcium ions."}, {"title": "Calcium and Calmodulin .txt", "text": "The question is why?"}, {"title": "Calcium and Calmodulin .txt", "text": "Well, to answer the question, let's recall a bit of general chemistry."}, {"title": "Calcium and Calmodulin .txt", "text": "So we know that when calcium binds to things like proteins, it creates conformational changes in the proteins, and that exposes hydrophobic regions of the protein to the aqueous environment."}, {"title": "Calcium and Calmodulin .txt", "text": "And what that means is the calcium protein complexes, for the most part, become insoluble in that aqueous environment."}, {"title": "Calcium and Calmodulin .txt", "text": "And so what that can lead to is precipitation."}, {"title": "Calcium and Calmodulin .txt", "text": "So if there is a high concentration of calcium for a very long period of time in a cytoplasm, that can actually cause damage, that can actually lead to the precipitation of many different types of proteins within that side of plasma."}, {"title": "Calcium and Calmodulin .txt", "text": "So during steady state conditions inside the cell, there is a very low concentration of calcium, about 100, that's much, much smaller than the outside concentration."}, {"title": "Calcium and Calmodulin .txt", "text": "And this is because calcium ions can readily bind to the negatively charged regions of proteins forming insoluble complexes that can be harmful to the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "Again, when the calcium binds to the protein, it usually exposes hydrophobic regions of the protein."}, {"title": "Calcium and Calmodulin .txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Calcium and Calmodulin .txt", "text": "But if that continues to happen for a very long period of time inside the cytoplasm that can be harmful."}, {"title": "Calcium and Calmodulin .txt", "text": "And so what the cell actually does is it uses these special membrane pumps, we call the calcium Atph to create electrochemical gradients, to basically pump these calciumines and store the calcium mines away from the proteins inside the cytoplasm."}, {"title": "Calcium and Calmodulin .txt", "text": "So we store these calciumines in the endoplasmic reticulum."}, {"title": "Calcium and Calmodulin .txt", "text": "And when we actually want to use the calcium ions, we have these membrane channels not shown diagram that can allow the movement of these calcium odds from the lumen into the cytoplasm of the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "So we see that this is why the cell pumps out the majority of the calcium and stores it in the endoplasm reticulum until it is actually needed."}, {"title": "Calcium and Calmodulin .txt", "text": "Because if the calcium is allowed to exist, if lots of calcium is allowed to exist for long periods of time in the cytoplasm, that can cause protein precipitation."}, {"title": "Calcium and Calmodulin .txt", "text": "And so the intrinsically low levels of cytoplasm, of cytoplasmic calcium allows the cell to actually detect even the smallest changes of increases in calcium."}, {"title": "Calcium and Calmodulin .txt", "text": "And we'll see, we'll talk about the actual protein called calmodulent that is used to detect this increase in concentration of calcium."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, let's move on to fact number two about calcium that makes it such a prevalent secondary messenger molecule."}, {"title": "Calcium and Calmodulin .txt", "text": "So calcium ions interact strongly with proteins."}, {"title": "Calcium and Calmodulin .txt", "text": "Why?"}, {"title": "Calcium and Calmodulin .txt", "text": "Well, calcium ions have a charge of positive two."}, {"title": "Calcium and Calmodulin .txt", "text": "And we know from Coulomb's law that the greater the charge is, the greater that interaction is, the greater that electrostatic force is."}, {"title": "Calcium and Calmodulin .txt", "text": "And so these calcium ions can basically locate the negatively charged side chain groups of proteins, or they can even bind to the oxygen of the carbonyl groups found on the backbone of the protein."}, {"title": "Calcium and Calmodulin .txt", "text": "And that can form strong interactions."}, {"title": "Calcium and Calmodulin .txt", "text": "And once those interactions form, the calcium can induce conformational changes in the structure of the protein, and that can bring the different domains in the protein together."}, {"title": "Calcium and Calmodulin .txt", "text": "It can basically expose important hydrophobic regions of the protein, and that can allow that protein to interact with other proteins, and that can stimulate many different types of reactions in the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "So, again, due to the positive charge, due to a positive charge of two, calcium odds can form strong interactions with the negatively charged side chain groups of proteins, as well as the oxygen atoms on the carbonyl groups of the protein backbone."}, {"title": "Calcium and Calmodulin .txt", "text": "As a result of this, when calcium bonds to proteins, it can cause conformational changes in the structure of the protein, that can link different domains in the protein."}, {"title": "Calcium and Calmodulin .txt", "text": "It can expose, as we've seen in the case of Camodulin, hydrophobic regions."}, {"title": "Calcium and Calmodulin .txt", "text": "And that can be beneficial to that protein."}, {"title": "Calcium and Calmodulin .txt", "text": "So this can stimulate the activity of target proteins, target enzymes, target pumps, and so forth."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, let's take a look at this important molecule called calmodul."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, calmodulen is actually a ubiquitous molecule."}, {"title": "Calcium and Calmodulin .txt", "text": "And what that means is it's essentially found everywhere in all the cells and many different types of organisms."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, if we take a look at a small portion of the calmodulen."}, {"title": "Calcium and Calmodulin .txt", "text": "This is what we see."}, {"title": "Calcium and Calmodulin .txt", "text": "And this domain is known as the EF hand."}, {"title": "Calcium and Calmodulin .txt", "text": "And actually it contains a few EF hands."}, {"title": "Calcium and Calmodulin .txt", "text": "So if you want to see the structure of calmodulen, look it up on Google or in a textbook."}, {"title": "Calcium and Calmodulin .txt", "text": "It basically contains these EF hands."}, {"title": "Calcium and Calmodulin .txt", "text": "And the reason we call it a hand is because it kind of looks like this, where this purple alpha helix is this structure here, this a dark purple region is this structure, and this green section is my thumb."}, {"title": "Calcium and Calmodulin .txt", "text": "And so it kind of looks like a hand."}, {"title": "Calcium and Calmodulin .txt", "text": "And so this pocket here that is formed as a result of this loop, this loop and this turn is basically where that calcium ion actually fits."}, {"title": "Calcium and Calmodulin .txt", "text": "And in fact, a single calcium or a single calmodulen can actually take up four calcium ions."}, {"title": "Calcium and Calmodulin .txt", "text": "And so these calmodulent proteins can actually be used by the cell to detect increase in calcium ion concentration."}, {"title": "Calcium and Calmodulin .txt", "text": "So if the calcium ion concentration increases to about five times of what it should be during steady state conditions, so from 100, about 500 nm, these calmodulent proteins can begin to bind those calcium ions."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, once they bind the calcium ions, what happens next?"}, {"title": "Calcium and Calmodulin .txt", "text": "Well, as soon as that calcium binds onto the calmodulant, as we saw in this particular discussion, it creates a conformational change in that calmodulent."}, {"title": "Calcium and Calmodulin .txt", "text": "And what that does is exposes crucial hydrophobic regions that weren't exposed before."}, {"title": "Calcium and Calmodulin .txt", "text": "And exposure of these hydrophobic regions on Calmodulen allows the calcium calmodulent complex to go on and bind to many important enzymes and affect the molecules."}, {"title": "Calcium and Calmodulin .txt", "text": "And one important enzyme, one important molecule that Calmodulen binds to is the calmodulendependent protein kinase, which basically depends on this complex here."}, {"title": "Calcium and Calmodulin .txt", "text": "So calcium being a secondary messenger, once it's released from the lumen and goes into the cytoplasm, it binds onto calmodulen and then informs the calcium calmojulin complex, which is a stimulating complex because it goes on and binds onto the calmodul independent protein kinase, which is activated and then goes on to phosphorylate many different types of enzymes and that stimulates many different types of pathways."}, {"title": "Calcium and Calmodulin .txt", "text": "So calmodulin is a regulatory protein that is used to detect changes in calcium ion concentrations."}, {"title": "Calcium and Calmodulin .txt", "text": "If the cytoplasmic concentration of calcium ions raises to about 500 nm, so five times what it should be under steady state conditions, calmodulant will begin binding these calcium ions."}, {"title": "Calcium and Calmodulin .txt", "text": "And a single calmodulant, because it contains a few of these, can actually bind four individual calcium mines."}, {"title": "Calcium and Calmodulin .txt", "text": "So one here, one here, and two here, which is not shown here."}, {"title": "Calcium and Calmodulin .txt", "text": "Now, upon binding, the calcium induces a structural change in the calmodulent that activates it."}, {"title": "Calcium and Calmodulin .txt", "text": "So it exposes these hydrophobic regions of calmodulen which weren't exposed before."}, {"title": "Calcium and Calmodulin .txt", "text": "And now these hydrophobic regions can basically move on and interact with other proteins, stimulating those proteins and inducing many different types of processes inside the cell."}, {"title": "Calcium and Calmodulin .txt", "text": "So, again, we see that calcium is a very important, very prevalent secondary messenger molecule because our cells have the ability to actually detect even the slightest changes in calcium as a result of this calmodulent."}, {"title": "Calcium and Calmodulin .txt", "text": "And number two, when calcium actually binds, it binds very well and creates these conformational changes that are able to actually activate proteins, enzymes, membrane, pumps, channels, and many different types of molecules."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The central dogma of molecular biology tells us that the flow of genetic information in all living cells, including our own human cells, is from DNA to RNA to proteins."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, what we mean by that is if our cell wants to actually synthesize proteins, it must first take that DNA molecule and copy the gene, the genetic information found in in the gene into the RNA molecule."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And what this does is it essentially makes a copy of that genetic information via a process known as transcription."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, it's not too difficult to actually imagine how transcription takes place because both DNA molecules and RNA molecules use the same exact language."}, {"title": "Central Dogma and Genetic Code .txt", "text": "They consist of the same exact monomers we call nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, when we go from RNA to proteins, things are a bit more complicated."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that's because RNA and proteins consist of two different languages."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The language used by RNA are these nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "But the language used by the proteins are amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And nucleotides and amino acids are two completely different types of molecules."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So the question is, in the process of translation, how do the ribosomes actually know to basically create that specific sequence of amino acids if the RNA consists of these different molecules we call nucleotides?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, the ribosomes of the cell basically use a system called the genetic code."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So the cells of our body and the cells of other liver organisms use the system called the genetic code."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And the genetic code is used to basically translate that sequence of nucleotides on the RNA molecule into its corresponding sequence of amino acids on that polypeptide chain."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, this is basically our genetic code, and we'll see exactly what it actually means in just a moment."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, there are four facts that you have to know about the genetic code."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Fact number one is a three nucleotide sequence, known as a codon is used to encode each amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Fact number two is the code does not actually overlap."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Fact number three, the code is read continuously."}, {"title": "Central Dogma and Genetic Code .txt", "text": "There is no punctuation in the code."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And number four, the genetic code is degenerative."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So let's begin by discussing what fact number one means."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So the question is, when we essentially go from the RNA molecule to the protein, how exactly do we pair up the nucleotide sequence to the amino acid sequence?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Is it one to one?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, what do we mean by one to one?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "So does a single nucleotide correspond to a specific amino acid?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, would that even be possible?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "We have four different types of nucleotides and 20 different types of amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And what that means is, if this was the case, if each nucleotide corresponded to a specific amino acid, because we only have four nucleotides, we would only be able to produce four amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that clearly doesn't work because in our body, we have 20 unique amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So there are 20 amino acids, but only four nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Therefore, a single nucleotide cannot be used to encode for a specific amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So that system does not work well if the relationship is not one to one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "What about two to one?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Can a sequence of two nucleotides correspond to a specific amino acid?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "So let's calculate this mathematically."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So remember, we want to get a number that is 20 or greater."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now if this was nucleotide number one, there are four possibilities for nucleotide number one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now if this is nucleotide number two, remember we have a pair, a sequence of two nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Also we have four possibilities."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now the total number of possibilities is simply the product of these two quantities."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And four times four gives us a value of 16 possibilities."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And we have 20 amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And because this is less than 20, once again that means a pair of nucleotides cannot be used to basically build a single amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So pairs of nucleotides cannot be used as well because that would only produce 16 unique possibilities."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And it turns out that cells use triplet nucleotide sequences known as codons to encode for that amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Because if we multiply four times four times four in our triplet, that would give us a value greater than 20."}, {"title": "Central Dogma and Genetic Code .txt", "text": "It would give us 64."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now we'll see why that's important in just a moment when we discuss fact number four."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So for example, the nucleotide SequenceL uracil, uracil."}, {"title": "Central Dogma and Genetic Code .txt", "text": "This corresponds to the specific amino acid phenylalanine, while UUG corresponds to the specific amino acid leucine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And we have many more examples as we'll see in just a moment."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, fact number two, the code does not actually overlap."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now what does that mean?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, when we take the RNA sequence, the RNA molecule, and place it into our ribosome of the cell, the ribosome reads the codons without actually overlapping those codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So what exactly do we mean by that?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, let's take a look at these two examples."}, {"title": "Central Dogma and Genetic Code .txt", "text": "In this particular case, as the ribosome reads our codons, there is overlap between the codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "But in this case there is no overlap."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And it turns out that this is how the ribosome actually reads that sequence of nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we have the sequence of nucleotides, this is the five prime and this is the three prime."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And we have twelve nucleotides as shown."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, when the ribosome reads our nucleotide sequence, it reads it via these codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So triplets."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we have one, two, three, and this green section is codon number one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Next it moves on to this sequence."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So first it's G-C-C. That's the green one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And then it's CCU, that's the orange one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The third sequence is C-U-U that's the purple one."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And notice that these three codons, the green codon, the orange codon and the purple codon all have overlapping sections."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that's because in this case, the ribosome essentially moves one nucleotide over every time it reads that RNA chain."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now this is not how our ribosome reads it."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The ribosome reads it like this."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Essentially, every time it reads a codon, it moves over three nucleotide sequences."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we have GCC, then we move over three units, then we go UUC, then we move over again."}, {"title": "Central Dogma and Genetic Code .txt", "text": "A single codon for three units, CGG."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And none of these actually have the overlapping regions."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that's exactly what we mean by fact number two."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now let's move on to fact number three."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The code is read continuously."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And what that means is it essentially goes sequentially, one codon after the next."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So it never skips codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "It never uses codons as pauses."}, {"title": "Central Dogma and Genetic Code .txt", "text": "It reads them continuously from beginning to end."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And fact number four, the genetic code is degenerative."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, what do we mean by that?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, remember in fact number one, we said that we have a sequence of one, two, three nucleotide."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So a codon, and this is basically used to correspond to those amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now we have four times four times four gives us 64 possibilities."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So there are 64 unique possibilities for our codon, and that's way more than the number of amino acids."}, {"title": "Central Dogma and Genetic Code .txt", "text": "We have 20 amino acids and 64 codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And what that basically means is we have these codons that are different but can correspond to the same exact amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that's exactly what we need by the code being degenerative."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So codons consist of three nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Since there are four types of nucleotides, there are four times four times four, so 64 unique codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And this is more than the 20 possible amino acids, which means that most amino acids are encoded by several codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "For instance, if we examine leucine, leucine contains six different codons, unique codons that essentially encode for that specific leucine amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And this means all these different codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we have 123456 so UA ugcu cu, g CUC and cua."}, {"title": "Central Dogma and Genetic Code .txt", "text": "All these six different codons will create the same exact amino acid, namely leucine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And these different codons that encode for the same exact amino acid are known as synonyms."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, what's the big deal about this idea that the genetic code is degenerative?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, what it means is the reason the code is degenerative is because that actually minimizes the number of mutations that arise in our cells."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So what do we mean by that?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, let's suppose we have the following case."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So this is our mRNA molecule, and it consists of these three codons."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So CGC UCC UUA CUG."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now let's suppose that some type of mutation arises in this mRNA molecule, and instead of producing this A, we essentially produce this g. So the mutation basically takes place on this red nucleotide."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, when this mRNA molecule is placed into that ribosome, that ribosome will begin to read the codons one at a time."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So first it reads CGC."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, what is CGC?"}, {"title": "Central Dogma and Genetic Code .txt", "text": "Well, we can use this table to basically determine what that amino acid is."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So the first nucleotide is this column."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The second nucleotide is this row, and the third nucleotide is this column as well."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we have C, and that's here."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Then we have G, and that's here."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So that's in this box."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And then we have C, which means we have Lucine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So C-U-C."}, {"title": "Central Dogma and Genetic Code .txt", "text": "I'm sorry."}, {"title": "Central Dogma and Genetic Code .txt", "text": "C. Okay."}, {"title": "Central Dogma and Genetic Code .txt", "text": "The second one is C. The first one is C. The second one is G. So we're in here."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So it's C g. And then we have C. So this is Arginine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Then we have UCC."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So it's UC and C. That Serine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Then we have so initially, without that mutation, we were supposed to have UA."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So UA gives us leucine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now there was a mutation in the third amino acid in the third nucleotide on this codon."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And it went from A to gene."}, {"title": "Central Dogma and Genetic Code .txt", "text": "Now, because the code is degenerative, what we see is this amino acid will still be the same amino acid that is produced in this case."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So UUA codes for leucine, and so will UUG."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So UU G will also code for leucine."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So even though there was a mutation in that nucleotide sequence, because the code is degenerative, what that means is the amino acid will still be that same amino acid and the protein that produced will still be that fully functional protein."}, {"title": "Central Dogma and Genetic Code .txt", "text": "So we see that the fact that the code is degenerative means that this will minimize the effects of mutations."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And once again, what this table describes is all the different types of amino acids that can be formed from some specific sequence of nucleotides."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And notice for most of these amino acids, we have several different types of codons that essentially code for a specific type of amino acid."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And notice that some of these sequences, for example, UAAG and UGA, they code for a stop signal."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And what that means is, as the ribosome is reading our mRNA molecule, when it gets to that specific stop signal sequence, that will tell it to basically stop the process of translation."}, {"title": "Central Dogma and Genetic Code .txt", "text": "And that basically means that's the end of that protein synthesis process."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So now that we have a general idea of what the electron transport chain actually does, let's discuss the details of what happens in the complexes of the electron transport chain."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And so we're going to begin our discussion by examining the details of what happens in complex one and complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So remember that these complexes are found in the inner membrane of the mitochondria."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So this is complex x one."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "This is the inner membrane of the mitochondria."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "This is the matrix of the mitochondria, and this is the intermembrane space."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, complex one is a very large complex."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "It's an L shaped multi subunit that contains about 46 individual polypeptide chains."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So complex one is a very massive complex."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, complex one is also known as NADH dehydrogenase or NADH oxidoreductase."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the reason we call it this is because this is the complex of the electron transport chain that ultimately accepts the high energy electrons from NADH molecules that we generate in processes such as the citric acid cycle and glycolysis."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So this L shape structure contains the horizontal component that lies in the membrane of the mitochondria, the inner membrane."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we have a vertical component that extends into the matrix of the mitochondria, and the NADH actually binds onto this extension that lies in the matrix of the mitochondria."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And along with the NADH, an H plus iron is also actually used."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we'll see why that H plus ion is needed in just a moment."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And so, in the process, we ultimately oxidize the NADH back into NAD plus."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And those two electrons are extracted by a group known as FMM, and the FMN stands for Flavin mononucleotide."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So within this vertical component of complex one, we have Flavin mononucleotide, which accepts those two high energy electrons from the NADH molecule."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, if we take a look at the structure of FMM, this is what it's going to look like in its fully oxidized form."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So oxidized basically means before it accepted those electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So we have this r component that contains a phosphate group not shown here."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we have this three ring structure and this three ring structure."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So one, two, three is known as the isoloxazine ring."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the isoloxazine ring in this flavin mononucleotide is the same exact isoxazine ring that is found in Fad molecules."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Remember, Fad stands for flavin adenineucleotide."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we find Fad in the citric acid cycle, and the Fad is able to extract those two electrons in the same exact way that FMN is able to use this same isoloxazine ring to actually extract those two electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "But the two electrons cannot actually bind onto the FMN by themselves."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "They need two H plus ions."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So we have two H plus ions and two electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "One H atom basically binds onto this nitrogen, and the other H atom binds onto this nitrogen."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we form the reduced form of flavin mononucleotide known as FMN H two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And that's why we need an additional H ion."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So one H ion comes from here, the other H ion comes from here."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the two electrons are found on the NADH."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And we ultimately oxidize the NADH into NAD plus and we form the SMN H two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And this takes place on the matrix side of this complex one."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So once again, the NADH molecule donates the two electrons onto an acceptor group found on the vertical component of complex one known as flavin mononucleotide fmmen."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "The FMN is reduced into FMM H two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And this prosthetic group contains the same isoloxazine ring that we find on the fad molecule."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So the fad is similar to FMN in the sense that they contain the same three member ring that is used to actually form that or actually use ticketstrack and collect those electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, once we reform the NAD plus, that NAD plus can be reused by the process of the citric acid cycle, or Glycolysis, where the NAD plus molecules are needed to actually oxidize the glucose derivative and abstract those electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "But what happens to the electrons once they are abstracted by FMM?"}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Well, once the electrons are abstracted by FMN, those electrons begin to move along a series of other groups known as iron sulfur clusters, iron sulfur groups."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And as these electrons actually move along these different groups we know from basic physics that whenever electrons flow along a certain area, that flow of electrons is what we call an electric current."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And that electric current can be used to power some type of process."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And in this particular case, the process that we power is the pumping of H plus ions."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So what we want to do is we want to establish a proton electrochemical gradient that will ultimately be used by ATP synthase to form ATP molecules."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And so protein complex one is actually a proton pump."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And as these electrons move and ultimately end up on Ubiquinone, as we'll see in just a moment four H plus ions are actually pumped by protein complex one from the matrix side through the intermembering space of the mitochondrion."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, as these electrons move, they ultimately end up on a carrier molecule known as coenzyme Q, or Ubiquinone."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, Ubiquinone accepts two electrons and it also actually accepts two H plus ions."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So it takes up two H plus ions from the matrix and it forms the fully reduced form of Ubiquinone, QH two, which is known as Ubiquinol."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So once again, the electrons, once they abstract and biflavin mononucleotide then move along a series of iron sulfur groups shown here and are ultimately transferred to coenzyme Q Ubiquinone."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "The Ubiquinone also uptakes two protons and that helps us establish that electrochemical gradient."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And those two H ions bind onto Q to basically form the reduced form of Ubiquinone known as Ubiquinol."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And as these electrons move along this proton complex it pumps four H plus ions from the matrix side onto the intermemmbrane side."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now let's move on to complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, complex two is actually not a proton pump."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So that's the main difference between complex one, three and four."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Complex two is not a proton pump."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "It will not pump any protons across the membrane."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And actually, because of that, less ATP molecules will be formed from fadh two than from NADH."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, the reason we mentioned fadh two is because complex one is actually complex two is actually responsible for extracting those electrons from fadh two molecules."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, let's think back to the citric acid cycle."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "In the citric acid cycle, the step that allowed us to form the fadh two molecule is this step here."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "In this step, Succinate is oxidized into fumarate, and the fad molecule is reduced into fadh two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So these two H atoms, along with one electron each, are extracted."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "They bind onto fad to form the fadh two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And these two electrons left over here, one here and one here, create a double bond to form this fumarate molecule."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the enzyme that catalyzes this step of the citric acid cycle is known as Succinate dehydrogenase."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And actually, Succinate dehydrogenase, the enzyme that catalyzes this step of the citric acid cycle, is found within complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So complex two is actually involved in the citric acid cycle in forming the fadh two molecule and extracting those electrons from Succinate to form fumerate."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, complex two, for that reason, is also known as Succinate reductase, because we essentially abstract those electrons from Succinate, we oxidize it into fumerate, and we reduce the fad into fadh two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Now, once we form the fadh two, the fadh two remains bound to complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And in complex two, the two electrons are abstracted from fadh two, and they move on to series of iron sulfur clusters, iron sulfur groups."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And ultimately, those two electrons end up being bound to Ubiquinone, coenzyme Q, the same coenzyme Q that we discussed in this particular case."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And again, the coenzyme Q, once it binds those two electrons, it abstracts two H plus ions to form Ubiquinol."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "The ubiquinol then departs."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "It detaches from the complex and moves on to complex three."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So once we form Ubiquinol here, and once we form Ubiquinol here, they detach and move on onto complex three, as we'll see in the next lecture."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So, to summarize, complex two, also known as Succinate reductase, is a protein complex that contains Succinate dehydrogenase, which functions in a citric acid cycle."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So complex two actually converts Succinate into fumarate and generates that fadh two molecule."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the fadh two molecule doesn't actually detach."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "It remains attached onto complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So this is complex two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "The fadh two remains bound onto the complex, and then it basically is oxidized back into fad."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "It basically kicks off those two H ions."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "Those two h. Yeah, the two H ions, as well as those two electrons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And those two electrons then travel through a series of these iron sulfur clusters and ultimately end up being bound onto that coenzyme cue the Ubiquinone."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "When the Ubiquinone uptakes those two H ions, it then forms Ubiquinol, which detaches and moves on to complex three, as we'll see in the next lecture."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And again, a very important distinction between complex one and complex two is the fact that complex one actually pumps those protons and helps generate that electrochemical gradient for hydrogen ions."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "But this one doesn't actually pump any protons."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And that's precisely why, as we'll see in a future lecture, NADH is able to actually form a greater number of ATP molecules compared to the Fadh two."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "So the complex oxidizes succinate into fumarate, in the process forming the Fadh two, which is then oxidized back into Fad, and that release the two electrons, which ultimately move through these FES clusters and onto Ubiquinone to then form Ubiquinol."}, {"title": "Complex I and II of Electron Transport Chain .txt", "text": "And the Ubiquinone is the electron carrier that shuttles these electrons from either complex one or two onto complex three of the electron transport chain."}, {"title": "Lung Capacity and Volume .txt", "text": "We now know how our lungs actually operate."}, {"title": "Lung Capacity and Volume .txt", "text": "And we are familiar with the gas exchange process as it takes place inside the alveoli of our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, let's focus on something called lung volume and lung capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "So in this lecture we're going to explore questions such as how much air is typically exchanged by our lungs every single time we take a break breath, and how much air can actually be stored inside our lungs in the first place."}, {"title": "Lung Capacity and Volume .txt", "text": "So let's begin by taking a look at the following diagram."}, {"title": "Lung Capacity and Volume .txt", "text": "The Y axis is the volume of air that is exchanged by the lungs given to us in milliliters."}, {"title": "Lung Capacity and Volume .txt", "text": "And the x axis is our time."}, {"title": "Lung Capacity and Volume .txt", "text": "Now notice as time increases, as time progresses, we have this fluctuating blue curve."}, {"title": "Lung Capacity and Volume .txt", "text": "And what the fluctuating blue curve essentially describes is it describes the process of breathing."}, {"title": "Lung Capacity and Volume .txt", "text": "Every time the blue curve increases, we essentially allow air into our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "And every time the blue curve decreases, we expel air from our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "So the increasing portion of our blue curve is the process of inhalation and the decreasing portion of the blue curve is the process of exhalation."}, {"title": "Lung Capacity and Volume .txt", "text": "So let's begin by describing something called the title volume."}, {"title": "Lung Capacity and Volume .txt", "text": "So earlier we asked how much air, on average is exchanged by our lungs when the individual is actually at rest every single time we take a breath."}, {"title": "Lung Capacity and Volume .txt", "text": "So if I stand here and I don't exercise, then I basically take about ten breaths of air every single minute."}, {"title": "Lung Capacity and Volume .txt", "text": "And every one of these breaths exchanges about 500 air inside our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "And this is what we call the tidal volume."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, the tidal volume is the portion between this top line and this bottom line."}, {"title": "Lung Capacity and Volume .txt", "text": "So this is our tidal volume."}, {"title": "Lung Capacity and Volume .txt", "text": "And so these fluctuations basically describe the normal breathing rate."}, {"title": "Lung Capacity and Volume .txt", "text": "So we essentially inhale and then we exhale and we exchange about 500 air every time we take that breath."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, what exactly is the maximum amount of air that the lungs can actually store?"}, {"title": "Lung Capacity and Volume .txt", "text": "This is called the total lung capacity and it's the distance between this maximum point and the zero line."}, {"title": "Lung Capacity and Volume .txt", "text": "And on average, for an average individual, it is equal to about 6000 ML or six liters of air."}, {"title": "Lung Capacity and Volume .txt", "text": "So if the person wishes, they can take a very deep breath."}, {"title": "Lung Capacity and Volume .txt", "text": "So if I take a very deep breath, let's say I start at this point, I go all the way up to this point and at the maximum point on this curve, this is this black line right here, and the distance from the black line all the way to zero."}, {"title": "Lung Capacity and Volume .txt", "text": "This is the total lunk of ounce that is equaling to about 6000 air."}, {"title": "Lung Capacity and Volume .txt", "text": "Now let's move on to something called the vital capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "The vital capacity is essentially this distance here."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, let's suppose we're taking our normal breath."}, {"title": "Lung Capacity and Volume .txt", "text": "So we're basically right here."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, eventually, when we're taking our normal breath, let's suppose we actually want to forcefully exhale all the remaining air in our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "So we take a breath and at this position we begin to forcefully exhale the remaining air."}, {"title": "Lung Capacity and Volume .txt", "text": "And at the maximum point of the forceful exhalation, we're going to be at this location and the distance from this purple line all the way to the top."}, {"title": "Lung Capacity and Volume .txt", "text": "This distance here is known as the vital capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "And the vital capacity is equal to about 4800 air per breath."}, {"title": "Lung Capacity and Volume .txt", "text": "So essentially, if we forcefully exhale our air, we're going to end up in this region."}, {"title": "Lung Capacity and Volume .txt", "text": "And then if we try to actually forcefully inhale as much air as possible, we're going to go from this location all the way to this location and the amount of air that will be exchanged by the lungs during that process is equal to 4800."}, {"title": "Lung Capacity and Volume .txt", "text": "So this line is about 1200."}, {"title": "Lung Capacity and Volume .txt", "text": "This line is 6000."}, {"title": "Lung Capacity and Volume .txt", "text": "Taking the difference gives us 4800 ML."}, {"title": "Lung Capacity and Volume .txt", "text": "Now let's move on to something called the residual volume."}, {"title": "Lung Capacity and Volume .txt", "text": "Now even when we actually forcefully expel all that air out of the lungs, we're going to end up on this purple line right here."}, {"title": "Lung Capacity and Volume .txt", "text": "So if we forcefully exhale, we end up right here."}, {"title": "Lung Capacity and Volume .txt", "text": "And notice inside the lungs we still have a certain amount of volume of air and this is known as the residual air."}, {"title": "Lung Capacity and Volume .txt", "text": "So no residual volume."}, {"title": "Lung Capacity and Volume .txt", "text": "So no matter how hard we try to breathe out, there will always be some amount of air inside our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "And this is known as the residual volume."}, {"title": "Lung Capacity and Volume .txt", "text": "The question is what exactly is the physiological importance of the residual volume?"}, {"title": "Lung Capacity and Volume .txt", "text": "So let's take a look at the following two diagrams."}, {"title": "Lung Capacity and Volume .txt", "text": "So inside our lungs, the specialized structure where gas exchange takes place is known as the alveolas."}, {"title": "Lung Capacity and Volume .txt", "text": "And we have many alveoli in our lung."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, the alveoli basically looks like a balloon and it could inflate as well as deflate."}, {"title": "Lung Capacity and Volume .txt", "text": "Now the reason we have residual volume, the reason that we have these air molecules inside our alveoli is to create a pressure so that our balloon, the alveoli valveolis doesn't actually deflate all the way, doesn't actually collapse."}, {"title": "Lung Capacity and Volume .txt", "text": "Because if all this residual volume, if all that air was actually removed from our alveolis, we would essentially create a vacuum, an absence of air."}, {"title": "Lung Capacity and Volume .txt", "text": "And when we have an absence of air molecules, we have no internal pressure."}, {"title": "Lung Capacity and Volume .txt", "text": "And because no pressure exists to actually push on the walls of our alveolis, in that case the walls would essentially push back and that would create this collapsed structure."}, {"title": "Lung Capacity and Volume .txt", "text": "So we want to keep that air inside the lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "We want to have the residual volume of air because we want to keep the bronchioles, the passageways, as well as the individual alveoli from actually collapsing because if they do collapse, that will make the process of breathing very, very difficult."}, {"title": "Lung Capacity and Volume .txt", "text": "So this distance here is our residual volume."}, {"title": "Lung Capacity and Volume .txt", "text": "Now if we take the sum of the residual volume and the viral capacity, that will give us the total lung capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "Now let's move on to something called the functional residual capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "But before we define what the functional residual capacity is, let's take a look at this ERV."}, {"title": "Lung Capacity and Volume .txt", "text": "ERV."}, {"title": "Lung Capacity and Volume .txt", "text": "Stands for expiratory reserve volume."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, what exactly is this?"}, {"title": "Lung Capacity and Volume .txt", "text": "Well, let's suppose we're taking our normal breath."}, {"title": "Lung Capacity and Volume .txt", "text": "So we're taking about 500 air every single breath."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, at the end of our breath, at this location, we essentially choose to expel."}, {"title": "Lung Capacity and Volume .txt", "text": "We forcefully expel all the remaining air from our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "And the amount of air that we can actually forcefully expel is given by the ERV."}, {"title": "Lung Capacity and Volume .txt", "text": "Value, the expiratory reserve volume."}, {"title": "Lung Capacity and Volume .txt", "text": "So, the expiratory reserve volume is this distance here."}, {"title": "Lung Capacity and Volume .txt", "text": "It's the difference between this height and this line here."}, {"title": "Lung Capacity and Volume .txt", "text": "So, this bottom portion line of the title volume and the residual volume line that gives us our ERV."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, if we take the sum of the residual volume and the expiratory reserve volume, well, that will give us something called a functional residual capacity, which is this distance here."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, we also have this volume, which is the inspiratory or inspiratory capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "And if we take the sum of the inspiratory capacity and the functional residual capacity, we also get the total lung capacity."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, the final concept that I'd like to briefly discuss that relates to lung volume and capacity and breathing is known as the anatomic death space."}, {"title": "Lung Capacity and Volume .txt", "text": "So, every single time we take a breath let's suppose we're taking a resting breath."}, {"title": "Lung Capacity and Volume .txt", "text": "We inhale."}, {"title": "Lung Capacity and Volume .txt", "text": "We exchange 500 air every single time we breathe."}, {"title": "Lung Capacity and Volume .txt", "text": "Now, only a portion of this air actually ends up in the alveoli of the lungs, where gas exchange actually takes place."}, {"title": "Lung Capacity and Volume .txt", "text": "The rest of that air is trapped within the passageways of our lungs, and that includes the trachea, that includes the bronchi as well as the bronchioles."}, {"title": "Lung Capacity and Volume .txt", "text": "And because gas exchange only takes place in the alveoli, no gas exchange takes place in the passageways."}, {"title": "Lung Capacity and Volume .txt", "text": "We call the air inside the passageways the anatomic death space because it's the air in the passageways that cannot be used for gas exchange because gas exchange only takes place inside the alveoli of our lungs."}, {"title": "Lung Capacity and Volume .txt", "text": "So it turns out that every single time we inhale 500 air at the normal resting rate, then what that means is only 350 of the air milliliters of the air actually ends up in the ALDE olive, because 150 air ends up in the bronchioles, in the trachea and the bronchi."}, {"title": "Lung Capacity and Volume .txt", "text": "And this is known as the anatomic death space."}, {"title": "Lung Capacity and Volume .txt", "text": "So about 30% of the air that we inhale, 30% of this quantity doesn't actually exchange anything with our body because it remains inside the passageways of our lungs, inside the bronchioles, inside our trachea, and inside the tube bronchi that connect to our lungs."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So now that we know what a signal transduction pathway is, let's actually take a look at an example that takes place inside our body."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So in this lecture, we're going to focus on epinephrine signaling, the epinephrine signal transduction pathway."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But before we actually get to that, let's discuss an important category of transmembrane proteins that are used as receptors by these signal transduction pathways."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And these are known as the seven transmembrane helix receptors, or simply 70 M receptors."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, the structure of these receptors basically consists of seven membrane spanning alpha helices, as shown in this particular diagram."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this is our phospholipid bilar membrane."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "We have 123-4567 of these membrane spanning alpha helices."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And notice they span the membrane in a snake like fashion."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that's why sometimes we call these seven transmembrane helix receptors helix receptors."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "We also call them serpentine receptors."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, this is the outside."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "This is the inside of our cell."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And any time a primary messenger wants to bind onto the structure, it binds on the outside portion the extracellular side of this seven TM receptor."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And so right here, we have an internal cavity that can fit that primary messenger."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So the primary messenger could be a neurotransmitter."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "It could be a hormone, as we'll see in this particular case."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "It can even be a synthetic drug that we create in the laboratory to basically inhibit the activity of the signal transduction pathway."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "In either case, it always binds onto the extracellular side of that receptor, and it doesn't actually move into the cytoplasm of that cell."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, in many cases so it's not shown in this diagram, but it's shown in this diagram."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And we'll talk about that in just a moment."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "In many cases, the seven TM domain actually contains additional protein domains attached onto the intracellular side of that structure, as we see in this particular case."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And those additional structures play very important, very specific roles."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So now let's move on to the epinephrine signaling pathway."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So in the epinephrine signal transduction pathway, the epinephrine is that primary messenger and binds into a special region of a protein we call the beta adrenergic receptor, the beta AR, which is a type of seven TM receptors."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this is what it looks like."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So we have the membrane, we have the outside, the inside."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "This is the epinephrine shown in red."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And instead of drawing out this complex structure, we're going to represent this complex structure with this green structure here."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this is the seven TM domain, and this pocket is the pocket shown here to which the epinephrine actually binds to."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now let's take a look at the structure of the beta adrenergic receptor."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, before the epinephrine actually binds to this section here, this is what it looks like."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So notice on the intracellular side, we have a heterotrimer structure."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And what that means is we have three different domains that create a trimer attached onto this seven TM domain."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "On the inside portion, of that structure."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So we have an alpha domain, a beta domain, and a gamma domain."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, the alpha domain is actually a g protein itself."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And what that means is it binds guanial nucleotides such as GDP and GTP."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, before the epinephrine actually binds, the alpha domain contains a GDP, a guanosine diphosphate."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And when the guanosine diphostate is bound to that alpha domain, the alpha domain has a very high affinity for the seven TM domain and these other two domains."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that's why we have this structure shown here."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "The alpha domain is bound to these two domains as well as to that seven TM domain."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So when epernphrine is not bound to the beta adrenergic receptor beta arm, the g protein binds guanosine diphosphate, GDP, and this keeps that trimeric domain intact and attached onto that seven TM domain, as we see in this diagram."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But what happens when the epinephrine actually binds onto this location here?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, as soon as that epinephrine binds, it creates conformational changes in this region of that seven TM domain, and that also creates conformational changes in the alpha domain."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So essentially what happens is there's a constriction in the region that holds the GDP and that expels that GDP."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And instead of having the GDP, there is a soluble GTP in solution inside the cytoplasm and goes on and binds onto a new location found in that alpha domain."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And as soon as that alpha domain, the g alpha protein."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this is also known as the Galpha protein because the alpha domain is a g protein."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So as soon as that g alpha domain binds the GTP, it loses its affinity not only for this seven TM membrane protein, it also loses affinity for this dimer structure here that consists of this beta in orange and the gamma in purple."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And so what happens is there is a dissociation process that takes place and this GTP that is or this GTP carrying structure essentially dissociates from not only the green structure, but also from this dimer structure we call the g beta gamma structure or the g beta gamma dimer."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So upon binding, the epinephrine induces conformational changes in the seven TM that stimulates the g protein, the alpha region, to release the GDP and bind the GTP guanosine triphosphate."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "This also causes the betagama or the g betagama dimer to dissociate from that Galpha protein, as shown in this diagram."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, this simply dissociates away."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But what happens to this GTP structure?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, before we examine that, let's mention the following important points."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this is the first stage where we have amplification taking place."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And so this is the first level of amplification."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But how is amplification actually achieved in this stage?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, a single epinephrine molecule, when it binds to this single structure, it not only induces the change of this g protein, it also induces the change of many other g proteins found in close proximity."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And so not only this will this alpha domain, lose the GDP and bind the GTP."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But also nearby alpha domains on other structures, on other seven TM domains will also expel that GDP and bind the GTP."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So a single Epinephrine can cause many G proteins to exchange the GTP for the GDP and this causes an Amplification effect."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "This is the first level of Amplification."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "The second level will discuss in just a moment."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So once this takes place, once the Epinephrine binds onto its side, it causes a conformational change that allows this structure to expel that GDP and instead of that, basically bind the GTP and that decreases the affinity of this G alpha protein to this structure and this dimer."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And so they dissociate."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, this structure basically goes on and binds until another transmembrane protein, an enzyme found in the membrane known as adenylate cyclase, which is shown here."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So the adenylate cyclist basically contains twelve membrane spanning alpha helices found in that membrane."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And then we also have two domains found on the intracellular side."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that GTP carrying G alpha protein goes on and binds onto this intracellular domain of the adenoid cyclist."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And it stimulates this enzyme to basically carry out its function to transform ATP molecules into the secondary messenger molecules we call cyclic adenosine monophosphates or simply camp."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So the dissociated G alpha domain in the GTP state moves and binds to another transmembrane protein, an enzyme, to be specific, called adenylyt cyclist."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "It stimulates the adenalyt cyclist to begin transforming the ATP into the cyclic Amp."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "These cyclic Amp molecules are what we call secondary messenger molecules."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that's because these secondary messenger molecules are intramolecular molecules found inside the cells that can diffuse into different regions and organelles found within that cell."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And they can basically induce and stimulate many different types of processes as we'll see in just a moment."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, this is the second level of Amplification."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So this was the first and this is the second."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Why?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, because a single G alpha protein goes on and binds to a single adenylate cyclist and then that single cyclase enzyme carries out many individual processes in which it produces many of these cyclic Amp molecules."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So we have a ton of these cyclic Amp molecules that then can diffuse into different regions in the cell."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, what exactly is the function of CA and P?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, camp can go on and basically stimulate many affector molecules and effectors can be enzymes or proteins or transcription factors."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But inside our body, the most important job of CA and P, in this particular case in the epinephrine signal and transduction pathway is the fact that the cyclic Amp goes on and stimulates it activates protein kinase A molecules."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, recall from our previous discussion on protein kinase A, or simply PKA."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "The structure of protein kinase A consists of two types of domains."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So we have two regulatory domains and we have two catalytic domains."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And in its inactive form, all these domains interact to form this tetrimer structure."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "But when cap molecules go on and bind to the protein kinase aid, they bind to the regulatory sites of the regulatory structures and that causes the dissociation of the catalytic sites."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And what that does is it opens up the active sites of the catalytic regions."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And those catalytic regions are what we call the activated PKA."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And now the activated PKA can go on to carry out its function."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So what is its function?"}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Well, basically the active PKA goes on and phosphorylates specific amino acids such as three an proteins and enzymes."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And what that does is it activates those molecules."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "So two important things that PKA does is the following."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Number one, PKA basically activates enzymes which are responsible for breaking down glycogen into glucose."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And then our cells can use the glucose to basically form ATP molecules."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And for instance, if we're discussing muscle cells, if this is the membrane of a muscle cell, the ATP can then be used to contract that muscle."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Another important function of PKA, among its many, many functions, is to activate special transcription factors that can basically go on, move into the nucleus of that cell and activate gene expression."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that can produce many important enzymes and proteins that must be used by that cell to carry out some type of physiological effect."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "Now, the next thing I'd like to focus on is how to actually terminate this specific epinephrine signal transduction pathway."}, {"title": "Epinephrine Signal Transduction Pathway.txt", "text": "And that will focus focus on in the next lecture."}, {"title": "Translation: Elongation and Termination.txt", "text": "The process of translation is the process by which we synthesize our proteins by using our mrname molecule, the ribosome, as well as tRNA molecules."}, {"title": "Translation: Elongation and Termination.txt", "text": "So let's recall what the first step of translation is."}, {"title": "Translation: Elongation and Termination.txt", "text": "As we discussed in the previous lecture, the first step is the initiation process."}, {"title": "Translation: Elongation and Termination.txt", "text": "And in this process, our mRNA molecule that codes for the protein finds the small subunit of the ribosome, and they find each other with the help of protein factors, protein molecules known as initiation factors."}, {"title": "Translation: Elongation and Termination.txt", "text": "So once our small subunit Binds to the mRNA molecule, the small subunit then moves along the mRNA molecule until it locates a specific nucleotide sequence on the mRNA known as the star codon."}, {"title": "Translation: Elongation and Termination.txt", "text": "So the star codon is the nucleotide sequence aug, where a is the atom nucleotide, u is the uracil nucleotide, and g is the guanine or the guanosine nucleotide."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, once our small subunit finds the star codon, it basically signals a tRNA molecule to go out and find the appropriate amino acid, which is the methionine amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "The tRNA then binds to our amino acid, and we form the amino acid tRNA complex."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically, our tRNA molecule that is bound to our amino acid is known as the amino acid tRNA or the charged tRNA."}, {"title": "Translation: Elongation and Termination.txt", "text": "And when somebody says it's an uncharged tRNA, that means the tRNA is no longer bound to our amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "So once our tRNA finds the methionine amino acid, it then brings that methionine amino acid to our mRNA molecule, and the tRNA binds to our mRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once that takes place, the large subunit of the ribosome binds the small subunit they associate, and they form a ribosome complex that is attached to that mRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically, the initiation process involves these steps, and ultimately, we form the following ribosome complex."}, {"title": "Translation: Elongation and Termination.txt", "text": "So we have the mRNA molecule that begins at the five end and ends on the three end."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the small subunit, we have the large subunit."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the charge tRNA or the amino acid tRNA that contains armethionine amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this is our tRNA shown in green."}, {"title": "Translation: Elongation and Termination.txt", "text": "So the amino acid Is shown in purple as the circle."}, {"title": "Translation: Elongation and Termination.txt", "text": "Our tRNA is shown in green."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this red region here is the start codon region."}, {"title": "Translation: Elongation and Termination.txt", "text": "It's a sequence aug. Now, basically, once our ribosome complex has formed, there are three locations within a ribosome that we have to be aware of."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the p side, we have the aside, and we have the east side."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, we'll talk about the a side and east side in just a moment when we discuss the process of elongation."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, the p side is basically the side to where the first charged tRNA actually binds to."}, {"title": "Translation: Elongation and Termination.txt", "text": "So following the process of initiation, once initiation actually takes place, the charged tRNA molecule that carries aromthion amino acid is found within the peaside of our ribosome."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, before we move on to the process of elongation and termination, which is the second and third stage of translation."}, {"title": "Translation: Elongation and Termination.txt", "text": "Let's briefly discuss what the structure of the tRNA molecule is."}, {"title": "Translation: Elongation and Termination.txt", "text": "So the three dimensional structure of tRNA molecule is basically that of a cloverleaf."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically, we have the following three dimensional regions."}, {"title": "Translation: Elongation and Termination.txt", "text": "So we have the five end of our RNA molecule and we have the three end of that RNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "And each one of these circles designates a single nucleotide."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, these red regions are the regions where there is hydrogen bonding taking place between the tRNA nucleotides."}, {"title": "Translation: Elongation and Termination.txt", "text": "So we have bonding here, here, here, and here taking place."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, there are two important locations on the transfer RNA molecule that you have to be aware of."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the three end that contains the proper nucleotide sequence that is responsible for binding to our amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically, when the tRNA molecule in the initiation process goes out and finds the methionine amino acid, the methionine amino acid binds to this sequence on the three end of the tRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "And the binding takes place with the help of a special protein, a special enzyme known as tRNA synthetase."}, {"title": "Translation: Elongation and Termination.txt", "text": "So tRNA synthetase uses a GTP molecule to basically bind our amino acid to the three end of our tRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, another important region on our tRNA molecule that we have to be familiar with is this region here, which is basically at the center of our tRNA strand."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this is shown in blue."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this region is basically a sequence of three RNA nucleotides that is complementary to the sequence on the codon."}, {"title": "Translation: Elongation and Termination.txt", "text": "And that's exactly why this region is known as the anticodon."}, {"title": "Translation: Elongation and Termination.txt", "text": "And basically the anticodon is the region that binds to the codon and on our mRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "So if this is our tRNA molecule shown here in green, then the bottom of this tRNA molecule will contain the anticodon that will bind to our codon region."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now let's move on to the process of elongation, which is basically the second step in the process of translation in which we synthesize our protein."}, {"title": "Translation: Elongation and Termination.txt", "text": "So once initiation actually takes place, once the ribosome complex is formed, and once our charged tRNA molecule that carries our methionine binds to the pside, the ribosome can then begin moving along our mRNA."}, {"title": "Translation: Elongation and Termination.txt", "text": "But before the movement actually takes place, before this entire ribosome begins to slide along our mRNA molecule, another tRNA molecule must find the appropriate amino acid and bring it to the a side of our ribosome."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this is the p side and the one to the left or to the right is our acytes."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically, once the p side and acytes are filled with the appropriate charged tRNA molecules as shown in the following step."}, {"title": "Translation: Elongation and Termination.txt", "text": "So in this step, we see that we have one tRNA molecule that contains the methionine in the pside and the second tRNA molecule that contains the next amino acid in line in the a side."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, we can basically undergo the process of peptide bond formation so a special enzyme known as peptidal transferase catalyzes the formation of the peptide bond between the amino acids in the p sides and the amino acid in the a side."}, {"title": "Translation: Elongation and Termination.txt", "text": "And when the peptide bond is formed between this amino acid here and this amino acid here, the amino acid detaches from the tRNA in the p side."}, {"title": "Translation: Elongation and Termination.txt", "text": "And we form the following complex."}, {"title": "Translation: Elongation and Termination.txt", "text": "So we have the small unit, we have the large subunit, we have our mRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the first tRNA that no longer contains our amino acid, and that is down in the pside."}, {"title": "Translation: Elongation and Termination.txt", "text": "And now we have the two amino acids that are attached to one another via the peptide bond that are both attached to the tRNA found in the a side."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this is our acide and this is our p side."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, in the next step, once we actually form this peptide bond, and once this amino acid breaks off from this tRNA molecule, we undergo the process of translocation."}, {"title": "Translation: Elongation and Termination.txt", "text": "So in the next step, the ribosome complex moves three nucleotides in the five to three direction along the mRNA."}, {"title": "Translation: Elongation and Termination.txt", "text": "So in this diagram, we move three nucleotides to the right."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this entire ribosome moves three nucleotide to the right, and that places our uncharged tRNA molecule, the tRNA molecule that does not contain the amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this tRNA molecule moves into the east side, which is this location here."}, {"title": "Translation: Elongation and Termination.txt", "text": "So we move three nucleotides this way, this uncharged tRNA moves into the e side, and our charged tRNA that contains the growing polypeptide chain moves from the a side and into the p side as shown in the diagram."}, {"title": "Translation: Elongation and Termination.txt", "text": "And now our a side shown here is empty."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once our a side is empty, what happens is this entire process can repeat itself."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, what exactly is the purpose of placing our uncharged tRNA into our easide?"}, {"title": "Translation: Elongation and Termination.txt", "text": "Well, the easide stands for the exit side."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once our uncharged tRNA molecule, the tRNA molecule that does not contain the amino acid, is moved into the east side, our ribosome then expels."}, {"title": "Translation: Elongation and Termination.txt", "text": "It removes our tRNA from the east side of our ribosome."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this entire process, the process by which our ribosome actually slides along the mRNA and these tRNAs are expelled from the ribosome, is known as the process of translocation."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, once the acide is empty, the process can repeat itself to add another amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this continues until the polypeptide chain is actually complete."}, {"title": "Translation: Elongation and Termination.txt", "text": "Now, the next question is, how do we know that our polypeptide chain is actually complete?"}, {"title": "Translation: Elongation and Termination.txt", "text": "Well, the last stage of translation is known as termination."}, {"title": "Translation: Elongation and Termination.txt", "text": "And just like there is a start codon that basically signals the process of initiation, there is also a codon known as the stop codon that signals the process of termination, where we stop the addition of our amino acid to the growing polypeptide chain."}, {"title": "Translation: Elongation and Termination.txt", "text": "So if the ribosome reads either the UAA, the UGA, or the UAG sequence a protein called the release factor protein will bind to the aside instead of a tRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "And this will ultimately cause the growing polypeptide chain to actually break off from our tRNA molecule and eventually the ribosome complex will dissociate and will create that polypeptide chain."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically these three diagrams describe what the process of termination actually looks like."}, {"title": "Translation: Elongation and Termination.txt", "text": "So basically this sequence of three nucleotides in the acide is our stop codon."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this aside contains our stop codon."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once our ribosome reaches our stop codon, we have a protein known as the release factor, shown in red, basically binds to the acid and that causes the dissociation of our polypeptide chain, shown in purple from our tRNA molecule."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once that dissociates, this tRNA molecule leaves our p side and the e and the tRNA and the e side also leaves our ribosome as shown in this diagram."}, {"title": "Translation: Elongation and Termination.txt", "text": "And in the final step, once we break the bond between the polypeptide and the tRNA molecule, the entire ribosome complex basically dissociates as shown in this step."}, {"title": "Translation: Elongation and Termination.txt", "text": "So this is the process known as translation that basically synthesize the proteins inside the cytoplasm of the cell."}, {"title": "Translation: Elongation and Termination.txt", "text": "So once again, translation incorporates three stages."}, {"title": "Translation: Elongation and Termination.txt", "text": "We have the initiation stage, the elongation stage, as well as the termination stage."}, {"title": "Translation: Elongation and Termination.txt", "text": "In the initiation stage, we basically assembled the ribosome complex that contains the mRNA molecule, the small and large subunit, as well as the first charged tRNA molecule in line that carries the methionine amino acid."}, {"title": "Translation: Elongation and Termination.txt", "text": "In the step of elongation, we have translocation taking place and we have the formation of our peptide bonds as well as the polypeptide chain."}, {"title": "Translation: Elongation and Termination.txt", "text": "And once we form our polypeptide chain, termination takes place in which the ribosome reads the stop codon."}, {"title": "Translation: Elongation and Termination.txt", "text": "And a special type of protein known as release factor binds to the acid of our complex and that causes the dissociation between the polypeptide and the tRNA molecule and that ultimately causes our dissociation of the entire ribosome complex complex as a whole."}, {"title": "Alternative Pathway of Complement System .txt", "text": "As we discussed previously, the complement system actually consists of two different major pathways."}, {"title": "Alternative Pathway of Complement System .txt", "text": "We have the classical pathway that we focus on previously and we have the alternative pathway that we're going to focus on in this lecture."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So what exactly is the major difference between these two pathways?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "Well, as we saw previously, to initiate and activate the classical path pathway, an antibody must find and must bind to its complementary antigen to form the antibody antigen complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then that antibody antigen complex goes on to the C One protein of the classical pathway and activates it."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then the C One protein can go on to activate the C two and C four."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And that forms a complex known as C four B, C two B complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then that activates C Three, which in turn activates C five and that produces our membrane attack complex mac mac."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And that basically initiates many different types of mechanisms that eventually protect our body from different types of pathogenic agents and antigens."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, what about the alternative pathway?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "Well, unlike the classical pathway, which needs the presence of our antibody antigen complex to initiate, the alternative pathway can be triggered even in the absence of the antibody antigen complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "The question is how?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "Well, it turns out that one of the major agents, one of the major proteins in the complement system we call C Three, does not actually need something to activate itself so it can spontaneously break down into its active form to form the C three B and C three A."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, the thing is, under normal conditions, when we don't have any pathogenic agents, for example, bacterial cells in our body, when we only have these normal cells around these molecules, what happens is the C three B quickly attaches onto a special inhibitory protein found on the membrane of nearby healthy cell."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And that inhibitory protein inhibits and deactivates the C three B molecule."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then that molecule is essentially recycled to form something else, perhaps another C Three molecule."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So under normal conditions, in the absence of any type of pathogens, this is usually what happens."}, {"title": "Alternative Pathway of Complement System .txt", "text": "C Three spontaneously breaks down, but then this is quickly recycled."}, {"title": "Alternative Pathway of Complement System .txt", "text": "It's inhibited and then recycled."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, what happens if we do have some type of pathogen, for example, bacterial cells nearby?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "This type of reaction, so this is shown in diagram two."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Let's suppose now we have the same spontaneous reaction that takes place to form the C three B and C three A."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, because we don't have any nearby healthy cell, we only have bacterial cells."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Those bacterial cells don't actually have any of these inhibitory or proteins to deactivate the three CB molecules."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And so because of that, the C three B molecules basically go on and react with another molecule, the protein known as factor B."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then when they combine, they form the C three BBB complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And this is the major agent that is involved in the alternative pathway what this molecule is."}, {"title": "Alternative Pathway of Complement System .txt", "text": "It's basically a three C three convertes."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And what that means is its main substrate is the C three molecule."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And it activates the C three in two ways."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So A is basically the following pathway."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So we have the C three that spontaneously breaks down into our C three A and C three B."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then the C three B quickly reacts with the factor B to form the C three BB complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, this complex can do one of two things."}, {"title": "Alternative Pathway of Complement System .txt", "text": "It can either once again react with another C three and then it forms the C three B and C three A."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then it combines with another C three B to form the C three BBC three B complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And then this is basically a molecule that can go on to activate the C five protein."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And remember from our classical pathway discussion, it's the C five that is responsible for essentially building the membrane attack complexes that can go on to the membrane of those infected or pathogenic cells and essentially build that water channel that will lyse that cell and kill off that cell."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So once we form this pathway in process A, once we form this complex in process A, it goes on, activates C five C five C five is broken down into C five A and C five B, and it's C five B that basically calls upon C six C seven C eight."}, {"title": "Alternative Pathway of Complement System .txt", "text": "They combine to form that membrane attack complex that forms that water channel on that membrane that license that cell."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, the other pathway is pathway B."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And pathway B is actually an amplification process."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So what do we mean by that is the following."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So we can either go this way, or this molecule can have a positive feedback effect on C three."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So basically it goes on back to C three."}, {"title": "Alternative Pathway of Complement System .txt", "text": "It cleaves the C three to form even more C three B molecules."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And now these same C three B molecules can be used again here with the fact that B to form even more of these complexes."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So this is a positive feedback loop because this that is formed in process B can go on to this to the beginning of the process and amplify the formation of this complex, which can then follow process A and go on to form many of these membrane attack complexes."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So this is essentially the other major pathway of the complement system we call alternative pathway."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So this one does not involve the presence or does not require the presence of antibody antigen complexes."}, {"title": "Alternative Pathway of Complement System .txt", "text": "On the other hand, the classical pathway actually needs these antibody antigen complexes to actually take place."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, the final component I'd like to talk about is how do we actually regulate the complement system?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "So we don't always want the complement system to actually be activated because it's very, very energy consuming."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And so if we don't have any types of pathogens in our body, why would we want the complement system to be activated?"}, {"title": "Alternative Pathway of Complement System .txt", "text": "Well, we don't."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And the way that we regulate it by using many different types of proteins, for example, three proteins that are commonly used by the body to basically regulate and deactivate some of these agents are the following three proteins."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So let's begin with factor I."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Factor I is a protein that can basically deactivate the C three B molecule."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So the C three B molecule that needs to be used with factor B to form this complex can basically be activated by factor I."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And once we deactivate this, it cannot combine with factor B, and so it cannot follow this alternative pathway."}, {"title": "Alternative Pathway of Complement System .txt", "text": "Now, another protein is factor H. And factor H actually removes the BB protein from this complex, once again, deactivating this pathway."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And finally, we also have another important agent that plays a role in the classical pathway, and that is the C one inhibitor."}, {"title": "Alternative Pathway of Complement System .txt", "text": "So remember, the C one is that initial protein that needs to be activated by the antibody antigen complex in the classical pathway."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And what this C one inhibitor does is it goes on to bind to that C one complex in the classical pathway and inhibits the activation of C two."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And and so that cannot form the C four B, c, two a C, two B complex."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And so we cannot activate C three."}, {"title": "Alternative Pathway of Complement System .txt", "text": "And so these proteins are commonly used, as well as many others, to basically down regulate and control our complement system, because we don't always want the system to actually be activated."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "The cells of our body use many different types of signal transduction pathways and some of these pathways utilize G proteins."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "For instance, we know that the epinephrine pathway and phosphonotype cascades used by the cells of our body utilize G proteins."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And because of that, we call these pathways Gproteincoupled signal transduction pathways."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So what I'd like to focus us on in this lecture is discussed how a specific type of bacterial pathogenic agent that infect our cells can actually cause the malfunction of G protein coupled signal transduction pathways."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And that can lead to many problems as we'll see in just a moment."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So what exactly is this bacterial pathogenic agent?"}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Well, we call it Vibriocolarae, which is basically that agent that causes cholera in humans."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So Vibrio simply means it's a raw shape gram negative bacterial cell."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "In fact, the raw shape is actually curved and so it looks like a comma."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now gram shape, gram negative basically means it contains a very thin layer of peptidoglycan in a cell envelope."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so if we stain it with the color purple, with the purple dye and then wash that purple dye away, that purple dye will not be able to remain in that cell wall and so it will be washed away and the bacterial cell will in fact appear pink under the microscope as shown here."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So Vibriocolari are curved, rod shaped grand negative bacteria that can infect human cells and in the presence of oxygen."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "They will in fact use oxygen to produce ATP molecules in a process we call aerobic cellular respiration."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now in the absence of oxygen, they will switch to fermentation to produce those ATP molecules."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now Vibrio cholera can only survive and grow under basic conditions."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "If we place them into an acidic environment where the PH is low, they will not be able to grow."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so eventually they will essentially die."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And what that means is these Vibrio cholerate are in fact acid labile."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And finally, as we'll see in just a moment, these bacterial cells actually affect the activity of G protein coupled signal transduction pathways as we'll see in this diagram, in just a moment."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So before we look at the details of this mechanism of infection, look to actually discuss how these bacterial cells can make their way into the, into our body."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's suppose we're in some third world country where they basically don't have some type of filtration system that basically filters the drinking water."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so you end up drinking contaminated water or eating contaminated food that contains this bacterial cell."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So eventually it makes its way into our stomach."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now in our stomach we have a very low PH, a PH of about two."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so what that means is these bacterial cells will not be able to grow in our stomach."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "In fact, the majority of these bacterial cells will in fact die off, but some may actually survive."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And when they pass into the small intestine, we know that in the small intestine the PH changes from acidic to basic."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So in the stomach it's around two but in a small intestine it's around 8.5."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this is the perfect PH for these bacterial cells to actually grow, thrive and ultimately be able to infect the cells of our body."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So what types of cells do these actually infect?"}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Well, it's the intestinal cells, the epithelial cells found in that small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's take a look at the following diagram."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's say we drink we drink the contaminated water that contains vibrio cholera."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "It makes its way into our stomach where the majority of them actually die off."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Because they are acid labeled they cannot survive under acidic conditions but a few of them actually make their way into the small intestine and that's where they begin to thrive, they begin to grow and they begin to infect the intestinal epithelial cells of that small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's take a small section of the small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Let's zoom in on this section."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this is basically what we get."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So we have the lumen of the small intestine and this is our Vibrio cholera."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now this is the membrane of the intestinal epithelial cell."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "This is the cytoplasm side and again this is the outside and these are all the different types of membranes that are membrane proteins that we might find in our membrane."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So we have the seven TM receptor which is also known as the G protein coupled receptor and it basically contains G protein but because it's activated that G protein has moved on and bound to adenyly cycling."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So if we think back to the epinephrine signaling pathway this is exactly what it looks like."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So we have our seven transmembrane helix receptor that basically is bound to the G protein."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "But when that ligand, the primary messenger shown in orange actually binds onto the seven TM receptor that G protein, the G alpha protein to be more specific actually detaches and goes on and binds onto a dentalt cyclase."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And then the cyclase basically transforms ATP into cyclic amp that goes on and binds and activates protein kinase A and protein kinase A goes on and affects different types of enzymes and protein effectors."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's suppose we have this bacterial cell and so basically in step one what the cell does is once it makes its way into the lumen it begins producing and releasing the cholera toxin we call cholera jen."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so this is basically what it looks like in step one."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now, what exactly is the structure of this particular toxin?"}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Well, basically it's a protein that contains six subunits."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Five of these subunits are identical and the other one is different."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So five of these units are known as the B chains and the other unit is known as the A chain."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "The A chain is shown in green and this is the enzymatic."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "It's the catalytic A chain that will cause its effect once it gets into the cell, as we'll see in just a moment."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And these five binding b chains basically create this cyclical structure that ultimately is used to actually bind into a special region of the membrane of the intestinal epithelial cells."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So once inside the loom of the small intestine, the cholera secretes, the cholera toxin we call chlorogen."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "This is a protein that consists of two types of chains, the A chains and the B chains."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And they combine to form a hexameric structure as shown in this particular case."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this is the region that basically binds onto special region in the membrane we call the GM one ganglioside."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So the collagen uses its B units to bind onto the membrane single lipid called the GM one ganglioside."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So a ganglioside is basically a single lipid that contains sugar molecules attached onto that polar section."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so this is what the g one ganglio side actually looks like."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "We have this lipid component inside the membrane and we also have these five sugars shown here, which are basically pointing towards the outside of that membrane they're found in the lumen of that small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so these five binding bee chains basically go on and bind onto this GM one ganglioside."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And once they bind, an endocytosis process takes place in which the cell membrane basically invaginates and it engulfs this structure."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And what happens is once that engulfing process takes place, this catalytic A chain is released into the cytoplasm."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So once bound, the catalytic A chain moves into the epithelial cell of the small intestine v the process of endocytosis."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now, what happens once it makes its way into our cell?"}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So let's suppose that our G protein coupled signal transduction pathway is actually turned on."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so what that means is this g protein is in its GTP phase and so it is bound onto the adenylate cyclase and it continually stimulates the cyclase to basically produce the camp, the cyclic adenosine monophosphate phosphates which stimulate the PKA."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now, in the absence of this catalytic A chain, this galphaprotein showed a red in the GTP phase, actually has a built in timer."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so it has Gtpa's activity."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And that means it can itself turn itself off by using a water molecule to hydrolyze the GTP back into GDP."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And remember, when the G protein is in its GDP phase, it is in fact turned off."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "But what happens here is this catalytic A chain moves on and binds onto this g protein in the GTP phase and it catalyzes a covalent modification process."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "It basically covalently attaches an ADP ribose component onto this G protein in the GTP phase."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this covalent modification stabilizes the structure of this g protein in the GTP phase and that ultimately traps this g protein in its active phase."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So once this binding takes place, this g protein continually stimulates the adenolid cyclist to produce the cyclic adenosine monophosphates, which in turn produce more active PKA molecules which in turn carry out their function, as we'll discuss in just a moment."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So the catalytic A unit, once it makes its way into the cell, it binds onto the alpha protein in the GTP phase where GTP stands for Guanosine triphosphate."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this GTP bound protein is attached onto the adenolate cyclist."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now, the A chain catalyzes the addition of an ADP ribosemoidi onto the arginine residue found on this g protein in the GTP phase."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so this covalent modification of that g protein in the GTP phase stabilizes the structure of the GTP phase."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so this structure will not be able to turn itself off and that traps it in its active state."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so if we move on to this region here, we see that the Galpha protein will be trapped in the active state, which implies that it will continually stimulate the cyclic Amp production, which in turn stimulates the activity of the protein kinase A."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And protein kinase A does two important things."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Number one is protein kinase A actually phosphorylates the sodium hydrogen antiporters."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So exchanges."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And remember, antiporters are these pumps, membrane pumps that essentially utilize the gradient of one molecule to actually move another molecule against its gradient."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so, because the PKA phosphorylates and deactivates the sodium hydrogen antiportic system, this basically inhibits the ability of these intestinal cells to reabsorb that sodium back into the cell."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so what that means is there is a net flow of sodium outside of the cell and the cell loses sodium ions to the lumen of that small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Now, number two, PKA also actually opens up chloride ion channels."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so chloride ions basically move down their electrochemical gradient from the inside to the outside the cell into the lumen of the small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so what we see happening is there's a net flow of these sodium chloride ions, sodium chloride salt, and it moves in a general direction to the outside of the cell."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And remember, as these salt ions basically move into this direction, what will follow?"}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "Well, water molecules will basically follow and water molecules will diffuse across the membrane and follow the net movement of the salt."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So we see that the net loss of sodium ions and chloride ions from the cells drives the movement of the water out of the cells and into the lumen of the small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this leads to the loss of large volumes of water and electrolytes."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And that's exactly why patients who have cholera basically experience very watery diarrhea."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And essentially all this water will be lost through the small intestine."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And this will lead to the dehydration of that individual."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "And so if the individual isn't treated, they will eventually die as a result of dehydration, as a result of loss of water and these electrolytes sodium ions and chloride ion."}, {"title": "Cholera and G-Protein Coupled Signaling .txt", "text": "So we see that it's very important that our cells actually be able to function these signal transduction pathways effectively and efficiently because if they actually, Malfunction, they can lead to very serious, very dangerous medical conditions."}, {"title": "Post Translational Modifications .txt", "text": "Ribosomes are the machinery of the cell that are responsible for translating and synthesizing our polypeptides, our proteins."}, {"title": "Post Translational Modifications .txt", "text": "And the way that they synthesize our proteins is by using the genetic code to translate the sequence of nucleotides into the sequence of amino acids."}, {"title": "Post Translational Modifications .txt", "text": "And we synthesize the polypeptides in that fashion."}, {"title": "Post Translational Modifications .txt", "text": "Now our polypeptides, once they're actually synthesized in the ribosome, are not complete before they actually arrive at the target location."}, {"title": "Post Translational Modifications .txt", "text": "And before they are activated, they have to undergo many different types of processes, many different types of modifications."}, {"title": "Post Translational Modifications .txt", "text": "And together all these modifications are known as posttranslational modifications of our polypeptide chains."}, {"title": "Post Translational Modifications .txt", "text": "Now the types of posttranslational modifications that we're going to briefly discuss in this lecture are shown on the board."}, {"title": "Post Translational Modifications .txt", "text": "So we have aspiration, methylation glycosylation, we have proteol lysis, we have nacetilation as well as lipidation."}, {"title": "Post Translational Modifications .txt", "text": "So let's begin with the process of phosphorylation."}, {"title": "Post Translational Modifications .txt", "text": "So phosphorylation is the addition of a phosphate group onto certain amino acids, usually the serine, three anine and our tyrosine, on our polypeptide chain."}, {"title": "Post Translational Modifications .txt", "text": "And the enzyme that basically catalyzes the addition of the phosphate group is known as protein kinases."}, {"title": "Post Translational Modifications .txt", "text": "So by adding our phosphate group onto our polypeptide chain, we're basically increasing the hydrophilic character of that protein."}, {"title": "Post Translational Modifications .txt", "text": "And as we'll see in a future lecture, this type of modification is usually used in the process of the cell cycle, in the cell growth process, as well as signal transduction."}, {"title": "Post Translational Modifications .txt", "text": "Now the second type of posttranslational modification is methylation."}, {"title": "Post Translational Modifications .txt", "text": "And methylation is basically the addition of a methyl group onto certain amino acids via the enzyme known as methyl transferase."}, {"title": "Post Translational Modifications .txt", "text": "So methylation usually increases the hydrophobic character of the enzyme."}, {"title": "Post Translational Modifications .txt", "text": "And so those polypeptides that are methylated basically increase their hydrophobic character as well."}, {"title": "Post Translational Modifications .txt", "text": "Now methylation is utilized in a process known as epigenetic regulation which is basically the regulation of gene expression that takes place during the process of transcription."}, {"title": "Post Translational Modifications .txt", "text": "Now let's move on to the third type of posttranslational modification known as glycosylation."}, {"title": "Post Translational Modifications .txt", "text": "So glycosylation is the process by which we add a sugar component onto our polypeptide chain."}, {"title": "Post Translational Modifications .txt", "text": "Now, by adding a sugar component we basically affect the proteins folding process as well as change the confirmation of that protein."}, {"title": "Post Translational Modifications .txt", "text": "Now one example of proteins that are glycosylated are those proteins that ultimately end up on the plasma membrane of the cell."}, {"title": "Post Translational Modifications .txt", "text": "And these proteins usually act as receptors for other important biological molecules such as, for example, neurotransmitters."}, {"title": "Post Translational Modifications .txt", "text": "Now let's move on to the fourth type of post translational modification process known as proteolysis."}, {"title": "Post Translational Modifications .txt", "text": "So proteollysis is basically the process by which certain types of enzymes known as proteases actually cut our proteins."}, {"title": "Post Translational Modifications .txt", "text": "Now why would we want to cut a protein?"}, {"title": "Post Translational Modifications .txt", "text": "Well, basically certain proteins are synthesized in their inactive or xiaomogen form."}, {"title": "Post Translational Modifications .txt", "text": "In order to actually activate those proteins, our enzymes called proteases must break certain peptide bonds in those proteins."}, {"title": "Post Translational Modifications .txt", "text": "Now many of the digestive enzymes in the stomach as well as in a small intestine undergo this process of proteolysis."}, {"title": "Post Translational Modifications .txt", "text": "Now, let's move on to the fifth type of posttranslational modification, known as nacetythylation."}, {"title": "Post Translational Modifications .txt", "text": "So, nacetylation is the transfer of an acetyl group from one molecule to an amino acid, or unto the polypeptide chain."}, {"title": "Post Translational Modifications .txt", "text": "Now, this process not only takes place after our translation took place, but it also actually takes place during the process of translation."}, {"title": "Post Translational Modifications .txt", "text": "So in most eukaryotic cells, when translation is still actually taking place, the first amino acid in the growing polypeptide chain, usually our methionine amino acid, is removed and replaced by our acetyl group."}, {"title": "Post Translational Modifications .txt", "text": "And this process is known as an acetylation."}, {"title": "Post Translational Modifications .txt", "text": "Now, an acetylation plays a crucial role in gene expression."}, {"title": "Post Translational Modifications .txt", "text": "Histones, those proteins that are involved in condensing our DNA into chromatids, can be meth or can be acetalylated, which reduces their ability to fold and opens up our DNA so that that DNA section can undergo the transcriptional process."}, {"title": "Post Translational Modifications .txt", "text": "Now, finally, the final process that we're going to discuss is lipidation."}, {"title": "Post Translational Modifications .txt", "text": "So lipidation is the process by which we add a lipid component onto our polypeptide chain."}, {"title": "Post Translational Modifications .txt", "text": "Now, why would we want to add a lipid component onto a polypeptide chain?"}, {"title": "Post Translational Modifications .txt", "text": "Well, basically, those proteins that ultimately end up in a membrane, for example, the mitochondrial membrane, the endoplasmic reticulum membrane, or the plasma membrane, these proteins that end up on a membrane need to actually incorporate themselves into those membranes."}, {"title": "Post Translational Modifications .txt", "text": "And because lipids, or because membranes consist of lipids, by adding a lipid component onto our protein, we're increasing that protein's affinity to the membrane."}, {"title": "Post Translational Modifications .txt", "text": "So this process is known as lipidation."}, {"title": "Post Translational Modifications .txt", "text": "So we saw that phosphorylation, methylation glycosylation, proteollysis, and acetylation and lipidation are six different processes that are known as posttranslational modification."}, {"title": "Post Translational Modifications .txt", "text": "So these are the ways by which our polypeptides are modified following the process of translation."}, {"title": "Post Translational Modifications .txt", "text": "Now, there are actually even more processes than we discussed in this lecture, and we'll discuss those in more detail when we get into biochemistry."}, {"title": "Post Translational Modifications .txt", "text": "Now, another type of process that takes place following our translation is the folding of the protein."}, {"title": "Post Translational Modifications .txt", "text": "So in order for the polypeptide to actually become active, it actually has to fold into the proper three dimensional form."}, {"title": "Post Translational Modifications .txt", "text": "And special types of proteins known as chaperones actually assist in this folding process."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Glycolysis as you might expect, is a very important process because it produces ATP molecules, the energy molecules used by the cell."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now, glycolysis actually has another important function."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "It is not only used to produce ATP molecules, but it is also used to produce the building blocks of our cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So molecules such as fatty acids and amino acids."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And we, and we'll focus on that in a future lecture."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So ultimately what I'd like to focus on in this lecture is skeleton muscle cells and how glycolysis in skeleton muscle cells is actually regulated."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, what's the entire point of using glycolysis in skeleton muscle cells?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, skeletal muscle cells basically want to contract skeleton muscle tissue and to contract those active MIT and filaments."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "What must happen is we have to have ATP."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so the predominant role that glycolysis plays in skeleton muscle cells is to actually form generate those ATP molecules."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "But how exactly is glycolysis actually regulated by these skeleton muscle cells?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "This will be the focus of this lecture."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So there are three regulatory points in glycolysis and these three regulatory points are actually enzymes."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "What enzymes?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, phosphor, fructokinase, hexokinase and pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now the question might be if we have so many different enzymes, we have ten enzymes in glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Why is it that these are the enzymes that are used to regulate the process of glycolysis?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, because unlike the other enzymes, these three enzymes are the most important enzymes."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Why?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, because they essentially regulate virtually irreversible processes that only take place in one direction."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So let's take a look at phosphor fructosekinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "This enzyme catalyzes step three and this happens to be the most important enzyme, why?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, because it regulates the commitment step of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So it transforms fructose six phosphate into fructose one six bisphosate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "When we're at this stage the fructose six phosphate before it has been transformed, it has a choice."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "It can either move into the active side of the phosphorinase, in which case it will be transformed into this product, or it can go on to form glycogen."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "But once we form the fructose 116 bits phosphate, this product has now been committed to the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So this is the most important enzyme because it essentially tells this molecule to continue and commit to that process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And there is no turning back for this molecule once it's committed, it has to carry out the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So that is why this enzyme is the most important regulation site in our cells in the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "It catalyzes that commitment step."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now, if we study the structure phosphor fructokinates, we're going to find catalytic regions and regulatory regions."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "The catalytic regions basically contain the active side that binds the substrate fructosex phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "But those regulatory domains contain the sites that an allosteric molecule or molecules can actually bind to."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "What are these molecules?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, before we look at these molecules, let's define something called the energy charge."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Of a cell."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "The energy charge of a cell is basically the ratio of ATP molecules to Amp molecules."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So if the energy charge of the cell is high that means we have a high ATP value relative to Amp."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "If the energy value is low we have a low ATP ratio relative to Amp."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And these are the two Alistaire regulatory molecules of phosphor fructokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So let's suppose we're at rest."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And what that means is our muscles aren't actually contracting."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So our muscles do not require ATP."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And there will be a build up of ATP in our cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And that means the energy charge value will be high."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Because if the energy charge value is high, that means ATP to amp ratio will be high."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So what happens is these excess ATP molecules move on and bind onto the regulatory side of phosphor fructokinase and what they do is they essentially decrease the affinity of phosphorinas for the substrate molecule the fructose six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so what happens is step three basically stops taking place."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And if step three stops taking place then we're not going to produce the ATP molecules and that makes sense because if we're not exercising if we have rest we don't want to produce ATP molecules and so that turns off the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "But what happens if the energy charge value is low?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So in the case of us exercising what happens is the ratio of ATP to Amp decreases and what that means is we want to produce those ATP molecules because we want to be able to contract our muscles quickly and effectively."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so what happens is the Amp goes on and binds onto the regulatory side to phosphor fructoclinates and that stimulates the activity of the enzyme to catalyze this process increase the rate of the process and increase the rate at which the ATP molecules are also being produced by glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "But the question is in the process of glycolysis we only find ATP molecules and ADP molecules."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Amp is not found in glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So why did that Amp and not ADP is that regulatory activator molecule for phosphor fructokinase?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, because something actually happens when we have a very low concentration of ATP inside our cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Instead of using glycolysis, our cell does something else."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So to basically be able to quickly produce the ATP molecules that are needed by the cell to basically contract those skeleton muscle tissue this is a process that takes place and it's catalyzed by adenylive kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So adenyolyt kinase takes two ATP molecules."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Two adenosine diphosphate molecules transfers one phosphoryl group from this onto the other molecule that produces very quickly an ATP molecule and an Amp molecule."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And these ATP molecules can be quickly taken by the cell to basically contract those skeletal muscle tissues."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And we also produce this amp molecule and it's this amp molecule that increases in concentration and that decreases the energy charge ratio and that causes the binding of the amp onto that phosphorptokinase to stimulate it to produce many more ATP molecules via the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So under low ATP conditions the cell will use adenylate kinase to create ATP from two ATP molecules in a process that generates Amp and ATP relatively quickly and that allows the cells to basically continue contracting those actin myosin filaments."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So let's summarize our result in the following overview in the following graph so we have the fructose six phosphate catalyzed by the phosphorchinas to produce this molecule not shown here."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Then some number of processes take place and ultimately reproduce the ATP molecules and pyruvate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now, when we're actually not exercising when we have lots of ATP molecules we don't want to produce the ATP molecules so they essentially go on and inhibit the activity of phosphorptokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So we see that ATP is an allosteric inhibitor of phosphorinase but Amp is an allosteric activator."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now actually something else also affects the activity of phosphor fructokinase and that is the PH inside that tissue."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So if there is a drop in PH what that means is there's an increase in the H plus ion concentration."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So why would we find a higher H plus concentration in exercising muscle cells?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, when muscle cells are exercising, sometimes there is not enough oxygen to actually go around those cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so to basically continue producing those NAD plus molecules, our cells begin lactic acid fermentation."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And when lactic acid fermentation takes place, we produce a lactic acid ionic acid molecule and that quickly dissociates into lactic acid and releasing that H plus ion."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so as the fermentation process takes place it increases the H plus concentration, that decreases the PH, increasing the acidity and that can cause damage to that exercising muscle tissue."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so what our cell does is to prevent damage due to that acidity our glycolysis process is shut down to prevent any further production of those H plus ions."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so we see a low PH can actually inhibit the activity of the phosphorptokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "This is because as the cells rush to meet the high ATP demands fermentation produces lactic acid which dissociates into H plus ions and lactate ions and that increases acidity, drives the PH down and that can cause damage to that tissue."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so to prevent this from happening the glycolytic cycle is essentially turned off by inhibiting the phosphor fructokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now let's move on to hexokinase and let's recall the first three processes in glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So in step one we have glucose transformed into glucosex phosphate by hexokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "This is also an irreversible process."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "We have a reversible process that is catalyzed by phosphlucose isomerase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "We transform glucose six phosphate into its isomer fructosex phosphate and then this third step takes place in which we transform the fructosex phosphate into this committed molecule fructose one six bisphosphate by phosphorptokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So let's suppose we're at rest and what that means is we're going to have high energy charge value."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "We're going to have many ATP molecules what will that cause?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, the ATP molecules will bind onto the regulatory sides of phosphorptokinase, inhibiting that molecule."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And if this molecule is inhibited, the enzyme is inhibited, this fructosex phosphate cannot go on to the next molecule."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so there will be a build up in the concentration of fructose six phosphates in our cell."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now fructose six phosphate is in equilibrium with glucose six phosphate and biliciously as principle."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "If we increase the concentration of this product, we're going to increase the concentration of this reactant as well."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So the increase in concentration of this increases the concentration of the glucose six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And when that takes place, the rise in the concentration of glucosex phosphate causes a negative feedback loop with the hexokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so it goes on and binds up to hexokinase and that causes hexokinase to basically inhibit its activity."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so we see that via the increase in the concentrations of these two molecules, the phosphorptokinase communicates to the hexokinase to basically stop carrying out its function, to basically stop the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So they work together to basically stop producing ATP molecules when we have plenty of ATP molecules in our cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So once again, hexokinase catalyzes the conversion of glucose into glucose six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And as the ATP level rises in the cell, phosphor fructokinase is disabled and this causes the buildup of the fructose six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And because fructose six phosphate is an equilibrium with glucosex phosphate that causes a rise in the concentration of glucosex phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And this rise in glucosex phosphate creates a negative feedback loop that essentially inhibits the activity of the hexokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And when this takes place, the cell essentially stops uptaking the glucose from that blood from that nearby environment."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so when the hexokinase is turned off, the glucose will remain in the blood in that surrounding environment."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And in this manner we see that the inhibition of the phosphor fructokinase by the ATP will ultimately inhibit the activity of the hexokinas."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And finally, let's move on to the Pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So pyruvate kinase is the enzyme that catalyzes the last process in glycolysis and this is also virtually irreversible."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "It only takes place in this direction."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So we have phosphorinopyruvate that is transformed into pyruvate molecules and ATP molecules by the activity of pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now just like phosphor, fructokinase is inhibited by ATP molecules."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So it's pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "So when there's a rise in ATP, when we have a high energy charge value in the cell, when we're not exercising, we have too many ATPs."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so the ATP acts as a signal to basically inhibit the activity of pyruvate kindness."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "It creates a negative feedback loop, an inhibition loop."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Now, as I mentioned in the beginning, glycolysis is not only used to actually create ATP molecules, it's also used to produce building blocks such as amino acids."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so there's no surprise that alanine is also an inhibitor to pyruvate kinase because pyruvate is actually used to produce alanine and so if there is an increase in the amount of alanine that we have in our cells, if we have too much alanine, then we don't want to produce the pyruvate anymore."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "And so the alena will go on and inhibit the activity of pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "The final thing I'd like to discuss is what happens if we have low concentrations of ATP?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "How will that affect the activity of pyruvate kinase?"}, {"title": "Regulation of Glycolysis in Skeletal Muscle .txt", "text": "Well, when we have a low amount of ATP, what that means is we'll essentially have the amp binding to the phosphor fructosekinase, stimulating the production of fructose one six bisphosphate and fructose one six bisphosphate will create a positive feedback loop with the pyruvate kinase."}, {"title": "Distal Convoluted Tubule.txt", "text": "The next segment of our nephron that we're going to focus on is called the distal convoluted tubule or simply DCT."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now if we take a look at our nephron, we see that the distal convoluted tubule is located within this section of the nephron."}, {"title": "Distal Convoluted Tubule.txt", "text": "So convoluted simply means it makes many twists and turns and distal means it's located relatively are from our renal corpusal."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now notice that the distal convolute connects the thick ascending loop of Henley to our collecting duct."}, {"title": "Distal Convoluted Tubule.txt", "text": "And just like the proximal convoluted tubial, this section here lies within the renal cortex of the kidney."}, {"title": "Distal Convoluted Tubule.txt", "text": "The distal convolute also is located within the renal cortex of the kidney."}, {"title": "Distal Convoluted Tubule.txt", "text": "So the renal cortex is simply the outer portion of our kidney."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now if we zoom in on the distal convoluted tubule, we basically get the following diagram."}, {"title": "Distal Convoluted Tubule.txt", "text": "So this is a cross section of our distal convoluted tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "So this inside portion, the cavity is the lumen of our distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "Everything outside the distal convolute tubule is our surrounding tissue, also known as the interstituel."}, {"title": "Distal Convoluted Tubule.txt", "text": "And these are the cells that are found that line the distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we have two types of cells that we should be familiar with that are found inside the distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "So let's begin with these cells shown in purple."}, {"title": "Distal Convoluted Tubule.txt", "text": "So if we examine this diagram here, we see that our distal convolute tubule, this section of our distal convolute tubule is actually found in close proximity to our glomerulus."}, {"title": "Distal Convoluted Tubule.txt", "text": "And these cells found within close proximity are shown in purple."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we essentially have our a fearing arterial running along this location and it empties out into the glomerulus which is located right here."}, {"title": "Distal Convoluted Tubule.txt", "text": "And these purple cells are known as the maculodeensa."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now recall that the maculodeensa are part of the juxtaglomeral apparatus, the structure found in the nephron that regulates and controls the functionality of the nephron."}, {"title": "Distal Convoluted Tubule.txt", "text": "So the question is what exactly is the purpose of these purple cells, the macular densa cells?"}, {"title": "Distal Convoluted Tubule.txt", "text": "Well, they serve two important functions."}, {"title": "Distal Convoluted Tubule.txt", "text": "Firstly, they can actually sense any fluctuation in sodium chloride concentration inside the lumen inside our distal convoluted tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "And if the sodium chloride concentration inside the tubule drops, then what the maculus densa cells do is they are capable of stimulating the African arterial, this blood vessel right here, to actually dilate an increase in diameter."}, {"title": "Distal Convoluted Tubule.txt", "text": "And that not only decreases the resistance of the blood flow, but it also increases the amount of blood that reaches arglomerilus and that increases the hydrostatic pressure in araglomerilus."}, {"title": "Distal Convoluted Tubule.txt", "text": "And this controls or regulates the filtration rate inside our glomerulus, also known as the glomerul filtration rate."}, {"title": "Distal Convoluted Tubule.txt", "text": "So function number one of macular density cells is to regulate the filtration rate within the nephron."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now the second function of macular density cells is to stimulate the release of certain types of molecules that go on to stimulate the other cells in the juxtaglomerelaparatus known as our granule cells."}, {"title": "Distal Convoluted Tubule.txt", "text": "It stimulates the granule cells to release Renan."}, {"title": "Distal Convoluted Tubule.txt", "text": "And Renan is the proteolytic enzyme that is responsible for controlling the Rena angiotensin aldosterone pathway which regulates our blood pressure in the body."}, {"title": "Distal Convoluted Tubule.txt", "text": "So these are the two functions of the macula densa cells."}, {"title": "Distal Convoluted Tubule.txt", "text": "They essentially control the release of Renan and they also control the dilation of our a fairing arterial, thereby controlling the filtration rate within our glomerulus."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, the other cells basically shown in brown are our epithelial cells and these are cuboidal epithelial cells."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, the major difference between the epithelial cells in the distal convolute tubule and the epithelial cells in the proximal convolute is the following in the proximal convolute, our epithelial cells contain microvilli and this increases the reabsorption in the proximal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "While in our distal convolute tubule, we don't have the microvilli on the tube oil epithelial cells."}, {"title": "Distal Convoluted Tubule.txt", "text": "And that's exactly why reabsorption takes place at a much lower rate inside the distal convolute tubule than inside our proximal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "In fact, most of the absorption in our nephron takes place within the distal convolute tubule and only about 5% of sodium and chloride is actually absorbed within the distal convolute tubule, as we'll see in just a moment."}, {"title": "Distal Convoluted Tubule.txt", "text": "So the question is, so we know that absorption and secretion takes place within the distal convolute tubule, but what exactly is absorbed and what exactly is secreted and how do these processes take place?"}, {"title": "Distal Convoluted Tubule.txt", "text": "So they occur as a result of the different types of protein transporters that are found on the membrane of these epithelial cells."}, {"title": "Distal Convoluted Tubule.txt", "text": "So let's discuss these different types of protein transporters found along our membrane of the cuboidal epithelial cells found in the distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "The first type of protein transport that we have to discuss is called NA K, sodium, potassium, Atpace pump."}, {"title": "Distal Convoluted Tubule.txt", "text": "And this is a pump, meaning it actually uses active transport."}, {"title": "Distal Convoluted Tubule.txt", "text": "It utilizes an ATP molecule to establish an electrochemical gradient."}, {"title": "Distal Convoluted Tubule.txt", "text": "So let's zoom in on this small cross section of our distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "We get the following diagram."}, {"title": "Distal Convoluted Tubule.txt", "text": "So this is the inside the lumen of our distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "This is this section here and this side of the cell is the apical side."}, {"title": "Distal Convoluted Tubule.txt", "text": "So that means the other side, this side that points towards the interstituum is our basil lateral side."}, {"title": "Distal Convoluted Tubule.txt", "text": "It points towards the basement membrane."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, on the basil lateral side, we have this Atpace pump."}, {"title": "Distal Convoluted Tubule.txt", "text": "And what it does is it uses a single ATP to move three sodium ions against its electrochemical gradient towards the outside of the cell towards the interstitium."}, {"title": "Distal Convoluted Tubule.txt", "text": "At the same time it moves to potassium into the cell."}, {"title": "Distal Convoluted Tubule.txt", "text": "And what this protein pump does is it establishes an electrochemical gradient in which we have a higher concentration of sodium on the lumen side than inside our cell."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, why is this important?"}, {"title": "Distal Convoluted Tubule.txt", "text": "Well, it's important because it allows the function of other proteins found within our cells, as we'll see in just a moment."}, {"title": "Distal Convoluted Tubule.txt", "text": "So let's move on to the second type of protein known as the potassium, the sodium chloride cotransport, a protein."}, {"title": "Distal Convoluted Tubule.txt", "text": "This is this protein here."}, {"title": "Distal Convoluted Tubule.txt", "text": "So this protein actually functions as a result of the Atpas pump, because the Atpas pump is able to establish this electrochemical gradient in which we have more sodium."}, {"title": "Distal Convoluted Tubule.txt", "text": "On the lumen side, this NaCl co transporter protein allows the movement of sodium down its electrochemical gradient from the lumen side to the inside of the cell."}, {"title": "Distal Convoluted Tubule.txt", "text": "At the same time, it also moves the chloride along with the sodium."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we see that we have the reabsorption of chloride and sodium taking place, and we basically move these ions into the interstitial, the surrounding tissue of our distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "And these are eventually reabsorbed by the peritubular cavities found within and around our nephron."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, the next type of protein channel that we have to consider is the calcium channel."}, {"title": "Distal Convoluted Tubule.txt", "text": "So the calcium channel, just like this protein, is found on the apical side, on the side that points towards our lumen."}, {"title": "Distal Convoluted Tubule.txt", "text": "And this allows the reabsorption the movement of calcium from the lumen into the cell and eventually into our interstituency."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we see that the three things that are reabsorbed inside the distal convolute tubule is calcium, it's chloride and its sodium."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, on the basil lateral side of the membrane, we also have our sodium calcium cotransporter protein."}, {"title": "Distal Convoluted Tubule.txt", "text": "And this allows the movement of calcium from within the cell to our interstitium."}, {"title": "Distal Convoluted Tubule.txt", "text": "And what this does is it allows our distal convoluted tubular to reabsorb our calcium into the surrounding tissue and eventually into the peritubular cavities, our blood system."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, you should note that a type of hormone known as the parathyroid hormone stimulates the reabsorption of calcium within our distal convoluted tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, let's move on to another type, or actually two sets of important channels known as the sodium potassium protein channels and sodium hydrogen channels."}, {"title": "Distal Convoluted Tubule.txt", "text": "So these two protein transporters are basically stimulated by a hormone known as aldosterone."}, {"title": "Distal Convoluted Tubule.txt", "text": "So aldosterone can activate these channels."}, {"title": "Distal Convoluted Tubule.txt", "text": "So this should be activated, it can activate these channels, and this allows the reabsorption of sodium into the cell and the secretion of potassium into our lumen."}, {"title": "Distal Convoluted Tubule.txt", "text": "So essentially, if this is our cell, this is the lumen side, the interstitium side, our aldosterone can act on the distal convolute tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "It can activate this protein here, which basically even further reabsorbs the sodium from the lumen."}, {"title": "Distal Convoluted Tubule.txt", "text": "At the same time, it dumps potassium into our lumen."}, {"title": "Distal Convoluted Tubule.txt", "text": "And it also stimulates a second type of protein known as the sodium hydrogen protein, that also reabsorbs our sodium and releases our hydrogen into our lumen."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we can summarize the function of the distal convolute tubial in the following table."}, {"title": "Distal Convoluted Tubule.txt", "text": "So, we absorb about 5% of the sodium and chloride that is found in our filtrate."}, {"title": "Distal Convoluted Tubule.txt", "text": "Notice this is much less than what is reabsorbed in the proximal convoluted tubule."}, {"title": "Distal Convoluted Tubule.txt", "text": "In the proximal convoluted tubule, we reabsorb about two thirds, about 65% of potassium in a chloride, while in the distal convolute tubule, we only reabsorb about 5%."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, we also reabsorb calcium and notice that we also reabsorb water."}, {"title": "Distal Convoluted Tubule.txt", "text": "In fact, the antidiatic hormone ADH can actually act on the final section of the distal convoluted tubule to basically activate special types of protein channels to reabsorb water from the lumen and into our instertitulum."}, {"title": "Distal Convoluted Tubule.txt", "text": "Now, we also see that as a result of our hormone known as aldosterone, we can basically increase the reabsorption of sodium as well as chloride, but at the same time we increase the amount of potassium and hydrogen that we secrete into our filtrate that is found within the lumen of our distal convolute."}, {"title": "Distal Convoluted Tubule.txt", "text": "So we see that the distal convolute tubule basically acts as a fine tuning mechanism."}, {"title": "Distal Convoluted Tubule.txt", "text": "It fine tunes, it reabsorbs a slight amount of sodium and chloride, about 5%, as well as a small portion of the water as well as our calcium."}, {"title": "Distal Convoluted Tubule.txt", "text": "So aldosterone, the antiduretic hormone and the parathyroid hormone can all act on the distal convolution blue tubule to affect the amount of solution that is absorbed by that tubule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Previously, we discussed the first two steps of stage three of the glycolytic pathway."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in this lecture, I'd like to finish our discussion on stage three."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we're going to discuss step three, step four and step five of stage three."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And this is the same thing as saying step eight, nine and ten of the overall glycolytic pathway."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So before we discuss step three, let's remember what happened in steps one and two of stage three of glycolysis."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in those two steps, two molecules of glyceroaldehyde, three phosphate are transformed into two molecules of three phosphoglycerate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so the beginning point of step three is this three phosphaglycerate molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so that's what we have shown on the board."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, this is carbon one, carbon two and carbon three."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And what happens in this reaction is an enzyme known as phosphoglycerate mutase, basically catalyzes the movement, the transfer of the phosphoryl group shown in blue from the third carbon onto this second carbon here."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so we go from three phosphaglycerate, two two phosphoglycerates."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now we'll talk about why that happens in just a moment."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So whenever you hear the word mutase, what that should basically tell you is you're dealing with some type of enzyme that catalyzes a reaction in which it moves some type of group from one point on the molecule to a different point on that molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so in this particular case, the mutase is a phosphoglycerate mutase."}, {"title": "Stage 3 of Glycolysis .txt", "text": "It moves a phosphoryl group within this phosphorylycerate molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in this step, an enzyme called phosphoglycerate mutase catalyzes the movement of a phosphoryl group from the third carbon on this three phosphaglycerate onto the second carbon of that same molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so this is what we form."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, this is the net overall reaction."}, {"title": "Stage 3 of Glycolysis .txt", "text": "But it's not actually this simple because we also have an important molecule involved that is present in catalytic amounts in a very small amount."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And this molecule is two or three bisphosphoglycerate or two three BPG."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, this is the same exact molecule that we discussed when we mentioned hemoglobin's ability to bind oxygen."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in that discussion, we mentioned that two, three BPG is actually an intermediate in the process of glycolysis."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And two, three BPG can basically affect the affinity of hemoglobin for oxygen."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, what exactly is the function of two three BPG in this reaction?"}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we see that this reaction doesn't actually take place in a single step because it involves the presence of a catalytic amount of two, three bisphosphoglyceride."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And what it does is it basically plays the role of maintaining, so keeping that catalytic histidine amino acid in its activosphorylated form inside the active side of the phosphoglycerate mutate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So basically, if we look at the active side of this mutase, we'll see a catalytic residue, a histidine."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And to actually be able to catalyze this reaction, that histidine has to be modified with the addition of a phosphoryl group."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And to see what we mean, let's take a look at these two steps."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in step one, we basically have this enzyme."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And inside the active side of the enzyme, we have the histadine that has been modified by the addition of the phosphoryl group."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so in step one of this reaction, what happens is this three phosphorylycerate moves into the active side, and in step one, this molecule, the enzyme, transfers this phosphoryl group from the histidine of that enzyme onto the second position of this molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So essentially, we attach this phosphoryl group onto carbon number two, and we form the two three by or bisphosphoglycerate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so we form this enzyme that does not contain the modified histidine, as well as a two, three BPG."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, this two, three BPG is only present in very small amounts."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Why?"}, {"title": "Stage 3 of Glycolysis .txt", "text": "Well, because it then reacts with this same enzyme, histidine complex, in a slightly different reaction."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So even though this reaction is possible, another reaction that can take place is the following."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So, in step two, we have that same enzyme, histidine complex, and that same two, three BPG."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Except now, instead of taking off that phosphoryl group from the second carbon, we take off that phosphoryl group from the third carbon."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so once we take off this phosphoryl group, this one here, we basically regenerate that enzyme histidine, with the modified group complex."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And we also form the final product, the two phosphaglycerate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And if we sum up these two reactions, we see that everything will cancel except these two molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so, by summing up these two steps, we get back this net reaction."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we see that in the first step, a phosphoryl group is transferred from that modified histidine on that enzyme onto the three phosphorglycerate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So at the second carbon position to form the two, three BPG."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And that two, three BPG doesn't exist for a very long period of time because it's not very stable."}, {"title": "Stage 3 of Glycolysis .txt", "text": "It has too much charge in close proximity."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So if we place two phosphoryl groups in close proximity, that increases the energy of that molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And that's why the two three BPG is higher in energy than this molecule or this molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so what that means is it's not going to exist for a very long time."}, {"title": "Stage 3 of Glycolysis .txt", "text": "It will either go back here and reform these reactants, or follow this pathway and form these products."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So that same histidine then removes the phosphoryl group from the third carbon, forming that rearranged two phosphoglycerate molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So that's how this step actually takes place."}, {"title": "Stage 3 of Glycolysis .txt", "text": "But the next question is why does this step actually take place?"}, {"title": "Stage 3 of Glycolysis .txt", "text": "What's the benefit of this step?"}, {"title": "Stage 3 of Glycolysis .txt", "text": "Well, basically, the reason this step takes place is to make this molecule slightly more reactive."}, {"title": "Stage 3 of Glycolysis .txt", "text": "The question is, why would this molecule here be more reactive than this molecule here?"}, {"title": "Stage 3 of Glycolysis .txt", "text": "Well, because in this case, this negative charge of negative two is farther away from this negative one charge."}, {"title": "Stage 3 of Glycolysis .txt", "text": "But in this case, these two negative charges are closer."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And we know from physics, whenever we have two light charges that are closer, that will increase that electric repulsive force between these two points in space."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so that's why this will be slightly higher in energy and more reactive than this molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we ultimately want to make the molecule more reactive in step three."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, let's move on to step four."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, in step four, what we basically want to do is we want to increase the phosphoryl transfer potential of this molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so we ultimately want to transform it into a molecule that will be able to better transfer a phosphoryl group onto an ADP molecule to form an ATP molecule and Pyruvate in step five."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So the entire point of step four is to create a molecule with a greater phosphoryl transfer potential."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in the step number four, an enzyme called Nalase converts the two phosphoglycerate that was formed in this step three into a phosphoenyl Pyruvate or Pet."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So this is the reaction shown here."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we begin with the same molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And now we basically label this H atom and this oh group."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And we also label this bond here, because what happens is we have a dehydration reaction that is catalyzed by the enolase."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And basically these two combine to form a water molecule and this bond breaks off and forms a pi bond between this carbon number two and this carbon number three."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so this is called an enolase because we form an ENL."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So if you remember back to organic chemistry, this is in fact an ENL and we call it phosphorinol Pyruvate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So what this dehydration reaction does, and we call it dehydration because the water molecule is lost."}, {"title": "Stage 3 of Glycolysis .txt", "text": "What this dehydration reaction does is increases the phosphoryl transfer potential of this molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So this molecule has a lower ability to give off asphalt groups than this molecule here."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so the phosphorynopyrulvate is much more likely to donate one of its phosphoryl groups onto that ATP molecule because ultimately, in the final step, step ten of Glycolysis, step five of stage three, we want to form ATP molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in the next step, this is the reaction that takes place."}, {"title": "Stage 3 of Glycolysis .txt", "text": "We take this phosphorinopyruvate, also known as pep."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Sope this is the molecule here."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so now we're going to basically label this phosphoryl group here."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And in the presence of ADP, this molecule here is very highend energy."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, one other thing I didn't mention is if you go back to organic chemistry and you compare the stability of ketones and enormolecules, we know that ketones exist in equilibrium with enormous, but the ketones are much, much more stable than those enols."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So the problem with this molecule is it's actually trapped in its ENL state."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So this molecule wants to transform into that more stable ketone, but it can transform because this oxygen is missing an H atom."}, {"title": "Stage 3 of Glycolysis .txt", "text": "If we somehow replace the phosphoryl group here with an H atom, then it will be able to transform spontaneously into the more stable ketone form."}, {"title": "Stage 3 of Glycolysis .txt", "text": "In fact, that's exactly what will happen in this reaction."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So this reaction takes place because this molecule has a very high phosphoryl transfer potential, even higher than ATP."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so in the presence of ADP, this phosphoryl group will be transferred onto that ADP."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And in the presence of an H plus ion, this will bind onto this oxygen."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so we form this Pyruvate molecule in the enol form as well as an ATP."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And remember what I said a moment ago."}, {"title": "Stage 3 of Glycolysis .txt", "text": "If an enol has the ability to transform into the ketone form, it will, because that ketone form is thermodynamically more stable lower in energy."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so what will happen here is once we form the Pyruvate in the ENL form and the ATP, this Pyruvate will spontaneously and quickly convert into its ketone form."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so ultimately, this is the molecule that we're going to form."}, {"title": "Stage 3 of Glycolysis .txt", "text": "Now, because we have two of these molecules, three phosphaglycerates going into this pathway, we ultimately produce two ATP molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So we see that in stage three, we produce a total of four ATP molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in step one and two, we produce two ATP molecules."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And in this step, we produce two."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And so two and two gives us four."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And because we used up two in stage one, we have a net amount of two ATP molecules produced when we break down a single glucose molecule."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So in the last step of glycolysis, step five of stage three, or step ten of glycolysis, we see that Pyruvate kinase, this enzyme catalyzes the phosphoryl transfer from the high phosphoryl transfer potential phosphorinl Pyruvate molecule onto the ADP."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And in the presence of H plus, we form the ENL form of this Pyruvate."}, {"title": "Stage 3 of Glycolysis .txt", "text": "And then it spontaneously breaks down into the more stable ketone form."}, {"title": "Stage 3 of Glycolysis .txt", "text": "So these are the three last steps of the process of glycolysis."}, {"title": "Law of Independent Assortment .txt", "text": "So far in our discussion on Gregory Mendel's principles of inheritance, we focused on a type of law that is known as Mendel's law segregation."}, {"title": "Law of Independent Assortment .txt", "text": "Now, we're going to move on to the second law that was devised by Gregor Mendel that became known as Mendel's Law of Independent Assortment."}, {"title": "Law of Independent Assortment .txt", "text": "Now, let's begin by actually stating what the law tells us."}, {"title": "Law of Independent Assortment .txt", "text": "Well, the law law states that members of one gene pair will separate from one another independently of the members of other gene pairs found within that same organism."}, {"title": "Law of Independent Assortment .txt", "text": "And to demonstrate what we mean by this law of independent assortment, let's take a look at the following organism of pea plants."}, {"title": "Law of Independent Assortment .txt", "text": "And we're focusing on a heterozygous pea plant."}, {"title": "Law of Independent Assortment .txt", "text": "So this pea plant is heterozygous for two different traits."}, {"title": "Law of Independent Assortment .txt", "text": "One trait is the height and the other trait is the color of the seeds."}, {"title": "Law of Independent Assortment .txt", "text": "Remember, the seed color, the green seed color, is dominant over the yellow seed color, while the tall height is dominant over the short height."}, {"title": "Law of Independent Assortment .txt", "text": "So because we're looking at a heterozygous individual for two different traits, that means the phenotype of this plant will be tall and green."}, {"title": "Law of Independent Assortment .txt", "text": "So we have our dominant gene for the color uppercase G and the recessive lowercase G. We have the uppercase T that is the dominant gene for the height trait."}, {"title": "Law of Independent Assortment .txt", "text": "And then we have the recessive lowercase T. So we have green uppercase G. We have orange yellowcase G, the blue uppercase T and the purple lowercase T. Now, if we examine the somatic cell of this particular p plant and we're only focusing on the chromosomes that carry these genes, we're going to get the following diagram."}, {"title": "Law of Independent Assortment .txt", "text": "So, within the nucleus of our somatic cell, this is what we're going to get."}, {"title": "Law of Independent Assortment .txt", "text": "So we have one homologous chromosome and we have a second homologous chromosome."}, {"title": "Law of Independent Assortment .txt", "text": "Now, within this Homologous chromosome pair, we have one of the chromosomes that carries the uppercase G. And the other chromosome within this Homologous pair carries the lowercase G. In this other Homologous pair, we have one of the chromosomes."}, {"title": "Law of Independent Assortment .txt", "text": "Carries the uppercase t and the other chromosome carries the lowercase t. Now, the reason that we have the law of independent assortment in the first place is because of the process of meiosis that takes place when this individual, when the organism forms gametes, before fertilization actually takes place."}, {"title": "Law of Independent Assortment .txt", "text": "So to see how that actually is, let's look at the meiosis process as it takes place within this particular organism."}, {"title": "Law of Independent Assortment .txt", "text": "So before meiosis one can actually begin, this cell must undergo interface."}, {"title": "Law of Independent Assortment .txt", "text": "And during the process of interface, we have replication taking place."}, {"title": "Law of Independent Assortment .txt", "text": "So each one of these individual chromosomes within the chromosome pair are replicated."}, {"title": "Law of Independent Assortment .txt", "text": "So this chromosome is replicated, and so is this chromosome replicated."}, {"title": "Law of Independent Assortment .txt", "text": "Likewise, this chromosome is replicated and this chromosome is replicated."}, {"title": "Law of Independent Assortment .txt", "text": "And at the end, we produce the following cell."}, {"title": "Law of Independent Assortment .txt", "text": "So these are basically our two homologous chromosomes and these are also two homologous chromosomes."}, {"title": "Law of Independent Assortment .txt", "text": "But the difference between this case and this case is each one of these actually consists of identical chromatids we call cystochromatids."}, {"title": "Law of Independent Assortment .txt", "text": "So if we zoom in on this picture, we basically get the following diagram."}, {"title": "Law of Independent Assortment .txt", "text": "So this is a homologous pair of chromosomes, and this is also a homologous pair of chromosomes."}, {"title": "Law of Independent Assortment .txt", "text": "But within each one of these pairs, we now have identical cystochromatids."}, {"title": "Law of Independent Assortment .txt", "text": "So this chromosome is identical to this one, and this one is identical to this one."}, {"title": "Law of Independent Assortment .txt", "text": "But these two are homologous with respect to one another."}, {"title": "Law of Independent Assortment .txt", "text": "So remember, what we mean by homologous is they carry similar genes."}, {"title": "Law of Independent Assortment .txt", "text": "They carry similar genes that code for proteins that express the same type of trade."}, {"title": "Law of Independent Assortment .txt", "text": "So in this particular case, we have the genes uppercase G and lowercase G that express the same type of trade, the color trades."}, {"title": "Law of Independent Assortment .txt", "text": "And in this case, we have these two genes that are homologous."}, {"title": "Law of Independent Assortment .txt", "text": "And what that means is they code for protein that expresses the same type of trait."}, {"title": "Law of Independent Assortment .txt", "text": "In this case, the high traits."}, {"title": "Law of Independent Assortment .txt", "text": "So we have one homologous chromosome pair, a second homologous chromosome pair."}, {"title": "Law of Independent Assortment .txt", "text": "And now each one of these chromosomes actually consists of two identical cystic chromatids."}, {"title": "Law of Independent Assortment .txt", "text": "So this is what we have following DNA replication that takes place during interface before meiosis actually begins."}, {"title": "Law of Independent Assortment .txt", "text": "Now let's suppose meiosis actually begun."}, {"title": "Law of Independent Assortment .txt", "text": "And now we're at the stage we call metaphase one of meiosis."}, {"title": "Law of Independent Assortment .txt", "text": "So during metaphase one of meiosis, what happens is these homologous pair of chromosomes actually arrange themselves along the equator of the cell."}, {"title": "Law of Independent Assortment .txt", "text": "So if this is the equator of the cell, this is how the homologous chromosomes are going to arrange themselves."}, {"title": "Law of Independent Assortment .txt", "text": "So we're basically going to have this homologous pair of chromosomes, like so, and this homologous pair of chromosomes like so."}, {"title": "Law of Independent Assortment .txt", "text": "Now, this is where we have to discuss the law of independent assortment."}, {"title": "Law of Independent Assortment .txt", "text": "So what the law of independent assortment actually takes, actually tells us is the members of one gene pair separate from one another independently of the members of the other gene pairs."}, {"title": "Law of Independent Assortment .txt", "text": "So these two will separate independently of these two."}, {"title": "Law of Independent Assortment .txt", "text": "And likewise, these two will separate or segregate independently of these two."}, {"title": "Law of Independent Assortment .txt", "text": "And what that means is, within the cell, these two can be arranged like so, or they can actually be switched, because that's what we mean by these being independent to the movement of these."}, {"title": "Law of Independent Assortment .txt", "text": "So it turns out about 50% of the cells have this arrangement, but the other 50% of the cells actually could also have this arrangement."}, {"title": "Law of Independent Assortment .txt", "text": "So these upper case TS can be on this side, and these lowercase TS can be on this side, or we can have this."}, {"title": "Law of Independent Assortment .txt", "text": "And these two, as we'll see in just a moment, will actually produce different types of gametes."}, {"title": "Law of Independent Assortment .txt", "text": "So let's carry out the process of meiosis for this particular cell type."}, {"title": "Law of Independent Assortment .txt", "text": "In this particular case, if at metaphase one of meiosis we have this arrangement, then what happens is these will separate to opposite poles, then cytokinesis takes place, and we form the following two cells."}, {"title": "Law of Independent Assortment .txt", "text": "So we have cell number one and cell number two."}, {"title": "Law of Independent Assortment .txt", "text": "So this is aware reduction of the chromosome number took place."}, {"title": "Law of Independent Assortment .txt", "text": "In this case, we have the two M number."}, {"title": "Law of Independent Assortment .txt", "text": "In this case, we have the Haploid number one N. So these two went to one cell producing this cell these two went to another cell, producing this cell."}, {"title": "Law of Independent Assortment .txt", "text": "And now this is what we have in metaphase two of Meiosis."}, {"title": "Law of Independent Assortment .txt", "text": "And now, once again, we have segregation or separation of these cystochromatis, which are actually identical take place."}, {"title": "Law of Independent Assortment .txt", "text": "So we have the separation take place and now we form the following two cells."}, {"title": "Law of Independent Assortment .txt", "text": "So one of the cells will carry the uppercase G, uppercase T to form this."}, {"title": "Law of Independent Assortment .txt", "text": "Somatic this gametes, sex cell then these two will go to this side will produce this gametes, this sex cell and in this particular case, because we're not taking into consideration the process of crossing over these two are identical in the same exact way these two cystochromatid chromosomes."}, {"title": "Law of Independent Assortment .txt", "text": "So we have one pair, and a second pair will separate and will form these two ganides."}, {"title": "Law of Independent Assortment .txt", "text": "So we have uppercase g, uppercase T, lowercase g, lower case T. Now, let's suppose that instead of beginning with this arrangement, we have this arrangement of the chromosomes along the equator."}, {"title": "Law of Independent Assortment .txt", "text": "So all we did was basically switch these two."}, {"title": "Law of Independent Assortment .txt", "text": "And this is true as a result of the law of independent assortment."}, {"title": "Law of Independent Assortment .txt", "text": "Or actually, what we say is because these can switch back and forth and 50% will be in this arrangement."}, {"title": "Law of Independent Assortment .txt", "text": "And 50% will be in this arrangement."}, {"title": "Law of Independent Assortment .txt", "text": "We call this process the law of independent assortment."}, {"title": "Law of Independent Assortment .txt", "text": "So this is the biological reason, the biological basis for the existence of the law of independent assortment as was devised, as was described by Gregor Mendel following his experiments with p plants."}, {"title": "Law of Independent Assortment .txt", "text": "So if this takes place, these will separate to produce this cell."}, {"title": "Law of Independent Assortment .txt", "text": "And this will be an arrangement of these chromosomes during metaphase two of meiosis."}, {"title": "Law of Independent Assortment .txt", "text": "And now these will segregate as well."}, {"title": "Law of Independent Assortment .txt", "text": "So these will go to one, these will go to another one producing upper case G, lower case T and these will go to separate sides producing lowercase G, uppercase T. So these are the possibilities the genotypes for the gametes that are formed for this particular heterozygous p plan so we have four different types of genotypes."}, {"title": "Law of Independent Assortment .txt", "text": "So we have uppercase G, uppercase T, this possibility."}, {"title": "Law of Independent Assortment .txt", "text": "We have lowercase G, lower case T, this possibility."}, {"title": "Law of Independent Assortment .txt", "text": "We have uppercase G, lower case G, this possibility and lowercase G, uppercase T, this possibility, this possibility and this is the same exact thing that we see when we carry out the Punnett square for this particular individual, this particular plant."}, {"title": "Law of Independent Assortment .txt", "text": "So once again we see that the law of independent assortment takes place during this process metaphase two of meiosis and what it basically means is the chromosome pairs, homologous chromosomes that organize themselves into this arrangement at the equator basically can organize themselves independently of the other genes that are found within that same organism."}, {"title": "Law of Independent Assortment .txt", "text": "So what that means is the members of one gene pair."}, {"title": "Law of Independent Assortment .txt", "text": "So these guys here will separate independently of the members of the other gene pairs of these guys right here."}, {"title": "Law of Independent Assortment .txt", "text": "And so we can have this type of arrangement, or because they're independent of one another, we can also have this type of arrangement."}, {"title": "Law of Independent Assortment .txt", "text": "These are no way linked to these."}, {"title": "Law of Independent Assortment .txt", "text": "And this is what we mean by the law of independent assortment."}, {"title": "Law of Independent Assortment .txt", "text": "And it takes place as a result of myosin during the formation of gametes."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Another method by which a cell can uptake material from the extracellular environment is via a process known as endocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, endocytosis requires energy and it's the process by which the cell membrane invaginates and engulfs the material found outside that cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, there are three different processes of endocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "We have pinocytosis, thygocytosis and receptor mediated endocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Let's begin with the most common type of endocytotic process known as pinocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, Pinocytosis takes place virtually in every single cell and it's the process by which our cell membrane invaginates and engulfs a relatively small quantity of the extracellular fluid."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, Pinocytosis is not a specific process meaning it doesn't engulf specific type of molecules."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "It's basically spontaneous and takes place continuously."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And for this reason, we sometimes refer to pinocytosis as cell drinking because it takes place spontaneously and the end result is the uptake of extracellular fluid."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, of course, if we have some type of small molecules found in close proximity to our cell membrane when pinocytosis takes place it can also engulf those types of small molecules as well as the extracellular fluid."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So this is the process by which pinocytosis takes place."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So whatever happens to be around the invaginating region on the cell membrane will end up being engulfed into that cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And that cell will form a vesicle."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So this vesicle contains a cell membrane that comes from the cell or it contains the membrane that comes from our cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So basically, the reason we have the cell membrane is to protect the actual cell from whatever might be inside that vesicle."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "That vesicle is then transported into the lysosome."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "The lysosome fuse is with our vesicle and the material inside that cell is basically digested."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, let's move on to a more specific type of endostatotic process known as phagocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Phagocytosis is a much more specific endocytotic process and only certain types of cells can actually undergo this process."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So one example is the phagocyte, that is, the cell found in the immune system of our body."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "We'll discuss more of the phagocytes when we discuss the immune system."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So in this process of phagocytosis some type of relatively large molecule such as a macromolecule or even a bacterium binds to specific protein receptors found on the cell membrane."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Once that protein receptor binds to the receptor on that molecule, let's say our bacteria the cell recognizes the material protrudes outward and engulfs that object."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And once inside that vesicle, because it's so large, is known as the phagosome."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, once the phagosome is formed, eventually it basically fuses with the lysosome of our body, of our cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And once they fuse, the lysosome contains special type of hydrolytic enzymes that can basically degrade and digest our materials."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So let's suppose we have a bacterial cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "The bacterial cell itself contains receptors and these receptors are shown in purple."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "When these receptors bind to our cell membrane receptors, that will signal the process of imagination."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So we have the protrusion taking place and that is pushed into our cell, forming our phagosome."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So, unlike penocytosis, in which we have a random type of process in which it's not specific this is more specific and it involves these protein receptors found on the cell membrane as well as on that object in this case, our bacterial cell."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, the final type of endocytotic process we're going to discuss is receptor mediated endocytosis."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So this is basically the most specific type of endocytotic process and it involves the ingestion of macromolecules such as sugars and hormones and we also have the binding to our receptor proteins."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, the main difference between phagocytosis and receptor mediated endocytosis is in phagocytosis, we have the bacterial cell that itself contains receptors that bind to a receptor proteins on the membrane."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "In this case, the actual molecule that is being ingested binds directly to the receptors of the cell membrane."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, once the binding process takes place that binding basically signals for invagination of the cell membrane to take place."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And not only that, it also signals for the formation of a special type of protein layer protein covering around the vesicle."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "And the protein inside the covering is called clathrin."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So that's exactly why this vesicle, once it's actually formed is called our clathrincoated vesicle."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So the two main difference between phagocytosis and receptor mediated endocytosis is in our phagocyte."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "In our phagosone, we do not have our protein covering but in this case, we do have our protein covering."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, in this case, the bacteria basically binds indirectly to the cell membrane."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "It binds through these receptors found on that bacteria."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "But in this case, it's the actual molecule being ingested, being engulfed that binds directly to the receptors found on our cell membrane."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So the main purpose in receptor mediated endocytosis is to ingest the macromolecules that bind directly to our receptor."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "But in phagocytosis, we have an indirect relationship so the bacteria doesn't directly bind onto the receptors."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "The bacteria contains its own receptors that bind to the receptors on the cell membrane and that is one important difference."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "The other one is the formation of our protein covering around our vesicle."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "Now, the third difference is the receptor mediated endocytosis process is more specific than our phagocytosis process."}, {"title": "Pinocytosis, Phagocytosis and Receptor-Mediated Endocytosis.txt", "text": "So this is least specific and it's most common and almost all cells undergo Pinocytosis but receptor mediate emphasis is much more specific than our pinocytotic process."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "All the different types of physical or chemical processes and reactions that exist in nature must obey the laws of thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And that means any type of biological reaction that you're going to come across in your study of biochemistry must obey these laws."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So in this lecture, we're going to focus on the first and second law of thermodynamics, because in the study study of biochemistry, these laws essentially dictate the conditions under which a certain biological reaction is favorable and the conditions under which that same reaction is not favorable."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we have to take into consideration these two laws in essentially every biological process that takes place."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So let's begin with the first law of thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So recall that any region of space that contains the atoms or molecules that we're studying, that is our system."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And all the molecules and atoms found outside the system, that is our surroundings."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what that means is if we take the sum of the molecules of our system and all the molecules in our surroundings, that will give us the molecules in our universe."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what the first law of thermodynamics tells us is if we sum up the energy of our system and the energy of our surroundings, that is always equal to the energy of the universe."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And the energy of the universe is always a constant value."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So it never decreases."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "It never increases."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "It always remains the same."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "It remains constant."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And what that means is energy is never destroyed, energy is never created."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "But energy can be transformed from one form to another."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And this is true for physical as well as chemical reaction."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So what we mean is let's suppose the following physical reaction."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So here we have an object, our marker."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And the marker has a certain amount of potential energy as a result of its position with respect to the ground."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So remember, the Earth exerts a gravitational force, and that gives it a certain amount of gravitational potential energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, as soon as I let go of my marker, the marker will begin to travel downward."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And so as the marker travels, its gravitational potential energy will begin to decrease."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "The question is, where does that gravitational potential energy actually go?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, that energy cannot be destroyed by the first law of thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And what happens to it is that gravitational potential energy begins to transform into the energy of motion of that object known as the kinetic energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So as the marker travels down, that potential energy is being transformed into kinetic energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And the same exact is true."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "The same thing is true for chemical and biological reactions."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Energy is never destroyed."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Energy is never created."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "But energy is readily transformed from one form to another."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And if we take the sum of the energy of the system and the surroundings, it is always equal to a constant value the energy of our universe."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And that never actually changes."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what about the second law of thermodynamics?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, the second law of thermodynamics is commonly described by using a term known as entropy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And entropy is this quantity that we use to basically measure the amount of randomness or disorder that is found in our universe."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what exactly does the second law of thermodynamics tell us?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, what it tells us is every time a real reaction takes place, be it physical or chemical, the change in entropy of the universe is always positive."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So the entropy of the Universe increases in any real reaction."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So the second law of thermodynamic states that the entropy of the universe always increases."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, that doesn't mean that the change in entropy of a system cannot be negative."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So the entropy of a system can still decrease as long as the entropy of the surroundings increases by greater amount, so that this is always true."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So the entropy of a system can decrease, can be negative, as long as the entropy of the surroundings is increased by a greater amount."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So that when we take the sum, we see that the change in entropy of the universe is always equal to a positive value."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "It is never equal to a negative value."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, the next question is what exactly do we mean by entropy?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, let's look at diagram A and diagram B."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "In diagram A, we have a situation in which this container is our system, and the molecules inside are also part of our system."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, in this particular case, we have this artificial barrier, or door, if you will, that essentially prevents the molecules from this side going into this side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So all the six molecules and each molecule carries a certain amount of energy are essentially localized or concentrated on the left side of our container."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, as soon as we open that door, what exactly happens?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, before we open the door, what can we say about the energy in our system?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So how much energy is found on this side and how much energy is found on this side?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, notice that we have six molecules on this side, and each one of these molecules carries a certain amount of energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So if the molecules are moving, they have a certain amount of kinetic energy and so forth."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So each one of these molecules has a certain amount of energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And the total amount of energy on the left side of this container is equal to the sum of the individual energies of these molecules."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we have molecule one, molecule two, molecule three, molecule four, molecule five, and molecule six."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So let's suppose that each one of these molecules carries the same amount of energy, and each energy is equal to one unit."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we have six molecules."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we have, let's say, six units of energy on this side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what about the amount of energy on this side?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, we have no molecules on this side, so we have zero units of energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And what that means is all that energy is concentrated on the left side and no energy is found on the right side inside our system."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, as soon as we remove this artificial barrier, as soon as we open up that door, what exactly will begin to take place?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, what the second law of thermodynamics tells us is whenever a system is given a chance to, or whenever something is given a chance to, it will always try to become as random as possible."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And so what that means is these molecules will begin to travel to the other side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, a much better way of saying that is in the following way."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Whenever energy is given the chance to, energy will tend to spread out and disperse along the tire space in which that energy is found in."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, in this particular case, because we had the barrier, energy could not have moved to this side because of that barrier."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "But as soon as we removed that, the molecules tend to move to the other side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And as the molecules move, they also carry that energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And mathematically, the most probable case is the case when we have three molecules on this side and three molecules on the other side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "This is the state that has the highest entropy because it's the most probable state."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And notice in this case we have three units of energy on this side because we have three molecules and we have three units of energy on the other side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And so what happened is, in this case, all that energy was localized on the left side, but now the energy has equally dispersed so that we have an equal amount of energy on this side and an equal amount of energy on this side."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So basically what the second law of thermodynamics tells us is when energy is given the chance to, it will disperse throughout all the space in which it actually exists."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And what we can say is, we can say that energy always travels from a high amount to a low amount."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we have a low amount here, a high amount here."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Energy will tend to move this way right from a high amount to a low amount until we reach thermal equilibrium, until the two sides have an equal amount of energy."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And this describes the highest entropy, the highest mathematical probability of our system."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, for every physical and for every biological reaction, these two thermodynamical laws must be obeyed."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, we can even use these laws to explain many different reactions and phenomena that exist in biochemistry."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "For example, we can use the second law of thermodynamics to basically explain the hydrophobic effect."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So let's suppose we have a beaker of pure water."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So inside the beaker, all we have are these water molecules that are moving about and which are interacting with other water molecules via hydrogen bonds."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, let's suppose we take two non polar molecules and place them into our beaker."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "What will happen initially?"}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Well, as soon as we place them into our beaker all these water molecules that were eventually moving around randomly and rapidly some of these water molecules will surround our non polar molecules and when they surround the non polar molecules they essentially are trapped."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "They become trapped to the non polar molecule and these water molecules can no longer move about as frequently and randomly as before."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So when the two non polar molecules in solution do not interact with one another we see that we have many of these water molecules found around the non polar surface and this basically decreases and limits the freedom of movement of the water molecule."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And this is not a favorable event."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "This is not a favorable reaction because the entropy basically decreases compared to when these two nonpolar molecules were not in our solution."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, what will happen is because of the second law of thermodynamics because when given a chance to, we want to increase the amount of entropy of our system and our universe in general."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "We have the hydrophobic effect take place and these non polar molecules will tend to aggregate because by aggregating, by combining we decrease the amount of water molecules that are found around the surface because we decrease the surface to volume ratio."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And so what that means is in this case we had 1234-5678, 910, 1112, 13, 14, 15, 16, 17, 18, 19, 20, 212-223-2425 water molecules that were trapped."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "But now because of the interaction between the two non polar molecules we only have 1234-5678, 910 eleven water molecules."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And the other set of molecules have now moved away and now are moving randomly inside that water solution."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And this is in accordance with the law of entropy, the second law of thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So if the two non polar molecules come together via the hydrophobic interactions they release many of the water molecules that were trapped before into the solution to interact with other water molecules."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And that forms intermolecular bonds we call hydrogen bonds."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "Now, this is in accordance with the second law of thermodynamics because the H 20 molecules are more disordered than before."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So in this particular case, they had a much greater order because they were surrounding those non polar molecules."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "But in this case, because some of those water molecules left they're now moving about randomly and rapidly."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And so the amount of entropy in our system basically increased."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "So we see that we can explain the hydrophobic effect by using the second law of the thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "And in the same exact way we can explain all the different types of reactions that take place in biochemistry by using the laws of thermodynamics."}, {"title": "First and Second Law of Thermodynamics .txt", "text": "That is, these reactions in biology must obey these laws of thermodynamics."}, {"title": "Function of the Skin .txt", "text": "Our skin is the largest organ of the body by mass as well as by size."}, {"title": "Function of the Skin .txt", "text": "And it's a multifunctional organ."}, {"title": "Function of the Skin .txt", "text": "And what that means is it's a set of tissues that work together to carry out a certain set of functions."}, {"title": "Function of the Skin .txt", "text": "And in this lecture, we're going to discuss seven different functions of the skin."}, {"title": "Function of the Skin .txt", "text": "So let's begin by recalling some basic structure of the skin."}, {"title": "Function of the Skin .txt", "text": "So the outermost portion of the skin is the epidermis."}, {"title": "Function of the Skin .txt", "text": "And this portion contains four specialized cells that we're going to discuss in just a moment."}, {"title": "Function of the Skin .txt", "text": "We have carotene sites, we have melanocytes, we have Langerhon cells, and we also have Merkel cells."}, {"title": "Function of the Skin .txt", "text": "Now, the middle portion, the middle section of the skin, is our dermis."}, {"title": "Function of the Skin .txt", "text": "And this contains not only the blood vessels, the arteries and the veins, but also our excretory glands, such as our sebaceous oil gland and the sweat gland."}, {"title": "Function of the Skin .txt", "text": "And finally, the lower, most portion of the skin is the hypodermis, also known as the subcutaneous layer."}, {"title": "Function of the Skin .txt", "text": "And this layer contains not only adipose cells that insulate our body, but also macrophages cells that engulf bacterial cells."}, {"title": "Function of the Skin .txt", "text": "So let's begin by discussing function number one of the skin."}, {"title": "Function of the Skin .txt", "text": "And this is perhaps the most obvious function of the skin."}, {"title": "Function of the Skin .txt", "text": "So the skin creates a physical barrier that protects us from a wide range of harmful things."}, {"title": "Function of the Skin .txt", "text": "So recall that inside the epidermis of the skin, we have cells known as carotenesides."}, {"title": "Function of the Skin .txt", "text": "And these cells secrete a protein fiber known as keratin."}, {"title": "Function of the Skin .txt", "text": "And keratin not only gives the skin its strength, but it also protects our skin from water."}, {"title": "Function of the Skin .txt", "text": "It makes our skin impermeable to water."}, {"title": "Function of the Skin .txt", "text": "Now, what else does the skin actually do?"}, {"title": "Function of the Skin .txt", "text": "Well, within the dermis, we have a network of collagen as well as elastin fibers."}, {"title": "Function of the Skin .txt", "text": "And we also have this within the hypodermis, within the subcutaneous layer."}, {"title": "Function of the Skin .txt", "text": "And together, our carotene, our collagen, as well as our elastin fibers give the skin strength and elasticity."}, {"title": "Function of the Skin .txt", "text": "And this is exactly what allows the skin to resist physical as well as mechanical pressures and forces."}, {"title": "Function of the Skin .txt", "text": "So basically, the skin ensures that our internal organs are well protected."}, {"title": "Function of the Skin .txt", "text": "For example, if we examine one particular important internal organ in our heart, the heart is not only protected by the sternum, bone and the ribcage."}, {"title": "Function of the Skin .txt", "text": "It is also actually protected by the layer of skin that exists on top of our sternum and ribcage."}, {"title": "Function of the Skin .txt", "text": "Now, aside from actually protecting our internal organs from physical damage, our skin actually protects us from many other things."}, {"title": "Function of the Skin .txt", "text": "For example, it protects us from excessive UV radiation."}, {"title": "Function of the Skin .txt", "text": "So although our skin actually needs UV radiation to ultimately synthesize vitamin D, a hormone that is used to basically regulate calcium and phosphate ions in our blood, excessive UV radiation is dangerous."}, {"title": "Function of the Skin .txt", "text": "Why?"}, {"title": "Function of the Skin .txt", "text": "Well, recall from physics that UV radiation is a type of electromagnetic wave and it carries more energy than normal visible light waves."}, {"title": "Function of the Skin .txt", "text": "And that's because it has a slightly higher frequency."}, {"title": "Function of the Skin .txt", "text": "So that means when UV radiation when UV rays actually hit the cells of our skin, they can end up damaging the organelles and the biological molecules such as DNA, found inside our skin cells."}, {"title": "Function of the Skin .txt", "text": "And that means excessive UV radiation can damage the skin and ultimately lead to things like cancer."}, {"title": "Function of the Skin .txt", "text": "And that's exactly why in the epidermis of our skin we have specialized cells known as melanocytes."}, {"title": "Function of the Skin .txt", "text": "And melanocytes release a chemical, a pigment known as melanin."}, {"title": "Function of the Skin .txt", "text": "And melanin doesn't only give us our skin color it also actually absorbs some of that UV radiation which protects us from damaging our skin."}, {"title": "Function of the Skin .txt", "text": "Now, not only that, but the skin actually creates a physical barrier that does not allow bacterial cells and viral agents to actually get into our body."}, {"title": "Function of the Skin .txt", "text": "The skin also protects us from dehydration and it protects us from a wide variety of different types of chemical agents and harmful chemical things."}, {"title": "Function of the Skin .txt", "text": "So if some type of harmful molecule gets onto our skin there is a very high probability that the skin will not allow that harmful chemical to actually go through the skin and enter our organs found inside our body."}, {"title": "Function of the Skin .txt", "text": "So this is the function in protection."}, {"title": "Function of the Skin .txt", "text": "Now, the second function of the skin is that in sensation."}, {"title": "Function of the Skin .txt", "text": "So on our skin and in our skin, we basically have a wide variety of different types of sensory or."}, {"title": "Function of the Skin .txt", "text": "Somatic, sensory receptors."}, {"title": "Function of the Skin .txt", "text": "For example, we have pressure receptors."}, {"title": "Function of the Skin .txt", "text": "We have light receptors."}, {"title": "Function of the Skin .txt", "text": "We have thermal receptors and that includes heat and cold receptors."}, {"title": "Function of the Skin .txt", "text": "We also have our pain receptors and many other receptors."}, {"title": "Function of the Skin .txt", "text": "So what allows me to actually feel it when I pinch my skin is the fact that there is a receptor in that skin that is connected to our nervous system and that allows me to basically sense that pinch, that touch."}, {"title": "Function of the Skin .txt", "text": "On top of that, the epidermis contains these specialized cells known as merkel cells that are involved or believed to be involved in sensation."}, {"title": "Function of the Skin .txt", "text": "Now, let's move on to function number three insulation and thermal regulation."}, {"title": "Function of the Skin .txt", "text": "So recall that the hypodermis, the subcutaneous layer, contains our adipose cells."}, {"title": "Function of the Skin .txt", "text": "And what these adipose cells do is they create a layer of insulation and that basically keeps us cool in the summer days and keeps us warm in the winter nights."}, {"title": "Function of the Skin .txt", "text": "Now, what about thermal regulation?"}, {"title": "Function of the Skin .txt", "text": "Well, recall that our body is in a constant state of homeostasis so it does what it can to maintain homeostasis."}, {"title": "Function of the Skin .txt", "text": "And one of the things that it does is it needs to actually maintain a constant core temperature."}, {"title": "Function of the Skin .txt", "text": "So, 36.7 degrees Celsius, if our temperature increases or decreases even slightly, our proteins basically lose their efficiency and cannot function properly."}, {"title": "Function of the Skin .txt", "text": "So what our body does is it uses the skin to actually maintain thermal regulation via the process of sweating, perspiration as well as evaporation and radiation, as we'll see in just a moment."}, {"title": "Function of the Skin .txt", "text": "So every exothermic process that takes place in the body for example, let's say cellular respiration produces excessive amounts of energy, excessive amounts of heat."}, {"title": "Function of the Skin .txt", "text": "And if that heat is not expelled by that body, it will increase the core temperature."}, {"title": "Function of the Skin .txt", "text": "And what that means is our body must actually get rid of that heat."}, {"title": "Function of the Skin .txt", "text": "And what it does is it takes the heat and it stores that heat in our blood."}, {"title": "Function of the Skin .txt", "text": "And as the blood actually travels in these blood vessels in the dermis section of our skin, this blood radiates the heat outward to the outside of our skin."}, {"title": "Function of the Skin .txt", "text": "Now, we also have the sweat glands which basically produce our sweat, which consists predominantly of water."}, {"title": "Function of the Skin .txt", "text": "And as the water gets onto the surface of our skin, the heat that basically rises and radiates from the moving blood in our blood vessels is used to actually vaporize that water from our skin."}, {"title": "Function of the Skin .txt", "text": "And this is an endothermic process."}, {"title": "Function of the Skin .txt", "text": "In fact, it's a very endothermic process because water has a high specific heat capacity."}, {"title": "Function of the Skin .txt", "text": "And so this is an important way by which we regulate the core temperature and homeostasis of our body."}, {"title": "Function of the Skin .txt", "text": "So once again, every exothermic process in the body produces excessive energy that must be dissipated by the body to prevent overheating."}, {"title": "Function of the Skin .txt", "text": "What happens is the blood vessels that run in the dermis of our skin, it can actually expel some of that energy, some of that heat via the process of radiation."}, {"title": "Function of the Skin .txt", "text": "So this energy, this heat simply rises to the top portion of our skin."}, {"title": "Function of the Skin .txt", "text": "Now, the skin can also expel heat via the endothermic process of evaporation."}, {"title": "Function of the Skin .txt", "text": "So sweating takes place and that rising heat basically vaporizes evaporates that water and endothermic process."}, {"title": "Function of the Skin .txt", "text": "And that's how we basically regulate the amount of energy in our body by using our heat."}, {"title": "Function of the Skin .txt", "text": "Now, at the same exact time when it's very cold outside, our skin can actually conserve heat."}, {"title": "Function of the Skin .txt", "text": "And how it conserves heat is it basically constricts our blood vessels found in the dermis and that redirects that shunts the blood away from the skin and that conserves energy because there is very little blood that actually radiates the energy out from our skin."}, {"title": "Function of the Skin .txt", "text": "So our skin cannot only dissipate that heat, but it can actually be used to store as much heat in the body as possible."}, {"title": "Function of the Skin .txt", "text": "Now, function number four, it also functions in excretion as well as secretion."}, {"title": "Function of the Skin .txt", "text": "So earlier we mentioned the existence of these sweat glands."}, {"title": "Function of the Skin .txt", "text": "So not only can our kidneys actually excrete waste products, ions and water, but our skin can also be used to actually excrete these molecules and ions."}, {"title": "Function of the Skin .txt", "text": "So the sweat glands basically produce sweat which consists of water, it also consists of waste products such as urea, as well as ourion, such as sodium."}, {"title": "Function of the Skin .txt", "text": "And so what these sweat glands do, and these sweat glands are shown in green, they basically produce this substance and secrete and excrete the substance onto the surface via these sweat pores."}, {"title": "Function of the Skin .txt", "text": "And then the heat that rises from the blood vessels moving that blood along the dermis is used to actually vaporize that water from our body, from the surface of our skin."}, {"title": "Function of the Skin .txt", "text": "Now, another thing that actually takes place on the skin is something called transepidermal water loss."}, {"title": "Function of the Skin .txt", "text": "And this is not the same thing as sweating."}, {"title": "Function of the Skin .txt", "text": "So actually, water can actually diffuse across the upper portion of our skin."}, {"title": "Function of the Skin .txt", "text": "So basically, water is lost as a result of this process of diffusion that takes place through the skin."}, {"title": "Function of the Skin .txt", "text": "And this is different than sweating."}, {"title": "Function of the Skin .txt", "text": "So, once again, the skin is an excretion organ as well as a secretion organ."}, {"title": "Function of the Skin .txt", "text": "It can excrete water to the skin surface via diffusion."}, {"title": "Function of the Skin .txt", "text": "Waste products such as urea, salt, such as sodium and water can all be excreted via the process of sweating, as well as via trans epidermal water loss."}, {"title": "Function of the Skin .txt", "text": "Now, function number five is that in immunity."}, {"title": "Function of the Skin .txt", "text": "So earlier we mentioned two types of immune cells."}, {"title": "Function of the Skin .txt", "text": "We mentioned Langerhon cells, which are cells found within the epidermis."}, {"title": "Function of the Skin .txt", "text": "And Langerhon cells are responsible for interacting with T cells of our immune system."}, {"title": "Function of the Skin .txt", "text": "And that basically helps us protect from bacterial agents."}, {"title": "Function of the Skin .txt", "text": "On top of that, the hypodermis, the subcutaneous lay of the skin, contains macrophages that can actually engulf bacterial cells."}, {"title": "Function of the Skin .txt", "text": "Now, function number six is that as our endocrine gland."}, {"title": "Function of the Skin .txt", "text": "So, remember earlier, I mentioned that the skin actually needs UV radiation."}, {"title": "Function of the Skin .txt", "text": "So certain cells in the epidermis of our skin are responsible for using UV radiation, the energy stored in UV radiation, to actually produce something called colic calcipheral."}, {"title": "Function of the Skin .txt", "text": "And this is basically an inactive form of vitamin D three."}, {"title": "Function of the Skin .txt", "text": "Now, once the skin produces Cola Calciphral, it travels into our liver, where we basically transform Cola Calcipher into calcidial."}, {"title": "Function of the Skin .txt", "text": "And then calcitial travels into our kidneys."}, {"title": "Function of the Skin .txt", "text": "And in the kidneys, that calcitial is transformed into the active form of vitamin D, calcitriol."}, {"title": "Function of the Skin .txt", "text": "Now, the function of calcitriol is to basically regulate the amount of calcium and phosphate ions found inside our skin."}, {"title": "Function of the Skin .txt", "text": "So we need vitamin D to basically regulate the amount of calcium found in our blood, as well as the amount of phosphate ions found inside our blood."}, {"title": "Function of the Skin .txt", "text": "And this is why the skin is an endocrine organ."}, {"title": "Function of the Skin .txt", "text": "It produces this pre hormone known as our colicalcipheral."}, {"title": "Function of the Skin .txt", "text": "Now, the final function, function number seven of the skin, is basically in growth."}, {"title": "Function of the Skin .txt", "text": "So we know that as the human grows, as the bone grows and the organ grows, the skin must grow along with everything else inside the human body."}, {"title": "Function of the Skin .txt", "text": "And that means the skin must be able to expand."}, {"title": "Function of the Skin .txt", "text": "Now, earlier we mentioned that the skin contains protein fibers known as elastin."}, {"title": "Function of the Skin .txt", "text": "And it's these elastin fibers that actually give our skin its flexibility and ability to basically expand as the organism grows."}, {"title": "Function of the Skin .txt", "text": "And that's exactly why the skin can expand span due to these elastic fibers."}, {"title": "Function of the Skin .txt", "text": "And therefore, as the organism grows, so does our skin."}, {"title": "Function of the Skin .txt", "text": "So these are seven important functions that the skin takes on."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's continue our discussion on the isoelectric points of proteins."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Previously we had example one and example two in which we actually determined what the isoelectric point of a protein was."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now let's look at example three."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So in example three, we want to basically determine the net charge on this protein that consists of five amino acids at these four different pieces h value."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's begin by actually drawing the structure of this protein."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's begin with histidine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have our actually, we're not going to have enough room, so let's draw it lower."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We have h three M, and we have our essential carbon atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "The h is going into the board and we have our group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For histidine, it basically looks something like this."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, we have a double bond here."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We have a double bond here."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We have an h here, and we have that."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's finish off the first amino acid with this carbonyl group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now let's move on to tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For tyrosine, we have a different side chain group, right?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So the side chain group for tyrosine is a phenyl group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have our benzene."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Then we have an oh, and this is an h. And let's finish off amino acid number two."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now we're at lysine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's draw our N atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Then we have our h going into the board."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for lysine, the side chain group is h is four of these carbon atoms."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then at the end of that, we have this amine group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then we finish off that amino acid for glutamate, so we have our nitrogen."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So for glutamate, it looks like this."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's remove that second bond and let's draw the resonance stabilized form of this group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then we have finally cysteine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have the nitrogen, then we have our central carbon."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We have this h going into the board."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for cysteine, the group, the side chain group is we have this ch two group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then we have the sulfur that is bound to our age."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And now we finish off this peptide by drawing the terminal alpha carboxyl group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, so this is our five amino acid peptide."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So amino acid one, two, amino acid three, four and five."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now the next step is to basically label all the groups on the peptide that can lose or gain an age atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And we have to also label their PKA value."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's begin on this side."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this right over here has a PKA value of 8.0."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's underline that this group here, or let's actually go to this group, this group here, which is our histidine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this nitrogen, right, can gain or lose an h atom at a PKA of 6.0."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, now let's go to tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For tyrosine, the PKA value is about 10.9."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For this one, which is lysine, the PKA value is 10.8."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So slightly below that for tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For glutamate, the PKA value is 4.1."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for this final one, which is what is it?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "It's 16."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "The PKA value is 8.3."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then for this N group, it's the PKA values 3.1."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have 123-4567 PK values that we have to consider in steps or in A-B-C and D. So let's begin with A."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, so at a PH of two, what is the net charge on this protein?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So, let's begin with this group and basically go one by one all the way to the 7th group, this alpha carboxyl group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So at the alpha amino group, we're a PH of two."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And since two is below 8.0, that means this will have a positive charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So once again, remember that what the PKA value tells us is so if the PH is equal to the PKA, that is when our H atom will be lost or gained."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And in this particular case, at a PH of eight or higher, this is when the H atom on this nitrogen will be lost."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So our first charge is a positive one charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now let's move on to the second group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "This group here, this is HistoGene."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for HistoGene, the PKA is 6.8."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And that means below a PK of 6.8, this nitrogen will be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And when this nitrogen is protonated, we basically have a positive charge on that nitrogen."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So 1234 bonds."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so this will have a positive charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we'll have a positive charge on that chain."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the next amino acid."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "This is tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For tyrosine, the PK valley is 10.8."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So below 10.8, below a PH of 10.8, this will be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So it will have a charge of zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's say neutral charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Or actually yeah, let's say neutral charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, so let's move on to this third amino acid."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have lying to, and Lynne has a PK of 10.8, which is above PH of two."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So that means this will have a positive charge on that nitrogen, right?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So the nitrogen is bound to 1234 atoms."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "It will have a positive one charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to this one here, which is Glutamate."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Glutamate has a 4.1 valley."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So what that means is above 4.1, the oxygen will be deprotonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "But below 4.1, the oxygen will be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And when the oxygen is protonated, it has a charge of zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the final amino acid."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "The cysteine has a PKA of 8.3, and below 8.3, this will be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so it will not have a charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have a charge of zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And finally, last but not least, this alpha carboxyl group that has a PK value of 3.1."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So what this means is below a PH of 3.1, this group will be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so this will have a charge of zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have one, two, three positive charges, no negative charges."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And that means that the total charge for this particular case will be positive three."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to B."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And B we're bumping up the PH to five."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So now things will change."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay, so let's begin at the beginning, where at a PH of five, which is below A, so that means this here is protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this one is protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Then we move on to histidine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So where five, which is once again below a PK of six."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So histidine will also be protonated."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And this nitrogen will have a positive charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the third one, tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So five is below 10.9."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So that means this will exist in its mutual form."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We're going to have a charge of zero for that particular case."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the fourth amino acid."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have one, two, three or one two three."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Yeah, so three."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So Lysine contains PKA of 10.8 on that side chain group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so we're at five, which is below 10.8."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this will have a positive charge on that nitrogen."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the next one."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we're at Glutamate."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For Glutamate, the PK is 4.1, and since five is above 4.1, that means this oxygen will have lost that H atom and so it will have a negative charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So finally we have at least one negative charge on our peptide."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the next 116."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So for 16, the PK is 8.3, which is above the PH of five."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so that means this will have a net charge of zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for this particular case, because we're at a PH of five, which is above this, this will also have lost that H atom and so it will have a negative charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have two negative charges and we have three positive charges."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So three positive charges and two negative charges gives us an overall net charge of negative or positive one."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we still have a positive charge, but it's a smaller positive charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to a neutral PH of seven, which is a physiological PH of our body."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's contain the process."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So in this particular case, we're still below a PH of eight."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So that means this will have a positive charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So let's move on to the side chain group of that amino acid number one."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We see that we have our histidine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so this at a PH of six or above, will begin to lose that H atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And since where at a PH of seven, what that means is this will have lost the H atom, it will have a neutral charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so now we have a charge of zero for the second case, for that first side chain group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now the second side chain group and the second amino acid is tyrosine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so we have a PKA of 10.9, which is above seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so what that means this will have a neutral charge, just like in the other two cases."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Let's move on to the third amino acid."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this one here, Lysine, PKA of 10.8, which is above seven, that means it will have a charge of positive one on that nitrogen."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We move on to the next amino acid in line, which is glutamate has a PK of 4.1, which is below our neutral PH of seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this will bear a negative charge on the oxygens here."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have a negative charge here."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "On the next one, we have cysteine."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so for cysteine, we have a PKA of 8.3 above seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so what that means is this will be neutral."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And finally this N group will be negatively charged, because the PKA of this is below the PH of seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have a negative charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And finally, if we add these charges up, we'll see that our charge, the net charge in this particular case, is zero."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so this can basically be used to find what the actual pi value of this protein is."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And we'll do that in just a moment."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So actually, let's add E, where in E we want to find the pi, okay?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And in D, so we follow these same procedures we basically have in the beginning, because our PH is eleven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Now, this will have lost the H atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so now we have a neutral charge there."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "This has lost that atom, the H atom, and so it has a neutral charge on the nitrogen."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For this particular case, eleven is above 10.9."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this lost that H atom."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so we have a negative charge, because once that oxygen loses our H atom, it gains a negative charge for this, 110.8."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So that means the nitrogen lost that H atom and it is neutralized, so it gains a charge."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Or the nitrogen has a charge of zero, because one of the H atoms is lost."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "For Glutamate, we're once again above 4.1."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this will have a charge of negative one."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And then for this side chain group, where above 8.3, we're at eleven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so that means we have a charge of negative one."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And for the final group, we see that we have the terminal Kurbano group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this that will have a negative charge as well, because eleven is above the PKA of this side chain group."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so if we sum up these charges, 1234 negative charges."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so that means we have full charge, or not a full charge, but a net charge of negative four."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Okay?"}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So out of all these cases seized, only one that can be used to find our pi value."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "Remember, to find the isoelectric point, the pi, we want to estimate the PH at which the net charge on a protein would be zero, which is choice C. So now we want to use this PH of seven to basically find what the average of the two PK values is above and directly below the PH of seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have 810.9, we have 4.13.18.310.8 and 6.0."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So what is the value, what is the PKA that is directly above this value of seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we have eight."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "We have ten point 910.88, .3 are all the values directly above it, and eight is the closest one to seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So that means we basically use eight as one of those values, and then the one directly below it, we have 3.14.1 and 6.0."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So we use this 6.0 value."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "And so if we add up these two and take the average, we see that the pi is in fact, at seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So for this particular case, for these particular conditions, when these are the PKA values of this protein, we see that the Pi is seven."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "It's the neutral physiological PH of our body."}, {"title": "Calculation of Net Charge on Proteins .txt", "text": "So this is how you find the Pi dielectric point of proteins."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "The fact that we have an ability to produce any type of monoclonal or polyclonal antibody in a laboratory setting is actually very useful."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And that's because it gives us a way to test for the presence of a protein inside a given sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And that sample, for example, could be a blood sample or it could be a urine sample coming from an individual."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So one important type of method that, that utilizes these monoclonal and polychlonal antibodies is Eliza."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And Eliza is not only used in biochemistry, it is also used in medicine."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So Eliza stands for enzyme linked Immunosorbin Assay."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And this is a method that utilizes these monoclonal or sometimes polyclonal antibodies to determine and quantify the presence of some type of protein in our sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, we're going to discuss two types of Eliza methods."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "In this lecture."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "We're going to examine indirect and sandwich Eliza."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And although these two methods are slightly different, they use the same exact concept, they use the same exact principle."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So let's begin by examining indirect Eliza."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the entire point of indirect Eliza is to basically test for the presence of some specific type of antibody."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So let's discuss the HIV agent."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So let's suppose we have an individual who contracts HIV, and what that means is in their blood sample, in their blood, they're going to contain the antibodies against the antigen found in the HIV agent."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So we can use indirect Eliza, for example, to test for the presence of the antibodies against that HIV agent."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And that's exactly what we're going to use to demonstrate how this process actually works."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So let's suppose we have a well, a container, and inside that well, so on the surface of that well, we essentially place the antigens that are found in the HIV agent."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the surface of the well is coated with a specific antigen that comes from that viral agent."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And these antigens are shown in red."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, once we coat the well, we then extract the blood sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "We extract the antibodies from the blood from that individual and we take these antibodies and we place them into this well."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, some of these antibodies will not be against the antigen and so they will not bind to that antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "But in the case of the person who contains HIV, because they do have those antibodies against the agent, they will bind onto the antigen shown in diagram B."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So these blue antibodies present in the blood of that person that contains HIV will bind onto the red antigens."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now the next question is how do we actually visualize the presence of this antibody antigen Complex well, we have to use a special antibody that we produced in the laboratory setting."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And this antibody is manufactured in a way to basically contain an enzyme."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So we have an antibody shown in green, and that antibody is created so that it contains an enzyme attached to it."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "That's why we call this method enzyme linked immunosorbin acid."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Enzyme link means we create this monoclonal antibody shown in green that can bind specifically to this blue antibody."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And that green antibody also contains an enzyme that will become important in step d. So in step c, an enzyme linked antibody that can bind to that antibody of interest, the blue one, is added to our mixture, to our well."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, if the antibody of interest, if that blue antibody is bound onto that red antigen, then our enzyme linked antibody will bind onto this antibody as shown in that diagram."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, in the next step, we basically want to first remove all the different types of molecules inside that sample that are not bound to anything."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so once we wash our sample, we remove anything that is not bound."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And once we wash, we then add that specific substrate, that specific molecule that is converted by this enzyme that is linked to our green antibody."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And once we add our substrate, that enzyme will begin to transform that substrate to some type of product."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And when that transformation takes place, that causes a color change in our sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And that tells us that the antibody is present inside that sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Because if the antibody was not present in our sample, then following that washing process, we basically would remove any antibody that was not bound."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And if that blue antibody was not bound to a red antigen, then we essentially remove everything that was present in our mixture, including these green antibodies that contain the enzyme."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so following the washing process, if we add the substrate because no enzyme is present in that mixture, the color change would not actually take place."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the color change signifies the presence of that antibody that we are actually searching for in the first place."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, the darker that color change is, the higher the concentration of that antibody inside our mixture."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So this method not only allows us to actually determine the presence of the antibody, it also allows us to quantify to determine what the concentration is of that particular antibody in our mixture."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the entire point of this indirect Eliza method is to basically test for that presence of our antibody inside that sample, for example, inside that blood sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, if the individual did not have HIV, they would not have these blue antibodies."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so if these blue antibodies were not present in our mixture, the green antibodies would not have anything to bind to."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so once we wash our well, those green antibodies would be removed."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so once we add the substrate, the substrate would have nothing to actually catalyze that reaction."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so no color change would actually take place."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So this is how we actually use to test for HIV."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "This is what we use to test for HIV."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "What about sandwich?"}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Ellis?"}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Well, Sandwich eli is very similar because it still uses this enzyme link molecule that we produce in a laboratory setting."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "But in the case of sandwich Eliza, we test for a specific type of antigen and not for a specific type of antibody."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So sandwich Eliza is generally used to detect the presence of an antigen rather than an antibody, as we saw in indirect Eliza."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So let's take a look at the following four diagrams."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So in diagram A of indirect Eliza, we coat the surface of the well with an antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "But in this particular case, we coat the surface with the antibody that can bind to that specific antigen that we are testing for."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the antibody specific to the antigen that we're testing for is attached to the bottom of the well."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And then we take our sample, for example, the blood sample, or it could be a urine sample, and we place it into our mixture."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And if the antigen is present in that mixture, it will bind to our antibody that is coated on the surface of our well."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So we form the antibody antigen complex."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And now in step C, we add that enzyme linked antibody that we synthesized in the laboratory setting, and we place it into our well."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And if the antibody antigen complex is present, if this complex exists, then the green antibody that contains the enzyme E will essentially bind to that antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So this enzyme linked antibody only binds to our antigen if it is bound itself to that blue antibody."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so if the antigen is present inside our mixture, we have this entire complex that is formed and notice it's like a sandwich, because we have two antibodies."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And in between the antibody, we have our antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so once again, as in step D, in step d for a sandwich allies that we wash our mixture to basically remove anything that is not bound."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And because this is bound, this is not removed."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And when we add our substrate into the mixture, because the enzyme will be present inside our solution, that enzyme will begin to readily convert that substrate into that product."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And when this transformation takes place, that once again causes a color change."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So we see the principle that we use is this color change reaction."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "It's the color change reaction that signifies the presence of either that antibody or that antigen in our sample."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "So the well is washed to remove anything that is not bound, and the substrate is added to react with the enzyme producing that product that gives off that color."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And just like in the case of indirect Eliza, in sandwich Eliza, the darker that color is, the higher the concentration of that antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And the lighter the color is, the smaller the concentration of our antigen."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "Now, if the antigen was not present in our mixture, then this enzyme linked antibody would have nothing to bind to."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so when we wash it in step D, we wash away that enzyme."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so when we add our substrate because the enzyme would not be present in our mixture, that substrate would not be catalyzed, and we would not form that product."}, {"title": "Indirect and Sandwich ELISA .txt", "text": "And so no color change would take place if the antigen was not present in our mixture."}, {"title": "Sarcomere .txt", "text": "In our discussion on the somatic nervous system, we said that the somatic nervous system is responsible for innervating and controlling a type of muscle known as the skeletal muscle."}, {"title": "Sarcomere .txt", "text": "And it's the skeletal muscle that is responsible for voluntary motion such as walking, riding a bicycle, swimming and so forth."}, {"title": "Sarcomere .txt", "text": "So anytime we want to basically consciously control our movement, and we can, this is our skeletal muscle that is involved."}, {"title": "Sarcomere .txt", "text": "Now, skeletal muscle is not the only type of muscle that is found in the body."}, {"title": "Sarcomere .txt", "text": "We also have cardiac muscle found in the heart."}, {"title": "Sarcomere .txt", "text": "And we have smooth muscle, for example, found lining our blood vessels."}, {"title": "Sarcomere .txt", "text": "Now, cardiac and smooth muscle is controlled by the autonomic nervous system and the smallest unit of the cardiac muscle and the skeletal muscle is known as the sarcomere."}, {"title": "Sarcomere .txt", "text": "Smooth muscle does not consist of the sarcommir."}, {"title": "Sarcomere .txt", "text": "So in this lecture, we're going to discuss the smallest functional unit of the skeleton muscle and the cardiac muscle known as the sarcomire."}, {"title": "Sarcomere .txt", "text": "So what exactly does the sarcomire actually look like?"}, {"title": "Sarcomere .txt", "text": "Well, this diagram basically describes our sarcomir."}, {"title": "Sarcomere .txt", "text": "We have a single sarcomere on this side and the sarcomere is basically lie adjacent to one another and they create long muscle fibers as we'll see in the next several lectures."}, {"title": "Sarcomere .txt", "text": "So we have a single sarcomir here, we have another sarcomere to the right side, we have another sarcome to the left side and so forth."}, {"title": "Sarcomere .txt", "text": "Now, from this diagram, we see we have different regions within our sarcomir."}, {"title": "Sarcomere .txt", "text": "We have the H zone, we have the A band, we have the Z lines, and we also have something known as the iband, which stretches over to sarcomeres."}, {"title": "Sarcomere .txt", "text": "Now, before we actually discuss what these regions are, let's discuss the composition of our sarcommerce."}, {"title": "Sarcomere .txt", "text": "So what types of proteins are found inside our sarcomir?"}, {"title": "Sarcomere .txt", "text": "So we have two types of filaments."}, {"title": "Sarcomere .txt", "text": "We have a thin filament, which are these black horizontal lines."}, {"title": "Sarcomere .txt", "text": "We have 1234-5678 for this particular sarcomere, and we have the thick filament which is shown in purple."}, {"title": "Sarcomere .txt", "text": "We have one, two, three of these thick filaments in this particular sarcommer."}, {"title": "Sarcomere .txt", "text": "Now, let's begin by discussing what the composition of our thin filament is."}, {"title": "Sarcomere .txt", "text": "The thin filament is composed of a type of globular spherical protein known as actin."}, {"title": "Sarcomere .txt", "text": "And these individual actin monomers basically join together and combine to form a polymer, a long chain of actin."}, {"title": "Sarcomere .txt", "text": "And two of these actin polymers basically intertwine with one another and form a helical structure that creates our thin filament."}, {"title": "Sarcomere .txt", "text": "So the thin filament consists of two long polymers and these polymers consist of our actin molecule, the actin protein."}, {"title": "Sarcomere .txt", "text": "Now on top of this actin protein found inside our thin filament, the thin filament also consists of two other proteins."}, {"title": "Sarcomere .txt", "text": "We have a protein known as troponin, and we have tropomycin."}, {"title": "Sarcomere .txt", "text": "And these two proteins are involved in muscle contraction, as we'll see in the next lecture."}, {"title": "Sarcomere .txt", "text": "So this is our diagram of the thin filament."}, {"title": "Sarcomere .txt", "text": "So if we zoom in on these horizontal black regions, we basically get the following diagram."}, {"title": "Sarcomere .txt", "text": "We have these individual spherical actin monomers that basically join together to form our polymers."}, {"title": "Sarcomere .txt", "text": "And two long polymer chains basically intertwine to form our helical fashion our helical structure."}, {"title": "Sarcomere .txt", "text": "And on top of that, we also have this long blue fiber known as our troponin."}, {"title": "Sarcomere .txt", "text": "And we have this green region known as our tropomycin."}, {"title": "Sarcomere .txt", "text": "And we'll discuss the function of these proteins in the next lecture."}, {"title": "Sarcomere .txt", "text": "They are involved in muscle, in muscle contraction."}, {"title": "Sarcomere .txt", "text": "Now, what about our thick filament?"}, {"title": "Sarcomere .txt", "text": "What exactly does the thick filament actually look like on the microscopic level?"}, {"title": "Sarcomere .txt", "text": "Well, basically the thick filament consists of a protein known as myosin."}, {"title": "Sarcomere .txt", "text": "And many of these myosin proteins combine together and intertwine to basically form our thick filament."}, {"title": "Sarcomere .txt", "text": "So these thick filaments basically wrap around one another, or these myosin wrap around one another to form our thick filament."}, {"title": "Sarcomere .txt", "text": "And on the edges, at the end of each of these thick filaments, we basically have extensions known as myosin heads."}, {"title": "Sarcomere .txt", "text": "And these myosin heads, as we'll see in the next lecture, are basically responsible for actually binding and interacting with our thin filaments."}, {"title": "Sarcomere .txt", "text": "So these heads are shown on this diagram, and these heads are responsible for interacting with the black region that thin filament."}, {"title": "Sarcomere .txt", "text": "And that's exactly what causes that contraction."}, {"title": "Sarcomere .txt", "text": "These myosin heads pull on our actin and that basically causes that contraction as we'll see in the next lecture."}, {"title": "Sarcomere .txt", "text": "So now that we know what the composition of the sarcomere is, let's discuss these different regions."}, {"title": "Sarcomere .txt", "text": "And let's begin with our H zone."}, {"title": "Sarcomere .txt", "text": "So the H zone is basically this entire region that is found on the single sarcomere."}, {"title": "Sarcomere .txt", "text": "And the H zone only contains our thick filament."}, {"title": "Sarcomere .txt", "text": "So this entire region only contains our thick filament, shown in purple."}, {"title": "Sarcomere .txt", "text": "And notice that it doesn't actually contain the entire thick filament inside the h zone."}, {"title": "Sarcomere .txt", "text": "It only contains the part that does not overlap with our thin filament."}, {"title": "Sarcomere .txt", "text": "So the H zone is the region of the sarcomere that only contains the thick filament."}, {"title": "Sarcomere .txt", "text": "Note that it does not include the entirety of the thick filament."}, {"title": "Sarcomere .txt", "text": "Let's move on to our eyeband."}, {"title": "Sarcomere .txt", "text": "The eyeband is this entire region that stretches not over a single sarcomere, but over two sarcommirs that are found adjacent to one another."}, {"title": "Sarcomere .txt", "text": "So just like the h zone contains only thick filament, the iband only contains our thin filament."}, {"title": "Sarcomere .txt", "text": "So it only contains these black regions, our thin filament, and it extends over two sarcommirs and not over a single sarcomere as our h zone does and the A band does."}, {"title": "Sarcomere .txt", "text": "So now let's move on to our egg band."}, {"title": "Sarcomere .txt", "text": "So the A band actually contains all of our thick filament."}, {"title": "Sarcomere .txt", "text": "So basically, beginning on this side of the filament and ending on the other side of the filament, that is our A band."}, {"title": "Sarcomere .txt", "text": "And notice that it actually also involves a portion of our thin filament because we have this overlap between the thin filament and our thick filament."}, {"title": "Sarcomere .txt", "text": "So the A band is the region that contains all the thick filaments in their entire length."}, {"title": "Sarcomere .txt", "text": "Notice that due to the overlap between the thin and thick filaments, the A band also includes a small portion of our thin filaments."}, {"title": "Sarcomere .txt", "text": "So these small black regions here."}, {"title": "Sarcomere .txt", "text": "Now, what about these Z lines?"}, {"title": "Sarcomere .txt", "text": "So the z line number one and the z line number two are basically the boundary lines for our sarcomir."}, {"title": "Sarcomere .txt", "text": "So the sarcomir begins on this z line and ends on the z line, while the second sarcommer here begins on the z line and ends on the other z line that is not shown."}, {"title": "Sarcomere .txt", "text": "And it's the z line that basically gives skeletal muscle as well as our cardiac muscle striped or its striped look."}, {"title": "Sarcomere .txt", "text": "So if we look on the microscope, our muscle will basically look like it's striped."}, {"title": "Sarcomere .txt", "text": "And that's because of these z lines."}, {"title": "Sarcomere .txt", "text": "So when a muscle actually contracts, the way that our sarcomir contracts is in the following way, as we'll see in the next lecture, these mycin heads basically attach to our actin, to our thin filament."}, {"title": "Sarcomere .txt", "text": "And when they attach, they basically contract."}, {"title": "Sarcomere .txt", "text": "And when they contract, they bring these actin, these thin filaments, close to one another and we have overlap taking place, but the entire length of our thick filament does not actually change."}, {"title": "Sarcomere .txt", "text": "So this is when our sarcomir is basically relaxed."}, {"title": "Sarcomere .txt", "text": "But when we have contraction, we basically move these z lines closer to one another."}, {"title": "Sarcomere .txt", "text": "So when a contraction takes place, these z lines come closer to one another, so that the distance between the z line and this z line actually decreases."}, {"title": "Sarcomere .txt", "text": "And what that means is this A band will also decrease."}, {"title": "Sarcomere .txt", "text": "I'm sorry, this A band won't, but this I band will also decrease in size, as well as the h zone will decrease in size."}, {"title": "Sarcomere .txt", "text": "But the A band, which actually includes the entire length of that thick filament will not change because the length of our thick filament does not actually change when our contraction takes place."}, {"title": "Sarcomere .txt", "text": "So notice that when our muscle contracts, the A band does not change because the thick filament does not change its length, its size."}, {"title": "Sarcomere .txt", "text": "However, both the h zone and the eye band do change."}, {"title": "Sarcomere .txt", "text": "In the case of our eyeband, it decreases, but in the case of our h band, it disappears entirely because the h zone is based, not the h band, the h zone."}, {"title": "Sarcomere .txt", "text": "The h zone contains only our thick filament."}, {"title": "Sarcomere .txt", "text": "And in this particular case, because we have an overlap, there is no region where we only have arithic filament."}, {"title": "Sarcomere .txt", "text": "So in this particular diagram, the h zone disappears altogether."}, {"title": "Sarcomere .txt", "text": "So once again, only cardiac muscles, muscles in the heart and skeletal muscles that are responsible for voluntary motion consist of these individual subunits."}, {"title": "Sarcomere .txt", "text": "Functional units known as the sarcomir."}, {"title": "Sarcomere .txt", "text": "Smooth muscle does not consist of sarcomeres."}, {"title": "Secondary Messenger Systems .txt", "text": "Previously we discussed the details of a synapse."}, {"title": "Secondary Messenger Systems .txt", "text": "And the synapse we focused on was the neuromuscular junction."}, {"title": "Secondary Messenger Systems .txt", "text": "This is the synapse between a neuron and our muscle cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, at the synapse, at the neuromuscular junction, we have the signal transduction process taking place."}, {"title": "Secondary Messenger Systems .txt", "text": "So this basically means we pass down the electrical signal from the neuron to our muscle muscle cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, how exactly does this actually take place?"}, {"title": "Secondary Messenger Systems .txt", "text": "Well, let's take a look at the following diagram and recap."}, {"title": "Secondary Messenger Systems .txt", "text": "Basically, the action potential travels down the axon of the neuron and to the axon terminal."}, {"title": "Secondary Messenger Systems .txt", "text": "This is the axon terminal of the presynaptic neuron cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, once the action potential arrives, it indirectly causes the release of these synaptic vesicles that carry a special type of chemical known as neurotransmitter."}, {"title": "Secondary Messenger Systems .txt", "text": "And a specific type of neurotransmitter involved in the neuromuscular junction is acetylcholine."}, {"title": "Secondary Messenger Systems .txt", "text": "So acetylcholine is released into this space known as Arisynaptic cleft."}, {"title": "Secondary Messenger Systems .txt", "text": "And it goes on and binds to a receptor protein channel found on the muscle cell, the postsynaptic membrane."}, {"title": "Secondary Messenger Systems .txt", "text": "So it binds onto these channels, it causes these channels to open up and there is an influx of these sodium ions into the cell and that causes the process of depolarization of the membrane and that essentially creates an action potential."}, {"title": "Secondary Messenger Systems .txt", "text": "And this is what we mean by the signal transduction process."}, {"title": "Secondary Messenger Systems .txt", "text": "So our electron potential or our action potential, the electric signal is transduced."}, {"title": "Secondary Messenger Systems .txt", "text": "It's passed down from our presynaptic cell indirectly to the postsynaptic cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, notice this electrical signal doesn't actually travel directly from the presynaptic cell to the post synaptic cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Instead, we have this intermediate molecule, the neurotransmitter, that actually passes down that electrical signal."}, {"title": "Secondary Messenger Systems .txt", "text": "So this neurotransmitter in this type of pathway is known as the first messenger or the primary messenger molecule."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, also notice that this neurotransmitter doesn't actually go inside the cell of the muscle cell."}, {"title": "Secondary Messenger Systems .txt", "text": "Instead, it stays on the outside."}, {"title": "Secondary Messenger Systems .txt", "text": "It attaches onto the receptor of the protein membrane found on the extracellular side of that membrane."}, {"title": "Secondary Messenger Systems .txt", "text": "And in most cases, this is what takes place."}, {"title": "Secondary Messenger Systems .txt", "text": "In most cases, our first messenger doesn't actually go into our cell and create that response."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, in the pathway that we described so far, this pathway involves only our first messenger."}, {"title": "Secondary Messenger Systems .txt", "text": "And the first messenger binds and causes that action potential to take place."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, in most other signal transduction processes we have the use of another molecule known as the secondary messenger."}, {"title": "Secondary Messenger Systems .txt", "text": "And these types of pathways are known as secondary messenger systems."}, {"title": "Secondary Messenger Systems .txt", "text": "And secondary messenger systems are most often controlled by special protein complexes that involve g protein."}, {"title": "Secondary Messenger Systems .txt", "text": "So what exactly is the pathway of such a signal transduction process?"}, {"title": "Secondary Messenger Systems .txt", "text": "So let's take a look at the following paragraph and then let's look at a specific example of a secondary messenger system."}, {"title": "Secondary Messenger Systems .txt", "text": "So our complex of proteins usually contains a transmembrane protein that is found on the membrane of that cell, the receptor cell that contains a binding side for the ligand and the ligand is the first messenger molecule."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, this binding side is usually found on the extracellular side of the membrane as in this case."}, {"title": "Secondary Messenger Systems .txt", "text": "So what happens is once our first messenger binds to our transmembrane protein, on the other side of that transmembrane protein we have other proteins attached as we'll see in just a moment."}, {"title": "Secondary Messenger Systems .txt", "text": "And once our first messenger actually binds to our transmembrane protein it causes the dissociation of one of these proteins and usually it's the G protein."}, {"title": "Secondary Messenger Systems .txt", "text": "Now, once our G protein detaches, it can go on and do several things."}, {"title": "Secondary Messenger Systems .txt", "text": "So it can activate other protein channels, it can activate our secondary messenger molecules or it can go on and activate other enzymes and it can also go on and actually transcribe genetic information as we'll see in a future lecture when we get into biochemistry."}, {"title": "Secondary Messenger Systems .txt", "text": "So let's take a look at a specific secondary messenger system that involves the activation of a protein known as protein kinase A."}, {"title": "Secondary Messenger Systems .txt", "text": "So recall in our discussion of enzymes that protein kinase A is a special type of enzyme that catalyzes the phosphorylation of other proteins to activate those proteins."}, {"title": "Secondary Messenger Systems .txt", "text": "So let's take a look at the following membrane."}, {"title": "Secondary Messenger Systems .txt", "text": "So this is the cytoplasm of our cell."}, {"title": "Secondary Messenger Systems .txt", "text": "This is the phospholipid bilayer of that receptor cell."}, {"title": "Secondary Messenger Systems .txt", "text": "It's the membrane and this is the extracellular environment."}, {"title": "Secondary Messenger Systems .txt", "text": "So usually our primary messenger is some type of neurotransmitter or some type of hormone."}, {"title": "Secondary Messenger Systems .txt", "text": "In this case, the hormone is epinephrine."}, {"title": "Secondary Messenger Systems .txt", "text": "So basically what happens is we have the epinephrine, we have the transmembrane protein, our protein that basically goes on from the outside to the inside of the cell through the membrane shown in green."}, {"title": "Secondary Messenger Systems .txt", "text": "And on the inner portion of the membrane, on the cytoplasmic side of this transmembrane, known as beta adrenergic receptor we basically have a complex of other proteins."}, {"title": "Secondary Messenger Systems .txt", "text": "We have the alpha subunit, the beta subunit and the gamma subunit."}, {"title": "Secondary Messenger Systems .txt", "text": "And the alpha subunit, as we'll see, is our G protein."}, {"title": "Secondary Messenger Systems .txt", "text": "So on a different section of that membrane we have another type of protein that is involved in this activation process."}, {"title": "Secondary Messenger Systems .txt", "text": "In the secondary messenger system process, this is known as the adenylate cyclase protein."}, {"title": "Secondary Messenger Systems .txt", "text": "So let's actually take a look and see what happens during our secondary messenger system signal transduction."}, {"title": "Secondary Messenger Systems .txt", "text": "So basically some type of cell, some type of gland in our body releases this hormone known as epinephrine."}, {"title": "Secondary Messenger Systems .txt", "text": "Eventually this epinephrine reaches the receptor of that specific cell and that receptor is found on the membrane."}, {"title": "Secondary Messenger Systems .txt", "text": "So this is the protein complex."}, {"title": "Secondary Messenger Systems .txt", "text": "The green is our beta adrenergic receptor."}, {"title": "Secondary Messenger Systems .txt", "text": "It contains the receptor that basically binds our epinephrine."}, {"title": "Secondary Messenger Systems .txt", "text": "So when the epinephrine binds to this section, it basically causes the alpha subunit to decrease its affinity for the beta subunit and the alpha subunit."}, {"title": "Secondary Messenger Systems .txt", "text": "And what happens is our GDP, which is the guanosine diphosphate, is converted into the guanosine triphosphate or GTP and that decreases the affinity of the alpha subunit, our G protein."}, {"title": "Secondary Messenger Systems .txt", "text": "And this goes on and bind onto this adenylate cyclase."}, {"title": "Secondary Messenger Systems .txt", "text": "And once it binds onto our adenylene cyclase it causes the conversion of ATP adenosine triphosphate to cyclic adenosine monophosphate or CA MP."}, {"title": "Secondary Messenger Systems .txt", "text": "And then this is our secondary messenger."}, {"title": "Secondary Messenger Systems .txt", "text": "So our epinephrine is the primary or first messenger involved in the signal transduction process and this is the second molecule involved."}, {"title": "Secondary Messenger Systems .txt", "text": "And so this is called our secondary messenger."}, {"title": "Secondary Messenger Systems .txt", "text": "And the secondary messenger, our cyclic Amp goes on and activates protein kinase A."}, {"title": "Secondary Messenger Systems .txt", "text": "So that now protein kinase A can go on and phosphorylate other enzymes inside our cell."}, {"title": "Secondary Messenger Systems .txt", "text": "So this is one specific example of a secondary messenger pathway."}, {"title": "Secondary Messenger Systems .txt", "text": "This is the pathway by which we pass down signals from one cell to a different cell in the body."}, {"title": "Secondary Messenger Systems .txt", "text": "So in this case we only had one intermediate molecule involved, the neurotransmitter."}, {"title": "Secondary Messenger Systems .txt", "text": "In this case we had two."}, {"title": "Secondary Messenger Systems .txt", "text": "We had our epinephrine was the first messenger or the primary messenger and a secondary messenger was our cyclic Amp."}, {"title": "Secondary Messenger Systems .txt", "text": "So once again, protein kinase A, the enzyme that thus farlates other proteins in the cell can be activated through a secondary messenger system."}, {"title": "Secondary Messenger Systems .txt", "text": "Now the first messenger is in this signal transduction pathway is the hormone also known as a neurotransmitter, in some cases is our epinephrine, also called adrenaline."}, {"title": "Secondary Messenger Systems .txt", "text": "It binds to a transmembrane protein called the betaandrinergic receptor and this causes a conformational change, a change in shape of this transmembrane protein which forces our alpha subunit, our G protein to change the GDP to GTP."}, {"title": "Secondary Messenger Systems .txt", "text": "This decreases definitive of our alpha subunit to this, this and this section."}, {"title": "Secondary Messenger Systems .txt", "text": "So it detaches this associates this, goes on and binds onto the adenylene cyclase and that causes the transformation of ATP molecules to camp molecules, cyclic Amp and then the secondary messenger, our cyclic Amp goes on and activates protein kinase A."}, {"title": "Secondary Messenger Systems .txt", "text": "So in this process we basically transduce."}, {"title": "Secondary Messenger Systems .txt", "text": "We pass down a signal from one cell to a different cell and tell that cell to basically activate protein kinase A so that the cell can use protein kinase A and activate other proteins involved in other processes."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So, as we now know, the matrix of the mitochondria is where we break down our fatty acids."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "We can oxidize the fatty acids into acetyl coenzyme molecules, and then we can use those molecules to basically generate ATP molecules via the citric acid cycle."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, although the majority of the fatty acids are oxidized, are broken down, in the matrix of the mitochondria, there is another location of oxidation and fatty acids that occurs inside our cells, and this is inside proxy home."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So remember that proxosomes are membrane bound organelles that also contain enzymes involved in the fatty acid oxidation process."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, what types of fatty acids do we generally oxidize and break down in our peroxisomes?"}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Well, it's the fatty acids that contain 20 or more carbon atoms."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So these are known as very long chain fatty acids or simply VLCFA."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, what exactly the major difference between the beta oxygen process that takes place inside our mitochondria and inside proxosomes?"}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Well, the major difference is step one of beta oxidation."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So remember that in step one of beta oxidation, inside the matrix of the mitochondria, we have an enzyme that catalyze the reaction in which we basically oxidize the fatty acid and that helps us generate an Fad H two molecule."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, what about inside the proxosomes?"}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Well, inside the proxysome, it's this step that takes place."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So let's suppose we have some type of very long chain fatty acid."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Let's suppose our N value here is 16 or greater so that this entire molecule contains at least 20 carbon atoms."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, in step one, we basically transform this single bond between carbon number two and three into a double bond."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And at the same time, we basically reduce the Fad molecule into an Fadh two molecule."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, this group, the Fad, is actually found bound to the acyl coenzyme a dehydrogenase."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So this is a flavor protein dehydrogenase, and it's different."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And it's different than the enzyme that catalyzes step one of the beto oxation process that we typically see in the matrix of the mitochondria."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, this process doesn't stop here."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Remember that in the matrix of the mitochondria, we generate that Fadh two molecule that then can be used by the electron transport chain."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "But in the paroxysome, those electrons are then transferred onto an oxygen molecule."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And that oxygen molecule is formed, is used to form an H 02:02 molecule, hydrogen peroxide."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And this is a very toxic molecule."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And that's exactly why inside the paroxysome, we find another enzyme known as catalase."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And it's the catalase that helps detoxify this hydrogen peroxide into oxygen and water."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So once this process takes place and we form the H 202 molecule, it's the catalyst that acts on two moles of these molecules to form two moles of water and 1 mol of oxygen."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, once we generate this intermediate molecule and then follows the same exact identical steps that we typically find in the matrix of the mitochondria, and this process of the normal beta oxidation continues until we form a fatty acid that contains eight carbon atoms."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And once we form that, that is then transported into the matrix of the mitochondrion, where that oxidation process is completed to form the CETO coenzyme, a molecules that can be used to generate the high energy ATP molecule."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So this is what we basically find in the proxosomes."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, what is the importance of proxosomes if we have those mitochondria to basically help us undergo the fatty acid oxidation process, why do we need paroxysomes in the first place?"}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Well, to answer that condition, we can basically study a set of genetic disorders that are known as the Zellwegger spectrum syndromes."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, the Zellwegger syndrome is the very severe form of the Zellwegger spectrum syndrome, while the Adrenal leukodystrophy is a slightly less severe form."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "Now, in both of these cases, there is some type of genetic mutation in proteins known as paroxins."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And these proteins, called paroxins, are basically responsible for actually forming the paroxysome."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So in patients, in individuals with these genetic conditions, the paroxysomes don't actually form correctly or don't form at all."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And so what that means is these very long chain fatty acids will not be broken down, and they will increase in concentration in those individuals."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "In addition, paroxysomes have other functions."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "For instance, paroxysomes also synthesize those lipid molecules that are found in the myelin sheath around neurons, around the axons of neurons."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And so if paroxysomes do not actually form correctly, what that means is we cannot form the myelin sheath."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And so individuals with these conditions will basically have problems with their muscle tissue, with their liver, with their kidneys, as well as with the nervous system and other tissues."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "So, to summarize, we see that our fatty acid oxidation doesn't only take place in the matrix of the mitochondria, it also takes place in the paroxysome."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "And what the peroxide oxosome ultimately does is it helps us take the very long chain fatty acids."}, {"title": "Peroxisomal oxidation of fatty acids .txt", "text": "It helps us actually shorten those fatty acids so that they can be then transported into the matrix of the mitochondria and broken down by the beta oxidation step that takes place inside the matrix of the mitochondrion."}, {"title": "Mitosis and Cytokinesis.txt", "text": "The cell cycle of an animal cell consists of two stages."}, {"title": "Mitosis and Cytokinesis.txt", "text": "One of these stages, the first stage is known as interface."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And this is what we focus on."}, {"title": "Mitosis and Cytokinesis.txt", "text": "In the previous lecture, we said that interface involves the synthesis of proteins the production of organ nouns and the replication of DNA that are used in the second stage of the cell cycle of the animal cell known as the M stage."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So the second stage is known as the M stage or the mitotic stage."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now, the mitotonic stage consists of two processes."}, {"title": "Mitosis and Cytokinesis.txt", "text": "We have mitosis as well as cytokinesis."}, {"title": "Mitosis and Cytokinesis.txt", "text": "But these two processes are actually interconnected as we'll see in just a moment."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So mitosis, although it is one continuous process we usually divide mitosis into four individual phases."}, {"title": "Mitosis and Cytokinesis.txt", "text": "We have ProPhase, metaphase, anaphase and telephase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And then we have cytokinesis."}, {"title": "Mitosis and Cytokinesis.txt", "text": "But actually cytokinesis, as we'll see in just a moment begins in the process of telephase in the phase of mitosis, known as telephase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So let's go through each one of these individual phases of mitosis and let's describe what takes place in each one of these phases beginning with ProPhase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now recall in the first stage of the cell cycle of our animal cell known as interphase the DNA is continually being transcribed into RNA so that we use the RNA to form the proteins that are needed by the cell."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And that means our DNA and interface exists predominantly in the chromatin states."}, {"title": "Mitosis and Cytokinesis.txt", "text": "However, in mitosis we no longer actually need to transcribe or replicate our DNA."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And that means as soon as the cell enters ProPhase of mitosis the DNA condenses from chromatin into chromosomes."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So during the process of ProPhase our DNA is being condensed into chromosomes."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now recall that each animal cell contains a single centrosome and the centrosome is the region of the cell that contains two identical Centrios."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now, what happens in ProPhase is these two centriots begin to move to opposite ends as shown in the following diagram."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And as they move to opposite ends the centrioles begin to synthesize the spindle apparatus also known as the mitotic spindle apparatus."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And what the mitotic spindle apparatus consists of is special types of spindle fibers that are made from microtubules."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So as our two centrioles move apart to opposite ends of the cell to opposite poles of the cell our microtubules, the spindle fibers, also known as asters, begin to grow and they radiate outward towards the center of our cell, towards our nucleus."}, {"title": "Mitosis and Cytokinesis.txt", "text": "At the same time that happens our nuclear membrane begins to deteriorate and the nucleolus disappears altogether."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And what this basically does is it allows the spindle fibers to make its way into the nucleus region of our cell so that our spindle fibers, as we'll see in just a moment can actually attach to a special region on the centromere."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So basically, each one of these chromosomes are connected by a centromere or the region where they connect is called the centromere."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And what also happens in ProPhase is the centromeres of the chromosomes develop these attachment points known as kinetochores."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So this concludes ProPhase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now let's move on to the second phase, known as metaphase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So in metaphase, these two centrioles have now moved to opposite ends, to opposite poles of the cell."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And now what happens is these spindle fibers basically radiate outward and attach onto the kinetic core of the centromere of our chromosome pairs."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So this is shown in the following diagram."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And what also happens is these spindle fibers, which are now connected, they move our chromosomes to the center of our cell and they align our chromosomes on the center line, also known as the equatorial line, which is basically the Y axis shown on the diagram here."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So we have our chromosomes align along the equatorial plate, and this is metaphase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now let's move on to anaphase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So, during the process of anaphase, we undergo a process known as this junction."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And this junction is basically the process by which we separate our cystochromatids."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So recall, in the process of interphase, we actually replicate every single DNA molecule in the cell."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So if we're talking about a human cell, during the process of the cell cycle, we have 46 individual DNA molecules."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And each one of these 46 DNA molecules is replicated."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And we join them by using our proteins in the region known as the centromere."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So in this diagram, we only have four of these pairs, but for humans, we have 46 of these chromosome pairs."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And each one of these individual chromosomes in the pair is also known as a chromatid, or a sister chromatid."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So basically, this is one sister chromatid, and this is a second sister chromatid."}, {"title": "Mitosis and Cytokinesis.txt", "text": "This is one sister chromatid, and this is a second one, and so forth."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And these cystochromatids are identical because in interface, we replicate, we use the first original to form the second replicated cystochromatid."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So during this phase of anaphase, the spindle fibers pull the identical chromosome pairs apart by breaking our centromeres."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And this is shown in this diagram."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And when we break the centromeres, each one of these chromatids has its own unique centromere region."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now, the identical chromosomes in any pair, also known as sister chromatids, begin to move to opposite ends, as shown in the diagram."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And this separation of chromosomes is known as this junction."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now let's move on to telephase."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So in telephase, these spindles basically move our cystochromatids to opposite ends, so that once we are in telephase, each end of the cell now contains the identical set of chromosomes."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So we have four on the left end and four on the right end."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now, what also begins to happen is the nuclear membrane begins to reform, but it begins to reform on both sides."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So that now we begin to develop the nuclear membrane and the nucleolus, and it basically encloses these two sets of identical chromosomes."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So the spindle apparatus also begins to deteriorate, and we basically take our chromosomes and we decondence our chromosomes back into the chromatid."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And this basically prepares our cell for the interface."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So once telephase and cytokinesis ends, the cell will once again, once again inter interface where it will need to basically transcribe the DNA into RNA to synthesize the proteins."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And that's exactly why the chromosome must uncoil and decondence into chromatin to get ready for transcription in the process of interface."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And in telephase, cytokinesis actually begins."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So what exactly is cytokinesis?"}, {"title": "Mitosis and Cytokinesis.txt", "text": "So cytokinesis begins in telephase and then it continues after telephase ends."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So basically cytokinesis is the breaking of the cytoplasm."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So this is the process by which the cell membrane begins to divide, the cytoplasm begins to separate and the organelles and the organelles are basically distributed among two cells equally."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So we have two identical daughter cells that are the same in size and which have the same exact genetic information."}, {"title": "Mitosis and Cytokinesis.txt", "text": "And notice that our chromosomes are no longer chromosomes because they decondence into the chromatin form as shown in the following diagram."}, {"title": "Mitosis and Cytokinesis.txt", "text": "So these are two identical daughter cells that have the same exact genetic information and which are smaller than this original cell because we basically divide this in half."}, {"title": "Mitosis and Cytokinesis.txt", "text": "Now, once these cells enter interface, they can once again grow and enlarge and eventually, actually, each one of these cells will be exactly the same as our original cell in terms of size and the amount of cytoplasm found inside those cells."}, {"title": "Introduction to Immune System .txt", "text": "Unlike most of the systems of our body, the immune system is special because it is not localized to a specific region or a specific organ of the body."}, {"title": "Introduction to Immune System .txt", "text": "Instead, our immune system is spread out throughout the entire body."}, {"title": "Introduction to Immune System .txt", "text": "It is found in many different regions of the body."}, {"title": "Introduction to Immune System .txt", "text": "Now, as we'll see in the next several lectures, what the immune system does is it utilizes a series of internal defense mechanisms that ultimately protect the cells of our body from pathogens."}, {"title": "Introduction to Immune System .txt", "text": "And a pathogen is any type of agent, it can be living or non living that brings harm to the cells of our body."}, {"title": "Introduction to Immune System .txt", "text": "So a bacterial cell, a virus, a chemical that can harm our cells, all these different things are considered to be pathogens."}, {"title": "Introduction to Immune System .txt", "text": "Now, for a pathogen to actually cause damage, cause harm to the cells of our body, these pathogens must enter our body."}, {"title": "Introduction to Immune System .txt", "text": "And the most common ways by which pathogens enter our body is through the simple process of breathing when we exchange air inside our lungs that can bring different types of pathogens into our body."}, {"title": "Introduction to Immune System .txt", "text": "Pathogens can also enter our body through the food that we eat, through the water that we drink or through some type of cut that is found on our skin."}, {"title": "Introduction to Immune System .txt", "text": "Now, in order for our immune system to actually be effective and efficient, it must have a way to actually differentiate, to actually distinguish between its own cells of the body and these foreign pathogens that can cause harm to those cells of the body."}, {"title": "Introduction to Immune System .txt", "text": "Now, such recognition is actually possible because the cells of our body contain special unique macromolecules."}, {"title": "Introduction to Immune System .txt", "text": "For example, proteins or lipoproteins that are found on the membrane of the cells of the body."}, {"title": "Introduction to Immune System .txt", "text": "And our immune system can use these unique biological molecules on the membrane to recognize its own cells."}, {"title": "Introduction to Immune System .txt", "text": "Now, on the other side of things, if we examine a pathogen, for example, a bacterial cell, bacterial cells also contain their own unique biological molecules, macromolecules on the membrane."}, {"title": "Introduction to Immune System .txt", "text": "And our immune system can ultimately use these foreign macromolecules to stimulate the immune system to initiate a response that ultimately destroys and kills off that pathogen."}, {"title": "Introduction to Immune System .txt", "text": "And in general, anytime we have a substance such as the macromolecule found in the membrane of the bacterial cell that stimulates any type of immune response, this substance is known as an antigen."}, {"title": "Introduction to Immune System .txt", "text": "So our immune system uses these foreign antigens to basically stimulate these internal defense mechanisms that ultimately catch these pathogens and destroy these pathogens."}, {"title": "Introduction to Immune System .txt", "text": "So, to see what we mean, let's take a look at the following diagram."}, {"title": "Introduction to Immune System .txt", "text": "So these are two human cells."}, {"title": "Introduction to Immune System .txt", "text": "This is a pathogen, for example, a bacterial cell."}, {"title": "Introduction to Immune System .txt", "text": "Notice that both of these cells actually contain these membrane bound macromolecules."}, {"title": "Introduction to Immune System .txt", "text": "For example, let's suppose they're lipoproteins."}, {"title": "Introduction to Immune System .txt", "text": "Now, these lipoproteins that the human cell contains are easily recognized by the cells of our immune system."}, {"title": "Introduction to Immune System .txt", "text": "And so these membrane protein of human cells can be used by the immune system in self recognition and that ensures that our own immune system doesn't actually destroy our own cells."}, {"title": "Introduction to Immune System .txt", "text": "On the other hand, these foreign macromolecules, or antigens, can be recognized by the immune cells as foreign objects."}, {"title": "Introduction to Immune System .txt", "text": "And so our immune system can initiate a series of internal defense mechanisms that ultimately destroy our foreign object, our bacterial cell."}, {"title": "Introduction to Immune System .txt", "text": "Now, if we take our immune system, the immune system can basically be divided into two types."}, {"title": "Introduction to Immune System .txt", "text": "The first type is known as the nonspecific, or the innate immune system."}, {"title": "Introduction to Immune System .txt", "text": "And the second division is known as the specific, or the acquired immune system."}, {"title": "Introduction to Immune System .txt", "text": "So, if we look at our immune system, it could be subdivided into two categories."}, {"title": "Introduction to Immune System .txt", "text": "We have the Innate Immunity, also known as non specific Immunity, and we have the Quiet Immunity, also known as the specific Immunity."}, {"title": "Introduction to Immune System .txt", "text": "Now, what exactly is the difference between these two Immunity systems?"}, {"title": "Introduction to Immune System .txt", "text": "Well, this takes in effect immediately, as soon as that pathogen actually enters our body, while our acquired Immunity takes several days to actually kick in."}, {"title": "Introduction to Immune System .txt", "text": "Now, the innate Immunity doesn't actually involve any process of learning, but the acquired Immunity requires the process of learning."}, {"title": "Introduction to Immune System .txt", "text": "For example, if a bacterial cell actually infects our body, then the next time that same type of cell infects our body, it's the acquired immune system that is responsible for initiating the response that recognizes that specific type of bacterial cell and kills off that bacterial cell."}, {"title": "Introduction to Immune System .txt", "text": "So, this is very specific to the type of cells, the type of pathogens it actually attacks."}, {"title": "Introduction to Immune System .txt", "text": "While this type of system does not actually discriminate, it attacks all different types of pathogens equally."}, {"title": "Introduction to Immune System .txt", "text": "So, let's begin by discussing our innate Immunity and the different components that make up our innate Immunity."}, {"title": "Introduction to Immune System .txt", "text": "And let's begin with the physical barrier our skin."}, {"title": "Introduction to Immune System .txt", "text": "So, our skin is the largest organ of our body, and one of the more important functions of our skin is to actually physically protect our body from different types of pathogens for example, UV radiation, as well as bacterial cells and viruses."}, {"title": "Introduction to Immune System .txt", "text": "So, our skin creates a physical barrier that prevents pathogens from entering our body and attacking our cells."}, {"title": "Introduction to Immune System .txt", "text": "Now, if we examine the passageways inside our body, the air passageways, including the nasal cavity, the trachea, the bronchi, as well as the bronchioles found in the lungs, these air passageways are lined with a special type of mucus membrane."}, {"title": "Introduction to Immune System .txt", "text": "And this sticky and sliding mucus membrane is responsible for trapping the pathogens that enter our body through the process of breathing."}, {"title": "Introduction to Immune System .txt", "text": "And once these pathogens are trapped inside our mucous membrane, the cilia found inside the pathogeways carry those pathogens up to the outside of our body and sometimes into our stomach."}, {"title": "Introduction to Immune System .txt", "text": "And that leads us directly to number three fluid secretions."}, {"title": "Introduction to Immune System .txt", "text": "So, why would we want any sort of pathogen to actually enter our stomach?"}, {"title": "Introduction to Immune System .txt", "text": "Well, basically, if we ingest any type of food that contains a pathogen, or if the pathogens inside the mucous membrane are eventually expelled into our stomach."}, {"title": "Introduction to Immune System .txt", "text": "The reason this actually takes place is because inside our stomach we have specialized types of cells known as parietal, cells that are responsible for secreting a very acidic substance known as hydrochloric acid."}, {"title": "Introduction to Immune System .txt", "text": "And the hydrochloric acid creates a very low PH, a very acidic environment that most pathogens cannot actually survive in."}, {"title": "Introduction to Immune System .txt", "text": "On top of that, our skin, our mouth and eyes also contain special types of glands that secrete other fluids that contain enzymes such as lysozymes that can essentially kill off our bacterial cells pathogens because they break down the cell membrane of those bacterial cells."}, {"title": "Introduction to Immune System .txt", "text": "Now, the fourth type of Innate Immunity section is the phagocytes and neutrophils."}, {"title": "Introduction to Immune System .txt", "text": "These are two types of cell specialized immune cells that are part of the innate immunity response."}, {"title": "Introduction to Immune System .txt", "text": "Now, these two cells are essentially cells that can engulf our pathogen and destroy that pathogen once they actually engulf."}, {"title": "Introduction to Immune System .txt", "text": "Now, these cells aren't specific to the type of pathogen they actually engulfed."}, {"title": "Introduction to Immune System .txt", "text": "They engulf anything that is foreign to the body."}, {"title": "Introduction to Immune System .txt", "text": "And finally, we also have the process of inflammation and fever."}, {"title": "Introduction to Immune System .txt", "text": "So different types of chemicals inside our body can initiate the process of inflammation."}, {"title": "Introduction to Immune System .txt", "text": "And as we'll see in the next several lectures what inflammation actually does, it localizes our infection and it helps bring different types of immune agents, for example, phagocytes and neutrophils to that infected area."}, {"title": "Introduction to Immune System .txt", "text": "Now, fever is another type of innate Immunity response because what fever basically does is it increases the temperature of our body and that can destroy the bacterial cells because cells cannot actually survive in that particular temperature environment."}, {"title": "Introduction to Immune System .txt", "text": "Now, let's move on to acquired immunity."}, {"title": "Introduction to Immune System .txt", "text": "So we have two divisions of acquired immunity, which takes usually several days to actually kick in."}, {"title": "Introduction to Immune System .txt", "text": "We have cell mediated immunity, also known as T cell immunity."}, {"title": "Introduction to Immune System .txt", "text": "And we also have antibody mediated immunity, also known as B cell immunity or humoral immunity."}, {"title": "Introduction to Immune System .txt", "text": "So the major difference between these two types of divisions of the quiet immunity is one uses a type of cell known as a T lymphocyte or a T cell."}, {"title": "Introduction to Immune System .txt", "text": "And the second type uses a type of cell known as a B lymphocyte or a B cell."}, {"title": "Introduction to Immune System .txt", "text": "And number two, this uses a special type of biological molecule known as an antibody."}, {"title": "Introduction to Immune System .txt", "text": "And we'll see what that is in just a moment."}, {"title": "Introduction to Immune System .txt", "text": "So let's begin with the cell mediated immunity."}, {"title": "Introduction to Immune System .txt", "text": "So this immune response involves special defense cells, immune cells known as T lymphocytes."}, {"title": "Introduction to Immune System .txt", "text": "And we have several types of T lymphocytes or T cells."}, {"title": "Introduction to Immune System .txt", "text": "We have killer T cells, we have suppressor T cells, we have helper T cells."}, {"title": "Introduction to Immune System .txt", "text": "We also have memory T cells."}, {"title": "Introduction to Immune System .txt", "text": "And we'll discuss these different types of T lymphocytes in the next several lectures."}, {"title": "Introduction to Immune System .txt", "text": "Now, the main function of these T lymphocytes is to actually recognize different types of pathogens, different types of bacterial cells and infected cells by using the antigens found on the surface of those infected and bacterial cells."}, {"title": "Introduction to Immune System .txt", "text": "So these cells have a special protein on their membrane that can recognize foreign antigens and kill off those pathogens."}, {"title": "Introduction to Immune System .txt", "text": "Now, let's move on to the antibody mediated immunity."}, {"title": "Introduction to Immune System .txt", "text": "So this involves not T lymphocytes but B lymphocytes or B cells."}, {"title": "Introduction to Immune System .txt", "text": "And we also have different types of B cells."}, {"title": "Introduction to Immune System .txt", "text": "We have plasma B cells and we have memory B cells and we'll discuss their unique individual function in the next several lectures."}, {"title": "Introduction to Immune System .txt", "text": "So these cells are responsible for producing a type of biological immune or defense molecule known as the antibody."}, {"title": "Introduction to Immune System .txt", "text": "So antibodies are essentially these proteins that circulate throughout our blood and they can attach and recognize the antigens of bacterial cells and other pathogens."}, {"title": "Introduction to Immune System .txt", "text": "And by binding to these antigens, what the antibodies do is they help our immune system initiate these defense mechanisms that ultimately kill off those harmful pathogens."}, {"title": "Introduction to Immune System .txt", "text": "So these are the two different types of divisions of the immune system or two responses."}, {"title": "Introduction to Immune System .txt", "text": "We have the innate immune response that takes an effect immediately and we have the quiet immunity response that usually takes several days to actually take an effect."}, {"title": "Introduction to Immune System .txt", "text": "Now, innate immunity is not learned by the body."}, {"title": "Introduction to Immune System .txt", "text": "We are essentially born with this type of immunity because we are born with skin, we are born with the mucous membranes and so forth."}, {"title": "Introduction to Immune System .txt", "text": "But this is the type of system that utilizes these different specialized cells that carry out a specific type of function and which kill off and destroy specific type of pathogens that enter our body."}, {"title": "Biological Buffer Systems Part II .txt", "text": "Basically remain."}, {"title": "Biological Buffer Systems Part II .txt", "text": "And that's exactly why we use this particular acid conjugate based buffered system."}, {"title": "Biological Buffer Systems Part II .txt", "text": "In fact, inside our body, these concentrations are about the same because of what we discussed earlier."}, {"title": "Biological Buffer Systems Part II .txt", "text": "So this is how our body basically resists these drastic changes in PH because these drastic changes in PH age can basically disrupt the molecular structure of the different types of biological molecules that are used by our body."}, {"title": "Secondary Structure of Proteins .txt", "text": "The primary structure of a polypeptide describes that polypeptide as being a linear polymer of a specific sequence of amino acids."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, once the polypeptide forms its primary structure, what happens next?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, next, that primary polypeptide begins to twist and begins to turn via these regular patterns."}, {"title": "Secondary Structure of Proteins .txt", "text": "And there are four different types of regular patterns."}, {"title": "Secondary Structure of Proteins .txt", "text": "We have alpha helixes, we have beta pleated sheets, we have beta turns, and we have omega loops."}, {"title": "Secondary Structure of Proteins .txt", "text": "And these four different types of regular patterns compose the secondary structure of our protein, of our polypeptide."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now the question is, how exactly does the polypeptide begin to twist to form these four different types of structures?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, inside the polypeptide, we have different bonds."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, the peptide bonds are the bonds holding the amino acids inside the polypeptide together."}, {"title": "Secondary Structure of Proteins .txt", "text": "And these peptide bonds have a double bond character."}, {"title": "Secondary Structure of Proteins .txt", "text": "And what that means is they don't actually rotate, but all the other single bonds inside the polypeptide chain do rotate."}, {"title": "Secondary Structure of Proteins .txt", "text": "And it's the rotation of these other single bonds inside the polypeptide chain that allows the linear polypeptide to eventually fold into the beta pleated sheet, into the alpha helix, into the beta turn and our omega loop."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, once we form these regular patterns, the question is what exactly stabilizes these structures and allows them to exist in the first place?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, it's the hydrogen bonds that exist between the amino acids in that polypeptide chain, as we'll see in just a moment, that allows each one of these secondary structures to actually exist in the first place."}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's begin with the alpha helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "So what exactly is an alpha helix?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, an alpha helix is formed when we have our polypeptide chain and that polypeptide chain begins to twist to form a rodlike structure."}, {"title": "Secondary Structure of Proteins .txt", "text": "And inside that rod like structure, we have the backbone."}, {"title": "Secondary Structure of Proteins .txt", "text": "And on the outside we have those R chain groups that are pointing outside of that alpha helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the alpha helix is a rod like structure as shown on the board, that contains the backbone being in the inside of that helix and the side chain groups on the outer portion of that helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, let's suppose that this is our axis of rotation."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the axis of rotation along which that alpha helix actually forms runs along the x axis in this direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So this is the beginning of our polypeptide and this is the end."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we see that in this case, we go into the board, then we come out of the board, we go into the board, out of the board, we go into the board, out of the board, we go into the board, out of the board, and so forth."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the screw sense of our alpha helix basically describes the directionality of rotation about the axis of rotation for that particular alpha helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, what do we mean by that?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, if this is the axis of rotation, and if we look at the axis of rotation and we examine the directionality of that rotating alpha helix, the rotating polypeptide chain."}, {"title": "Secondary Structure of Proteins .txt", "text": "In this case, it will point in the clockwise direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So going this way is clockwise."}, {"title": "Secondary Structure of Proteins .txt", "text": "And in this particular case, the screw sense of this alpha helix is clockwise."}, {"title": "Secondary Structure of Proteins .txt", "text": "And this is known as the right hand helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, we can also have a left hand helix in which the directionality is reversed."}, {"title": "Secondary Structure of Proteins .txt", "text": "It would be counterclockwise."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, the left handed helix is much less stable because there is more steric hindrance."}, {"title": "Secondary Structure of Proteins .txt", "text": "There is a greater number of collisions between the Archanes of arapoli peptide."}, {"title": "Secondary Structure of Proteins .txt", "text": "And so because of that, the energy level of the left handed helix is higher than the energy level of the right handed helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "And what that means is for the majority of the proteins that contain the alpha helix, it will be the right handed helix and not the left handed helix that will exist within that protein."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the right handed alpha helix predominates because there is less steric hindrance between the side chains on our alpha helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, the final thing I'd like to mention about the alpha helix is the actual hydrogen bonding that exists between our amino groups."}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's suppose that this is our amino acid that we're actually examining."}, {"title": "Secondary Structure of Proteins .txt", "text": "So this is our amino acid, and this green bond is the peptide bond that does not rotate, that connects this amino acid to the next amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "Then we have this peptide bond that connects to this amino acid and so forth."}, {"title": "Secondary Structure of Proteins .txt", "text": "So remember, these green bonds are peptide bonds."}, {"title": "Secondary Structure of Proteins .txt", "text": "And because those peptide bonds are resonant stabilized, they have a double bond character and they will not rotate."}, {"title": "Secondary Structure of Proteins .txt", "text": "But these other bonds are single bonds and they do rotate, and it's their rotation that allows this helix and the other structures of the secondary structure to actually form in the first place."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, once we form them, it's the hydrogen bonds that exist between the NH group of one amino acid and the co group of another amino acid that stabilizes these structures and allows them to exist for an extended period of time."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, let's focus on this amino acid here."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we see that we have this NH group of this amino acid here that interacts with the co group of this amino acid here."}, {"title": "Secondary Structure of Proteins .txt", "text": "The question is, what is the numerical relationship between this group here and this group here?"}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's count."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we have this peptide bond here."}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's call this amino acid number one."}, {"title": "Secondary Structure of Proteins .txt", "text": "Then we have this peptide here."}, {"title": "Secondary Structure of Proteins .txt", "text": "We have amino acid number two."}, {"title": "Secondary Structure of Proteins .txt", "text": "We have this peptide here, amino acid number three."}, {"title": "Secondary Structure of Proteins .txt", "text": "And finally we have this peptide here and amino acid number four."}, {"title": "Secondary Structure of Proteins .txt", "text": "And so what we see is if this is our amino acid that contains the NH group, that it will interact with the co group, with the co group of the amino acid that is found four units ahead of that particular amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "And this is always true for the alpha helix."}, {"title": "Secondary Structure of Proteins .txt", "text": "So it's the NH group of one amino acid that interacts with the co group of the amino acid that is found four units ahead of that amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "And the reason this takes place is because these are the groups that are found in closest proximity and are able to interact strongly."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now let's move on to the beta pleated sheets."}, {"title": "Secondary Structure of Proteins .txt", "text": "We see that in the alpha helix we have this helical directionality of our polypeptide."}, {"title": "Secondary Structure of Proteins .txt", "text": "But in the beta pleated sheets, these polymers are linear."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the polypeptide is linear and they're basically stacked on top of one another."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, just like in the helical case, where we have two different types of alpha helixes, we have the right handed and the left handed."}, {"title": "Secondary Structure of Proteins .txt", "text": "We also have two types of beta pleated sheets."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we can have these two linear peptides or polypeptide chains basically point in the opposite directions or they can point in the same direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So anti parallel directionality basically means they are stacked on top of one another, but they point in opposite directions."}, {"title": "Secondary Structure of Proteins .txt", "text": "And the parallel data sheet basically means they're stacked on top of one another and they point in the same direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's begin with the anti parallel case and let's discuss how the bonding actually takes place within the anti parallel beta pleated sheets."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, because we essentially have one of these chains running in this direction and the other one is reversed, we see that these groups actually line up with one another perfectly."}, {"title": "Secondary Structure of Proteins .txt", "text": "And what that means is if we examine this amino acid here and this amino acid here, their groups that are able to interact line up perfectly."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we have this hydrogen accepting group that interacts with this hydrogen donating group on the other amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "And here we have this hydrogen donating group that interacts with this hydrogen accepting group of the other opposing amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "So in the antiparallel beta sheets, we see that the NH and the co groups of an amino acid on one strand interact with the Co and NH groups of the opposing amino acid on the other strand."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we have a one to one perfect interaction between our groups on opposing amino acids."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, how exactly can this actually exist?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, let's imagine we have our polypeptide that runs in the following direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "And somewhere here we have a turn that will take place."}, {"title": "Secondary Structure of Proteins .txt", "text": "And that turn can be a beta turn that we're going to discuss in just a moment."}, {"title": "Secondary Structure of Proteins .txt", "text": "And once that turn takes place, it extends and moves in the opposite direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "And so we have the anti parallel arrangement of our two strands of polypeptide."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, in this particular case, the only difference is there's still a parallel with respect to one mill, but now they run in the same direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "And what that will do is it will change the type of interaction that exists between our amino acids."}, {"title": "Secondary Structure of Proteins .txt", "text": "In this case, we have a one to one interaction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So one amino acid interacts with opposing amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "But here we have one amino acid interacts with two different amino acids on the opposing strand."}, {"title": "Secondary Structure of Proteins .txt", "text": "So let's call this amino acid number one."}, {"title": "Secondary Structure of Proteins .txt", "text": "This let's call amino acid number two."}, {"title": "Secondary Structure of Proteins .txt", "text": "And this amino acid number three."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we have the MH bond of amino acid number one interacts with the co bond of amino acid two on the opposing strand."}, {"title": "Secondary Structure of Proteins .txt", "text": "And the co bond of this amino acid number one interacts with the NH, a group of a different amino acid on that opposing strand."}, {"title": "Secondary Structure of Proteins .txt", "text": "We call that amino acid three."}, {"title": "Secondary Structure of Proteins .txt", "text": "So in the parallel beta sheet, the adjacent strands run in the same direction, and an amino acid on one strand connects to two amino acids on the opposing strand via the hydrogen bond."}, {"title": "Secondary Structure of Proteins .txt", "text": "So we see that not only do we have these opposing directions, but because in this case, we have the opposing directions, they line up perfectly."}, {"title": "Secondary Structure of Proteins .txt", "text": "But in this case, because they run in the same direction, they don't line up perfectly."}, {"title": "Secondary Structure of Proteins .txt", "text": "And so we have this type of one to two interaction as opposed to one to one in this case."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, the final type of secondary structure that I'd like to discuss are the beta turns."}, {"title": "Secondary Structure of Proteins .txt", "text": "So what do we mean by beta turn?"}, {"title": "Secondary Structure of Proteins .txt", "text": "And why do our polypeptides need to create these beta turns in the first place?"}, {"title": "Secondary Structure of Proteins .txt", "text": "Well, if we examine the three dimensional structure of polypeptides will see that the structure is very, very compact."}, {"title": "Secondary Structure of Proteins .txt", "text": "And the compactness of that polypeptide is because the polypeptide is able to make many sharp turns as it conforms into that three dimensional structure."}, {"title": "Secondary Structure of Proteins .txt", "text": "And this ability to form these turns is known as beta turning."}, {"title": "Secondary Structure of Proteins .txt", "text": "And these turns themselves are known as beta turns or reverse turns."}, {"title": "Secondary Structure of Proteins .txt", "text": "So the compact nature of proteins is in part due to the polypeptide's ability to make these sudden turns known as the beta turns."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, in the same way that the alpha helix and the beta pleated sheet are stabilized by hydrogen bonds, these abrupt turns are also stabilized by h bonds."}, {"title": "Secondary Structure of Proteins .txt", "text": "And to see what we mean, let's take a look at the following diagram."}, {"title": "Secondary Structure of Proteins .txt", "text": "So, let's suppose we have polypeptide that runs eventually turns in a following direction."}, {"title": "Secondary Structure of Proteins .txt", "text": "So this is, let's say, the nth amino acid in our sequence."}, {"title": "Secondary Structure of Proteins .txt", "text": "This is the n plus one amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "This is the n plus two amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "This is the n plus three amino acid, and so forth."}, {"title": "Secondary Structure of Proteins .txt", "text": "Now, to actually stabilize the beta turn and to make sure that it is stabilized and exists for an extended period of time, we have to have a bond that forms between the co group."}, {"title": "Secondary Structure of Proteins .txt", "text": "So, wow, this is an h, not an n. So if we examine the nth amino acid, the co group of the nth amino acid interacts with the NH group of the n plus three amino acid."}, {"title": "Secondary Structure of Proteins .txt", "text": "And this is the hydrogen bond that stabilizes our beta turns."}, {"title": "Secondary Structure of Proteins .txt", "text": "And these beta turns are usually found on the surface of that polypeptide."}, {"title": "Secondary Structure of Proteins .txt", "text": "And what that means is these archains found on the beta turns are the ones that interact with the polar nature, the polar solvents found outside our protein as well as with the molecules, the macromolecules that interact with our protein in general."}, {"title": "Secondary Structure of Proteins .txt", "text": "So these are the different types of secondary structure that exist at makeup are polypeptide."}, {"title": "Tryptophan Operon.txt", "text": "The way that prokaryonic cells such as bacterial cells regulate gene expression is by using these units of DNA we call Operons."}, {"title": "Tryptophan Operon.txt", "text": "Now we already spoke about the lac opera and we said that generally speaking, an Operon is this segment of DNA that not only contains the special structural genes that are needed to produce some type of enzyme or enzymes, but it also contains other important segments of DNA such as the operator section and the promoter section."}, {"title": "Tryptophan Operon.txt", "text": "Now in this lecture we're going to focus on a type of opera that is used by bacterial cells in anabolic processes."}, {"title": "Tryptophan Operon.txt", "text": "Now an anabolic process is simply a process in which we synthesize some type of molecule that is needed by the cell, by the bacterial cell."}, {"title": "Tryptophan Operon.txt", "text": "And the type of Operon we're going to focus on is a repressible opera."}, {"title": "Tryptophan Operon.txt", "text": "Now a specific example of a repressible Operon used by bacterial cells is a tryptophan Operon."}, {"title": "Tryptophan Operon.txt", "text": "So what exactly is a repressible Operon?"}, {"title": "Tryptophan Operon.txt", "text": "Well, a repressible Operon is the most common type of Operon used by bacterial cells in anabolic processes."}, {"title": "Tryptophan Operon.txt", "text": "And a repressible opera is usually on, but sometimes under certain circumstances it can be turned off as we'll see in just a moment."}, {"title": "Tryptophan Operon.txt", "text": "So a tryptophan Operon is an Operon that is used by bacterial cells to basically regulate the synthesis of the tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "So let's take a look at the different components of the tryptophan opera."}, {"title": "Tryptophan Operon.txt", "text": "So notice that the tryptophan Operon contains the blue section and that is the promoted section."}, {"title": "Tryptophan Operon.txt", "text": "Now the promoted section is important because this is where the RNA polymerase binds to."}, {"title": "Tryptophan Operon.txt", "text": "So when the RNA polymerase approaches the promoter, it binds onto the promoter."}, {"title": "Tryptophan Operon.txt", "text": "And if there's nothing bound to the operator, that RNA polymerase can move along the structural genes and synthesize the mRNA molecule that is needed to create the enzymes that are involved in synthesizing the tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "So for the case of the tryptophan opera, there are five structural genes that code four different enzymes needed to synthesize the tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "Now let's take a look at the operator."}, {"title": "Tryptophan Operon.txt", "text": "So what is the purpose of the operator?"}, {"title": "Tryptophan Operon.txt", "text": "So the operator is a segment of this Operon to which a repressive protein in its active form binds to."}, {"title": "Tryptophan Operon.txt", "text": "Now what exactly is a repressive protein?"}, {"title": "Tryptophan Operon.txt", "text": "Well, the repressive protein is what this Operon actually uses to turn off the expression of these genes."}, {"title": "Tryptophan Operon.txt", "text": "So notice upstream."}, {"title": "Tryptophan Operon.txt", "text": "So to this side of the promoter we have this red gene known as the repressor gene."}, {"title": "Tryptophan Operon.txt", "text": "And this repressor gene is also part of this opera."}, {"title": "Tryptophan Operon.txt", "text": "That repressor gene basically codes for an inactive so, not an active repressor protein."}, {"title": "Tryptophan Operon.txt", "text": "And to activate that inactive repressor protein so that it can bind onto the operator segment, a special thing must happen."}, {"title": "Tryptophan Operon.txt", "text": "Tryptophan must bind onto the inactive form of that repressive protein to activate it."}, {"title": "Tryptophan Operon.txt", "text": "And only then will that repressive protein bind onto the operator and inhibit the expression of these genes."}, {"title": "Tryptophan Operon.txt", "text": "And therefore inhibit the expression, the formation of tryptophan."}, {"title": "Tryptophan Operon.txt", "text": "So let's look at the two cases when our opera is on and when the opera is off."}, {"title": "Tryptophan Operon.txt", "text": "So let's begin with A."}, {"title": "Tryptophan Operon.txt", "text": "So let's suppose inside the cell we have very little tryptophan present and this is usually the case."}, {"title": "Tryptophan Operon.txt", "text": "So usually we have a low intracellular concentration of tryptophan."}, {"title": "Tryptophan Operon.txt", "text": "So inside the cell we have a relatively low amount of tryptophan."}, {"title": "Tryptophan Operon.txt", "text": "Now what exactly will that mean?"}, {"title": "Tryptophan Operon.txt", "text": "Well, if we have a low amount of tryptophan inside the cell then our inactive repressive protein will remain inactive because there isn't enough tryptophan to actually bind onto the allosteric side of this inactive repressive protein to activate it."}, {"title": "Tryptophan Operon.txt", "text": "So usually what happens is this gene is expressed to produce the repressor mRNA and then that mRNA is used to form the inactive repressor protein."}, {"title": "Tryptophan Operon.txt", "text": "And because we don't have enough we don't have a lot of tryptophan in our cell."}, {"title": "Tryptophan Operon.txt", "text": "The tryptophan will not bind to this protein."}, {"title": "Tryptophan Operon.txt", "text": "It will not activate it and so nothing will bind to the operator section and nothing will block the transcription of these genes."}, {"title": "Tryptophan Operon.txt", "text": "And what that means is the RNA polymerase will easily bind onto the promoter section, the blue section."}, {"title": "Tryptophan Operon.txt", "text": "It will move along these five structural genes."}, {"title": "Tryptophan Operon.txt", "text": "It will produce the mRNA and then the mRNA will be used by the ribosomes to produce the enzymes and then the enzymes will be used to produce the tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "So this is usually what is happening within the cell because the cell is usually continually producing the tryptophan that is needed to produce the many different proteins and enzymes that are found within the cell."}, {"title": "Tryptophan Operon.txt", "text": "Now what happens when the concentration of tryptophan rises?"}, {"title": "Tryptophan Operon.txt", "text": "Now let's suppose there is a very high intracellular concentration inside that cell."}, {"title": "Tryptophan Operon.txt", "text": "So the tryptophan concentration inside is very high in this case because we do have a lot of the tryptophan molecules."}, {"title": "Tryptophan Operon.txt", "text": "We have an excess of these tryptophan molecules floating around in the cell."}, {"title": "Tryptophan Operon.txt", "text": "Some of these tryptophan molecules will act as a co repressor."}, {"title": "Tryptophan Operon.txt", "text": "They will bind onto the allosteric side of that inactive repressor protein and that will activate the protein by changing its three dimensional shape."}, {"title": "Tryptophan Operon.txt", "text": "And now the active form of this repressor protein will go on and bind onto the operator section, the green section of the opera and once down that will basically inhibit that will block RNA polymerase from actually transcribing these five genes."}, {"title": "Tryptophan Operon.txt", "text": "And so in this case when we have a high concentration of tryptophan inside the cell we're not going to produce any mRNA molecules and so we will not synthesize these enzymes and will not synthesize the tryptophan."}, {"title": "Tryptophan Operon.txt", "text": "And that makes sense because if inside the cells we have a lot of tryptophan that bacterial cell wants to conserve as much energy as possible."}, {"title": "Tryptophan Operon.txt", "text": "And so there's no need to form the tryptophan because the cell already has a high amount of tryptophan inside."}, {"title": "Tryptophan Operon.txt", "text": "But if the tryptophan concentration is low as the case is in part A, then what happens is we need to form more tryptophan so that the cell can function properly and effectively, so that the cell can form the many different proteins and enzymes that require this tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "And so what will happen is our operon will be turned on because this inactive repressive protein will remain in its inactive form."}, {"title": "Tryptophan Operon.txt", "text": "It will not bind to the tryptophan because we will not have enough tryptophan inside that cell."}, {"title": "Tryptophan Operon.txt", "text": "So this is what we mean by a repressible operon."}, {"title": "Tryptophan Operon.txt", "text": "So a repressible operon is the most common type of opera that is used by bacterial cells when it comes to anabolic processes, processes in which we have to synthesize some type of important molecule."}, {"title": "Tryptophan Operon.txt", "text": "In the case of the tryptophan opera, it's the tryptophan amino acid that we have to synthesize."}, {"title": "Tryptophan Operon.txt", "text": "Now, for a repressible operon, usually this is what we have case A."}, {"title": "Tryptophan Operon.txt", "text": "So usually the repressible opera is turned on because we need to continually synthesize that biomolecule, in this case, the tryptophan amino acid."}, {"title": "Tryptophan Operon.txt", "text": "But if we actually get a high concentration of this molecule, only then will that molecule act as a co repressor bind onto this repressive protein, activating it, and then that active form of the repressive protein will move on to the operator action and block the transcription of these genes."}, {"title": "Tryptophan Operon.txt", "text": "And so in this case, the opera is said to be off."}, {"title": "Branching of Glycogen.txt", "text": "The process by which our cells build glycogen molecules is relatively complicated and actually consists of many individual processes."}, {"title": "Branching of Glycogen.txt", "text": "And all these processes basically work together to ultimately synthesize that glycogen molecule."}, {"title": "Branching of Glycogen.txt", "text": "So, as we discussed in the previous lecture, before we can actually attach a glucose molecule onto a growing polysaccharide chain, we have to activate that glucose molecule."}, {"title": "Branching of Glycogen.txt", "text": "We have to make it much more reactive."}, {"title": "Branching of Glycogen.txt", "text": "And so what we do is we take a glucose one phosphate and we transform it into a urine diphosphate glucose, UDP glucose, and the UDP glucose is much more active."}, {"title": "Branching of Glycogen.txt", "text": "And now an enzyme known as glycogen synthase can actually synthesize an Alpha one four glycocitic bond, attach that glucose onto that elongating chain."}, {"title": "Branching of Glycogen.txt", "text": "Now, the thing about glycogen synthase is it cannot simply begin from scratch."}, {"title": "Branching of Glycogen.txt", "text": "It actually requires a primer."}, {"title": "Branching of Glycogen.txt", "text": "And that primer has to be more than four glucose molecules long."}, {"title": "Branching of Glycogen.txt", "text": "So the question that I like to begin in this lecture is what exactly synthesizes that primer that allows the glycogen synthase to begin the elongation process, to begin building that glycogen molecule and creating the Alpha one four glycocity bond."}, {"title": "Branching of Glycogen.txt", "text": "So it's basically an enzyme known as glycogenin."}, {"title": "Branching of Glycogen.txt", "text": "So before glycogen synthase can begin glycogen synthesis, another enzyme called glycogenin must create a glycogen primer."}, {"title": "Branching of Glycogen.txt", "text": "And this primer is a short sequence of glucose molecules which are connected by Alpha one four glycocytic bonds."}, {"title": "Branching of Glycogen.txt", "text": "Now, glycogenin is a dimer molecule."}, {"title": "Branching of Glycogen.txt", "text": "It consists of two identical polypeptide chains."}, {"title": "Branching of Glycogen.txt", "text": "And so what the glycogenin does is it basically creates the primer from scratch."}, {"title": "Branching of Glycogen.txt", "text": "It creates the primer by basically using the activated glucose molecule, the urine divide, phosphateate glucose molecules."}, {"title": "Branching of Glycogen.txt", "text": "And as soon as that primer is actually synthesized by glycogenin, that's when glycogen synthase actually takes over and begins synthesizing the Alpha one four glycocitic bonds."}, {"title": "Branching of Glycogen.txt", "text": "Now, the thing about glycogen synthase is not only does it actually require that primer, but it can only synthesize the Alpha one four glycocitic bonds."}, {"title": "Branching of Glycogen.txt", "text": "It cannot create the Alpha one six glycocitic bonds that we also find in glycogen."}, {"title": "Branching of Glycogen.txt", "text": "So what exactly creates these Alpha one six glycocity bonds?"}, {"title": "Branching of Glycogen.txt", "text": "Well, before we discuss the enzyme that actually creates these Alpha 1416 glycocitic bonds, let's answer the following important question."}, {"title": "Branching of Glycogen.txt", "text": "Why do these branching points remember the Alpha one six glycocitic bonds actually create the branching points in glycogen?"}, {"title": "Branching of Glycogen.txt", "text": "Why do these branching points actually exist?"}, {"title": "Branching of Glycogen.txt", "text": "And generally, how do these branching points in glycogen actually benefit the molecule as a whole?"}, {"title": "Branching of Glycogen.txt", "text": "Well, there are two important benefits of these branching points."}, {"title": "Branching of Glycogen.txt", "text": "Remember that in skeletal muscle cells or in liver cells or any other cell of our body that contains these glycogen, the glycogen molecules are stored in tiny granules found in the cytoplasm."}, {"title": "Branching of Glycogen.txt", "text": "And the cytoplasm is predominantly water."}, {"title": "Branching of Glycogen.txt", "text": "And water is a polar molecule."}, {"title": "Branching of Glycogen.txt", "text": "And ultimately what branching does is it increases the solubility of the glycogen inside that cytoplasm, inside these tiny granules found in the cytoplasm, the cell."}, {"title": "Branching of Glycogen.txt", "text": "Now, another important thing that adding these branching points does is it actually increases the rate at which glycogen synthesis and breakdown actually takes place."}, {"title": "Branching of Glycogen.txt", "text": "Why?"}, {"title": "Branching of Glycogen.txt", "text": "Well, remember that glycogen breakdown and synthesis actually takes place on the terminal non reducing residues of that polymer."}, {"title": "Branching of Glycogen.txt", "text": "And so adding branches to glycogen increases the number of terminal glucose residues, which raises the rate of glycogen synthesis and breakdown."}, {"title": "Branching of Glycogen.txt", "text": "So if we compare this linear polymer to this branched polymer, we see that we have many more branching points here."}, {"title": "Branching of Glycogen.txt", "text": "And as a result, we have many more of these terminal non reducing glucose residues than compared to this particular case."}, {"title": "Branching of Glycogen.txt", "text": "And so the rate at which synthesis and breakdown takes place on this molecule is much higher than on this linear molecule."}, {"title": "Branching of Glycogen.txt", "text": "So now that we know why this process takes place, let's discuss how it actually takes place."}, {"title": "Branching of Glycogen.txt", "text": "So what's the enzyme that forms these Alpha One Six glycocytic bonds?"}, {"title": "Branching of Glycogen.txt", "text": "Well, the enzyme is known as glycogen branching enzyme."}, {"title": "Branching of Glycogen.txt", "text": "And what it basically does is it synthesizes these Alpha One Six glycocitic bonds that lead to the branching of glycogen."}, {"title": "Branching of Glycogen.txt", "text": "So what the enzyme actually does is it first breaks an Alpha One four glycocitic bond and it detaches a group of glucose molecules that are usually seven residues in length."}, {"title": "Branching of Glycogen.txt", "text": "So this group that we're detaching basically must contain a terminal non reducing residue and we'll see exactly what that looks like in just a moment."}, {"title": "Branching of Glycogen.txt", "text": "So the glycogen branching enzyme detaches a group of seven or more glucose residues that contain a terminal residue and attach that group via an Alpha One Six glycocitic bond, somewhere on the interior of that particular glycogen molecule."}, {"title": "Branching of Glycogen.txt", "text": "Now, the branching enzyme actually requires two things."}, {"title": "Branching of Glycogen.txt", "text": "Firstly, it requires that the original glycogen chain on which we begin working on is at least eleven residues in length."}, {"title": "Branching of Glycogen.txt", "text": "And it also requires that it is placed at least four residues away from any preexisting branching point."}, {"title": "Branching of Glycogen.txt", "text": "And to see what all that means, let's take a look at the following hypothetical example."}, {"title": "Branching of Glycogen.txt", "text": "So let's suppose this is our initial glycogen molecule that we begin with."}, {"title": "Branching of Glycogen.txt", "text": "So we have all these Alpha One four glycocity bonds here."}, {"title": "Branching of Glycogen.txt", "text": "We have all these Alpha One four glycocitic bonds here."}, {"title": "Branching of Glycogen.txt", "text": "And this one bond here is the Alpha One six glycocitic bond."}, {"title": "Branching of Glycogen.txt", "text": "So this is our preexisting branching point."}, {"title": "Branching of Glycogen.txt", "text": "Now what the glycogen branching enzyme requires is the segment that it detaches must be around seven residues in length."}, {"title": "Branching of Glycogen.txt", "text": "So usually seven or more."}, {"title": "Branching of Glycogen.txt", "text": "So we have 123-4567 and one of these, this one here at the end is a terminal non reducing residue."}, {"title": "Branching of Glycogen.txt", "text": "What that means is on the fourth carbon it contains a free hydroxyl group."}, {"title": "Branching of Glycogen.txt", "text": "And so now what this enzyme does is it cleaves this Alpha One four glycocitic bond and it basically detaches this entire segment."}, {"title": "Branching of Glycogen.txt", "text": "Now what it does next is it basically attaches it via an Alpha 16 glycocitic bond somewhere around this region."}, {"title": "Branching of Glycogen.txt", "text": "But it must attach it so that it exists at least four residues away from that preexisting branch."}, {"title": "Branching of Glycogen.txt", "text": "So if we count, for example, 1234, it has to create it on the fifth one here, it has to be four full glucose residues away from that preexisting one."}, {"title": "Branching of Glycogen.txt", "text": "And so this is where we can hypothetically place that branching point."}, {"title": "Branching of Glycogen.txt", "text": "So now we have one, two, alpha, one, six glycocity bond so this is the process by which our cells are actually capable of synthesizing these glycogen molecules."}, {"title": "Oogenesis.txt", "text": "The female gonads are known as the ovaries."}, {"title": "Oogenesis.txt", "text": "And inside the ovaries, an important process known as Ogenesis takes place."}, {"title": "Oogenesis.txt", "text": "Now, Ogenesis is the process by which these special stem cells down inside female individuals known as Ogonium or Ogonia, if we're talking about many cells, basically differentiate and eventually develop into the female gamma meets the female sex cells known as X cells or ovum."}, {"title": "Oogenesis.txt", "text": "Now, an ovum is a single excel, but an OVA means many excels."}, {"title": "Oogenesis.txt", "text": "So the major difference between male individuals and female individuals is that in female individuals, all the primary oocytes are formed before that individual is actually born."}, {"title": "Oogenesis.txt", "text": "They are formed during fetal development."}, {"title": "Oogenesis.txt", "text": "So all these stem cells we call ogonia inside our developing fetus basically differentiate into the primary oocyte."}, {"title": "Oogenesis.txt", "text": "And this happens before the birth of that female individual."}, {"title": "Oogenesis.txt", "text": "So once that female individual is born, all these stem cells have become the primary oocytes."}, {"title": "Oogenesis.txt", "text": "And these primary oocytes are frozen."}, {"title": "Oogenesis.txt", "text": "They remain in ProPhase one of meiosis until puberty is reached."}, {"title": "Oogenesis.txt", "text": "And when that female individual reaches puberty, she begins the process known as the menstrual cycle."}, {"title": "Oogenesis.txt", "text": "And what the menstrual cycle describes is it describes the process by which the primary ocy eventually develops into that X cell, that single ovum that can be fertilized by the sperm cell to produce the zygote."}, {"title": "Oogenesis.txt", "text": "So when the female reaches puberty, a cycle begins known as the menstrual cycle, in which one primary oocyte will eventually undergo meiosis one to produce a secondary oocide which will remain frozen in metaphase II of meiosis until the process of fertilization."}, {"title": "Oogenesis.txt", "text": "And during fertilization, meiosis II will be completed and aromature ovum, the excel, will be formed."}, {"title": "Oogenesis.txt", "text": "So to see exactly what we mean by that, let's take a look at the following diagram."}, {"title": "Oogenesis.txt", "text": "So this diagram describes a cross section of the ovary."}, {"title": "Oogenesis.txt", "text": "So this is one of the ovaries of that female individual that has reached puberty."}, {"title": "Oogenesis.txt", "text": "So let's suppose this is the ovary."}, {"title": "Oogenesis.txt", "text": "This is our attachment point to the uterus and this is our fallopian tube which acts as a passageway to carry that oicide, that ovum from the ovary into the uterus."}, {"title": "Oogenesis.txt", "text": "And if fertilization takes place, we form the zygote."}, {"title": "Oogenesis.txt", "text": "When the sperm cell combines with the ovum and that zygote is implanted onto the wall, onto the lining of the uterus known as the endometrium."}, {"title": "Oogenesis.txt", "text": "So let's focus in on this ovary."}, {"title": "Oogenesis.txt", "text": "Inside the ovary we have these blood vessels, the arteries that carry nutrients and oxygen to the cells of the ovary."}, {"title": "Oogenesis.txt", "text": "And we have the veins, the blue vessels that carry away the waste products and carbon dioxide and ammonium away from the cells of the ovary."}, {"title": "Oogenesis.txt", "text": "Now let's focus in on the following pathway that basically describes the maturation, the development of that primary oicide into that ovum."}, {"title": "Oogenesis.txt", "text": "So because we're assuming this female individual has been born, that means all these oocides are now primary oocides."}, {"title": "Oogenesis.txt", "text": "All the Ogonia differentiated into primary oocides."}, {"title": "Oogenesis.txt", "text": "Now, these oocides, the primary oocides, do not exist as individual cells."}, {"title": "Oogenesis.txt", "text": "Instead these Oocides are found inside these fluid filled structures known as Ovarian follicles."}, {"title": "Oogenesis.txt", "text": "So an Ovarian follicle is the fluid filled structure found inside the Ovary that contains not only that developing Oicide but it also contains important cells, other different types of cells that also assist in the process of ogenesis."}, {"title": "Oogenesis.txt", "text": "And we'll discuss what these other cells are in just a moment."}, {"title": "Oogenesis.txt", "text": "So we have the primary follicle that contains the diploid primary Oocide."}, {"title": "Oogenesis.txt", "text": "And the primary follicle during the process, during the menstrual cycle will eventually develop into the secondary follicle."}, {"title": "Oogenesis.txt", "text": "And the secondary follicle is much larger because it contains much more fluid, it contains many more cells and it also contains the secondary Oocide."}, {"title": "Oogenesis.txt", "text": "So the primary follicle contains the primary Oocide which is a diploid cell."}, {"title": "Oogenesis.txt", "text": "And then we have the secondary follicle that contains the secondary Oocide which is a haploid cell."}, {"title": "Oogenesis.txt", "text": "So primary Oocide undergoes meiosis one to produce the secondary Oocide as well as another cell known as a polar body."}, {"title": "Oogenesis.txt", "text": "And this is the first polar body that is formed."}, {"title": "Oogenesis.txt", "text": "Now, the secondary Oocide contains the majority of the cytoplasm that came from the primary Oocide but the polar body only obtained a very small amount of that cytoplasm."}, {"title": "Oogenesis.txt", "text": "In fact, the polar body will essentially degenerate and the body will recycle this polar body and use its contents for other things."}, {"title": "Oogenesis.txt", "text": "So basically the polar body doesn't actually develop into anything useful, it's the secondary Oicide that develops into that excel."}, {"title": "Oogenesis.txt", "text": "So we have a haploid secondary Oocide found inside that secondary follicle."}, {"title": "Oogenesis.txt", "text": "Now let's actually focus on the structure of that secondary follicle and let's take a look at the following diagram."}, {"title": "Oogenesis.txt", "text": "So we have the secondary Ovarian follicle as shown."}, {"title": "Oogenesis.txt", "text": "Now notice the actual secondary Oocide is found in the following region."}, {"title": "Oogenesis.txt", "text": "It's actually a small component of this entire follicle because around that cell we have other components."}, {"title": "Oogenesis.txt", "text": "We have these green cells which are known as granulosa cells and we have these orange cells known as the Thicka cells and we also have this fluid found inside."}, {"title": "Oogenesis.txt", "text": "Now, what exactly is the function of the granulosa cells and our FECA cells?"}, {"title": "Oogenesis.txt", "text": "Well, it turns out that the FECA cells are stimulated by a hormone produced in our body known as the luteinizing hormone LH."}, {"title": "Oogenesis.txt", "text": "And what the luteinizing hormone does is it stimulates the FECA cells to basically transform cholesterol into androgens."}, {"title": "Oogenesis.txt", "text": "And then these androgens are released into the grainylosis cells and the follicle stimulating hormone also produced inside our body stimulates these granolosis cells, the green cells to transform androgen by using a special type of enzyme into a type of sex steroid hormone known as estrogen."}, {"title": "Oogenesis.txt", "text": "And we have different types of estrogen."}, {"title": "Oogenesis.txt", "text": "Now, what exactly is a function, what's the purpose of estrogen?"}, {"title": "Oogenesis.txt", "text": "Well, what estrogen basically does is it thickens, it increases the layer of the wall of the uterus, it increases the size of the endometrium and it prepares the endometrium for implantation by the zygote if fertilization actually takes place."}, {"title": "Oogenesis.txt", "text": "So what that means is if that excel fuses with the sperm, eventually the zygote that is formed will make its way into the uterus and it will implant itself into that endometrium."}, {"title": "Oogenesis.txt", "text": "And what estrogen does is it ensures that the endometrium is just the right layer, it's just the right thickness."}, {"title": "Oogenesis.txt", "text": "So basically, we have this secondary follicle."}, {"title": "Oogenesis.txt", "text": "And eventually what happens to our secondary follicle is it approaches this side of the membrane of the ovary and it ruptures."}, {"title": "Oogenesis.txt", "text": "It essentially ruptures, releasing that secondary oicide into this area, which eventually this area is known as the peritonal canal or the peritonal cavity."}, {"title": "Oogenesis.txt", "text": "And then from the peritonal cavity, that secondary oicide goes directly into that fallopium two."}, {"title": "Oogenesis.txt", "text": "And now the secondary ocyte, which by the way, is still in metaphase II of meiosis, will begin to travel along our philopium two."}, {"title": "Oogenesis.txt", "text": "Now, notice that the remaining cells that came from the secondary follicle remain in our ovary."}, {"title": "Oogenesis.txt", "text": "And the remaining portion of that secondary follicle will eventually develop into a structure known as the corpus luteum."}, {"title": "Oogenesis.txt", "text": "And the corpus luteum is essentially an endocrine gland that continues to release different types of hormones that are responsible for maintaining the thickening, the thick layer of that endometrium inside the uterus."}, {"title": "Oogenesis.txt", "text": "And this is in the case that when the sperm cell fuses with the XL, we form the zygote and the zygote eventually implants onto the uterus."}, {"title": "Oogenesis.txt", "text": "Now, if there is a sperm cell found inside our philopium tube, it basically combines it fuses with our secondary OSI."}, {"title": "Oogenesis.txt", "text": "And as soon as the interaction between the sperm cell and the secondary OASI takes place, as soon as contact takes place, our secondary OSI and metaphase two of meiosis will finish meiosis two and it will form the mature ovum, the mature xcel."}, {"title": "Oogenesis.txt", "text": "And at that point, the membrane of the two cells fuses, the nuclei essentially fuse and the diploid number of that organism is restored."}, {"title": "Oogenesis.txt", "text": "So the sperm cell contains a haploid number, 23 chromosomes that came from the male parent."}, {"title": "Oogenesis.txt", "text": "And the xcel contains a haploid number 23 chromosomes that came from the female parent."}, {"title": "Oogenesis.txt", "text": "And so once they fuse, the nuclei fuse as well."}, {"title": "Oogenesis.txt", "text": "So 23 plus 23 and we form a diploid number, 46 chromosomes."}, {"title": "Oogenesis.txt", "text": "So this is an important point to remember that our xcel actually remains in metaphase two until the fusion of the sperm cell and that XL takes place."}, {"title": "Oogenesis.txt", "text": "And only during fertilization does our xcel finish meiosis."}, {"title": "Oogenesis.txt", "text": "And only then do we actually, actually form that mature ovum, that mature ex cell."}, {"title": "Oogenesis.txt", "text": "And when fusion takes place, fertilization takes place, we form the zygote."}, {"title": "Oogenesis.txt", "text": "And the zygote eventually travels into the uterus and it implants itself onto the endometrium, the wall lining of that uterus."}, {"title": "Oogenesis.txt", "text": "And then the embryological development process initiates."}, {"title": "Tertiary Structure of Proteins .txt", "text": "The tertiary structure of a polypeptide refers to the spatial arrangement of the amino acids that are found far away from one another in that polypeptide chain."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, said another way, the poly, the tertiary structure of the polypeptide is simply the three dimensional arrangement of atoms, the three dimensional shape that the polypeptide chain will take within in its local environment."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, the next question is what exactly are the factors, what are the interactions that play a role in creating and forming that tertiary structure of the polypeptide?"}, {"title": "Tertiary Structure of Proteins .txt", "text": "So by far the most important factor, the driving force that forms the tertiary structure, is the hydrophobic effect and hydrophobic interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, that's because the majority of the proteins inside our body and inside our cells fold and create the tertiary structure in an aqueous solution, in a solution where water is the dominant solvent molecule."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, we also have vanderballs interactions, disulfide bridges, hydrogen bonds and ionic interactions that also play a role in forming the tertiary factor."}, {"title": "Tertiary Structure of Proteins .txt", "text": "But the hydrophobic effect is that predominant force."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So, as I mentioned earlier, most proteins exist in aqueous solutions and most proteins form in aqueous solutions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And what that basically means is we have the hydrophobic effect that takes place."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So remember, what the hydrophobic effect tells us is if we take non polar molecules, hydrophobic molecules, and place them into a solution where water is that dominant molecule, because water is a polar molecule, what will happen is we'll find that those non polar molecules will basically aggregate together to form larger systems, larger chunks of nonpolar molecules."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And that's because that system that is formed is thermodynamically stable."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, what does that have to do with the folding of the proteins and the formation of the tertiary structure?"}, {"title": "Tertiary Structure of Proteins .txt", "text": "So remember that proteins are polypeptides, consist of 20 different types of amino acids."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And these amino acids differ from one another based on their side chain group."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So we have different types of side chains."}, {"title": "Tertiary Structure of Proteins .txt", "text": "We have non polar side chains, which are hydrophobic, and we also have polar side chains, which are hydrophilic."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So it turns out if we take our polymer of amino acids, if we take the polypeptide and place it into an aqueous solution, the hydrophobic effect and hydrophobic interactions will take into effect."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And what that means is all those amino acids that contain the nonpolar hydrophobic groups, for example, Valine, Alanine, Leucine, isolucine, methionine, Tryptophan, phenylalanine, and so forth, all these different non polar side chains will end up aggregating together in the core at the center of that protein."}, {"title": "Tertiary Structure of Proteins .txt", "text": "While all those amino acids that contain the polar side chains, for example Lysine or Arginine, Aspartate, and so forth, all these charged and polar amino acids will be found on the surface of that protein."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So this is what we mean by the hydrophobic effect, essentially dictating the way that the tertiary structure is actually formed."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So let's suppose, let's take a look at the following diagram."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So, in this diagram, we have our protein."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So let's suppose that these red regions here are hydrophobic regions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So let's label these as hydro."}, {"title": "Tertiary Structure of Proteins .txt", "text": "That is not spelled correctly."}, {"title": "Tertiary Structure of Proteins .txt", "text": "One moment."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So we have these hydrophobic red sections, and these blue sections here are hydrophilic."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So remember, hydrophilic is water loving and hydrophobic is water hating."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So what happens is when we place them into a solution that contains water as a solvent."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So these are the water molecules here."}, {"title": "Tertiary Structure of Proteins .txt", "text": "These blue sections will tend to point on a surface, lie on the surface, while these red sections, these amino acids that contain hydrophobic side chains, will tend to aggregate at the center and form the core of that protein."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So a protein in an aqueous environment will have a hydrophobic core and a hydrophilic surface."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, if we go into that core, inside that core, we have many of these hydrophobic nonpolar side chains that are packed together."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, what types of interactions will we find between those non polar side chains?"}, {"title": "Tertiary Structure of Proteins .txt", "text": "Well, the interactions are known as London Dispersion Forest."}, {"title": "Tertiary Structure of Proteins .txt", "text": "It's also known as Van der Valal interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And these are the interactions that exist between the instantaneous dipole moments on those non polar side chains."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And even though on an individual basis, these instantaneous dipole interactions might be very weak, because we have many of these non polar side chains in the core, we have many of these vandervals interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And that aggregate creates a relatively substantial effect that binds those amino acids in the core together and holds them in place so that they are away and don't interact with the water molecules found in close proximity outside of that protein."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, these interactions are inter molecular interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "What about intramolecular interactions?"}, {"title": "Tertiary Structure of Proteins .txt", "text": "So we also have a specific type of intramlecular interaction, a covalent bond that can also dictate that tertiary structure."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And these are known as disulfide bridges or disulfide bonds."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So it turns out that if we have 215 amino acids that are in close proximity, if an oxidation reaction takes place, we can form a covalent bond between our sulfur groups."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So basically, an oxidation reaction takes place."}, {"title": "Tertiary Structure of Proteins .txt", "text": "We take away this H atom, this H atom."}, {"title": "Tertiary Structure of Proteins .txt", "text": "We take away two electrons, and we form the following single covalent bond between the two sulfurs."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And this is known as a disulfide bond or a disulfide bridge."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So some proteins, specifically those proteins that are destined to be in the extracellular environment, these polypeptides, can be cross linked by these disulfide bonds."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And once we form the unit of these two cystine molecules, that is known as acsteine."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So this spelling and this spelling are not the same."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So this is pronounced cystine."}, {"title": "Tertiary Structure of Proteins .txt", "text": "This is pronounced cysteine."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So we have the hydrophobic interactions that basically drive the formation of that tertiary structure."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And then that hydrophobic core is held together by Van der Valle's interaction."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And we can also have a special type of covalent bond known as the disulfide bridge that also holds our structure together."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So here we have one disulfide bond, a second disulfide bond, and a third disulfide bond between these 15 amino acids."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, we can also have hydrogen bonds, and we can have ionic interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, if we examine those polar molecules on the surface, the side chains of those polar amino acids can basically interact and form hydrogen bonds with the water molecules that are found in close proximity, and that can stabilize the structure, the tertiary structure of our polypeptide."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And finally, we can also have ionic interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "Now, remember, certain amino acids contain side chains that carry a full charge."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So some amino acids contain side chains that carry a positive charge."}, {"title": "Tertiary Structure of Proteins .txt", "text": "For example, Lysine and arginine, these carry a full positive charge on their side chain."}, {"title": "Tertiary Structure of Proteins .txt", "text": "We also have acidic amino acids, and these are the amino acids that carry a full negative charge on their side chain."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And so, for example, if we have the amino acid Lysine, that contains a positive charge on a side chain, is in close proximity with our amino acid Aspartate, which contains a full negative charge on that particular side chain."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And if these two are close enough, they can form an ionic bond."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And that ionic bond can also stabilize the tertiary structure of that polypeptide."}, {"title": "Tertiary Structure of Proteins .txt", "text": "So we conclude that the tertiary structure of that polypeptide, although IoT, is affected by many different factors, the main driving force that leads to the formation of our tertiary structure of that polypeptide are these hydrophobic interactions."}, {"title": "Tertiary Structure of Proteins .txt", "text": "And that's because the majority of these proteins are folded in an aqueous solution, in a solution that contains water as that dominant solvent molecule."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Previously in our discussion on the Edmund degradation process, we alluded to the fact that the admin degradation process has its limitations."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So although it's a very useful process, we cannot use the admin degradation under certain circumstances."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we said that if our polypeptide is over 50 amino acids in length, we basically cannot use this process as now the question is why?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Well, the answer is simple."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Just like many processes in nature, the Edmund degradation is not a perfect process and sometimes it does make a mistake, it does create an error."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So it turns out that the Edmund degradation process in some cases does not release that amino acid, the first amino acid in that polypeptide chain."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now to demonstrate how this can be a problem, to demonstrate how this affects accuracy of our procedure, suppose that the efficiency of a single admin degradation process is 97% and that's a high value."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what that means is every time the Edmund degradation process takes place, there's a 97% chance that the process will take place correctly."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We will label that initial amino acid and then release that amino acid."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now this isn't a problem when we have relatively small quantity of amino acids, but what happens if we have, let's say, 50 amino acids in our protein?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we want to calculate mathematically what the probability is of determining the correct sequence by using the ethnic degradation process for protein with 50 amino acids."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So there should be an O after this N. So here we have our amino acid, so here we have our protein, we have amino acid number 1234, we have five, six, seven, not shown all the way to 49 and then 50."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So if we carry out the Edmund degradation process on this entire polypeptide, what is the probability that we're going to obtain a correct sequence of amino acids?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Well, to calculate this probability we simply have to multiply the individual probabilities of each one of those processes."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have zero 97 for the first process, zero 97 for the second process, zero 97 for the third process and so forth all the way to the 50th process when we basically release this final amino acid."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so we have zero point 97 to the 50th power and that gives us about zero point 22 and that is equivalent to a 22% likelihood."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So that's a relatively small likelihood."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what that means is there is a 78% chance that our sequence will not be the correct sequence of amino acids."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so we can see mathematically that's exactly why we cannot use the eggman degradation process on very long polypeptides."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what we conclude is even though the admin degradation process is a very useful process when our amino acids are very short, it becomes pretty inaccurate pretty quickly when our amino acid, when our amino acid number increases in that polypeptide."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So how do we solve this problem?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Well, the way that we solve the problem is if we have a long polypeptide, we divide that polypeptide, we cut up that polypeptide into very small fragments by using special types of molecules and biological enzymes."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so once we cut up the polypeptide into these fragments, we can then isolate and separate those fragments by using some type of purification technique, for example gel electrophoresis."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And then we can use the Edmund degradation process on those individual small fragments."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Because we just saw that if we have a small fragment, then we can use the Edmund degradation process, for example, to demonstrate that, let's calculate what the likelihood is of our sequence being correct."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "If our amino acid, if our protein or fragment, let's say is ten amino acids in length."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So all we have to do is basically multiply."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Let's see if my iPhone has the option to multiply to zero 97, we want to raise to the power of ten."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so this gift no, that is not it."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Try it again."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "No, zero point 97 to the power of, let's say ten."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Okay, so if the likelihood that our administration is process is correct is 97% and we raise that to the power of ten, that gives us so point 97 to the power of ten is about 74% likelihood that it's correct."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what that means is if we break down the polypeptide into small fragments, the likelihood of it being correct increases tremendously."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so that's exactly what we normally have to do."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So to solve the problem, we can cleave the protein into many smaller fragments and then use the Edmund degradation process on each individual process."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So let's suppose we have the following polypeptide."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we take that polypeptide, we mix it with some type of molecule that cleaves those peptide bonds."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so for example, if you use a specific type of biological enzyme, for example, let's say we cleave it in this position and in this position."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so we produce fragments A, B and C. Now we can separate the fragments, for example, based on size by using SDS polyacrylamide, gel electrophoresis."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so what that does is it allows us to isolate these three different fragments and then we can use the Edmund degradation process on each one of these fragments individually."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so for example, for fragment one, once we carry out Edmund degradation, we know that for example, this is amino acid 12345 and six."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now we carry the same process out with fragment B."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We know this is fragment one, two, three and four in that order."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And then for C we have 12345."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now what we don't know is what the order of these fragments is."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So if the order, for example, A plus B plus C, so if this is A, fragment A and B and C, do we actually order them in this way?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Or is it, for example, A, C and B?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So once we determine the specific sequence of amino acids in that in each segment, we still need to actually determine what the order of those segments is with respect to one another."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now, the question is, how do we determine what the correct order is?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now, before we look at that, let's take a look at the following chart or table."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "What the table basically tells us is it gives us some of these examples of these chemicals or biological enzymes that are capable of cleaving our peptides at specific amino acid sequences."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "For example, we have a special molecule, a chemical known as Cygn bromide."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And what it does is it cleaves our peptide at the carboxyl side of methionine amino acids."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "For trypsin."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "This is a biological molecule that is found in our digestive system."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And what trypsin basically does is it cleaves our peptide at a specific site."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So at the carboxyl side of Lysine and Arginine are two basic amino acids."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We also have chimotrypsin and chimotrypsin cleaves at the carboxylan of tyrosine, methionine, phenylalanine, tryptophan, and leucine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So basically, if we have some type of amino acid that contains an aromatic ring, this is our protein enzyme that cleaves it."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And finally, another example is thrombin."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And this is found in our blood clotting cascade."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what thrombin does is it cleaves at the carboxyl side of arginine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And we have many, many more examples of such biological enzymes in our body as well as in other organisms."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So let's go back to this question."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Once we know what the sequence is of these individual segments, how do we order those segments together?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what we have to do is so we take this polypeptide and we first expose it to one type of cleaving agent, and then we take that same polypeptide again and we expose it to another different type of Cleaving agent."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So once we expose it to these two different cleaving agents, we have two sets of fragments."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And then we can use the overlapping regions of those fragments to basically piece the information together, just like in a puzzle."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So to see exactly what we mean by that, let's take a look at the following example."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So, in this example, we have some type of polypeptide."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And when we take the polypeptide and we expose it to Trypsin, we get these two fragments."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now we take that same polypeptide in its full polypeptide form, and we now expose it to chimetrypsid, and we get three fragments that look like this."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So what we basically want to do is so assuming that we actually use the Edmund degradation process on each one of these fragments, so we know exactly what the sequence is."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now, what we want to do is we want to piece these fragments together."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We want to find what the correct order is of these fragments by using these overlapping regions."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Now, what do I mean by overlapping regions?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Well, notice I have Valine and then I have Arginine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And the only time I have valine and Arginine in this section is right over here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So I have Valine, and I have Arginine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So I have Valine, then Arginine, and then essentially, it cuts off here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "But in this case, according to this fragment, we have Glycine, glycine, then tryptophan and so forth."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So if we have Valine, Arginine, and then it cuts off, and the Glycine glycine tryptophan begins on this side, then what that means is this Arginine should be balanced at this Glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And we were able to determine that by piecing these overlapping regions together."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So let's see exactly what we mean by that by putting it in the following."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We have glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Glycine?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So let's see."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We have serine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We have phenylalanine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We have Valine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Then we have arginine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And then the second piece here is Glycine Glycine tryptophan."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Then we have Alanine, and we have Lysine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Okay, so that's segment number one."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So if we just carry out this procedure here, we don't know if this comes first or if this comes first, right?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We don't know if it goes here or if it goes here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "But this information allows us to basically determine which one goes where."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So let's look at this section here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have Valine, Arginine, which basically appears here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have Valine, we have Arginine, and then we have, if you continue, Glycine glycine tryptophan."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Again, glycine glycine and tryptophan."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Okay?"}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so what these overlapping regions tell us is there should be a bond in this section here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So there should be a bond connecting Arginine and Glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And by using this region here and this region here, we can basically determine where these two fragments go."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So Serene and Phenylalamine should basically go here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And Alanine Lysine should basically go here."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we have our Serine, Phenylalanine, and then here we have Alanine, Lysine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And so the final sequence is so we have Serine, Phenylalalanine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Then this should connect."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Valenine arginine glycine glycine."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Then we have tryptophan and then Alanine and lysine So this is exactly what we mean by using the overlapping regions."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "After we expose our polypeptide to not just one proteolytic enzymes, but several proteolytic enzymes to basically determine what the order of our segments are."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So step number one is we take the long polypeptide."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We essentially cleave it with these different types of proteolytic enzymes and proteolytic molecules."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "We produce these segments."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Then we essentially isolate the segments by using some type of purification method."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "Once we isolate them, we use the Edmund degradation process to sequence them so that we know exactly what the sequence is in each one of our segments is."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "And then we use the overlapping region information to basically determine how those segments should be arranged with respect to one another."}, {"title": "Sequencing Amino Acids by Proteolytic Cleavage .txt", "text": "So we see that even though the admin degradation process does not actually work on very long polypeptides, if we simply cleave the polypeptides into these small fragments, we can then use that process, the Admin degradation process, successfully to determine what the sequence of our polypeptide is."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "In the previous lecture, we discussed the Epinephrine signal transduction pathway, and we finished off by saying the following when a cell uses the Epinephrine signal pathway, it must be able to actually turn off that pathway at the right."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Moment in time."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Because if it can turn off that pathway, that will lead to many different types of negative effects, as we'll discuss in the future lecture."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So what I'd like to focus on in this lecture is I'd like to answer the following question."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So, once that Epinephrine signal transduction pathway actually carries out its ultimate goal of producing that specific type of physiological response due to some type of stimulus, how is it that the cells can actually shut down this pathway?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "What methods can they actually use to shut down this Epinephrine signal pathway?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Well, basically, there are two points in the Epinephrine pathway that the cell can actually use and shut down that pathway."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So we have point A and point B."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And let's begin our discussion by focusing on point A."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So in point A, we basically have that alpha G protein adenylit cyclist complex."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And when this complex exists, as shown, that adenylate cyclists will basically continue transforming the ATP molecules into the cyclic Amp molecules, which are the secondary messengers in this Epinephrine pathway."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So ultimately, what causes the alphagy protein to actually bind and stimulate that adenylate cyclist?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Well, basically, it's the GTP."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "When the GTP Guanosine triphosphate is bound onto that AlphaG protein, it increases its affinity for that adenolid cyclist."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so it goes on and binds until special site found on the intracellular portion of this cyclist."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And once it binds, it increases its catalytic activity and causes it to basically transform the ATP into the cyclic adenosine monophosphate molecules."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So ultimately, what the cell has to do is somehow remove the GTP and bind the GDP Guanosine diphosphate."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Because once the Guanosine diphosphate binds onto the alphagy protein, that will cause a decrease in the affinity of the alphagy protein for that cyclist and that will cause it to actually detach, terminating this cyclist's ability to form those cyclic adenosine monophosphate molecules."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So it turns out that this alphagy protein actually has a built in timer."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "A few seconds to a few minutes following the activation of the alphae protein by the attachment of the GTP, the alphagy protein itself can actually take a water molecule from the cytoplasmic environment and use that water molecule to hydrolyze the GTP back into GDP."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And as soon as that takes place, as soon as we replace the GTP in place a GDP, that will decrease the affinity of the alphagy protein for the cyclist, causing it to dissociate from that cyclist."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And once it dissociates, it goes out and finds those beta and gamma units to basically reform this primer molecule."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And once it detaches, that inactivates that adenylate cycling."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So once again, as long as that GTP is bound to the alphagy protein, that alphagy protein will remain attached to that adenylate cyclist, which will in turn continue producing those cyclic adenosine monophosphate molecules."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So if that G protein is to detach from that cyclase, the GTP must be transformed into GDP."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And it turns out that the alphagin has something we call Gtpa's activity, the ability to actually take a water molecule and hydrolyze that GTP into GDP."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Now, this hydrolysis doesn't take place immediately after activation of that alpha G protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And that's because we want to give that alpha G protein the cell wants to give that alphagy protein some time to actually carry out its function before being activated."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so the hydrolysis usually occurs within a few seconds to a few minutes after the alphagy protein is activated."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And this gives us plenty of time to actually carry out its function."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so, to summarize, let's take a look at this diagram."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So we have the inactive version of adenylit cyclase."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "To activate it, we basically take that GTP form of the G protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "It goes on and binds, and that stimulates that cyclist to produce those cyclic amp molecules."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "After a few seconds to a few minutes, once the signal pathway basically carries out its physiological response, what happens is, because of this internal GTase activity, it takes a water molecule from that cytoplasm."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And we have plenty of water molecules in a cytoplasm."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So it's never a problem."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "The water molecule is taken and basically is used to hydrolyze the GTP into GDP."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so we release a single phosphate molecule."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so once this is formed, the affinity of the G protein decreases for that adenocyclase, it basically dissociates and goes on and finds that dimer to form this trimmer protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Now, let's move on to diagram B."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So this is the second site, the second point in the pathway where the cell can actually deactivate, shut down that pathway, and this is when that epinephrine is bound onto the site on the beta adrenergic receptors."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So what is the function of this structure?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Well, basically the epinephrine receptor complex actually is used to stimulate the transformation of the GDP alphagin form into the GTP alphagin form."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And the question is, how can the cells inactivate the epinephriceptor complex and prevent any further activation of the alpha G proteins?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So there are two different ways."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Let's begin by discussing this pathway here."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So one very simple way to actually deactivate this particular structure is for the epinephrine to actually be released, for the epinephrine to simply dissociate."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So if the epinephrine dissociates from that site, as shown in this diagram, what that does is it basically inactivates the ability of this beta receptor to basically activate the alphagy proteins."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And if the alphagy proteins cannot be activated, they cannot go on and activate those adenylus cyclaces."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Now, under what conditions will the epinephrine actually dissociate?"}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Well, let's use a bit of chemistry."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Let's discuss Lusciously's Principle."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So, according to Lucid Liar's principle, if the concentration of the free epinephrine molecules found in the surrounding area decreases."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "To basically compensate for that decrease in the free floating epinephrine concentration."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "We know that the epinephrine that is bound will begin to dissociate and we see that this process takes place with great likelihood only when that epinephrine, the free epinephrine concentration is low."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So one method of inactivation involves the epinephrine actually dissociating out of that cavity."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Of that seven TM receptor shown here, this is the cavity and this is a seven TM receptor."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "Now, when the epinephrine concentration drops in the outside bind lashes layers principle to basically compensate for that drop in concentration of the free epinephrine, that epinephrine that is bound actually dissociates."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So if we have a high concentration of epinephrine in that extracellular environment in its free form, it will not be likely to dissociate."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And that's why we actually have to depend on this second method."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So in the second method we have a special protein kinase we call the beta Adrenergic receptor kinase and it's basically a kinase protein which means it uses ATP to actually add or phosphorylate that particular protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So the beta Adrenergic receptor kinase uses ATP to actually phosphorylate the carboxyl terminal side of this protein which is found on the intracellular side."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "And so we essentially add these negatively charged phosphate groups onto this structure and that decreases its affinity to basically go on and activate these alphagy proteins."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "On top of that, we have a second type of molecule, a protein we call beta arrestin that goes on and binds to these phosphate groups and that further decreases the ability of these complexes, the epinephrine receptor complex, to actually activate those alphagy proteins."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So in a second mode of inactivation, the beta Adrenergic receptor kinase basically phosphorylates the carboxylic terminal end of that ethanephone receptor complex on the intracellular side of that protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So this protein kinase uses ATP to put asphorylated and then the beta arrestin binds onto these phosphate groups and that inactivates the receptor's ability to stimulate those alphagy proteins to basically transform the GDP into the GTP form of that alpha g protein."}, {"title": "Termination of Epinephrine Signaling .txt", "text": "So these are the different ways by which the cells that use the epinephrine pathway can actually deactivate or shut down the pathway from and thereby preventing different types of negative side effects as we'll discuss in Electra to Come."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "When a blood vessel of our cardiovascular system is injured for instance we have a rupture in the wall of that blood vessel the process of hemorrhage will take place."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And hemorrhage is the medical condition that describes the process by which blood escapes out of the cardiovascular system and into the surrounding area found outside the blood vessel."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, hemorrhage can be very dangerous."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It can cause cause damage to the tissues and organs of our body."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And so to prevent hemorrhage from actually taking place and causing damage we have the blood clot in cascade that is immediately initiated."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And when the blood clot in cascade is initiated we produce these blood clots and the blood clots are used to create temporary seals along that area where the cut actually exists on that blood vessel."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So we know that blood clots can be very, very beneficial."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "But on the other hand, if we form too many blood clots or if we can't break down the blood clots properly or if those blood clots escape that localized area where that injury took place that can lead to many, many problems."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, one problem is thrombosis."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So thrombosis is basically the process by which we form the blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And if these blood clots are formed excessively they can basically escape into the cardiovascular system and eventually they can aggregate at the wrong place and that can block the flow of blood."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And this is known as an embolism."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So an embolism is the process by which these blood clots aggregate abnormally and they block that flow of blood to some area, some tissue or some organ of our body."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And that can lead to many problems."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "For instance, if we have an embolism that takes place in the coronary artery that can lead to a heart attack and obviously, a heart attack is very, very dangerous."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So there is a very, very fine line between thrombosis and hemorrhage."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And to prevent either one of these from taking place and damaging our organs and tissues our body must be able to very precisely and very effectively regulate the coagulation cascade."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And so previously, we discussed the activation of this process."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now we're going to discuss the inhibition."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So how exactly do we down regulate and inhibit the different enzymes involved in the coagulation cascade process?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So this is what we're going to focus on in this lecture and we're going to discuss several important key factors that inhibit the enzymes that are part of the coagulation cascade."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So let's begin with the molecule known as tissue factor pathway inhibitor or simply TFPI."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, this is a polypeptide."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And what the polypeptide does is it ultimately binds onto a complex that is part of the extrinsic pathway of the blood clotting cascade."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So if we think back to the blood clotting cascade we have these two different pathways."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "We have the intrinsic and the extrinsic pathway and this polypeptide blocks essentially that extrinsic pathway from taking place."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So in the extrinsic pathway, we have the tissue factor."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "The glycoprotein found on the membrane of the endothelium of the blood vessel basically forms a dimer complex with factor seven."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And once we form this complex, this complex then reacts with factor ten to basically activate it and begin the final common pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, what the tissue factor pathway?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "What the tissue factor pathway inhibitor does is it binds unto the tissue factor, factor seven complex, and it inhibits its activity."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And it also has domains on this polypeptide that can bind onto the individual factor seven, and that factor ten, and it can inhibit both of these different molecules."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, what about our intrinsic pathway?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So let's take a look at protein C. Protein C is a vitamin K dependent protease."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And what that means is it depends on the presence of vitamin K to actually effective correctly, to actually function correctly and effectively."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So if we don't have vitamin K, if we have a vitamin K deficiency in our body, that will basically mean that protein C cannot actually function properly."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, protease basically means when it acts with its target molecule, it hydrolyzes, it breaks the peptide bonds at specific sites on the target molecule."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So protein C is a protease, meaning it digests its target molecule."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So protein C, interestingly, is actually activated by thrombin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And thrombin is that very same molecule that is used to actually form fibrin from fibrinogen."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And fibrin is used to form the blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So thrombin has a dual purpose."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It not only actually forms the blood clots, but it also is responsible for inhibiting the coagulation process by activating protein C, because what protein C does is it breaks down and digests two important stimulating proteins, part of that coagulation cascade, namely factor five and factor eight."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, factor five, if we remember from the previous several lectures, is basically that stimulating protein that binds onto factor ten and that activates thrombin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "On the other hand, we have factor eight, which is also known as the antihemophilic factor."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And this is responsible for binding onto factor nine, which activates factor X into its active form."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So protein C is responsible for essentially inhibiting the intrinsic pathway, while tissue factor pathway inhibitor is responsible for inhibiting the extrinsic pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So now let's take a look at another important molecule that acts as an irreversible inhibitor to thrombin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And this is antithrombin three."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So antithrombin three is a glycoprotein whose structure actually resembles the structure of an inhibitor we spoke about previously, alpha one antitrypsin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So if you remember, alpha one antitrypsin is that irreversible inhibitor that inhibits elastase as well as trypsin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Well, in the same exact way, antithrombin three basically binds to the acticide and inhibits the activity of thrombin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And by inhibiting thrombin, we basically inhibit the final common pathway and we inhibit the formation of blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, antithrombin three can also form complexes with many other factors."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So if we think back to the intrinsic pathway, we know that intrinsic pathway contains factor twelve, factor eleven, factor nine, and these three factors can also be inhibited by antithrombin three."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And antithrobin three can also inhibit factor ten, which is basically that converging point between the extrinsic and the intrinsic pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It's the beginning of that final common pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So we see that antithrombin three is a glycoprotein that resembles the structure of alpha one antitrypsin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now it binds with very high affinity to thrombin and it activates its activity and it also blocks it forms complexes with other factors of the intrinsic pathway and the final common pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So we have factor twelve, we have factor eleven and we have factor nine that are part of the intrinsic pathway and then we have the factor ten which is basically the initiation of the final common pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It's that factor that is part of that converging point between the intrinsic and the extrinsic pathway."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now let's move on to heparin and heparin cofactor two."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So heparin cofactor two is actually a molecule that enhances the activity of heparin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So let's begin by discussing what heparin actually is."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So if we examine the connective tissue found surrounding our blood vessels we're going to find immune cells known as mast cells."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So mast cells are these immune cells, part of our adaptive immune system which basically release an important glycos aminoglycan known as heparin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And heparin is this negatively charged glycos aminoglycan that basically enhances the activity of antithrombin three."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It stimulates antithrombin three to basically form these irreversible inhibited complexes with not only thrombin but all these other factors."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So factor twelve, factor eleven, factor ten and factor nine."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So heparin acts as an anticoagulant by stimulating the binding of antithronbin three to thrombin and the other serum proteases, these ones that we mentioned just a moment ago."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now what do we mean by anticoagulant?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Well, the process of coagulation means to form the blood clot."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So anticoagulation means to not form the blood clots and that's exactly what the heparin does."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "It stimulates antithrobin three to basically inhibit the activity of throbin which means we cannot form those blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And as I mentioned a moment ago, heparin or heparin cofactor two is basically this protein that floats around our plasma, the blood plasma, and it basically assists heparin to basically bind onto the antithrombin three to inactivate inhibit the activity of thrombin."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So everything we spoke about up to this point basically involved actually inhibiting these specific enzymes and proteins that are found within the coagulation cascade."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "But the next question is, once we actually form those blood clots, once we actually form those fiber and mesh like structures we call blood clots, that actually seals off and creates that temporary protective layer that prevents hemorrhage, what actually happens to the blood clots once the cells actually once the cells actually fix that ruptured area in that blood vessel?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So blood clots are temporary solutions to sealing off ruptures in the blood vessels."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And once those ruptures are fixed by the cells of our body."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "How exactly does our body actually remove and digest these blood clots?"}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Because of these blood clots must actually be hydrolyzed, digested and broken down by the cells of our body."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Well, we have the function of a very important protease, seren protease known as plasmid."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So Plasmid is basically this seren protease that once activated, it finds it locates these fibrin molecules and then hydrolyzes those fibrin molecules into smaller pieces."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And those smaller pieces dissolve into our blood plasma and they travel to the liver and the liver cells basically hydrolyze and break down these even further."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And then different components are basically recycled by our cell."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Now, plasma, like most of these different enzymes involved in a coagulation cascade, initially exist in their inactive precursor zymogen form."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And the zymogen of plasma is Plasminogen."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So plasminogen is activated by another molecule known as tissue type plasmaigen activated so TPA."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So essentially Plasminogen is a Zionogen, an inactive form of plasma that has a very high affinity for Fibon."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "But before it actually becomes active, it must be activated by tissue tie plasminogen activated TPA."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And once TPA activates plasmidogen, the plasma then locates that blood clot that consists of those fibrin molecules."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And it cleaves, it breaks the peptide bond in those fibrin molecules."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And then the fibrin molecules basically dissociate from that blood vessel wall and they travel to the liver cell and the liver cells essentially digest and recycle those blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So Plasmid is a serum protease which is responsible for actually breaking down and digesting those blood clots."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And that ultimately prevents the process of thrombosis from actually taking place."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "For instance, if we examine an individual that basically develops an embolism in the coronary artery."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So essentially, if we give an individual that is experiencing a heart attack the tissue tie plasmidgen activator, if we inject it into the blood of that individual, what happens is this tissue type plasmidogen activator initiates these plasmid molecules."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So activates transforms the plasmidogen into plasma."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And what plasma does is plasma moves into that coronary artery of the heart of that individual experiencing the heart attack and it basically begins to break down the blood clot that is formed as a result of that embolism."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And so by giving an individual who is experiencing a heart attack the tissue type plasmidogen activator, that greatly increases the likelihood that an individual will actually survive that heart attack."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "So we can see that these different molecules can be used for medicinal purposes in many different ways."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "But generally speaking, because there is this very fine line between thrombosis, which is basically the formation of the blood clots, and hemorrhage, which is the process by which blood leaks out of the blood vessels."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "Because there's a very fine line between these two processes, our body must be able to actually not only activate the coagulation cascade process, but also inhibited."}, {"title": "Inhibition of Coagulation Cascade .txt", "text": "And so these are the different molecules that are basically used to control and inhibit the activity the formation of the blood clots the activity of the coagulation cascade."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Suppose we have a test tube and inside that test tube we have a bunch of cells."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, we take those cells and we grind those cells down so that we break the cell membrane and we basically expose all the components, structures and biological molecules found inside the cell."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So now we have a homogeneous mixture that consists of all these different types of things like the cell, nucleus, eye, mitochondria and other organelles, ribosomes, proteins and so forth, mixed in into our test tube."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, if we take the test tube and we place it inside a centrifuge, a process known as centrifugation takes place."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And centrifugation is this process by which we use angular motion."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "We basically accelerate our test tube to very high rotational speeds."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And what this allows us to do is it basically allows us to separate the different components inside our homogenic mixture based on things like mass, density, size and shape, as we'll see in just a moment."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "But first, let's actually discuss briefly the physics behind the process of centrifugation."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Let's see how it actually works."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So let's suppose we take our test tube and we place it inside our centrifuge and it begins to rotate in the counterclockwise direction."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So basically in this direction, as shown."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So this is position one."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And sometime T afterwards, this is position two."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, let's suppose this is the particle shown in blue that we are studying inside our homogeneous mixture."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so this is the particle that we basically want to discuss and we want to basically answer the following question what forces are acting on that particle?"}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Well, first of all, because this test tube is being rotated in a circular motion, what that means is we know from physics this particle will have a certain tangential velocity."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And the velocity here, the vector, will point tangent with respect to the circle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So this is why the velocity basically points this way for this particular particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, even though the tangential velocity points this way, because this particle is suspended inside a fluid, that fluid will create a force, will exert a force on that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And this is the force that creates the centripetal acceleration of that object, of the particle that makes it move in a nearly circular fashion."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, the reason the particle doesn't actually move in a perfect circle is because the particle has inertia."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And because of the inertia of that particle, that will create a slight motion that will point outward."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so if we follow a perfect circle from position one to position two, this is where that particle should technically end up."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "But because of the inertia of our object, of that particle, that inertia will resist that force."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so it will push it slightly outward."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so instead of being here, that particle will be located here."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And as our object rotates, this particle basically keeps on moving outward."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And the density, the mass, the shape and the size of the particle basically determines the rate at which it moves outward, as we'll see in just a moment."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So said another way, we can imagine that there's this force known as the centrifugal force that points outward and it's that force that causes it to move outward along our test tube."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So we have this force due to the fluid, let's say force resistance, that basically acts on that object and it causes it to move this one."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So that is what creates that centripetal acceleration and centripetal force."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so we have this other force known as the force centrifugal that basically causes it to move in the other direction."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "In fact, that's why this process is known as centrifugation, because it's the result of this centrifugal force."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now the next question is how exactly do we describe the rate at which different particles move inside our rotating test tube during the process of centrifugation?"}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So in biochemistry, we describe the rate of the movement of the particles inside our test tube by using a quantity known as the sedimentation coefficient, and that is given with the lowercase S. So lowercase S is equal to the mass of that particle multiplied by one minus v bar multiplied by row divided by f. Now, in the next lecture, we're going to use physics to basically derive this equation."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now let's discuss what these quantities actually mean."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So S is our sedimentation coefficient and it is given in units known as cevetberg units."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now M is the mass of that particular particle that we are examining."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "In this particular case, the mass is the mass of this blue biological particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now V bar is known as the partial specific volume and more specifically, it's the reciprocal of the density of that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So V bar is equal to one divided by the density of that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now this row is basically the density of our medium and F is basically the frictional coefficient of that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And this has to do with the shape of that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So the more spherical our particle is, the lower the value of F is and the less spherical that particle is, the higher the value of F is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So we see that the higher the F is, the higher the sedimentation coefficient is, the higher the sedimentation speed is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And that means the faster that particle will move along and down that test tube."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And by down, we mean towards this end of our test tube and not towards this end."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now let's take a look at the following equation and let's try to see what this equation actually tells us with respect to how these different types of factors actually influence the sedimentation speed and the sedimentation coefficient of our particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So from this equation we obtained four important principles."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Number one, the greater the mass of that particle is, the greater the sedimentation coefficient is and the greater the sedimentation speed is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if we are examining two particles, let's say the blue particle a and the green particle B."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "If these particles have the same shape, have the same size, have the same density, but they have different masses, the mass that is greater will basically move with a higher sedimentation coefficient."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So we'll have a higher sedimentation speed."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if the mass of the blue particle is greater than the mass of the green particle, but the size and shape is the same, then the higher mass travels down a test tube more rapidly."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And that can be seen from the following diagram."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Because if everything is kept constant but the mass is increased, this S value will increase."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And we know the high this S value is, the faster the move of the particle along that test tube is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now let's move on to principle number two."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "The shape of the particle also affects the sedimentation speed."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, from these different quantities, which one describes the shape of the particle?"}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Well, DS describes the shape of the particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "The F. The frictional coefficient of the particle basically is related to its shape."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And we said earlier that the more spherical our particle is, the lower the F value is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And if the F value is lowered and everything else is kept the same, then what that means is if our denominator is lower but the numerator is kept constant, then the S value will increase."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so the more spherical our particle is, the higher arrow sedimentation speed is."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So more spherical particles have lower frictional coefficient values F than less spherical particles of equal mass."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So what equal mass means we're basically keeping all these other constants, all these other quantities constant, but we're changing the F value."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So therefore, more spherical particles move more rapidly than less spherical particles do."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So in a following diagram, if these two masses, let's say the blue masses mass A and the green mass is mass B, if they have the same exact masses, but this one is more spherical and this one is more elongated, then the spherical one will travel down the test tube with a greater sedimentation rate."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "With a greater sedimentation speed."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, number three, a more dense particle moves quicker than a less dense particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So remember, the density of our particle in this equation is basically given by the V bar."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So the partial specific volume, the partial specific volume is equal to one divided by the density of that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if the density of that particle increases, then this fraction decreases."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so v bar decreases."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "If V bar decreases, this quantity decreases and this numerator gets larger."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And what that means is if the numerator gets larger, the S value increases."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And if the S value is greater, that means that particle will move faster."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So a denser particle moves faster than a less denser particle because it experiences a smaller resistive force."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now let's move on to four."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Density of the fluid also affects the sedimentation speed."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So the fluid is basically that fluid that is found inside our homogeneous mixture."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So we have all these different types of particles that basically are floating around inside that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And the fluid has its own density."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now let's take a look at the following value."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So the question is, what exactly is the product of V bar and row?"}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So row is the density of that medium, that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And V bar is basically one divided by the density of the particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So this is equal to so let's call this row the density of the fluid divided by so z is the density of the fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And this V bar is basically one divided by a density of the particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So multiplied by one divided by a density of the particle, which is equal to this right over here."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So we see that this product is simply the ratio of the densities of the fluid to our particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, if the density of the fluid is equals the density of the particle, then this ratio is simply equal to one."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And if this ratio is equal to one, then that means if the density of those two particles is if the density of the particle is the same at the density of the fluid, that fluid and that particle will not move with respect to one another."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if this ratio is equal to one, that particle will not move inside the fluid because their densities are equal."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So remember, from physics we know that an object will float or an object will sink."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And that depends on the density of that object with respect to the density of that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "Now, if the product of V Bard row is greater than one, then that means the fluid has a higher density than that particle."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so that particle will float on top of that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if this is true, the particle will float."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And in that particular case, one minus a value that is greater than one will give us a negative quantity."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so this value will be a negative value."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So if we get a negative value for our sedimentation coefficient, that means that particle essentially floats on top of our fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "It will not travel through the fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "On the other hand, if the product of V and Rho, V bar and row is less than one, what that means is the density of the particle will be greater than the density of the fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And so our object, the particle, will sink in the fluid and that means that it will travel down along the fluid and to the end of that test tube."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And if we look at this equation, if this quantity is less than one, then one minus a value less than one is a positive quantity."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "That means the S value, the sedimentation coefficient, will, in fact be a positive value."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So a positive sedimentation coefficient means it will move through that fluid while a negative means it will float on that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And if this is zero, that means it will not move inside that fluid."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "So this is the equation that we use to basically describe the rate of movement of particles inside our centrifuge when the process of centrifugation is taking place."}, {"title": "Centrifugation and Sedimentation Coefficient .txt", "text": "And in the next lecture, we're going to see where this equation actually comes from."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "The cell envelope refers to the structure found outside our bacterial cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And this includes the actual plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "It includes a cell wall, and in some cases, it also includes a second membrane, a second phospholipid bilayer, as we'll see in just a moment."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, generally speaking, we have two different types of bacterial cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "We have gram positive and gram negative."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And the way we differentiate between these two different types of bacterial cells is by using a technique known as Gram staining."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, before we discuss these two types of bacterial cells, let's discuss what the structure and the function of the cell wall is inside our bacterial cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So the main function of the cell wall is to basically maintain hydrostatic pressure to be able to resist the hydrostatic pressure that builds up within our cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, because our cytoplasm of the bacterial cell contains many different proteins and other macromolecules, as well as molecules and ions, we see that the bacterial cell is actually found within a hypertonic environment."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And that means we have much more solid inside the cell than outside the cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And this means that water will flow from a low solid concentration to a high solid concentration."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So water will flow as a result of osmosis into that cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And as the water from the outside flows into the inside, that increases the hydrostatic pressure inside our bacterial cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And what the cell wall actually does as our hydrostatic pressure increases, as the turger pressure increases, that cell wall is basically able to resist that increase in hydrostatic pressure."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And so, if that cell wasn't there, as our osmosis takes place and more and more water flows into that cell, that cell would eventually burst if it actually did not contain that cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So the cell wall of bacterial cells basically functions to withstand the hydrostatic pressure that exists inside our cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, in bacterial cells, the cell wall is made of a special type of molecule known as Peptidoglycan."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So peptide means we have some type of peptide bond, and Glycoin means we have some type of sugar molecule."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And that's exactly what our Peptidoglycan is."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Peptidoglycan is a polymer of sugar as well as amino acids that create a mesh like structure."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, each disaccharide within our Peptidoglycan contains several amino acids that basically connect to other amino acids attached to adjacent sugar chain."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, to see exactly what we mean, let's take a look at the following diagram."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, the cell wall is found right outside the inner plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So let's imagine this is the inner plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "To that side, we have the cytoplasm."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "This small section is known as the periplasm."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "It's basically the fluid between our plasma membrane and this cell wall here."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And this is actually our cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, where exactly is our disaccharide unit?"}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, the entire structure of Peptidoglycan is composed of only two different types of sugars."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "We have the red sugar, and we have the blue sugar."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And this creates our disaccharide unit."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And each disaccharide unit contains several amino acids in a chain."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So this purple dashed line basically corresponds to our amino acid chain."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So this is our disaccharide unit that contains our amino acids."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these disaccharides create a long polysaccharide chain."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these are connected as a result of a type of glycocitic bond known as the beta one four glycocytic linkage."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, notice that we have polysaccharide chain one, polysaccharide chain two, polysaccharide chain three, and so forth."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these individual polysaccharide chains that themselves consist of disaccharide units, are connected to one another as a result of cross linkages or cross links."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So basically, these amino acids connect to one another as a result of a bridge known as the Interbridge."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So basically, we have one of the amino acids on this chain, connects to one of the amino acids on this chain, and this is known as an Interbridge."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So if we, for example, zoom in on this region, we get the following diagram, as shown."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, the Peptidoglycan consists of two types of amino sugars or sugars, connected by beta one four glycocytic linkages, creating a polysaccharide chain."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So these are the polysaccharide chains, and these individual sugars are connected by beta one four glycosytic linkages."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, two or more polysaccharide chains."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So one and two."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So let's say these two polysaccharide chains are connected by cross links between these amino acids, shown in purple."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these amino acids are connected by into bridges."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So we see that the cell walls of our entire structure within our cell envelope consist of this type of molecule known as or this type of structure known as Peptidoglycan."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And Peptidoglycan, generally speaking, contains relatively large pores."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these pores or holes within our cell wall basically allow relatively large molecules to actually pass into this region here, which is known as the periplasm."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So the periplasm actually contains different types of important enzymes, different types of important hydrolytic enzymes that break down different products that end up within this space."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And that helps our bacterial cell actually digest and break down different types of molecules, which then are ingested into our cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, earlier, I mentioned that there are two different types of bacterial cells."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So how exactly do we categorize different types of bacterial cell?"}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, bacterial cells can be categorized based on their structure of the cell envelope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And we use a technique called Gram staining to basically differentiate between these two different types of bacterial cells."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So we have Grampositive bacteria and Gram negative bacteria."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, Grampositive bacteria contain a very thick peptidogly cell wall, about four times as thick as the actual plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And because of this relatively large thickness of the Peptidoglycan cell wall, when we actually stain our bacteria with some type of purple dye, that purple color remains within that cell because it cannot leave, it cannot leak out of our relatively thick Peptidoglycan wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And so, under the microscope, when we actually take our bacteria, the Grampositive bacteria, and stain it with the purple dye, those bacterial cells will appear purple under the microscope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So Grampositive bacterial cells are cells that are characterized by thick cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "When we stain the cell with our purple dye, the thick layer of Peptidoglycan prevents the purple stain from leaking out back into our surroundings when we wash those bacterial cells with water."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So under the microscope, Grampositive bacterial cells appear purple."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, in both types of these cells, the periplasmic space, as I mentioned earlier, basically contains important hydrolytic enzymes that break down different types of molecules that are then ingested into the cell so that the cell can use them to basically function properly."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, let's move on to the Gram negative bacteria."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So the main difference between Gram positive and Gram negative is the thickness of our cell wall of that Peptidoglycan layer."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So these bacterial cells are characterized by a thin Peptidoglycan cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, because the cell wall is so thin, when we actually stain our bacterial cells with our purple dye, because the layer is so thin, that purple dye can easily wash out when we wash it with water."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So that means under the microscope, all that purple dye will be removed after washing and our bacterial cell will appear pink under the microscope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, on top of having a thin Peptidoglycan layer, the other difference between Gram negative and Gram positive is that in Gram negative, we also have a second phospholipid body layer found right outside our peptidogly cancell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And this phospholipid bilayer is more permeable than our inner plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So it actually allows relatively large molecules to pass through that phospholipid bilayer, for example, it allows sugar molecules to pass right through."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And the sugar molecules, because the actual wall contains pores, will end up within this section."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And then those sugar molecules can either be broken down by the hydrolytic enzymes or they can be ingested directly into our cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, another difference between our Gram negative and Gram positive is because our Gram negative contains this second phospholipid bilayer."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "That phospholipid bilayer contains special types of molecules known as lipopolysaccharides."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So it contains lipopolysaccharides protruding from the membrane, which can protect the bacteria from being killed off by different types of drugs as well as antibodies found within our body."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So basically, these types of bacteria can resist the different drugs that we develop in the laboratory to kill off the different type of bacterial cells found in our body."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So basically, one important part that our cell envelope contains is the Peptidoglycan."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So basically, we can develop different types of drugs that actually break the cross links between our polysaccharide chains within the Peptidoglycan and that kills off our bacterial cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Other different types of drugs that we can use can also break our bonds between the disaccharides, between this red and this blue."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And that can also kill off our cell membrane, our cell, because once we break that cell wall, it can no longer resist that hydrostatic pressure that our internal environment of the cell actually contains."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And if we break our cell wall, that bacterial cell will actually burst."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, let's look at our description of the grampositive and our gram negative cell envelope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So, the cell envelope of grampositive basically contains the inner membrane, the phospholipid membrane, and a relatively thick peptidoglycan cell wall."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, the gram negative contains this inner membrane, a thin cell wall, and an outer membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And the outer membrane contains these polysaccharides, which are based or lipopolysaccharides, which are basically the lipids attached to long chains of sugars."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And these sugars create a net negative charge around the entire cell bacterial cell, and that protects it from different types of drugs."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, we also have a section that connects the cell wall to our outer membrane, and this is our poly, our lipoproteins."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So these brown regions are lipoproteins, also known as browns lipoproteins."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And the entire or the main function of these brown lipoproteins, is to actually hold together via covalent bonds, the thin cell wall as well as our outer membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "So we see that when we discuss bacterial cells, there are two main categories of bacterial cells."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "We have gram positive and gram negative."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And the way we differentiate these two different types of bacterial cells is by the cell envelope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "The cell envelope contains our cell wall, which is made of a material known as a peptidoglycan, and it also contains the inner plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "In some cases, we also have an outer plasma membrane."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Basically, our grampositive bacteria contain a very thick peptidoglycan cell wall, and that allows the purple dye to remain inside that cell."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And that's exactly why on the microscope, these types of bacterial cells appear purple."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "But because of the thin cell wall of our gram negative, that purple dye can be easily washed off."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "And so these gram negative bacterial cells appear pink under our microscope."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, one of the main functions of the cell wall made of peptidoglycan is to basically resist that hydrostatic pressure, that trigger pressure that builds up within that cell as a result of the hypertonic environment."}, {"title": "Bacterial Cell Envelope, Gram Positive and Gram Negative Bacteria .txt", "text": "Now, if we examine the outer membrane of our gram negative bacterial cells, we see that we have these lipopolysaccharides, which play a very important role in creating a protective barrier around that bacterial cell."}, {"title": "Cartilage and Joints.txt", "text": "Bone is a very strong but very rigid type of connective tissue."}, {"title": "Cartilage and Joints.txt", "text": "Another type of connective tissue that is also strong but is much more flexible is known as cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And that's exactly why cartilage is found in those regions of our body that require a greater degree of flexibility, such as, for example, our nose, our outer ear, our bronchial tubes inside our lungs, our ribcage, our trachea, the epiglottis, as well as our joints."}, {"title": "Cartilage and Joints.txt", "text": "So on top of discussing cartilage, we're also going to discuss the three types of joints in our body."}, {"title": "Cartilage and Joints.txt", "text": "The fixed joints, also known as the fibrous or removable joints, the synovial joints, as well as our cartilaginous joints."}, {"title": "Cartilage and Joints.txt", "text": "So what exactly is cartilage?"}, {"title": "Cartilage and Joints.txt", "text": "Well, cartilage is a type of connective tissue that consists of cells known as contracytes, as well as the extracellular matrix."}, {"title": "Cartilage and Joints.txt", "text": "And the extracellular matrix of this cartilage is made up of three types of substances."}, {"title": "Cartilage and Joints.txt", "text": "We have the collagen fibers, we have elastin fibers, and we have proteoglycans."}, {"title": "Cartilage and Joints.txt", "text": "So proteoglycans are proteins that contain our sugar components."}, {"title": "Cartilage and Joints.txt", "text": "The collagen fibers are those proteins that give our cartilage its strength, and the elastin fibers of those proteins that give the cartilage its flexibility."}, {"title": "Cartilage and Joints.txt", "text": "So we have three types of cartilage connective tissues."}, {"title": "Cartilage and Joints.txt", "text": "We have the highland cartilage, we have the elastic cartilage, and we have our fiber cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And these different types of cartilage differs from one another based on the concentration of these substances inside the matrix of that particular cartilage."}, {"title": "Cartilage and Joints.txt", "text": "So let's begin with the highland cartilage."}, {"title": "Cartilage and Joints.txt", "text": "So the highland cartilage is basically a transparent type of cartilage, so we can see through that cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And this highland cartilage is made up of predominantly collagen fibers."}, {"title": "Cartilage and Joints.txt", "text": "So that means it's a very strong type of cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And our highland cartilage is the most common type of cartilage in the body because it basically lines our bones where the bones are connected to one another via joints."}, {"title": "Cartilage and Joints.txt", "text": "So it's the highland cartilage that is found around our bones and around the joints."}, {"title": "Cartilage and Joints.txt", "text": "And this highland cartilage reduces the friction between bones."}, {"title": "Cartilage and Joints.txt", "text": "It also absorbs some of that shock as a result of the forces that we experience due to our daily movement."}, {"title": "Cartilage and Joints.txt", "text": "Now, the second type of cartilage is the elastic cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And this cartilage contains a high proportion of elastin fibers, and that makes it very flexible."}, {"title": "Cartilage and Joints.txt", "text": "And so it's no surprise that elastic cartilage is a type of cartilage that is found in our outer ear."}, {"title": "Cartilage and Joints.txt", "text": "So it's very, very flexible as well as our epiglottis that constantly has to move, and so it must remain flexible."}, {"title": "Cartilage and Joints.txt", "text": "The epiglottis is found inside our neck."}, {"title": "Cartilage and Joints.txt", "text": "Now, the fiber cartilage is the final type of cartilage that consists of two types of collagen fibers type one and type two."}, {"title": "Cartilage and Joints.txt", "text": "And it's the fiber cartilage that is found in the intervertebral discs inside our spine."}, {"title": "Cartilage and Joints.txt", "text": "So as we mentioned earlier, carthage consists of cells known as chondrocytes."}, {"title": "Cartilage and Joints.txt", "text": "And these chondrocytes are the cells that create the extracellular matrix."}, {"title": "Cartilage and Joints.txt", "text": "The matrix surrounding those conducive."}, {"title": "Cartilage and Joints.txt", "text": "And this is known as the conjun."}, {"title": "Cartilage and Joints.txt", "text": "So the conjuren is the matrix of our cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And it's the conron, it's the extracellular matrix that is composed of these three different types of substances in different proportions, in different proportions."}, {"title": "Cartilage and Joints.txt", "text": "Basically those proportions depend on the type of cartilage that we are examining."}, {"title": "Cartilage and Joints.txt", "text": "So if we examine the high limb cartilage, that is found, for example, on the top portion of long bones, and that is shown here."}, {"title": "Cartilage and Joints.txt", "text": "So this is also known as articular cartilage because it is also connected to our joints."}, {"title": "Cartilage and Joints.txt", "text": "And if we zoom in on this type of highland cartilage, we basically will find the matrix, the chondrin and our chondrocytes ourselvess."}, {"title": "Cartilage and Joints.txt", "text": "And this chondrin will be composed predominantly of our collagen fibers, because hyland cartilage consists predominantly of collagen."}, {"title": "Cartilage and Joints.txt", "text": "So now, let's move on to the three different types of joints."}, {"title": "Cartilage and Joints.txt", "text": "We have the fixed joints, the synovial joints, as well as our carthalaginous joints."}, {"title": "Cartilage and Joints.txt", "text": "So the fixed joints are also known as our immovable or fibrous joints."}, {"title": "Cartilage and Joints.txt", "text": "And these are the joints that connect our bones and hold those bones very strongly, very tightly."}, {"title": "Cartilage and Joints.txt", "text": "And so these fibrous joints basically allow no movement between the bone and these fibers."}, {"title": "Cartilage and Joints.txt", "text": "Joints are found in the skull as well as around our teeth."}, {"title": "Cartilage and Joints.txt", "text": "So when our human is born, the skull actually consists of individual bones."}, {"title": "Cartilage and Joints.txt", "text": "But as the organism develops, as the human develops, these bones basically fuse together."}, {"title": "Cartilage and Joints.txt", "text": "And the regions where they fuse, that is known as a suture."}, {"title": "Cartilage and Joints.txt", "text": "So we have the corona suture, we have the squamous suture, we have the lambdoid suture, as shown in the diagram."}, {"title": "Cartilage and Joints.txt", "text": "And if we zoom in on either one of these three sutures, we basically get the following image."}, {"title": "Cartilage and Joints.txt", "text": "So, we have the bone section and we have this joint shown in blue."}, {"title": "Cartilage and Joints.txt", "text": "And this is our fibers joint, also known as the fixed or immovable joint."}, {"title": "Cartilage and Joints.txt", "text": "And the same thing on the teeth."}, {"title": "Cartilage and Joints.txt", "text": "If we zoom in on this single upper tooth, that is connected to our upper jaw, also known as our maxilla."}, {"title": "Cartilage and Joints.txt", "text": "So basically, the maxilla is connected to our tooth via this joint, known as our fixed joint, shown in blue."}, {"title": "Cartilage and Joints.txt", "text": "So basically, when the human is born, they begin to develop and the density of fibers inside this joint basically increases tremendously."}, {"title": "Cartilage and Joints.txt", "text": "It becomes very dense."}, {"title": "Cartilage and Joints.txt", "text": "And the fibers in the joint are the collagen fibers and that's exactly what makes this joint so strong."}, {"title": "Cartilage and Joints.txt", "text": "Now, the second type of joint is a synovial joint."}, {"title": "Cartilage and Joints.txt", "text": "And these are the joints that basically create a very wide range of movement."}, {"title": "Cartilage and Joints.txt", "text": "These are joints found in our elbows as well as in our knees."}, {"title": "Cartilage and Joints.txt", "text": "So let's say this is bone number one."}, {"title": "Cartilage and Joints.txt", "text": "This is bone number two."}, {"title": "Cartilage and Joints.txt", "text": "We have the purple regions, our ligaments that connect bone to bone."}, {"title": "Cartilage and Joints.txt", "text": "We have these, the brown regions, which are the articular cartilage, the highland cartilage that we spoke about earlier, that reduces friction and that absorbs some of that shock."}, {"title": "Cartilage and Joints.txt", "text": "And we have this blue region shown."}, {"title": "Cartilage and Joints.txt", "text": "Now the blue region is basically a cavity known as the synovial cavity."}, {"title": "Cartilage and Joints.txt", "text": "And inside this synovial cavity we basically contain our synovial fluid."}, {"title": "Cartilage and Joints.txt", "text": "And this synovial fluid does not only lubricate and provide nutrients to our cartilage but it also contains macrophages cells that basically engulf different type of harmful bacteria that can harm our cartilage."}, {"title": "Cartilage and Joints.txt", "text": "So basically this joint, the synovial joint consists of our ligaments, it consists of this synovial fluid that basically nourishes this cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And it also consists of this highland cartilage that absorbs the shot and also basically reduces the friction between our bones so the bones don't actually rub against one another."}, {"title": "Cartilage and Joints.txt", "text": "So the synovial joint consists of a cavity that contains our synovial fluid which acts to nourish our cartilage found nearby."}, {"title": "Cartilage and Joints.txt", "text": "It also contains macrophages that eat up harmful material."}, {"title": "Cartilage and Joints.txt", "text": "These joints provide a wide range of movement to our connecting bones."}, {"title": "Cartilage and Joints.txt", "text": "Unlike in this case where the range of movement was none."}, {"title": "Cartilage and Joints.txt", "text": "The purpose of fixed joints is to basically hold our bones in place whereas the point of synovial joints is to basically create a wide range of movement to allow a wide range of movement."}, {"title": "Cartilage and Joints.txt", "text": "Now, the final type of joint is our cartilaginous joint and our cartilageinous joint basically allows very little movement to no movement."}, {"title": "Cartilage and Joints.txt", "text": "So usually the movement due to these joints is slightly more than our fixed joints but it's much less than our synovial joint."}, {"title": "Cartilage and Joints.txt", "text": "And these types of joints consist entirely of cartilage, either hyland cartilage or the fiber cartilage."}, {"title": "Cartilage and Joints.txt", "text": "And these are the joints that are found in our rib cage as well as in our pubic synthesis which is our bone found in our hip."}, {"title": "Cartilage and Joints.txt", "text": "So basically, if we think of our rib cage, the ribcage actually has to expand back and forth as we breathe in and out."}, {"title": "Cartilage and Joints.txt", "text": "So we have to have a slight ability of our bones to actually move."}, {"title": "Cartilage and Joints.txt", "text": "And that's exactly why this carthlaginous joint basically allows a slight amount of movement while the fixed joint does not."}, {"title": "Cartilage and Joints.txt", "text": "So we don't want these bones to actually move while the bones in the ribcage we do want them to move because as we breathe in and out we want our ribcage to continually be able to expand as well as compress with our breathing rhythm."}, {"title": "Protective Capabilities of Lungs .txt", "text": "On average, the resting adult takes about twelve breaths every single minute."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, this number can greatly increase if the individual is undergoing some type of strainuse activity for example, running or swimming."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, for that same resting individual the lungs are capable of exchanging about 500 volume of air every single breath."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So this is known as the title volume and we'll talk about what the title volume is and how it's measured in the next several electrodes."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, if we take the number of breadths that are made by the rest individual every single minute and we multiply by the tidal volume, the amount of volume that is exchanged by the lungs every single breath and we multiply these two values we get 6000 ML or six liters."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And this describes the total volume of air that is exchanged by the lungs every single minute."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So if we wait a minute, our lungs exchange six liters of air."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, the question is how many molecules are found within six liters of air assuming we're at room temperature and at atmospheric pressure so how many molecules does this represent at room temperature?"}, {"title": "Protective Capabilities of Lungs .txt", "text": "At a temperature of about 21 degrees Celsius and a pressure of about one atmospheric pressure, one ATM."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So to calculate the number of molecules exchanged by the lungs every single minute we have to calculate the number of moles of air that is exchanged and to calculate the moles we can use the ideal gas law."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So n is equal to where n is our number of moles is equal to the pressure in ATM multiplied by the volume in liters divided by the gas constant r multiplied by the temperature given to us in Kelvins."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, the pressure we're assuming is one ATM the volume we calculated to be six liters the ideal gas law is 0.20.81 ATM times liter divided by kelvin times mole and the temperature in Kelvin is equal to 21 plus 273 and that gives us about 294 Kelvins."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, if we multiply and divide we get about zero point 25 moles."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, this is the number of moles and we know inside 1 mol we have abogandro number of molecules and so to find number of molecules we take this many moles multiplied by avogadro's number 6.2 times ten to 23 molecules per mole the moles cancel and we're left with about 1.51 times ten to the 23 molecules."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So this is the number of molecules that are exchanged by our lungs every single minute assuming that the individual is at rest."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, what's the point of calculating this value?"}, {"title": "Protective Capabilities of Lungs .txt", "text": "Well, it was basically to show you that our lungs are capable of exchanging a great number of different molecules and although most of these molecules are oxygen and nitrogen molecules, a good portion of these are actually harmful particles such as pollutants, contaminants, allergens."}, {"title": "Protective Capabilities of Lungs .txt", "text": "They can also be viruses and bacterial cells and this can cause a problem because our lungs creates a barrier, a boundary between the outside and the internal environment."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And so, in order to ensure that none of these harmful things actually end up inside our body and cause harm to our body, the lungs have to have some type of protective capability."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So our lungs have several important methods by which they can actually protect themselves from these different types of agents that enter our body when we breathe in air."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So number one is mucus membrane."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So inside our passageways, we basically have specialized types of cells known as goblet cells."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And these goblet cells can produce and secrete a special type of sticky and slimy material or substance that essentially forms the mucous membrane."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And this mucus membrane essentially lines our passageways."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And when we breathe in the air, these harmful agents and harmful things, as they travel through with the air, they can essentially get stuck inside this mucus membrane."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And if we move on to number two, we also have these hair like structures that can essentially move in a wavelike fashion that are found along the cells that line our passageways."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And as these cilia actually move in a wavelike fashion, they can actually move those harmful things that get stuck inside the mucous."}, {"title": "Protective Capabilities of Lungs .txt", "text": "They can move these things back out into our larynx."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And within the larynx, they can either go into the esophagus and into our stomach, where the acidity will kill that harmful thing, or they can be expelled via the process of spitting."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So, once again, mucous membrane within the trachea, the bronchi and the bronchioles, as well as within our nasal cavity, we have specialized cells called goblet cells."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So these cells secrete a substance that forms a very sticky and slimy mucous membrane along the pathogeways within which our air actually moves."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, when harmful particles and agents move with the air, they can get stuck within this mucus membrane."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And the mucous membrane, as I mentioned earlier, is also found within our nasal cavity of the nose."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, we also have tiny hairlike structures found along the cells lining the airways, and these can help carry the pollutants to our pharynx."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So if we take a look at the diagram of our respiratory system, this is our trachea, these are the bronchi."}, {"title": "Protective Capabilities of Lungs .txt", "text": "These are our bronchioles."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And if we zoom in on the terminal portion of our bronchioles, we get our alveolar."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And we'll see how the alveolar also helps us protect from these pollutants in just a moment."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, this is our larynx."}, {"title": "Protective Capabilities of Lungs .txt", "text": "It's the voice box."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And the larynx connects our trachea to the pharynx, which is found right here."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And the pharynx basically is the connection point between the esophagus, our mouth, as well as our larynx."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So the cilia can move the pathogens along our trachea."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And ultimately, those pathogens end up in our pharynx."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And then those pathogens either can be swallowed through our esophagus and end up in our highly acidic and highly deadly environment inside our stomach which can ultimately kill off that pathogen or we can expel that pathogen or harmful substance via the process of spitting."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, inside the nasal cavity, we also have actual tiny hairs."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And what these hairs actually do is they can help trap our dust particles and other particles inside the nasal cavity before it actually goes into our lungs."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, if we check out this structure, which are basically these saclike structures where gas exchange actually takes place within the alveoli of our lungs, we have specialized immune cells known as the alveolar macrophages."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And these are specialized cells that can engulf and digest any harmful agent and substance that the cell actually comes across."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, we also have something called airway constriction."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So if we examine our air passageways, we have trachea, we have the bronchi, we have these bronchioles, these are lined with our muscles."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And these muscles can actually constrict."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And when they constrict, they create a more narrow system of canals and that basically decreases the likelihood that our contaminant or harmful substance will pass into our body via our alveolar."}, {"title": "Protective Capabilities of Lungs .txt", "text": "So the air passageways of the lungs contain rings of muscle."}, {"title": "Protective Capabilities of Lungs .txt", "text": "When the passageways are irritated by, let's say, some type of allergen these muscles can constrict."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, although this does make the airway more narrow and this decreases the likelihood that our pathogen will actually end up in our lungs and in our body, specifically in the alveoli of our lungs."}, {"title": "Protective Capabilities of Lungs .txt", "text": "It also actually has a bad effect because if we constrict, if we narrow in our passageways, that will make it very difficult for us to actually breathe."}, {"title": "Protective Capabilities of Lungs .txt", "text": "Now, the most common protective capability that you're probably familiar with is the process of coughing."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And this is the process by which some type of irritant, when it gets into our lungs, into our passageway, it causes this reflex we call coughing."}, {"title": "Protective Capabilities of Lungs .txt", "text": "And that expels that irritant along with all the other things that are stuck within the mucous membrane very quickly to the outside of our body."}, {"title": "Protective Capabilities of Lungs .txt", "text": "These are the six different methods by which our lungs basically protect themselves and our body from these harmful agents and harmful pathogens."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Aerobic cellular respiration is the process by which a cell uses oxygen to synthesize ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And our aerobic cellular respiration actually involves four important processes."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have the process of glycolysis, we have pyruvate decarboxylation, we have citric acid cycle, also known as known as the KREP cycle or the tricarboxylic acid cycle."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And we have the electron transport chain that involves oxidative phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So let's discuss each one of these processes briefly and then let's summarize our results into the following table that basically describes how many ATP molecules are synthesized by each one of these individual processes."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And let's begin with the process of glycolysis."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, glycolysis is the breakdown of a glucose molecule into two ATP molecules, into two NADH molecules and two Pyruvate molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, actually glycolysis produces a total of four ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "But because it uses up two ATP molecules, the net result is four minus two or two ATP molecules per single glucose molecule."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, glycolysis takes place in the fluid portion of the cytoplasm of our cell and this is known as the cytosol of our cell."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And the production of ATP molecules without using the proteins of the electron transport chain is known as substrate level phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, the production of ATP molecules using the electron transport chain, as we'll see in just a moment, is known as oxidative phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So substrate level phosphorylation is the production of ATP in glycolysis."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And substrate level phosphorylation also occurs in the citric acid cycle, as we'll see in just a moment."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, although aerobic respiration means we have oxygen present in the cell, glycolysis takes place regardless of whether or not we have oxygen present inside the cell."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So that implies glycolysis is the first step of aerobic as well as anaerobic respiration."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, once we actually synthesize our two pyruvate molecules via glycolysis, if we have oxygen present in the cell, those two pyruvate molecules will then be transported into the mitochondrial matrix of the mitochondria of aracel."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And once inside the mitochondrial matrix of aracel, our two pyruvate molecules undergo a decarboxylation process in which we produce two carbon dioxide molecules, two NADH molecules, as well as two acetyl coenzyme A molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "No ATP molecules are actually synthesized directly in the process of pyruvate decarboxylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now let's move on to our citric acid cycle."}, {"title": "Summary of Aerobic Respiration .txt", "text": "The citric acid cycle, also known as the KREP cycle or the tricarboxylic acid cycle, basically involves using our acetyl coenzyme A molecules produced in pyruvate decarboxylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So basically, the citric acid cycle is an eight step cycle that transforms a single acetyl coenzyme A molecule into three NADH molecules, one GTP molecule that is later transformed into ATP, as well as one Fadh two molecule."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And since we have two acetyl coenzyme A molecules produced from one glucose, the breakdown of a single glucose basically leads to the production of six NADH, two Fadh twos and two GTPs, which is basically two multiplied by these quantities that we discussed earlier."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, in the same way that the production of ATP and glycolysis takes place via substrate level phosphorylation producing our GTP, our Guanosine triphosphate and then ATP from the GCP takes place via the substrate level phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now let's move on to the electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, the electron transport chain is basically a series of protein complexes that are found on the inner membrane of the mitochondria."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And what happens is the NADH molecules and the Fad H two molecules basically transport or transfer the electrons onto our electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And these electrons basically eventually end up reducing oxygen and forming water."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And in the process, our electron transport chain establishes an electrochemical gradient between the intermembrane space of the mitochondria and the mitochondrial matrix."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And one of the proteins of the electron transport chain known as ATP synthase utilizes the electrochemical gradient to synthesize our ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now we see that a single NADH molecule produced in the mitochondrial nature creates three ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So that means our NADH that is formed in Pyruvate decarboxylation and the citric acid cycle which both take place in the mitochondrial matrix each produce three ATP molecules while the NADH that is formed in the cytosol of our cell via glycolysis produces only two ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And that's because we actually have to use a single ATP molecule per one NADH to transport that NADH from the cytoplasm to the mitochondrial matrix."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, we also see that a single fadh two that is formed in the citric acid cycle produces two ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And the process by which ATP synthase one of the enzymes of the electron transport chain phosphorylates ATP into ATP to produce our adenosine triphosphate is known as oxidative phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So basically, when ATP molecules are produced without using the electron transport chain, as the case was in glycolysis and the citric acid cycle, that is known as substrate level phosphorylation but using the electron transport chain to produce ATP, that is known as oxidative phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now let's actually summarize our results by looking at the following table."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So this table describes how many ATP molecules are actually formed either directly or indirectly by using glycolysis, Pyruvate decarboxylation and the citric acid cycle."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So let's begin by looking at glycolysis."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So glycolysis actually synthesizes two or a net result of two ATP molecules by substrate level phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have a result of net two ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Remember, glycolysis actually forms four but it uses up two."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we form a net of two ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now, glycolysis also forms our two NADH molecules and each one of these NADH molecules eventually end up in the electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And because we have two NADH molecules form in glycolysis, we form two times two."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So four ATP molecules, for a total of six ATP molecules form either directly or indirectly by glycolysis."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Now let's move on to Pyruvate carboxylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So this process does not form ATP molecules directly but it forms two NADH molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And remember, a single NADH molecule formed in the mitochondrial matrix produces three ATP molecules on the electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have two multiplied by three each."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have six ATP molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have a total of six ATP molecules formed indirectly as a result of pyruvate decarboxylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And finally, let's discuss the citric acid cycle."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So it turns out that the citric acid cycle actually is involved in forming the majority of the ATP molecule."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So in the citric acid cycle, we form six NADH molecules."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And because this occurs in the mitochondrial matrix, we have six multiplied by three."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So 18 ATP molecules are formed when the six NADH end up on the electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "Because we have two fadh two molecules and each one forms two ATP, we have a total of four ATP molecules form when the fadh twos are on our electron transport chain."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And finally, we form two GTP molecules as a result of substrate level phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And each one of these GTPs is transformed into our ATP."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we have two ATP molecules for a total of 24 ATP molecules that are formed in the citric acid cycle after our electron transport chain basically undergoes the oxidative phosphorylation."}, {"title": "Summary of Aerobic Respiration .txt", "text": "So we see that when a single glucose molecule is broken down in the process of aerobic respiration, we form a net result of 36 ATP molecules when we break down that single glucose molecule."}, {"title": "Summary of Aerobic Respiration .txt", "text": "And this concludes our summary of aerobic respiration."}, {"title": "Function of the Liver.txt", "text": "The liver is a very important multifunctional organ that exists in the human body."}, {"title": "Function of the Liver.txt", "text": "So in this lecture, we're going to focus briefly on the several important functions of the liver."}, {"title": "Function of the Liver.txt", "text": "Now, let's begin by describing what the liver looks like and where the liver is found in the body."}, {"title": "Function of the Liver.txt", "text": "So the liver is located in the upper right abdomen portion of the body."}, {"title": "Function of the Liver.txt", "text": "It's found to the right of of our stomach."}, {"title": "Function of the Liver.txt", "text": "So the liver consists of the left lobe, shown here, and the right lobe."}, {"title": "Function of the Liver.txt", "text": "And in between the lobes, we have our ligaments, we have the coronary ligament and we have the falciform ligament."}, {"title": "Function of the Liver.txt", "text": "And these ligaments play a role in connecting our liver to other parts of the body."}, {"title": "Function of the Liver.txt", "text": "For example, the falciform ligament connects the liver to the anterior portion of the body."}, {"title": "Function of the Liver.txt", "text": "Now, within our liver, we have many ducts, we have many canals that function to allow the pathogeway and movement of certain substances that are produced by our liver."}, {"title": "Function of the Liver.txt", "text": "So we see that the liver is not only an endocrine gland, it is also an exocring gland."}, {"title": "Function of the Liver.txt", "text": "And we'll see what that means in just a moment."}, {"title": "Function of the Liver.txt", "text": "Now, another important structure that functions with the liver is known as the gallbladder."}, {"title": "Function of the Liver.txt", "text": "And we'll see what the gallbladder does in just a moment."}, {"title": "Function of the Liver.txt", "text": "So let's begin by discussing function number one."}, {"title": "Function of the Liver.txt", "text": "So the liver functions in macromolecule metabolism, so the metabolism of carbohydrates of fats and proteins."}, {"title": "Function of the Liver.txt", "text": "And this includes the synthesis of the breaking down of and a storage of these molecules inside our body."}, {"title": "Function of the Liver.txt", "text": "So let's begin with carbohydrate metabolism."}, {"title": "Function of the Liver.txt", "text": "So the liver is responsible for maintaining, for controlling the proper levels of glucose inside our blood plasma."}, {"title": "Function of the Liver.txt", "text": "The liver cells are responsible for maintaining homeostasis of blood glucose levels."}, {"title": "Function of the Liver.txt", "text": "So let's suppose in our blood plasma, in our blood, we have a high concentration of glucose."}, {"title": "Function of the Liver.txt", "text": "The pancreas basically releases a hormone known as insulin."}, {"title": "Function of the Liver.txt", "text": "And insulin acts on the liver cells to cause those liver cells to absorb as much glucose as needed, to basically maintain a proper concentration of glucose inside the blood."}, {"title": "Function of the Liver.txt", "text": "So liver cells absorb the glucose and transform that glucose into the polymer form known as glycogen."}, {"title": "Function of the Liver.txt", "text": "Now, on the other hand, let's suppose our glucose concentration inside the blood is very low."}, {"title": "Function of the Liver.txt", "text": "In this case, the pancreas releases a hormone known as glucagon."}, {"title": "Function of the Liver.txt", "text": "And glucagon acts on liver cells and it causes, it stimulates those liver cells to break down glycogen into glucose and release that glucose into that blood, maintaining a proper level of glucose inside the blood."}, {"title": "Function of the Liver.txt", "text": "On top of that, it also stimulates our liver cells to undergo process known as gluconeogenesis."}, {"title": "Function of the Liver.txt", "text": "And gluconyogenesis is the production of glucose of sugar molecules from non sugar constituents such as for example, lactic acid and other precursors."}, {"title": "Function of the Liver.txt", "text": "Now, let's move on to fat metabolism."}, {"title": "Function of the Liver.txt", "text": "So we know that when we ingest our lipids or fats, they eventually end up in the small test and inside the small test."}, {"title": "Function of the Liver.txt", "text": "And because fats are hydrophobic they aggregate to form large fat globules."}, {"title": "Function of the Liver.txt", "text": "Now, what the liver does is it acts as an excretory gland, as an exocrine gland."}, {"title": "Function of the Liver.txt", "text": "And what that means is it produces a substance known as bile."}, {"title": "Function of the Liver.txt", "text": "So the liver cells produce bile, the bile is released into the dust and the bile is eventually stored in the gallbladder until we begin our digestion process in our small intestine."}, {"title": "Function of the Liver.txt", "text": "At this point, the bile is released from the gallbladder and it travels into our small testin."}, {"title": "Function of the Liver.txt", "text": "Now, what the bile does is it basically emulsifies our fat globules, it breaks them down into smaller mole, into smaller particles, and then the enzymes can act on those smaller particles and break down the fats."}, {"title": "Function of the Liver.txt", "text": "And those fats are eventually absorbed by the cells of the small intestine."}, {"title": "Function of the Liver.txt", "text": "Now, those absorb fats eventually end up in our blood system and the liver cells are capable of absorbing those fatty acids and they store the fatty acids in the form of triglycerides."}, {"title": "Function of the Liver.txt", "text": "Now, when the cells of our body, when our body needs energy, what the liver cells can also do is they can also actually break down the fatty acids and use the fatty acids to form ATP molecules, energy molecules, in a reaction known as beta oxidation."}, {"title": "Function of the Liver.txt", "text": "And finally, what the liver cells can also do is if we eat too much sugar or too much protein, what the liver cells do is they transform the sugars or the protein into fat."}, {"title": "Function of the Liver.txt", "text": "Now, let's move on to our protein, the final type of macromolecule that we ingest into our body and that our body actually needs to survive."}, {"title": "Function of the Liver.txt", "text": "So we actually ingest ten essential amino acids that our body cannot actually manufacture, but the other ten none essential amino acids are produced by the liver cell."}, {"title": "Function of the Liver.txt", "text": "So the liver can produce the ten non essential amino acids."}, {"title": "Function of the Liver.txt", "text": "And the liver can also use the 20 total amino acids to basically produce important types of proteins, such as, for example, albumin and fibrinogen."}, {"title": "Function of the Liver.txt", "text": "So albumin is the protein carrier of fatty acids in the blood plasma, while fibrinogen is an important type of enzyme, an important type of protein that is involved in the blood clotting cascade, as we'll see in a future lecture."}, {"title": "Function of the Liver.txt", "text": "Now, finally, in terms of the protein metabolism, liver cells can also convert ammonia in the blood into urea, which is then excreted by our kidneys."}, {"title": "Function of the Liver.txt", "text": "So when our glucose concentration in the blood runs low, when it is very low, what the liver cells can do is they can actually break down proteins into amino acids and they can use those amino acids to transform the amino acids into ATP molecules."}, {"title": "Function of the Liver.txt", "text": "In the process, we produce ammonia, which is a toxic substance."}, {"title": "Function of the Liver.txt", "text": "So what the liver does is it takes the ammonia, a toxic substance, and it basically transforms it into urea, which is excreted by the kidneys to outside of our body."}, {"title": "Function of the Liver.txt", "text": "So the second important function of the liver is in detoxification."}, {"title": "Function of the Liver.txt", "text": "So this basically means taking toxic substances that are detrimental to our body and transforming them into less toxic substances that can be released by our body."}, {"title": "Function of the Liver.txt", "text": "So the liver cells are responsible for reading the body of a wide range of toxic of poisonous substance."}, {"title": "Function of the Liver.txt", "text": "For example, drugs that we ingest into our body, alcohol that we ingest, different types of metabolic end products such as, for example, lactic acid, as well as ammonia that we just described above."}, {"title": "Function of the Liver.txt", "text": "So remember, when we break down amino acids into ATP molecules we produce ammonia, a toxic substance."}, {"title": "Function of the Liver.txt", "text": "And what the liver does, it transforms that ammonia into urea, which is a nontoxic substance that can be excreted by our kidneys."}, {"title": "Function of the Liver.txt", "text": "Now, the liver also detoxifies pollutants, various types of contaminants and many, many other things."}, {"title": "Function of the Liver.txt", "text": "So the liver converts these toxins, which are usually fat soluble, into water soluble waste products that can easily be excreted in either our bile, which eventually ends up in our feces and is excreted by the large intestine."}, {"title": "Function of the Liver.txt", "text": "It can end up in the urine, which is excreted by the kidneys, or it can end up in the sweat, which is excreted by our skin."}, {"title": "Function of the Liver.txt", "text": "And we'll talk more about sweat and the skin structure in a future lecture."}, {"title": "Function of the Liver.txt", "text": "Now, the third function of our liver is in blood storage blood filtration and the recycling of Erythrocytes, also known as red blood cells."}, {"title": "Function of the Liver.txt", "text": "So the liver can actually expand, so the blood vessels inside the liver are capable of expanding and that means the liver can actually act as a storage system for blood."}, {"title": "Function of the Liver.txt", "text": "So the blood vessels in the liver can expand to store extra blood that might be needed by the body in a future time."}, {"title": "Function of the Liver.txt", "text": "Now, specialized phagocytic cells inside the liver, known as cup force cells, are responsible for fagatizing, for eating up, engulfing and breaking down infectious bacterial cells that are found inside our blood plasma and found inside our liver."}, {"title": "Function of the Liver.txt", "text": "And on top of that, these same copper cells can also recycle and break down the old red blood cells that no longer function properly."}, {"title": "Function of the Liver.txt", "text": "So these red blood cells are also known as erythrocytes."}, {"title": "Function of the Liver.txt", "text": "Now, function number four of the liver is to basically store important types of vitamins such as, for example, vitamin D, as well as iron that are essential for our body."}, {"title": "Function of the Liver.txt", "text": "Now, earlier we mentioned in a previous lecture, we basically mentioned that our liver can also act as an endocrine gland."}, {"title": "Function of the Liver.txt", "text": "It can produce a special type of enzyme, special type of protein that acts as a hormone."}, {"title": "Function of the Liver.txt", "text": "So basically, liver produces thrombopolietin, which is a glycoprotein hormone that is responsible for controlling the blood clotting cascade, as we'll see in a future lecture."}, {"title": "Function of the Liver.txt", "text": "It is responsible for producing platelets that are involved in the blood clotting process."}, {"title": "Function of the Liver.txt", "text": "Now, finally, it acts as an exocrine gland."}, {"title": "Function of the Liver.txt", "text": "It produces the special type of bile substance that we spoke of earlier that is needed to actually multiply and break down our fats inside the small intestine."}, {"title": "Function of the Liver.txt", "text": "So the liver also has other functions."}, {"title": "Function of the Liver.txt", "text": "But these are the five or six primary functions of the liver."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So as we'll see in much more detail, the way that our body synthesize proteins is quite different than the way that we synthesize proteins in the lab."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "For instance, in our body, ribosomes build proteins by beginning at the terminal amino end and ending at the terminal carboxylan."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "But in the laboratory, we begin building proteins at the terminal carboxyl end and we move backwards towards that terminal amino n. So we build proteins in the opposite direction to how the proteins are built inside ourselves."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now, how does this procedure actually work and how do we build these proteins in a laboratory setting?"}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So in this lecture, we're going to discuss the solid phase method of building proteins in the lab."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So what exactly is the major point of the solid phase method?"}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Well, there are two important points."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Point number one is we begin at the amino acid that is at the terminal carboxyl end, and we take this amino acid and we attach it onto a solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "We basically anchor our amino acid on that solid surface and we continually attach amino acids one at a time."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And that entire growing polypeptide chain is attached onto a solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And that's to keep that protein, the polypeptide, from actually being washed away."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Because as we add each amino acid, we essentially wash our solution to basically remove all the unwanted things from that solution."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so we want to anchor that growing polypeptide and keep it in place."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now, the second important point of the solid phase method is we have to use different types of molecules, activating and blocking agents to basically promote that particular reaction, the formation of peptide bond that we actually want to form."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So in step number one, in order to promote and increase the specificity of the reaction and decrease the number of unwanted products from actually forming, we have to use these different types of molecules to direct the correct synthesis of the protein."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Because remember, in any given amino acid, we have different types of groups and these different types of groups react in different ways."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so we can have a variety of different types of competing reactions and competing products."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And to basically minimize these unwanted products, we have to use two important agents."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "One of them is DCC, and that's an activating agent and it activates the carbon atom on the carboxyl group of the amino acid."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So D stands for dye, c stands for cyclohexyl, and second, C stands for carbal diamide."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And the blocking agent that we're going to use that essentially attaches and blocks the nitrogen on the amino group of that amino acid, es, tbock and B stands for butyl O stands for oxy."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "MC stands for Carbonal."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So we have DCC and Tbock that must be used in this method to basically prevent different types of competing reactions and competing products from actually forming."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So in step number one, what we want to do is we want to prepare these amino acids."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So by reacting our amino acids, so this molecule here with DCC, we're forming this attachment and that activates this carbon."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And by reacting that same amino acid with Tbock, we're essentially adding this entire component onto the nitrogen and that blocks and deactivates this nitrogen."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "What that means is this nitrogen no longer forms peptide bonds, but this carbon becomes much more likely to form peptide bonds and that will become important in just a moment."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So once we prepare our amino acids, let's go to step number two."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "In step number two, we actually want to take that first amino acid in line from the terminal carboxyla and attach it onto that solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So in step two, an amino acid that has been protected as the amino group by Tbock is attached onto a solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this will be the amino acid found on the terminal carboxyl end of that growing polypeptide chain."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So this is our group that will be attached onto the solid surface that will react with the carbon of the carboxyl group of this amino acid number one."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Or let's call it amino acid number N, assuming that we have a number of amino acid in that eventual polypeptide chain."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And notice we block our nitrogen, because we don't want this nitrogen to form any bonds with this molecule, we only want to form a bond with this carbon here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so by reacting these two groups, we essentially form the following molecule."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So now we have the initial amino acid at the terminal carboxyl end that is attached onto that solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And now we anchor our molecule in place."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so as we continually add our amino acids, as we'll see in just a moment, this growing polypeptide chain will essentially remain anchored onto this solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so we can easily wash our polypeptide many, many times over."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And that polypeptide will not be washed away because it will be physically attached onto that solid surface."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now let's move on to step three."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "In step three, we basically want to remove the tea bag group before we actually want to add this molecule and form that peptide bond between this amino acid and this amino acid here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So next in step three, we deprotect the nitrogen by removing our Tbock and we mix this molecule with a dilute acid."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So for example, we have triflora acetic acid."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So CF three, COOH if we mix this with this molecule, we essentially remove our TBA group."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so what that does is now in step four, if we mix this molecule here with this molecule here, this carbon will be activated to form a peptide bond by the DCC molecule."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And because this nitrogen will be missing that Tbag group, it will be very likely to form that peptide bond."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this nitrogen, because we still have the Tbock attached here, it will not be reactive at all."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so in step four, the activated amino acid that is also blocked by that Tbox."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So the molecule we form in step number one is then mixed with amino acid attached onto that solid surface that we form in step three."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this forms a peptide bond."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So in this diagram, we take this molecule here and we mix it with this amino acid attached onto our solid surface as shown."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And we form a peptide bond between this carbon here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So this carbon right over here and this nitrogen right over here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And notice that this oxygen is actually lost and that's because we also form a molecule known as dicyclohexyluria."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so what happens is this entire molecule is essentially broken off to form this stabilized molecule that is resonance stabilized between this nitrogen, this nitrogen and this oxygen."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so this is the first peptide bond that is formed in our polypeptide chain."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now, if we repeat step number three and step number four many times, we essentially can add many of these amino acids onto our growing polypeptide chain."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So each time we essentially want to remove the TBA group and then we want to add this molecule here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So for instance, in the next step here, we say repeat many times."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "But in the next step, we once again mix this molecule with CF three COOH our trifloroacetic acid, a dilute acid."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "If we mix it with this, that will remove the TBA group."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And then we mix this molecule minus the TBA group with this amino acid and that will form a tripepptide."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And we essentially continue that until we form that polypeptide that we actually want to form."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So let's suppose we followed that step many, many times and eventually we formed the following polypeptide chain that consists of N number of amino acids."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So this is the first amino acid that contains the group R one."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this is the last amino acid that contains the r group RN."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so this is the amino acid that we began with."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this is the final amino acid that is found on the alpha amino terminal N, while this is the one that is found on the alpha carboxyl terminal end of that polypeptide chain."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now, in the final step, once we actually form this polypeptide chain, what we have to do is a, we have to break this bond here and detach our polypeptide from this solid surface and b, we also want to remove this T bog group."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Now, the tea bog group can be simply removed by mixing it with this molecule here."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "But how do we break this bond here?"}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So the question is, how do we break this bond without breaking any of the peptide bonds in that polypeptide chain?"}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "Well, we have to mix it with hydrofluoric acid."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "If we mix it with HF in the presence of this molecule here, that essentially removes this teapot group and any other blocking group found on any of the side chains."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And we also basically break this bond here without actually breaking any of those peptide bonds."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So at the end of the synthesis the protein is released from the solid surface by adding hydrofluoric acid into our mixture."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And this breaks the carboxyl acid bonds to this bond without breaking any of the peptide bonds."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And so it leaves those peptide bonds intact."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And then we remove our protective groups by using these types of molecules."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So for example trifloroacetic acid and at the end we form our polypeptide that we wanted to form."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "So this is how we basically form our proteins in a laboratory setting."}, {"title": "Solid-Phase Synthesis of Proteins .txt", "text": "And we'll see that it's much different in the way that we form proteins in the cells of our body."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Bone is a very rigid type of connective tissue."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So that basically means bones are dense, bones are strong, and bones are hard."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So they have the ability to resist both tensile as well as compressive forces."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "The question is why?"}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "What exactly is found inside the bone that gives bone these types of properties?"}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So basically, it's the extra, extracellular matrix that is found surrounding our cells and in between our cells that actually gives the bone these types of properties."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So, before we discuss the different types of cells inside the bone and the structure of the bone, let's discuss the extracellular matrix of the bone."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the extracellular matrix consists of organic matter as well as inorganic matter."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "The organic component consists predominantly of a type of protein known as collagen."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And it's the collagen that gives the bone the ability to resist tensile forces, it gives the bone tensile strength."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "On the other hand, the inorganic component of the extracellular matrix of the bone gives our bone the ability to resist compressive strength, compressive force, and it gives the bone compressive strength."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And that's because in our inorganic component of the extracellular matrix, we have crystals known as hydroxyapatite."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And hydroxyapatite crystals themselves consist of calcium of phosphate as well as hydroxide ions."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the collagen gives the bone tensile strength, but it's the hydroxy appetite of the extracellular matrix that gives the bone compressive strength."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So now let's discuss the different types of cells found inside our bone."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So we have osteoblasts, we have osteocides, and we also have osteoclasts."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So let's begin with the osteoblasts."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the osteoblasts are basically those cells inside the bone that are responsible for building that bone, for building and secreting the extracellular matrix."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So that means these osteoblasts are capable of secreting collagen into our extracellular matrix."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these cells are capable of taking up calcium as well as phosphate from the blood and depositing it into the extracellular matrix."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So basically, these are the cells that are responsible for building bones."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "They secrete organic as well as inorganic matter such as collagen, calcium as well as phosphates, and are responsible for creating the extracellular matrix that we just discussed above."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, eventually, when these cells completely surround themselves and enclose themselves with the matrix, they basically become, they differentiate into a second type of cell known as an osteocide."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, what exactly is an osteocide?"}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Well, basically, the osteocide is the most common type of cells found in the bone."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And the osteocide is responsible for providing the bone with nutrients that the bone actually needs to survive."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the osteocide is connected to the blood vessels that carry the different types of nutrients, as we'll see in just a moment."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So osteocides are the most common types of cells found inside bone and they are responsible for obtaining nutrients from the blood as well as dumping any type of waste products into our blood so that those waste products are recycled."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So osteocides contain extensions that are known as processes."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So these two purple regions are the osteocides and these blue extensions are our processes."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now these processes radiate outward and eventually they connect with canals."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these canals are known as canal liquili."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So these canal liquili basically are canals that connect one osteocide to a second osteocide."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these can alliculi basically are responsible for exchanging different types of materials between our adjacent osteocytes."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, the final type of cell that I'd like to mention is our osteoclasts."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So if these osteoblasts basically build bone, and one way to remember osteoblast, building bone is the fact that we have a B in osteoblast."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the B stands for building."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So osteocides build bones, but osteoclasts do the opposite of building."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "They basically resorb our bone."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "They break down the extracellular matrix of the bone and they secrete that into the blood."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "For example, they can break down our hydroxy appetite and they can release the calcium, the phosphate, back into the blood."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So osteoclasts are the cells responsible for resorbing bone and that basically means they break down bone and they break down the extracellular matrix and release the minerals such as calcium and phosphate into the blood."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, at times that can actually be helpful because let's say our muscle cells require calcium to contract."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And if we need our calcium, this is how our bone basically releases the calcium so that the muscles can actually contract."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And when we discuss the process of reforming and remodeling our bone, the osteoclast and the osteoblast basically play a crucial role in that process."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the bone is a living tissue, it's continually being reformed."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So that means it's continually being broken down and reformed."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And that's exactly why these two cells are crucial."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, what about the structure of the bone?"}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So just like our muscle cells, our skeletal muscle cells and cardiac muscle cells consist of individual units known as sarcomeres."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "The bone also consists of individual units known as osteons."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, the osteon consists of concentric rings, concentric circles that are known as lamelle."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these lamelle are basically our extracellular matrix that we spoke of earlier."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So this is the top view of our osteon."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "We have these concentric circles we call Lamelli."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So this is one lamelle, a second Lamelli, a third Lamelli."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "These are the regions shown in white."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And the Lamelli is basically our extracellular matrix that consists of collagen and our hydroxy appetite."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, along our Lamelli, we basically have these spaces, these space regions known as our Lacuni."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these Lacuni are basically shown in black."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So these are the spaces."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And within these spaces we basically have the osteoblasts that secreted our extracellular matrix and eventually became our osteocides."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So these purple dots are basically our osteocides."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these blue extensions are the processes, as well as our canals known as our canal liquili."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So we have these blue extensions, we have our canals known as canaliculi, and we also have this center region at the center of our osteon known as a hoversion canal."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, this hoversion canal is basically a central canal that consists of lymph vessels, it consists of blood vessels and it also consists of neurons, so, nerve cells."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So, in the center of the osteon, the building block of the bone, we have a canal known as our Herbertian Canal or the central canal."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And this canal contains the blood vessels, our lymph vessels that basically carry away different types of waste products."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "The blood vessels bring different types of nutrients and we also have neurons that basically innervate our bone."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, bone contain many of these individual osteons."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So if we actually take a small cross section of our bone, we basically get the following diagram."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So, we have many of these osteons."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "In this case, we have 123456 of these concentric cylindrical regions we call osteons."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And at the center of each osteon we have our central canal known as the Herbertian canal."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And within this her version canal, we basically have the blood vessels, lymph vessels and our nerve cells, our nerve fibers."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, what about the connecting regions between these hiversion canals?"}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So, the Herversion canal of one asteon is connected to the hererson canal of a different adjacent osteon via a canal known as our Volkmans canal."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So the volcano canal is basically our canal that bridges that connects adjacent harvesting canals as shown in the following cross sectional diagram."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "So once again, the building unit of our bone is known as an osteon."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And the osteon consists predominantly of this matrix, the extracellular matrix that is created by osteoblast."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And once we create this matrix, the osteoblasts basically differentiate into our osteocides shown by these purple regions."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "These osteocides basically have these extensions known as processes."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these processes connect to one another via these canals known as our canaliculi."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And these canaliculi basically connect and allow adjacent osteocides to exchange important types of materials, important types of nutrients."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, within our center region of the osteon, we have our harvestion canal which contains our blood vessels, lymph vessels, as well as our nerve cells, our neurons."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, these concentric regions of matrix is known as our Lamelli."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And the space is where we have the osteocides that is known as Lacuni."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "Now, inside the matrix, we have collagen as the main organic matter and we have the hydroxy appetite as the main inorganic matter."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And inside bone, we have three types of cells osteoblasts that build the matrix and build the bone osteocides that allow the exchange of nutrients between other osteocides as well as our blood and lymph vessels."}, {"title": "Compact Bone Structure and Osteon System .txt", "text": "And we have the osteoclasts that basically absorb our bone, break down the bone and release the different types of materials, minerals into our blood."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Six out of 20 amino acids can readily be metabolized into Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And because of that, we call them glucogenic."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Remember, inside our liver, we can transform Pyruvate into oxylacetate, and then the oxyloacetate is transformed into glucose via glucaniogenesis, and that's why we call them glucogenic."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, some of these are actually ketogenic as well, but let's not talk about that."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So let's begin with cystine."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So we see that Cysteine Alanine Tryptophan, glycine, serene and threatening can all be transformed into Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So let's begin with cysteine."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, the conversion of cysteine into Pyruvate is actually pretty complicated because there are several different pathways by which cysteine can be transformed into Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So we're not going to look at the details of those steps or those pathways."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "But I will mention that in the conversion of cysteine to Pyruvate, we have to somehow remove this sulfur atom."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so, depending on the pathway that is followed, that sulfur atom is released as either thiocyanate, hydrogen sulfide or sulfur trioxide, and we ultimately form the Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now let's move on to the conversion of Alanine into Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, we actually discussed this before, so we saw that Alanine could be transformed to Pyruvate in a single step, in a single transamination step."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And the enzyme that catalyzes this is known as Alanine aminotransferase."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So this enzyme utilizes a co enzyme, PLP, so, paradoxyl phosphate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so Alanine basically reacts with alpha keylutrate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So we essentially transfer the amino group from Alanine to alpha ketogliate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "We form Pyruvate and Glutamate as a result."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And the Pyruvate we see is formed in a single step."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, in the second step, not shown here, we have the glutamate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And we transform that Glutamate into well, we actually release the ammonium, the ammonium group, from the glutamate, and we reform that alpha key to glutarate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And in this process, we have to use an NAD plus or NADP plus, as well as a water molecule to basically remove that ammonium from glutamate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So that's how we go from Alanine to Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, Tryptophan basically is transformed into Pyruvate by first converting Tryptophan to Alanine, and then Alanine basically follows this step to form the Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now let's move on to Serene."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So serene can be transformed to Pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And we actually saw before that this was a two step process, and this was catalyzed by Serene Dehydrates."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So in the first step, we basically have a water molecule that leaps."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So we have the combination of this hydroxide."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So the hydroxide group combines with this H plus ion to form a water."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And the two electrons in this bond basically form a double bond between this carbon and this carbon."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And we form this high energy intermediate molecule, amino acrylate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And then the amino Acrylate basically undergoes a hydrolysis step or said another way, a diamondination step, in which we have the water molecule kicking off this ammonium group."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so we form this Pyruvate as a result."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so, again, the enzyme that catalyzes step is serene dehydrates."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, glycine can actually be transformed into pyruvate by first transforming the glycine into serene."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And the way that we form the serine from glycine is by adding a hydroxy methyl group."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So where does that hydroxy methyl group come from?"}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Well, from a molecule known as phyton methylene THF, where THF stands for tetrahydropholate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So we have glycine in the presence of water and in the presence of this molecule."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Phy ten methylene tetrahydrophoblate basically undergoes a reaction that is catalyzed by serine hydroxy methyl transferase."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so what this enzyme does is it ultimately transfers this group here, shown in blue, as well as uses the water molecule to actually attach that hydroxide group onto glycine."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So ultimately, we attach a hydroxy methyl group onto the glycine to form our serene."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "And so then the serine, we actually also form the THF, the tetrahydrophobate, and then the serene basically follows the steps that we have on the board."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "Now, what about the last one, three anine."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So, three anine can be transformed into pyruvate via an intermediate molecule known as two amino, three ketobutyrate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So first we transform three anine into two amino, three ketobutyrate, and then we transform that molecule into pyruvate."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "So these are the six amino acids that can readily be transformed into pyramid iruvate molecules."}, {"title": "Metabolism of amino acids to pyruvate .txt", "text": "We have cysteine tryptophan, glycine, aline, serine, and three anine."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Another important measurement that we have to be familiar with, that describes the way that our blood flows inside blood vessels of our cardiovascular system is a measurement known as the resistance of our blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, in this lecture, we're not only going to focus on resistance, we're also going to discuss the relationship between resistance and something called the volume flow rate of of our blood."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So let's begin by describing the factors that influence our resistance of the blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we have three different factors that determine the resistance to blood flow in a given blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So factor number one is the viscosity of our blood, and the viscosity is the internal resistance inside the blood that exists because of the attraction between the molecules and particles themselves that are found within our blood."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So the more attraction we have inside the blood between the individual particles, the higher our internal resistance is and the greater our viscosity is."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And we'll talk about what the actual relationship between Viscosity and the resistance is in just a moment."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, factor number two that affects resistance is the length of our blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And factor number three is the radius or diameter of that particular blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, by far, the most important physiological factor that influences the resistance inside our blood vessel is the blood vessel diameter."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that's because the blood vessel length."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And our viscosity of that blood under normal conditions does not actually change considerably."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "But because our autonomic nervous system innervates and controls the smooth muscle found inside the blood vessel, the diameter and the radius can easily be controlled by our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that's exactly why it's the diameter that actually influences the resistance of blood vessels the most in our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So the next question is, what exactly is the relationship between the resistance and these three different factors that we mentioned just a moment ago?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So the relationship is given by this equation."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So our upper case R. The resistance of the blood vessel is equal to eight multiplied by the viscosity multiplied by the length of that blood vessel divided by pi multiplied by R raised to the power of four."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, from this equation, we see that the resistance depends directly on the viscosity and on the length."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So if we increase the length or if we increase our viscosity, we increase the resistance of our blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "But by increasing our radius, we basically increase the denominator, and that decreases our resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we see we have an inverse relationship between our resistance and our radius."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "In fact, we see that by changing our radius, that actually affects our resistance the most."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that's because the radius is raised to the power of four."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So to see what we mean, let's take a look at the following three bullet points."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, in bullet point number one, we basically want to double the length of our blood vessel while keeping everything else constant."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So if L is doubled Then we see."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "We multiply this left side by two."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we have to multiply the right side by two."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So that increases our resistance by a factor of two."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So doubling the length will double our resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And likewise, if we double the viscosity but we keep everything else the same, then we also double our resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So by doubling the length or by doubling our viscosity, we can increase the resistance by a factor of two."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "But let's see what happens if we double our radius."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "By doubling our radius, we not only double our denominator, we actually increase our denominator by a factor of 16."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that's because the radius is raised to the power of four, and two to the power of four is 16."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So if the radius is doubled but everything else is allowed to stay the same, then we decrease our resistance by a factor of 16."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that means, in general, changing the radius will affect the resistance much more than if we change the length or if we change our viscosity."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So from this discussion, we can basically conclude that our body actually changes the resistance of our blood vessels not by changing the viscosity or the blind length, the blood vessel length, but rather by changing the radius, the diameter of our blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So it's no surprise that our body uses the blood vessel's diameter to control the resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And this ultimately controls the volume of blood that actually reaches our tissue or organ of our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, let's discuss something known as the volume flow rate."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So the volume flow rate is simply the volume of blood that passes our blood vessel over some given period of time."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And in physics and from fluid dynamics, we know that our volume flow rate of the blood queue is equal to the change in pressure between some .1 and some .2 inside our blood vessel divided by the resistance of that blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, if we take this equation and we plug it in for the resistance, we basically get the following equation."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So Q is equal to pi radius, the power of four multiplied by the change in pressure divided by a multiplied by the viscosity multiplied by the length of that blood vessel."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now this equation influid dynamics is known as placier's equation."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And as long as we assume that the blood is incompressible and that the fluid is flowing, the blood is flowing in laminar or streamlined flow, then we can use this equation to study and understand the way that our blood flows inside our blood vessels."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, why is this equation important?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Well, this equation is important because it describes the volume flow rate to the resistance indirectly."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So notice that we have a radius on the left side of the equation."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And we know that the radius depends on the resistance, or the radius determines the resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So let's say by increasing the radius, we decrease our resistance."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And from this equation, if we increase the radius, we ultimately increase the volume flow rate."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So what this means is if we increase the radius even by a small amount, we increase the volume flow rate by a much greater factor."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And this can be seen from the following graph."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So if we assume that l the length, the viscosity and the change in pressure is constant and we plot our relationship this equation, we basically get the following curve."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now the y axis is the relative volume flow rate Q and the x axis is the relative radius given by lowercase r. So from this relationship we see that even a tiny change in the radius can greatly increase the relative flow rate of our blood."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now what this means is our body can actually adjust the radius and the diameter of small arteries and arterios in order to actually meet the metabolic requirements of oxygen and nutrients that our organs and tissues of our body actually need."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So to see, to demonstrate what this actually means and how our body controls the resistance and ultimately the volume flow rate, let's take a look at the following example."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So let's suppose we are being chased by a dog and at the moment as we begin to run away from that dog, our skeletal muscle in our body begins to work much more vigorously."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And what that means is we're going to increase the amount of oxygen and nutrients that the skeletal tissue, skeletal muscle tissue will actually need."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now the question is how exactly can the body actually increase the volume flow rate to the tissue of our body that needs the increase in metabolic nutrients and oxygen?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Well, one way is to increase our pressure."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So let's take a look at the following equation plusier's equation which is rewritten right here."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now let's suppose that our skeletal muscle tissue requires five times as much blood as in a normal situation when the skeletal tissue is fully relaxed."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that means what we want to do is we basically want to multiply Q by a factor of five."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now, how exactly do we multiply Q by a factor five?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Well, one way to increase the right size of the equation is to increase the change in pressure by a factor of five."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we see that one way to actually meet this increase requirement of the skeletal muscle tissue is for the body to actually increase the change in blood pressure to 500% of its original value."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Now the problem with this is if we increase the pressure by that much that can basically pop our blood vessels, it can blow up those arteries and that can lead to many many problems."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we see by increasing the pressure by that much that can actually be dangerous."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So what the body does instead, a much less dangerous and a much more effective way to actually regulate the volume flow rate to the skeletal muscle tissue is by controlling the resistance of our blood vessel, by changing the radius."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So let's take a look at that same equation."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we multiply the cube by five."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "The question is, what can we do to the left side to get the factor of five?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Well, basically, we can increase the radius by factor of 1.5, and that's equivalent to only increasing the radius by 50%."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that's because 1.5 raised the power of four, gives us approximately five."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we see that in this case, to get the same volume flow rate, we have to increase the pressure by factor five."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And that can be very dangerous."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So instead of actually blowing up those blood vessels, popping those blood vessels, our body instead chooses to increase the radius only by 50% to basically get that same body and flow rate to our skeletal tissues."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So what exactly can we conclude from our discussion?"}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "Well, we see that our body can regulate the amount of blood that actually it delivers to some given tissue over some time period by either vassal constricting or by vassal dilating by changing the radius of our arterial the small arteries in our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So we see that this is actually done because a small change in the diameter of these blood vessels will basically greatly change the resistance and that will greatly influence the volume flow rate of blood inside our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "So once again, resistance is controlled by changing the radius inside our body."}, {"title": "Resistance of Blood Vessels and Volume Flow Rate .txt", "text": "And by changing the radius, we also change our cue the volume flow rate by the greatest percent amount compared to other factors such as pressure, length as well as the skin of the blood."}, {"title": "Adrenal Gland.txt", "text": "The next endocrine gland that we're going to focus on is the adrenal gland."}, {"title": "Adrenal Gland.txt", "text": "Now, the adrenaline gland is found on top of our kidney and because we have two kidneys, that means we have two adrenal glands."}, {"title": "Adrenal Gland.txt", "text": "We have the right adrenal gland found on top of the right kidney and the left adrenaline gland found on top of the left kidney."}, {"title": "Adrenal Gland.txt", "text": "So these glands are shown in orange."}, {"title": "Adrenal Gland.txt", "text": "Now, if we cut our adrenal gland in half, we basically get the following diagram."}, {"title": "Adrenal Gland.txt", "text": "So we see that we have an outer portion known as the adrenal cortex and the inner portion known as our adrenal medulla."}, {"title": "Adrenal Gland.txt", "text": "And each one of these divisions basically is responsible for creating and secreting their own set of hormones."}, {"title": "Adrenal Gland.txt", "text": "So let's begin by focusing on the adrenal medulla."}, {"title": "Adrenal Gland.txt", "text": "Now, the medulla is the inner portion of our adrenal gland and it is responsible for secreting those hormones that essentially help us respond to physically and emotionally stressful and challenging situations."}, {"title": "Adrenal Gland.txt", "text": "Now, the cells of the medulla are actually connected to the sympathetic division of the autonomic nervous system and that's because these hormones that are used by this endocrine gland are also used by the nervous system as neurotransmitters."}, {"title": "Adrenal Gland.txt", "text": "And we'll see what that means in just a moment."}, {"title": "Adrenal Gland.txt", "text": "So the adrenal gland is responsible for secreting two types of hormones."}, {"title": "Adrenal Gland.txt", "text": "We have epinephrine, also known as adrenaline, and we have norepinephrine, also known as noradrenaline."}, {"title": "Adrenal Gland.txt", "text": "Now, these two hormones are tyrosine derivatives and that means they are produced from tyrosine amino acid."}, {"title": "Adrenal Gland.txt", "text": "And that's exactly why epinephrine and norepinephrine are part of a group of molecules that are collectively known as cater colonines."}, {"title": "Adrenal Gland.txt", "text": "Now, our epinephrine and norepinephrine are also water soluble."}, {"title": "Adrenal Gland.txt", "text": "And what that basically means is they can easily dissolve inside our blood and they do not actually need any type of protein carrier to transport them inside the blood to their target cell."}, {"title": "Adrenal Gland.txt", "text": "Now, the fact that they're water soluble and not lipid soluble means that they cannot actually pass across the cell membrane of the target cell and they bind onto receptors on target cell membranes and they create a secondary messenger response to basically initiate some type of effect inside the target cell."}, {"title": "Adrenal Gland.txt", "text": "So epinephrine and norepinephrine are very similar in the type of response that they create inside our cell and inside our body as a whole."}, {"title": "Adrenal Gland.txt", "text": "So epinephrine is responsible for increasing the rate of our heart, the rate at which our heart pumps blood, and also the force with which our heart actually pumps that blood."}, {"title": "Adrenal Gland.txt", "text": "So that means because of epinephrine, the blood can get to our tissue faster and more blood can get to those tissues."}, {"title": "Adrenal Gland.txt", "text": "Now, what this also does is it increases the rate of respiration so that we breathe more and more oxygen basically gets to our tissues."}, {"title": "Adrenal Gland.txt", "text": "Now, epinephrine also increases the breakdown of glycogen inside our liver cells into glucose so that we have more glucose in our blood readily available to be used by our cells of the body to create ATP for energy."}, {"title": "Adrenal Gland.txt", "text": "And it also dilates blood vessels as well as constrict other blood vessels."}, {"title": "Adrenal Gland.txt", "text": "And the net result is more blood flows into our skeletal muscle as well as our brain, and less muscle and less blood flows into certain internal organs, such as our digestive system."}, {"title": "Adrenal Gland.txt", "text": "Now, norepinephrine is the hormone that is used to basically constrict our blood vessels, and that means that increases the blood pressure inside our blood vessels."}, {"title": "Adrenal Gland.txt", "text": "Now, these two molecules are also used as neurotransmitters by the nervous system."}, {"title": "Adrenal Gland.txt", "text": "But the major difference between the neurotransmitter and a hormone is the hormone actually creates a much longer lasting effect than our neurotransmitters."}, {"title": "Adrenal Gland.txt", "text": "So although the nervous system also uses these two molecules, it uses them as neurotransmitters."}, {"title": "Adrenal Gland.txt", "text": "And that means it's a much shorter type of effect than our endocrine system that uses them to create a much longer lasting effect."}, {"title": "Adrenal Gland.txt", "text": "Now let's move on to our outer portion known as the cortex."}, {"title": "Adrenal Gland.txt", "text": "So the adrenal cortex of our adrenal gland is responsible for secreting a group of hormones known as our corticosteroids."}, {"title": "Adrenal Gland.txt", "text": "Now, Corticosteroids simply means they are derived from steroids, specifically from cholesterol, and that makes them lipid soluble."}, {"title": "Adrenal Gland.txt", "text": "So that means all of these hormones are basically not water soluble."}, {"title": "Adrenal Gland.txt", "text": "So that means they do need carriers, protein carriers, to transport them inside the blood plasma."}, {"title": "Adrenal Gland.txt", "text": "And they basically can easily cross the cell membrane of the target cell because the cell membrane is lipid soluble, as are these hormones."}, {"title": "Adrenal Gland.txt", "text": "So we have several different groups of hormones that we have to be familiar with."}, {"title": "Adrenal Gland.txt", "text": "We have aldosterone, we have Cortisol and Cortisone and also our."}, {"title": "Adrenal Gland.txt", "text": "Androgen so let's begin with aldosterone."}, {"title": "Adrenal Gland.txt", "text": "Now, we'll discuss aldosterone in much more detail when we'll discuss the structure and the function of our kidneys."}, {"title": "Adrenal Gland.txt", "text": "So basically, aldosterone is a type of mineral, corticoid."}, {"title": "Adrenal Gland.txt", "text": "And what that basically means is it is responsible for ensuring that we have a healthy as well as a good mineral balance inside our bodies."}, {"title": "Adrenal Gland.txt", "text": "So we have a good balance of ions inside our blood plasma."}, {"title": "Adrenal Gland.txt", "text": "Now, what aldecerome does is it actually affects our kidneys, and more specifically, it affects the distal convoluted tubial and the collecting duct found inside our kidney."}, {"title": "Adrenal Gland.txt", "text": "What it does is it increases the amount of sodium and chloride ions that are reabsorbed back into our blood and increases the amount of hydrogen and potassium ions that are secreted back into our urine."}, {"title": "Adrenal Gland.txt", "text": "So the net result is a higher flow, a higher movement of ions into our blood plasma."}, {"title": "Adrenal Gland.txt", "text": "And that basically drags more water into our blood plasma."}, {"title": "Adrenal Gland.txt", "text": "So that increases the blood volume inside our blood, and that basically increases the blood pressure inside our blood vessels."}, {"title": "Adrenal Gland.txt", "text": "Now, the next set of hormones that are secreted by the adrenaline cortex is Cortisol and Cortisone."}, {"title": "Adrenal Gland.txt", "text": "So Cortisol and Cortisone are very similar in their structure as well as in their functionality."}, {"title": "Adrenal Gland.txt", "text": "And these are hormones that fall into a category known as glucocorticoids so the glucose portion simply means that these hormones are responsible for increasing the rate of production of glucose."}, {"title": "Adrenal Gland.txt", "text": "And the process that they use is basically gluconeogenesis."}, {"title": "Adrenal Gland.txt", "text": "So gluconeogenesis is the production of our glucose from non carbohydrate sources such as lactic acid, amino acids and glycerol."}, {"title": "Adrenal Gland.txt", "text": "So they increase the rate of glucomogenesis in the liver cells and gluconeogenesis is the formation of glucose from non sugar sources such as amino acids, glycerol and lactic acid."}, {"title": "Adrenal Gland.txt", "text": "Now, Cortisol and Cortisol also basically increase the rate at which our liver cells actually break down adipose tissue and release our fatty acids and glycerol into our bloodstream."}, {"title": "Adrenal Gland.txt", "text": "So remember, our adipose tissue basically stores our triglycerides and these triglycerides can be broken down into fatty acid and glycerol released into our bloodstream."}, {"title": "Adrenal Gland.txt", "text": "And then the cells can pick up those fatty acids and glycerol and use them to basically synthesize glucose and synthesize our ATP and use it as energy sources."}, {"title": "Adrenal Gland.txt", "text": "Now, Cortisol and Cortisone are also basically used to decrease the overall rate of protein synthesis in our body and they also decrease the effectiveness of our immune system."}, {"title": "Adrenal Gland.txt", "text": "And that means they decrease inflammation and swelling responses."}, {"title": "Adrenal Gland.txt", "text": "And that's exactly why these hormones are commonly used by athletes to basically decrease the amount of swelling and inflammation that takes place as a result of some type of minor injury."}, {"title": "Adrenal Gland.txt", "text": "Now, the third category of hormones that is released by the adrenal cortex is the antigens."}, {"title": "Adrenal Gland.txt", "text": "And these are basically the male sex hormones."}, {"title": "Adrenal Gland.txt", "text": "And we'll discuss these in much more detail when we'll discuss the reproduction cycle of the human organism."}, {"title": "Adrenal Gland.txt", "text": "Now, the final thing that I'd like to briefly discuss is how our body actually controls the amount of corticosteroids released by our body."}, {"title": "Adrenal Gland.txt", "text": "So how much of these hormones are found in our bloodstream?"}, {"title": "Adrenal Gland.txt", "text": "So recall in our discussion of the hypothalamus and our anterior pituitary gland, we said that the anterior pituitary gland releases a hormone known as our adrenal corticotropic hormone or ACTH."}, {"title": "Adrenal Gland.txt", "text": "And ACTH is itself released and stimulated by a hormone released by the hypothalamus known as the corticotropic releasing factor."}, {"title": "Adrenal Gland.txt", "text": "So the Hypothalamus stimulates the release of corticotropic releasing factor which basically stimulates the interior pituitary gland to release ACTH."}, {"title": "Adrenal Gland.txt", "text": "And then ACTH enters our bloodstream and travels down into our adrenal cortex, an adrenal gland, and basically stimulates the release of our corticosteroids, such as, for example, cortisol."}, {"title": "Adrenal Gland.txt", "text": "Now, the way that our concentration of cortisol and other corticosteroids is maintained in our blood is via a negative feedback loop."}, {"title": "Adrenal Gland.txt", "text": "And what that basically means is these corticosteroids, as the concentration of these steroids increases inside our blood, they can travel back up to our hypothalamus and they can basically inhibit the release of these molecules, specifically of ACTH."}, {"title": "Adrenal Gland.txt", "text": "And that will in turn decrease and maintain the proper concentration of these hormones inside our bloodstream."}, {"title": "Organogenesis.txt", "text": "Organogenesis is the process by which the different types of tissues and organs and systems are formed by that developing embryo in that developing fetus."}, {"title": "Organogenesis.txt", "text": "So in this lecture, we're going to focus on which organs and which systems are formed by these three different germ layers."}, {"title": "Organogenesis.txt", "text": "But first, let's begin by discussing the early process known as gastrolation."}, {"title": "Organogenesis.txt", "text": "So during early embryological development, we have a process known as gastrolation that takes place."}, {"title": "Organogenesis.txt", "text": "So we have the Blastocyst implanticon cells onto the endometrium, the lining of the uterus and then gastrolation takes place and gastrolation produces the three different germ layers."}, {"title": "Organogenesis.txt", "text": "So let's take a cross section of the gastrola stage of embryological development."}, {"title": "Organogenesis.txt", "text": "We get the following diagram."}, {"title": "Organogenesis.txt", "text": "So let's begin with these out of those cells known as the Trophy Blast cells."}, {"title": "Organogenesis.txt", "text": "Now, these Trophy Blast cells eventually give rise to the coriane and the placenta while all these inside cells, inner cells, make up the three different germ layers."}, {"title": "Organogenesis.txt", "text": "And all these germ layers eventually give rise to all the different structures and organs and tissues and systems found inside that adult human individual."}, {"title": "Organogenesis.txt", "text": "So let's focus on the inner mass, on the inner portion of this gastrula."}, {"title": "Organogenesis.txt", "text": "So we have three different types of cells."}, {"title": "Organogenesis.txt", "text": "We have these light purple cells that make up the ectoderm layer, the innermost layer."}, {"title": "Organogenesis.txt", "text": "We have these red mesodermal cells that make up the middle mesoderm layer."}, {"title": "Organogenesis.txt", "text": "And then we have the innermost cells, these brown cells that make up the endoderm germ layer."}, {"title": "Organogenesis.txt", "text": "And each one of these germ layers gives rise to many different types of structures and organs."}, {"title": "Organogenesis.txt", "text": "So let's begin by focusing on the ectoderm."}, {"title": "Organogenesis.txt", "text": "So the cells of the ectoderm basically make up the outer portion of that developing embryo."}, {"title": "Organogenesis.txt", "text": "And so there's no surprise that the ectoderm layer basically forms the outer portion of our body and that includes our skin, our integumentary system."}, {"title": "Organogenesis.txt", "text": "So basically the outer layer of the skin, the epidermis of the skin, is formed by the ectoderm as well as all the accessory structures down inside our skin."}, {"title": "Organogenesis.txt", "text": "For example, we have the nails, we have the hairs and we have the hair follicles."}, {"title": "Organogenesis.txt", "text": "We have the sebaceous glands, the oil glands."}, {"title": "Organogenesis.txt", "text": "We also have the sweat glands that are formed by the ectoderm germ layer."}, {"title": "Organogenesis.txt", "text": "We also form the sensory cells as well as melanocides."}, {"title": "Organogenesis.txt", "text": "So melanocides are those cells that not only give us pigment but also protect us from UV radiation that comes from the sun."}, {"title": "Organogenesis.txt", "text": "So the integrationary system found on the outside is formed from the ectoderm, which is the outermost layer of that developing embryo."}, {"title": "Organogenesis.txt", "text": "These lipurpose cells shown in this diagram."}, {"title": "Organogenesis.txt", "text": "Now, we also actually form different types of structures that are found inside that developing embryo."}, {"title": "Organogenesis.txt", "text": "The question is, how does that happen?"}, {"title": "Organogenesis.txt", "text": "How do cells that are initially on the outer portion of that developing embryo eventually form structures found on the inside of that embryo, on the inside of that fetus?"}, {"title": "Organogenesis.txt", "text": "Well, as it turns out, this process of embryological development is actually a complicated process and we not only have cell differentiation and cell growth and cell proliferation but all these cells also move around many times and rearrange themselves inside that developing embryo."}, {"title": "Organogenesis.txt", "text": "In fact, as we discussed in the process of neuralization when we produce the nervous system it's the ectodermal cells that eventually invaginate and move into that embryo and form the neural crests and the neural tube."}, {"title": "Organogenesis.txt", "text": "Now it's the neural tube that gives rise to the central nervous system that makes up the brain and a spinal cord and it's the neural crest, the cell of the ectoderm that end up inside that embryo that eventually gives rise to the peripheral nervous system."}, {"title": "Organogenesis.txt", "text": "All the nerve cells down on the outside of the central nervous system the cells we call the ganglia."}, {"title": "Organogenesis.txt", "text": "So the entire nervous system and the entire or essentially the entire integumentary system is formed by the ectoderm."}, {"title": "Organogenesis.txt", "text": "As we'll see in just a moment the inner layer of the skin known as the dermis is actually formed from the mesoderm layer."}, {"title": "Organogenesis.txt", "text": "Now what other organs found on the outside and the inside are also formed from the exoderm?"}, {"title": "Organogenesis.txt", "text": "Well, basically we have sensory organs."}, {"title": "Organogenesis.txt", "text": "Not only are the sensory cells on the skin formed from the exoderm but the lens of the eye and the cornea of the eye are also formed from the ectoderm."}, {"title": "Organogenesis.txt", "text": "Now we also form the epithelium of the mouth and the anus from the ectoderm."}, {"title": "Organogenesis.txt", "text": "The majority of the digestive system as we'll see in just a moment is actually formed from the endoderm layer."}, {"title": "Organogenesis.txt", "text": "But the epithelium of the mouth and the anus are in fact formed from the actoderm germ layer."}, {"title": "Organogenesis.txt", "text": "Now we also form the epithelium of the pituitary gland found in the brain as well as the penial gland."}, {"title": "Organogenesis.txt", "text": "And that makes sense because these structures are found close to our nervous system inside our brain."}, {"title": "Organogenesis.txt", "text": "Now remember on top of our kidneys we have this type of hormonal gland known as the adrenal gland and we have the adrenal medulla and the adrenal cortex."}, {"title": "Organogenesis.txt", "text": "So the adrenal medulla portion, the inner portion of that adrenal gland is actually formed from the ectoderm."}, {"title": "Organogenesis.txt", "text": "And we'll see in just a moment that the other portion, the adrenal cortex is formed from the mesoderm germ layer."}, {"title": "Organogenesis.txt", "text": "Finally the hour covering of our teeth known as the tooth enamel is formed from the actoderm germ layer as well."}, {"title": "Organogenesis.txt", "text": "So all of these structures and organs and systems are formed from the actoderm germ layer these light purple cells shown in the diagram."}, {"title": "Organogenesis.txt", "text": "Now let's move on to these middle red cells that make up the mesoderm germ layer."}, {"title": "Organogenesis.txt", "text": "So essentially many of the different Oregon structures that are found in between these two layers are formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "So that includes all the different types of muscle."}, {"title": "Organogenesis.txt", "text": "So the skeletal muscle, the cardiac muscle and a smooth muscle is formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "And that's actually easy to remember because both of these begin with the letter M. Now if we form the cardiac muscle and the smooth muscle from the mesoderm, then that implies the entire cardiovascular system which consists of the heart that is formed from cardiac muscle and the blood vessels and blood are also formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "So the cardiovascular system, the circulatory system is found, is formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "Now blood is a connective tissue and the mesoderm not only forms this connective tissue, it also forms other connective tissue."}, {"title": "Organogenesis.txt", "text": "So what other connective tissue do we have in our body?"}, {"title": "Organogenesis.txt", "text": "Well, bone, bone is a type of connective tissue and so the skeletal system is also formed from the mesoderm germ layer."}, {"title": "Organogenesis.txt", "text": "And that makes sense because it is located in between these two layers."}, {"title": "Organogenesis.txt", "text": "So we have the bone and the bone marrow, the red bone marrow and the yellow bone marrow are basically formed from our mesoderm layer as well as our cartilage."}, {"title": "Organogenesis.txt", "text": "Now together the cardiac muscle which consists of these two types of muscle, the cardiovascular system which consists of these two types of muscle as well as the skeletal system, makes up the musculoskeletal system."}, {"title": "Organogenesis.txt", "text": "And so the entire musculoskeletal system which begins with M, is formed from the mesoderm germ layer."}, {"title": "Organogenesis.txt", "text": "Now what else is formed from the mesoderm germ layer."}, {"title": "Organogenesis.txt", "text": "So what else contains vessels?"}, {"title": "Organogenesis.txt", "text": "Well, the lymphatic system contains vessels."}, {"title": "Organogenesis.txt", "text": "And so what that means is the entire lymphatic system is also made from the mesoderm."}, {"title": "Organogenesis.txt", "text": "And the lymphatic system, if you recall, not only plays a role in immunity, in protecting our body from pathogenic infections, but it also plays a role in basically removing that extra fluid that is found in the interstitial space between our cells in the body."}, {"title": "Organogenesis.txt", "text": "Now recall that the adrenal modula, the inner portion of that adrenal gland is formed from the exoderm."}, {"title": "Organogenesis.txt", "text": "But the mesoderm forms the adrenal cortex, the outer portion of those adrenal glands."}, {"title": "Organogenesis.txt", "text": "Now it's the ectoderm that forms the outer portion of the skin but the inner portion of the skin is formed from the macederm."}, {"title": "Organogenesis.txt", "text": "So the dermis, the inner portion is formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "Now that actually makes sense because the dermis of the skin consists predominantly of blood vessels."}, {"title": "Organogenesis.txt", "text": "And because blood vessels are formed from the mesoderm, it makes sense that the dermis is also formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "And finally the excretory system and that includes the kidneys and the ureter as well as the reproductive system."}, {"title": "Organogenesis.txt", "text": "Our gonats are formed from the mesoderm."}, {"title": "Organogenesis.txt", "text": "So in female individuals, the ovaries and males, the testes are formed from the mesoderm layer."}, {"title": "Organogenesis.txt", "text": "Now finally, let's move on to our andoderm germ layer."}, {"title": "Organogenesis.txt", "text": "The endoderm germ layer basically consists of the innermost portions of our body and that includes or the majority of the epithelial layer of our body."}, {"title": "Organogenesis.txt", "text": "So recall that the epithelial layer of the mouth and the amus is formed from the actoderm but the rest of our digestive tract and the rest of our digestive system is formed from the endoderm."}, {"title": "Organogenesis.txt", "text": "So the epithelium of the stomach, the small and large intestine are all formed from the endoderm."}, {"title": "Organogenesis.txt", "text": "And not only that, but as the embryo actually develops our endodermal cells basically create algorithms that eventually form the accessory organs of our digestive system and that includes things like the liver, which forms the bile and the bile eventually stored inside the gallbladder."}, {"title": "Organogenesis.txt", "text": "So the gallbladder is also formed from the endoderm germ layer and we form the pancreas because as we know the pancreas produces many of the digestive enzymes that are used by that digestive system."}, {"title": "Organogenesis.txt", "text": "So essentially the entire digestive system, not including the mouth and the anus, is formed from the endoderm germ layer."}, {"title": "Organogenesis.txt", "text": "So what else do we form?"}, {"title": "Organogenesis.txt", "text": "Well, the thyroid gland, the parathyroid gland and the thiamus gland."}, {"title": "Organogenesis.txt", "text": "All these glands are essentially formed by the endoderm germ layer."}, {"title": "Organogenesis.txt", "text": "Now, the lungs, and more specifically the epithelial layer of the lungs is also formed from the endoderm as well as the epithelial of our reproductive ducts, our reproductive system, our urethra and our bladder."}, {"title": "Organogenesis.txt", "text": "So to summarize, our ectoderm basically forms the outer portion of the skin as well as some organs found inside of our body."}, {"title": "Organogenesis.txt", "text": "And that takes place because a lot of these ectodermal cells actually invaginate and end up inside that developing embryo."}, {"title": "Organogenesis.txt", "text": "Now, the mesoderm forms everything in the middle so that includes the muscle, the cardiovascular system, the skeletal system, the reproductive organs, our gonas, the connective tissues."}, {"title": "Organogenesis.txt", "text": "So bone and cartilage."}, {"title": "Organogenesis.txt", "text": "We have the dermis of the skin, we have the adrenal cortex and the endoderm basically forms the majority of the epithelium, the epithelial layer of our body."}, {"title": "Organogenesis.txt", "text": "So it forms almost the entire digestive system."}, {"title": "Organogenesis.txt", "text": "It forms these three different types of glands."}, {"title": "Organogenesis.txt", "text": "It forms our respiratory system, the lungs as well as the epithelial of the reproductive system the urethra, as well as arabilators."}, {"title": "Organogenesis.txt", "text": "So these are the three different types of germ layers that eventually form all the different types of organs in a process known as organogenesis."}, {"title": "Gene Transfection .txt", "text": "So far in our discussion on recombinant DNA technology, we discussed two important applications of prokaryotic cells."}, {"title": "Gene Transfection .txt", "text": "So we said that we can use bacterial cells to basically replicate gene molecules to make many copies of a single DNA molecule of interest."}, {"title": "Gene Transfection .txt", "text": "And previously we also said that if we modify a eukaryotic gene gene in a specific way by basically removing those introns and splicing together the exons to create this modified gene and then if we introduce that gene into a bacterial cell, the bacterial cell can actually be used to produce the protein that is encoded by that eukaryotic gene."}, {"title": "Gene Transfection .txt", "text": "So these are two important applications of prokaryotic cells."}, {"title": "Gene Transfection .txt", "text": "Now, there's a problem with the second method."}, {"title": "Gene Transfection .txt", "text": "The second method does not always work."}, {"title": "Gene Transfection .txt", "text": "Why is that?"}, {"title": "Gene Transfection .txt", "text": "Well, that's because there is another difference that exists between prokaryotic and eukaryotic cells."}, {"title": "Gene Transfection .txt", "text": "Unlike in eukaryotic cells, in prokaryotic cells, once the protein is synthesized following translation, that protein is not modified in any way."}, {"title": "Gene Transfection .txt", "text": "But in many eukaryotic cells, many eukaryotic proteins are actually modified in different ways in the Golgi apparatus following translation."}, {"title": "Gene Transfection .txt", "text": "And so what that means is we can add different types of components onto our protein, for example, sugar molecules and lipid molecules."}, {"title": "Gene Transfection .txt", "text": "We can also cleave proteins in eukaryotic cells post translationally."}, {"title": "Gene Transfection .txt", "text": "And these things cannot be done inside prokaryotic cells."}, {"title": "Gene Transfection .txt", "text": "So prokaryotic cells simply don't have the machinery, they don't have the Golgi apparatus and other organelles to basically modify the proteins posttranslationally."}, {"title": "Gene Transfection .txt", "text": "And what that means is the second method described here, producing eukaryotic proteins by introducing eukaryotic genes into prokaryotic cells cannot be done for all eukaryotic proteins because of what we just described."}, {"title": "Gene Transfection .txt", "text": "And that leads us directly to the next question."}, {"title": "Gene Transfection .txt", "text": "Can we actually introduce foreign eukaryotic genes into other eukaryotic cells?"}, {"title": "Gene Transfection .txt", "text": "So instead of using prokaryotic cells to produce a desired eukaryotic protein, can we use eukaryotic cells, for example, animal cells, to actually produce copies of proteins that extract the proteins and use those proteins for a variety of different purposes?"}, {"title": "Gene Transfection .txt", "text": "So it turns out that we can actually introduce recombinant DNA molecules, foreign DNA molecules, into certain eukaryotic cells, such as, for example, malcells, as we'll see in just a moment."}, {"title": "Gene Transfection .txt", "text": "And then these genes can basically use to express proteins, produce different types of proteins."}, {"title": "Gene Transfection .txt", "text": "Now, there are three methods that we normally use to basically inject a certain gene into a eukaryotic cell."}, {"title": "Gene Transfection .txt", "text": "Method number one, we'll call injection with microPET."}, {"title": "Gene Transfection .txt", "text": "Method number two, we're going to call injection with a viral agent, specifically with the retrovirus."}, {"title": "Gene Transfection .txt", "text": "And method number three, we're going to call transfection with calcium phosphate."}, {"title": "Gene Transfection .txt", "text": "Transfection simply means the introduction, the injection of that DNA molecule, the foreign DNA, into a eukaryotic cell without using any viral agent."}, {"title": "Gene Transfection .txt", "text": "That's what we mean by transfection."}, {"title": "Gene Transfection .txt", "text": "So let's begin with injection with the micro pipette."}, {"title": "Gene Transfection .txt", "text": "So we essentially have this very, very small instrument called a micro pipette that contains a very small diameter."}, {"title": "Gene Transfection .txt", "text": "And we can essentially hold the nucleus of the cell."}, {"title": "Gene Transfection .txt", "text": "So let's suppose this is the nucleus of our mouse cell."}, {"title": "Gene Transfection .txt", "text": "We can hold the nucleus on one end with some type of instrument, for example a larger pipet, we can hold this in place while at the other end we poke with a special type of micropipet that contains that DNA fragment that we want to inject."}, {"title": "Gene Transfection .txt", "text": "And so by injecting this nucleus of the cell can essentially accept and incorporate that DNA molecule into its genome."}, {"title": "Gene Transfection .txt", "text": "And in the lab about 2% of the mouse cells that essentially are injected with this method will incorporate this DNA molecule into their cell genome."}, {"title": "Gene Transfection .txt", "text": "Now let's move on to method number two injection with viral agents."}, {"title": "Gene Transfection .txt", "text": "And the viral agents that are very effective are retroviruses."}, {"title": "Gene Transfection .txt", "text": "Why?"}, {"title": "Gene Transfection .txt", "text": "Well, because retroviruses are these special viruses that contain reverse transcriptase and what this enzyme does is it essentially reverse transcribes the RNA molecule into the DNA molecule."}, {"title": "Gene Transfection .txt", "text": "And once we produce that viral double stranded DNA molecule in that cell that viral double strand DNA molecule is injected."}, {"title": "Gene Transfection .txt", "text": "It is incorporated into the cell's genome to produce something called a provirus or a proviral DNA."}, {"title": "Gene Transfection .txt", "text": "The profiral DNA is the genome, it's the DNA of that whole cell that has incorporated that viral DNA that we injected."}, {"title": "Gene Transfection .txt", "text": "And the great thing about these retroviruses is most of the time they don't actually kill that cell, at least not immediately."}, {"title": "Gene Transfection .txt", "text": "So retroviruses can be very effective vectors, they can be used to bring four recombinant DNA molecules into the host animal cell and can incorporate it that viral DNA molecule that we want to into that host genome without actually killing that cell."}, {"title": "Gene Transfection .txt", "text": "Now once we incorporate that DNA molecule into the host genome, that DNA is known as a provirus or proviral DNA and we can now use the cell, can use the proviral DNA to basically synthesize the proteins and one of these proteins would be the protein that is encoded by that viral DNA molecule that we injected."}, {"title": "Gene Transfection .txt", "text": "So this is described by the following diagram."}, {"title": "Gene Transfection .txt", "text": "So this is a retroviral vector."}, {"title": "Gene Transfection .txt", "text": "So it basically is our virus that contains these blue molecules."}, {"title": "Gene Transfection .txt", "text": "The blue molecules are a molecule called integrase and integrase is an enzyme that is used to actually incorporate that DNA molecule into the host cell's genome."}, {"title": "Gene Transfection .txt", "text": "We have these purple molecules which are the reverse transcriptase molecules which reverse transcribe the RNA into the DNA."}, {"title": "Gene Transfection .txt", "text": "And so when these green molecules, these dark green molecules are injected into that cell, these are the RNA molecules, this purple the reverse transcriptase, the purple enzyme basically creates this lighter green strand which is basically our DNA molecule and then this one also creates a DNA molecule."}, {"title": "Gene Transfection .txt", "text": "Those two DNA strands essentially combine to form a double helix DNA molecule and then that goes into the cell and the blue enzyme that integrates molecule now incorporates that into the host genome and that forms the proviral DNA."}, {"title": "Gene Transfection .txt", "text": "And now this DNA can be used to synthesize the proteins of interest."}, {"title": "Gene Transfection .txt", "text": "Now, a common type of retrovirus that we use when we're dealing with mouse cells is the Maloney urenne leukemia virus."}, {"title": "Gene Transfection .txt", "text": "And this is used because it can accept DNA molecules as large as 6000 nucleotides in length."}, {"title": "Gene Transfection .txt", "text": "Now, the final method we're going to focus on briefly is known as transfection with calcium phosphate."}, {"title": "Gene Transfection .txt", "text": "And once again, transfection means the injection of that DNA molecule without actually using any type of viral agent."}, {"title": "Gene Transfection .txt", "text": "Now, what we do is we basically create a solution of calcium chloride DNA."}, {"title": "Gene Transfection .txt", "text": "So we have a solution in that solution, we have calcium chloride and we have a DNA molecule."}, {"title": "Gene Transfection .txt", "text": "And then we mix it with a special solution that contains phosphate ions."}, {"title": "Gene Transfection .txt", "text": "And once we mix these two solutions, that calcium phosphate will essentially form a precipitate with that DNA molecule."}, {"title": "Gene Transfection .txt", "text": "And by a mechanism that we don't yet quite know, don't yet quite understand, the cell incorporates that complex, including that DNA, into the cell by some type of endocytotic process."}, {"title": "Gene Transfection .txt", "text": "Endocytosis, it's simply the process by which we have a receptor mediated process by which the cell invaginates and takes that into the cytoplasm of the cell."}, {"title": "Gene Transfection .txt", "text": "So basically, as shown in the following diagram, so we have that double stranded DNA molecule that we want to inject into our cell."}, {"title": "Gene Transfection .txt", "text": "We have this calcium phosphate solution that combines with the DNA to basically form a precipitate."}, {"title": "Gene Transfection .txt", "text": "And then the cell uptakes that molecule, including that recombinant DNA into the cell."}, {"title": "Gene Transfection .txt", "text": "And then that DNA is incorporated into the cell's genome inside the nucleus."}, {"title": "Gene Transfection .txt", "text": "And by this method, we can basically produce proteins that are found within this DNA molecule."}, {"title": "Gene Transfection .txt", "text": "And so these are the three common methods by which we can basically inject our DNA molecules, these genes into eukaryotic cells."}, {"title": "Gene Transfection .txt", "text": "So we see that not only can we use these prokaryotic cells to produce desired eukaryotic proteins, but we can also use, in some cases eukaryotic cells to express and produce the proteins of interest."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Another important organ that is not only involved in the human reproductive cycle but also involved in the development of the child following childbirth is the human female breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And this will be the focus of this lecture."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So we're going to begin by briefly focusing on the anatomy of the breast and then we're going to focus on its function."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So let's begin by taking the following, by looking at the following diagram that describes the cross section of one of the female human breasts."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, to the right of the actual breast we have the ribcage and these are the ribs shown in brown."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now connecting the ribs are the inter custardal muscles shown in red."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And in front of the entire ribcage we have these muscles shown in pink, known as the pexiralis muscle."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So we have the major and the minor pectoralis muscle and the pectoralis muscle is actually connected to the breast via connective tissue."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, what about the breast itself?"}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So the breast is down to the left of the pectoralis muscle and it's this entire structure here."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now at the center of the breast we have the mammary gland and the mammary gland consists of the lobules of granular tissue also known as alveoli, as well as the milk ducts."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, the lobes of granular tissue are these grapelike structures that consist of specialized gland cells, specialized secretory cells that produce and release milk."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And when the milk is produced and released, it is released into these milk ducts and these ducts act as passageways."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "They allow the movement of the milk from the lobules of granular tissue and to the nipple where the nipple has very tiny holes that allows the passageway of the milk out of that breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, the nipple also contains nerve endings as we'll see in just a moment."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And when the baby sucks on the nipple, the nerve essentially creates action, potentials electrical signals that propagate all the way to the hypothalamus."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And the hypothalamus stimulates the posterior and anterior pituitary gland to basically release special hormones as we'll see in just a moment."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And these hormones stimulate the process of lactation the production and the release of milk."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, we also have these ligaments of Cooper."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And the ligaments of Cooper are essentially these fibers, bands of connective tissue that connect the entire breast to the skin, that encloses the breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And we also have this adipose tissue, the fat tissue shown in orange."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And the fat tissue basically determines the size of the breast and it also determines the softness of the breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So the more fat we have in the breast, the larger the breasts are."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now we also have these blood vessels and the blood vessels consist of arteries as well as of veins."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "The arteries carry the oxygenated and nutrient filled blood to the cells of the breast while the veins carry away the deoxygenated and deoxygenated blood that contains the waste products away from the cells found inside the breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And finally, around the nipple we have this relatively dark region of tissue known as the Arola."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So the areola is a small circular structure that is colored differently than the surrounding tissue and this is found around the actual nipple."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So this is the brief structure, the brief anatomy of the human female breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now let's move on to the function of the female human breast."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Well, the primary function of the female breast is to basically produce milk via process known as lactation as we'll discuss in just a moment."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And the purpose of the milk is to basically provide that child with the nourishment that the child needs to basically grow and develop into a fully functional individual and the milk is also used to boost to increase the immunity of that child as we'll see in just a moment."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So during the process of pregnancy when that woman is carrying that fetus and the fetus is undergoing different types of developmental processes, that woman is actually releasing estrogen as well as progesterone."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So initially these two hormones are released by the corpus luteum found in the ovary but eventually the placenta takes over this job and begins to release estrogen and progesterone."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And what these two hormones do is they stimulate the lobules of granular tissue and the ducts to actually increase in size and this ultimately increases the size of the breast themselves."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, for a few days following childbirth the breasts will produce a fluid known as cholesterol."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, cholesterol is also known as first milk and cholesterol is a yellowish substance that is rich in protein and lactose but has a relatively low concentration of fat and this is usually produced before childbirth and following childbirth."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "For several days also following childbirth, what happens is the interior pituitary gland will release a hormone known as prolactin and what prolactin does is it stimulates the memory gland, it stimulates the gland cells in the memory gland to basically produce milk that is different than cholesterol."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, the major difference between milk and the first milk is that milk actually contains a high concentration of carbohydrates as well as fat."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And what the milk does is it once again provides immunity to the child by giving the child special types of antibodies."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And the antibodies can be used to fight off different types of pathogens that might infect that growing child."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, what the milk also does is it provides the proteins and the carbohydrates and the nutrients, the minerals that are needed by that child to actually develop into a fully functional individual."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now let's actually discuss how the process of lactation actually takes place and let's take a look at the following diagram."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So we have the child and we have the breast of the mother."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now these are the memory glands."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So this is the memory gland, it contains the lobes of granular tissue as well as our ducts."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now let's zoom in on one of these lobes."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So we basically get the following diagram."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "We have these gland cells that can produce the milk as well as release the milk."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And outside the outside the cells, we have a layer of muscle and this is our milk."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Duct that can receive the milk and carry that milk to the mouth of that child."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So when the child essentially sucks on that nipple, the nipple contains nerve cells."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And these nerve cells generate action, potential electrical signals and the electrical signals is carried to the hypothalamus of the brain of that mother."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And what the hypothalamus does is it stimulates the posterior pituitary gland to release a hormone known as oxytocin."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And what oxytocin does is it travels."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Via the blood system and eventually reaches the muscle layer of this particular diagram."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So when the muscle layer receives the oxytocin, what the oxytocin does is it stimulates the muscle layer to actually contract."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And by contracting what the muscle layer does is it forces that milk."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "It squeezes that milk out of the cells and into these milk ducts."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "And then the milk travels via the ducts, through the tiny holes in the nipple and eventually into the mouth of that baby."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So this is how lactation actually takes place."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "This is how we form the milk and eventually release the milk into the mouth of that fetus."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So, once again, what exactly are the effects, the positive effects of the process of breastfeeding?"}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So we see that during breastfeeding our hypothalamus stimulates the inferior pituitary gland to basically release oxytocin."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "Now, oxytocin doesn't only stimulate the release of the milk but it also actually stimulates the mother's uterus to return to its normal size and shape."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "So function number one of breastfeeding is it stimulates the uterus of the mother to return to its original size and function number two and perhaps the more obvious function and effect of breastfeeding is it provides nutrients to that growing child and it also provides antibodies to that child which actually boosts the immunity of that child."}, {"title": "Anatomy and Function of Female Breasts .txt", "text": "It gives the child passive immunity and it increases the likelihood that pathogens that might invade that child will be found by the child's immune system and will be killed off before actually infecting that child."}, {"title": "Small Intestine.txt", "text": "The majority of the digestion."}, {"title": "Small Intestine.txt", "text": "And almost all absorption in the human body takes place in a digestive organ known as the small intestine."}, {"title": "Small Intestine.txt", "text": "Now, the small intestine is shown on the board and we can break down the small intestine into three sections."}, {"title": "Small Intestine.txt", "text": "The beginning portion is where the digestion actually takes place."}, {"title": "Small Intestine.txt", "text": "This is known as our duke."}, {"title": "Small Intestine.txt", "text": "So within our duodenum, we basically have the breakdown of the macromolecules into our amino acids, the fatty acids, and into our monosaccharides."}, {"title": "Small Intestine.txt", "text": "Now, in the middle portion, known as our geunum, and our end portion, known as the ilium, this is where we absorb those nutrients."}, {"title": "Small Intestine.txt", "text": "So the intestinal cells of the jugunum and our ilium, known as in terrace, basically absorb those individual nutrients into the cells and then transport those nutrients into the blood system and our lymph system, as we'll see in just a moment."}, {"title": "Small Intestine.txt", "text": "So let's describe what the actual structure is inside the small intestine."}, {"title": "Small Intestine.txt", "text": "And let's take a cross section of the small intestine."}, {"title": "Small Intestine.txt", "text": "We basically get the following diagram."}, {"title": "Small Intestine.txt", "text": "Now, the outer portion, shown in red, is the thick and a thin layer of smooth muscle which is controlled by the autonomic nervous system."}, {"title": "Small Intestine.txt", "text": "And this smooth muscle basically contracts in a wavelike fashion and that creates the process of peristalsis, which basically moves our kind, the food, along our small intestine."}, {"title": "Small Intestine.txt", "text": "Now, the region right below the smooth muscle layer is the epithelial layer."}, {"title": "Small Intestine.txt", "text": "And attached to our epithelial layer, we basically have many of these projections which are known as villi."}, {"title": "Small Intestine.txt", "text": "And inside this cavity, this is the lumen of our small intestine."}, {"title": "Small Intestine.txt", "text": "This is where the food, the kind, actually travels along."}, {"title": "Small Intestine.txt", "text": "Now, if we zoom in on a single villas, we basically get the following microscopic structure."}, {"title": "Small Intestine.txt", "text": "So notice along the border of our villas we basically have many, many of these intestinal cells we call anterocytes."}, {"title": "Small Intestine.txt", "text": "And each one of these interasides contains tiny hairlike projections known as microvilli."}, {"title": "Small Intestine.txt", "text": "So the villi and the microvilli, what the purpose of these structures are, is to basically greatly increase the surface area of the small intestine."}, {"title": "Small Intestine.txt", "text": "And that basically means the proteolytic enzymes have more room to actually break down those macromolecules."}, {"title": "Small Intestine.txt", "text": "Now, once we break down the macromolecules, they are absorbed by these intercepts and then they move into either the blood system, shown in red or the lymph system, shown in orange."}, {"title": "Small Intestine.txt", "text": "So this single orange vessel is known as the lactile."}, {"title": "Small Intestine.txt", "text": "It connects to the lymph system."}, {"title": "Small Intestine.txt", "text": "So fatty acids are absorbed into these intelligence and then are transported into the lactel, the lymph system, while amino acids and monosaccharides are absorbed and transported into our blood system."}, {"title": "Small Intestine.txt", "text": "Now, this entire hair like projection border is known as our brush border."}, {"title": "Small Intestine.txt", "text": "And as we'll see in just a moment at the brush border, we have digestion and absorption taking place."}, {"title": "Small Intestine.txt", "text": "So as we mentioned earlier, inside our dudum, we basically have our digestion taking place."}, {"title": "Small Intestine.txt", "text": "So the cells inside this region are capable of producing our proteolytic enzymes that break down our polysaccharides, the polypeptides as well as lipids."}, {"title": "Small Intestine.txt", "text": "On top of that, the brush border found in the dudenum also contains proteolytic enzymes that are attached onto the membrane of denterasides."}, {"title": "Small Intestine.txt", "text": "So when those macromolecules approach these microvilli of anterosos, that membrane of these intellicides contains these proteolytic enzymes that can break down the macromolecules into smaller units."}, {"title": "Small Intestine.txt", "text": "Now, in addition, we have specialized types of exocrine organs, exocrine glands in the human body, and one is aropankreas."}, {"title": "Small Intestine.txt", "text": "So the pancreas basically produces its own proteolytic enzymes and it mixes those proteolytic enzymes in a solution that is basic."}, {"title": "Small Intestine.txt", "text": "It consists of bicarbonate."}, {"title": "Small Intestine.txt", "text": "And the reason it's basic is because all the enzymes found in the small intestine only function at a PH that is basic at a PH that is equal to about 8.5."}, {"title": "Small Intestine.txt", "text": "So the pancreas produces proteolytic enzymes that are mixed in a basic solution composed of bicarbonate."}, {"title": "Small Intestine.txt", "text": "Bicarbonate is basically what makes it basic, what gives it a PH of about 8.5."}, {"title": "Small Intestine.txt", "text": "Now, this mixture of bicarbonate and proteolytic enzymes is known as the pancreatic juice."}, {"title": "Small Intestine.txt", "text": "And the pancreatic juice is secreted into our small intestine as soon as the chime actually travels into our dudenum of the small intestine."}, {"title": "Small Intestine.txt", "text": "Now, another type of organ that basically helps us digest things is the liver."}, {"title": "Small Intestine.txt", "text": "The liver produces a special type of mixture fluid known as bile."}, {"title": "Small Intestine.txt", "text": "And bile is basically a mixture of water, of fats such as cholesterol as well as bile salts."}, {"title": "Small Intestine.txt", "text": "And what bile does is it basically emulsifies our lipids into small intestine."}, {"title": "Small Intestine.txt", "text": "It mechanically digests, it breaks down our lipids into smaller pieces, it increases the surface area and it allows our livease the enzyme that breaks down lipids to actually break down the fats inside the small intestine."}, {"title": "Small Intestine.txt", "text": "So this bile is stored in a structure known as the gall bladder and it's released through a duct as soon as chime makes its way into our small intestine."}, {"title": "Small Intestine.txt", "text": "So once again, the liver produces bile and stores it in the gallbladder."}, {"title": "Small Intestine.txt", "text": "When chime enters the small intestine, the bile is dumped into the lumen of the small intestine, into this section here."}, {"title": "Small Intestine.txt", "text": "And what that bile does is it basically emulsifies."}, {"title": "Small Intestine.txt", "text": "It mechanically breaks down our lipids into smaller pieces so that our lipase, the proteolytic enzyme, can actually chemically digest and cleave those ester bonds inside the lipids."}, {"title": "Small Intestine.txt", "text": "This process is known as emulsification."}, {"title": "Small Intestine.txt", "text": "So without bile, we would have a lot of trouble actually breaking down our lipids."}, {"title": "Small Intestine.txt", "text": "And once again, all the enzymes that function in the small intestine function at a PH of about 8.5."}, {"title": "Small Intestine.txt", "text": "And what gives it a PH of 8.5, what makes it a basic solution inside the lumen of the small intestine is the bicarbonate that exists in the pancreatic juice."}, {"title": "Small Intestine.txt", "text": "Now, before we go on to absorption, one thing that I forgot to mention inside the small intestine is these specialized types of cells known as goblet cells."}, {"title": "Small Intestine.txt", "text": "So, just like in the stomach, we have mucus cells that secrete mucus inside the small intestine."}, {"title": "Small Intestine.txt", "text": "We also have these cells, known as goblet cells, that secrete mucus."}, {"title": "Small Intestine.txt", "text": "And the mucus basically protects the epithelial layer from being damaged by the environment found inside our small intestine."}, {"title": "Small Intestine.txt", "text": "Now, finally, let's briefly discuss the process of absorption."}, {"title": "Small Intestine.txt", "text": "So inside the gynom and the ilium, we have those nutrients that have been broken down are now absorbed by the intelligence of our villi, found on the border of the small intestine."}, {"title": "Small Intestine.txt", "text": "On the intersection of the small intestine."}, {"title": "Small Intestine.txt", "text": "Now we basically have those lipids."}, {"title": "Small Intestine.txt", "text": "The triglycerides are broken down into fatty acids, and these fatty acids can easily pass across the membrane of anterocytes, because the fatty acids are lipid soluble."}, {"title": "Small Intestine.txt", "text": "And then those fatty acids enter the lactel and are transported into our lymph system."}, {"title": "Small Intestine.txt", "text": "And eventually, they make their way into our blood system."}, {"title": "Small Intestine.txt", "text": "However, the amino acids and our sugars, our monosaccharides, such as glucose, are transported into the cells either via passive or active transport."}, {"title": "Small Intestine.txt", "text": "That means we have to use specialized types of integral proteins to actually transport the amino acids and our glucose, our monosaccharides."}, {"title": "Small Intestine.txt", "text": "And then those monosaccharides and amino acids are transported directly into the blood system via these red vessels, as shown."}, {"title": "Small Intestine.txt", "text": "So, fatty acids into the lymph system and then enter the blood system, but the amino acids and our monosaccharides into the blood system directly via these blood vessels, as shown."}, {"title": "Small Intestine.txt", "text": "And in the next lecture, we're going to focus on the specific types of proteolytic enzymes that are produced by the small attestant as well as by the pancreas."}, {"title": "ABC Transporters .txt", "text": "Previously we focused on ptype ATPases and we said that these are protein pumps that use ATP to basically create electrochemical gradients across the membranes found within our cells."}, {"title": "ABC Transporters .txt", "text": "Now, another important group of ATP driven pumps that we're going to focus on in this lecture is the ATP the ABC transporters."}, {"title": "ABC Transporters .txt", "text": "And ABC stands for ATP binding cassette."}, {"title": "ABC Transporters .txt", "text": "Now, actually this important class of ATP driven proteins was discovered as a result of our study of human disease."}, {"title": "ABC Transporters .txt", "text": "And what we studied was cancer."}, {"title": "ABC Transporters .txt", "text": "So we essentially took a tumor, we extracted cancer cells from that tumor and then we grew those cancer cells in a petri dish."}, {"title": "ABC Transporters .txt", "text": "Now, the cancer cells were exposed to some type of drug and what we saw happen was initially the drug carried out its effect and killed off some of those cancer cells."}, {"title": "ABC Transporters .txt", "text": "But over time, what happened was those cancer cells gained multidrug resistance MDR."}, {"title": "ABC Transporters .txt", "text": "And what that means is they gained the ability to not only resist that particular drug that we were using, but also resist closely related drugs to that initial drug that we began with."}, {"title": "ABC Transporters .txt", "text": "And that is what we call multidrug resistance, the ability to resist many different types of drugs."}, {"title": "ABC Transporters .txt", "text": "Now, the question was what exactly allowed these cancer cells to actually gain multidrug resistance?"}, {"title": "ABC Transporters .txt", "text": "Well, it turned out that the cancer cells began expressing a specific type of membrane protein within the membranes of those cancer cells."}, {"title": "ABC Transporters .txt", "text": "And what this membrane protein did was it used ATP to basically drive those molecules, the drugs, out of the cell."}, {"title": "ABC Transporters .txt", "text": "And it did that before the drugs could actually elicit their effects on the cancer cells."}, {"title": "ABC Transporters .txt", "text": "So these became known as MDR proteins or simply P glycoproteins."}, {"title": "ABC Transporters .txt", "text": "So actually they're not only proteins, they're glycoproteins because they have sugar components."}, {"title": "ABC Transporters .txt", "text": "So we see that multidrug resistance was shown to be a result of the expression of these membrane proteins that became known as multi drug resistant proteins."}, {"title": "ABC Transporters .txt", "text": "MDR proteins, they use energy to pump drugs out of the cell before the drugs can actually carry out or elicit their effects."}, {"title": "ABC Transporters .txt", "text": "And this is what our MDR protein looks like."}, {"title": "ABC Transporters .txt", "text": "So notice, the MDR protein consists of four domains."}, {"title": "ABC Transporters .txt", "text": "So even though in this case it's a single polypeptide chain, it contains four different domains."}, {"title": "ABC Transporters .txt", "text": "Two of these domains are shown here, they're essentially the transmembrane domains and the other two domains are shown here."}, {"title": "ABC Transporters .txt", "text": "They're called the ATP binding domains or ATP binding cassettes."}, {"title": "ABC Transporters .txt", "text": "So the MDR protein consists of four domains."}, {"title": "ABC Transporters .txt", "text": "Two are membrane spanning domains shown in brown and the other two are ATP binding domains, also known as ATP binding cassettes or simply ABCs because this is where the ATP will actually bind, as we'll see in just a moment."}, {"title": "ABC Transporters .txt", "text": "Now, it turns out we have many different types of examples of ABC transporters in our own cells as well as other eukaryotic cells and even prokaryotic cells."}, {"title": "ABC Transporters .txt", "text": "So both eukaryotic cells and prokaryotic cells, such as bacterial cells actually have ABC transporters but usually there are two important differences."}, {"title": "ABC Transporters .txt", "text": "So number one, eukaryotic cells usually contain ABC transporters that consist of a single polypeptide chain, a single polypeptide subunit, as we saw in the case of the MDR protein."}, {"title": "ABC Transporters .txt", "text": "So MDR proteins, found on the membrane of human cancer cells basically is a single polypeptide chain."}, {"title": "ABC Transporters .txt", "text": "Even though we have these four different regions within that polypeptide chain, it's only a single subunit."}, {"title": "ABC Transporters .txt", "text": "But prokaryotic cells typically express ABC transporters that contain many subunits."}, {"title": "ABC Transporters .txt", "text": "So sometimes we have dimers, sometimes we have tetrimers and so forth."}, {"title": "ABC Transporters .txt", "text": "Now, the second major difference is, as the case is, with the MDR protein, again found in humans, this basically moves that particular substrate molecule from the inside to the outside of the cell."}, {"title": "ABC Transporters .txt", "text": "But usually typically in prokaryotic cells, this ABC transporter moves the substrate molecule from the outside to the inside of the cell in revert."}, {"title": "ABC Transporters .txt", "text": "So eukaryotic cells generally use ABC transporters to export the molecule out of the cell."}, {"title": "ABC Transporters .txt", "text": "As we saw the case was with the MDR protein."}, {"title": "ABC Transporters .txt", "text": "But for prokaryotic cells, it's usually the opposite."}, {"title": "ABC Transporters .txt", "text": "They import these molecules from the outside to the inside."}, {"title": "ABC Transporters .txt", "text": "Now, the next question is what exactly are the details of the mechanism by which this process actually takes place?"}, {"title": "ABC Transporters .txt", "text": "So it's slightly different than the process in the ptype Atpas, and let's see exactly what it actually looks like."}, {"title": "ABC Transporters .txt", "text": "And of course, I forgot to finish off one of these membranes, so let's do it real quick."}, {"title": "ABC Transporters .txt", "text": "So we have the polar heads, and so some of you basically ask why I don't actually draw as I go along in the lecture."}, {"title": "ABC Transporters .txt", "text": "And that's because it takes up lots and lots of time and that's time that you don't want to lose."}, {"title": "ABC Transporters .txt", "text": "So I basically create these diagrams and write my notes ahead of time to basically save your time so that the lecture is as effective and efficient as possible so that you can get the information out as quickly as possible and go on with your lives."}, {"title": "ABC Transporters .txt", "text": "Okay, so there are essentially five different steps in this process."}, {"title": "ABC Transporters .txt", "text": "And let's begin with this diagram right here."}, {"title": "ABC Transporters .txt", "text": "And notice so this is our membrane, the phospholipid bilayer, and this is our protein pump, our ABC transporter."}, {"title": "ABC Transporters .txt", "text": "And this diagram that basically describes this transmembrane pump in its closed state."}, {"title": "ABC Transporters .txt", "text": "And what that means is the substrate molecules cannot actually enter this molecule."}, {"title": "ABC Transporters .txt", "text": "Now, what happens is it basically inter converts from the closed state and the open state."}, {"title": "ABC Transporters .txt", "text": "So it moves back and forth relatively quickly."}, {"title": "ABC Transporters .txt", "text": "So it's closed here, open here, closed here, open here, and only when it's open can the actual substrate molecules, shown here in red, actually enter this central cavity of the transmembrane domain."}, {"title": "ABC Transporters .txt", "text": "So remember, we have the two transmembrane domains that essentially create this internal cavity that can fit that substrate molecule."}, {"title": "ABC Transporters .txt", "text": "Now, once the substrate molecule actually goes into this central cavity, that closes these two domains, and it also causes these two green domains the ATP binding cassettes to actually interact with one another."}, {"title": "ABC Transporters .txt", "text": "So it creates conformational changes in these two green structures and that increases their affinity for ATP molecules."}, {"title": "ABC Transporters .txt", "text": "And so in the next step, what happens is because we have these two cavities on the ATP binding consents that means two ATP molecules can actually fit into these two locations."}, {"title": "ABC Transporters .txt", "text": "And so two ATP molecules go into these two locations and once the ATP molecules move into that location that creates conformational changes in the entire structure of the transmembrane domain."}, {"title": "ABC Transporters .txt", "text": "And what happens is that induces this opening on the other side, the posing side of the membrane where that molecule actually came in."}, {"title": "ABC Transporters .txt", "text": "So it came in, let's say from the inside."}, {"title": "ABC Transporters .txt", "text": "So let's say this is the inside of the cell, this is the outside and now it opens from the outside and once it opens that molecule the substrate molecule can leave that cell and exit that cell."}, {"title": "ABC Transporters .txt", "text": "So we see the ultimate result of this particular mechanism is the same exact result that we saw in the ptype Atpas."}, {"title": "ABC Transporters .txt", "text": "That is, we move these molecules across the membrane against their electrochemical gradient."}, {"title": "ABC Transporters .txt", "text": "Now, the final step in this process is these two ATP molecules are actually hydrolyzed by using two water molecules."}, {"title": "ABC Transporters .txt", "text": "So we have two water molecules, not one."}, {"title": "ABC Transporters .txt", "text": "We basically use two water molecules to hydrolyze each one of these ATP molecules and that produces and releases two ATP molecules and two phosphate molecules as shown here."}, {"title": "ABC Transporters .txt", "text": "And the important part here is the hydrolysis of these ATP molecules and the removal of these ATP molecules basically resets the entire confirmation, the entire structure of that protein so that now we go back to that closed state and this cycle can basically repeat itself."}, {"title": "ABC Transporters .txt", "text": "So we see that ptype ATPases and ABC transporters both carry out the same exact function."}, {"title": "ABC Transporters .txt", "text": "They transport these molecules against the electrochemical gradient and they basically use ATP energy molecules."}, {"title": "ABC Transporters .txt", "text": "But the mechanisms which they carry out these processes are slightly different as we saw just a moment ago."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Both prokaryotic and eukaryotic cells are enclosed in a semipermeable membrane known as the cell membrane or the plasma membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The plasma membrane functions in several important ways."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Firstly, it allows ions and molecules to travel into the cell and out of the cell."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "It creates an internal environment that allows the organelles cells to function effectively and efficiently."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "It protects the cell from the outside environment."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The cell membrane also creates attachment points for other molecules and other cells."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And finally, the cell membrane also functions in cell signaling and cell communication."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So the cell membrane is an extremely important type of structure."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The question is, what exactly is the structure of our cell membrane?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, the plasma membrane found in prokaryotes and eukaryotes is a phospholipid bilayer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The bilayer means we have two layers of phospholipids."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have an inner layer and the outer layer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, what exactly is a phospholipid?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "A phospholipid is a molecule that consists of a polar phosphate group attached to a nonpolar fatty acid via a group known as the glycerol group."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we have the nonpolar hydrophobic fatty acids."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have two of them."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "They can be the same or they can be different."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have our connection, the backbone, the glycerol group, and we have the phosphate group that bears a negative charge on the oxygen, which is delocalized among these two oxygens."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So there is an electric dipole moment in the phosphate group and that's exactly why it's a polar molecule."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So sometimes attached to our phosphate, we also have an additional polar group known as the choline."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The choline basically adds polarity to our phospholipid bilayer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we have the non polar fatty acid, the glycerol, that connects the fatty acids to our phosphate, the polar group, and then we have our choline."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, instead of actually drawing out this entire molecule, we usually use a shortcut method of drawing our phospholipids, and that's this depiction here."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So phospholipids can be described by using this pictorial image."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have this head, this spherical region that describes the phosphate as well as the choline, if we have that choline."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So this is the polar region of our phospholipid."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So the left side is the polar hydrophilic region, the right side is the non polar hydrophobic region."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So these two fatty acids that are described by using these tails, so two tails describe the two fatty acids and they're connected via the glycerol to the polar phosphate group."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now the question is, how exactly do the phospholipids arrange themselves inside the cell membrane to actually give our cell membrane its structure, the bilayer structure?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, before we discuss the structure, we have to mention the following important point."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, inside the cell, we have a fluid that is known as the cytosol."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And most of the cytosol is water."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So that means the cytosol is in fact polar."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, the fluid outside the cell is also usually polar."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And that means that the way our phosphol lipids are going to arrange themselves is in the following manner."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The tails will point inward, the heads will point outward."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we have our outer membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So if we imagine this to be the cell membrane, the cell membrane basically spans around the entire cell."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, we have inside the cell is the cytosol."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Outside the cell is the extracellular liquid, the fluid, which is also polar."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So these heads of the phospholipids are polar, so they're hydrophilic, they will point outward."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "These heads are polar, they will point inward."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And these hydrophobic tails, nonpolar tails, will basically aggregate in the middle."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So this section here is known as the intermembrane space, the section between the outside and our inside."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have the outer membrane region as well as the inner membrane region."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And the entire structure of our cell membrane is called the phosphol lipid bilayer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So two layers of phosphol lipids are arranged in the following manner."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, the outer membrane region has the hydrophobic heads pointing towards the surroundings and the hydrophobic tails pointing inwards."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The inner membrane, this section here, has the hydrophobic tails pointing away from the polar cytosol and the hydrophilic heads pointing towards that polar cytosol."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So this is our arrangement here."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, the next question is what else do we have inside the cell membrane?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So it turns out we not only have phospholipids, we also have proteins."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And proteins give the cell membrane its functionality, as we'll see in just a moment."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, embedded into the membrane are two types of proteins."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We have integral proteins as well as peripheral proteins."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So this is our example of an integral protein and this is our example of a peripheral protein."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So what exactly is an integral protein?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "It's basically a protein that contains hydrophobic regions and hydrophilic regions."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And the entire protein spans this entire bilayer membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we have the hydrophilic regions of the proteins, this region here and this region here."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And the rest of the protein found inside is hydrophobic."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "It's nonpolar, so it interacts with these hydrophobic nonpolar tails, our fatty acids."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, anterioral proteins extend throughout the entire bilayer membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And their usual function, because they extend through the entire membrane, is to transport things from the inner portion to the outer portion of our cell."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So basically to the outside, or vice versa, from the outside to our inside."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "For example, we have different types of proteins that allow ions to pass through, and other proteins exist that allow larger molecules, such as sugars, to basically pass through."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, what about the peripheral protein?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, peripheral proteins bind ionically via electric forces to either the integral proteins themselves or they could bind to our phospholipid bilayer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "In this case, we show the peripheral protein binding to our phospholipid bilayer."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And because these proteins do not actually span the entire bilayer, that means they usually do not act as transport proteins."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "These proteins do not span the entire membrane and function in adhesion or cell recognition, cell signaling or cell communication."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, both types of proteins, integral as well as peripheral, can have sugar or carbohydrate components which protrude outside the cell."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Remember, sugars are polar, and our cytosol, as well as the extracellular fluid is, in fact, polar."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So these sugar components will basically attach themselves to our integral proteins or peripheral proteins and will point directly outward, as shown."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And the sugar protein combinations are known as glycoproteins."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Glycoproteins are important because these sugar components can basically allow some outside type of molecule to bind onto our sugar component of that protein."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And we'll talk more about this when we get into biochemistry of cell membranes."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, the next aspect of the cell membrane that I'd like to discuss is a model known as the fluid mosaic model, which basically describes the way that our molecules down inside the cell membrane interact and move."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So the question is, do our phospholipids and proteins remain stationary in place or are they in a constant fluidlike state of motion?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, to answer this question, we have to note the following important point."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The bonds that basically hold the phospholipids together and the proteins together inside our cell membrane are intermolecular bonds."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "They're weak bonds, weak electric bonds."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "They're electric in nature."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And that means, because the bonds holding the phospholipids and proteins together are weak, that means they will not remain stationary in place, but rather, they will be found in a constant sideways motion."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So our phospholipids and proteins will be in a constant lateral state of motion."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So they will be moving sideways, as shown in the following diagram."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So, for example, this fossil lipid could move here, could move here."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The protein could also move into different locations."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, one important point that I must point out is the following."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Our phosphol lipids cannot actually jump back and forth."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we only have lateral or sideway motion."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We do not have vertical motion because if the vertical motion was to actually take place, that would result in very high electrostatic repulsion."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And so, because we don't want to have high electrostatic repulsion, we don't want to waste so much energy, our phospholipids will only move back and forth and will not jump vertically, as shown."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And this type of motion, a constant fluid like motion of our phospholipid bilayer, is known as the fluid mosaic model."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, the last part that I want to discuss is an important part of our phospholipid bilayer, that is our cholesterol."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So cholesterol is another important type of constituent that is found inside our cell membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And what cholesterol does, it basically controls the fluidity of our cell."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So how fluid or how rigid our cell is?"}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Now, in eukaryotes, our cholesterol basically controls the cell and membrane fluidity."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "In prokaryotes, it's another type of molecule that also looks like cholesterol, but it's called a hopinoid."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "Both of these types of molecules basically function in the same exact way."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So cholesterol is an extremely important component of the cell membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The polar hydroxyl groups of our cholesterol basically interact with the hydrophilic polar heads and the rest of the cholesterol molecule, which is basically a hydrocarbon backbone."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "The nonpolar region basically extends throughout the entire section of our cell membrane like this integral protein."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And so we see that by adding cholesterol into our cell membrane we basically control the fluidity of our cell membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "By adding cholesterol, we decrease the fluidity because we basically allow we pack these hydrophobic and hydrophilic sections closer together."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So we can imagine that by placing this wall we call the cholesterol into our cell membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We basically decrease the space between these regions and they aren't able to move as much because of that wall, our cholesterol that is placed inside that cell membrane."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "So cholesterol electrode decreases the fluidity of the membrane because it forces the phospholipids closer together."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "And of course, we're assuming a constant temperature."}, {"title": "Cell Membrane and Fluid Mosaic Model.txt", "text": "We're assuming the temperature is not changing because the temperature increases the range of motion of our molecule."}, {"title": "Introduction to Biotechnology.txt", "text": "The field of biotechnology also known as recombinant DNA technology is a field that allows us to study, manipulate and create nucleic acids."}, {"title": "Introduction to Biotechnology.txt", "text": "And by creating nucleic acids we can in turn create the proteins that the nucleic acids actually encode for."}, {"title": "Introduction to Biotechnology.txt", "text": "And that gives us many, many possibilities and many applications."}, {"title": "Introduction to Biotechnology.txt", "text": "And that's exactly why biotechnology is not only used in biochemistry it is also used in many different types of fields."}, {"title": "Introduction to Biotechnology.txt", "text": "For example, the field of medicine and the field of forensic science also used biotechnology."}, {"title": "Introduction to Biotechnology.txt", "text": "So in medicine, we can use biotechnology to synthesize a variety of different types of proteins and enzymes and hormones."}, {"title": "Introduction to Biotechnology.txt", "text": "So these biological molecules that are used by our body we can also detect the presence of different types of abnormalities and conditions that might be found in some specific individual."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, in forensic science we can use biotechnology for instance, to determine whether or not an individual might have been present at a crime scene or might have committed a crime as we'll see in just a moment."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, where did biotechnology actually come from?"}, {"title": "Introduction to Biotechnology.txt", "text": "How did it arise?"}, {"title": "Introduction to Biotechnology.txt", "text": "Well, biotechnology came from our understanding of how nucleic acids actually work how they function and how the biological systems in nature use these nucleic acids in the first place."}, {"title": "Introduction to Biotechnology.txt", "text": "So because we were able to determine the structure of nucleic acids we were able to basically determine the fact that we have the base pairing system and that allowed us to understand how transcription actually takes place."}, {"title": "Introduction to Biotechnology.txt", "text": "And then we were able to determine the fact that ribosomes use the genetic code to basically translate the sequence of nucleotides on the RNA into the sequence of amino acids on the protein because we were able to determine how these viral agents use nucleic acids to infect cells and then hijack the cell machinery to make many copies of that virus."}, {"title": "Introduction to Biotechnology.txt", "text": "So because we were able to withstand these nucleic acids that exactly where the field of biotechnology actually came from."}, {"title": "Introduction to Biotechnology.txt", "text": "And more specifically, there are six key factors that played a role in basically allowing this biotechnology field to actually arise."}, {"title": "Introduction to Biotechnology.txt", "text": "So let's briefly discuss what these six factors are and in the next several lectures we're going to take a look at these factors in much more detail."}, {"title": "Introduction to Biotechnology.txt", "text": "So let's begin with factor number one the existence of restriction enzymes."}, {"title": "Introduction to Biotechnology.txt", "text": "So restriction enzymes were essentially discovered and these biological molecules exist in bacterial cells and bacterial cells use these restriction enzymes to basically protect themselves from viral agents."}, {"title": "Introduction to Biotechnology.txt", "text": "So what these restriction enzymes do is they cleave DNA molecules or RNA molecules at specific locations at specific sites."}, {"title": "Introduction to Biotechnology.txt", "text": "And there are many different types of restriction enzymes also known as restriction and the nuclease that exist in nature."}, {"title": "Introduction to Biotechnology.txt", "text": "And so what that means is if we can extract and collect these restriction enzymes we basically have a very efficient way of cleaving our DNA molecules at specific locations."}, {"title": "Introduction to Biotechnology.txt", "text": "So, for instance, if we want to study the following DNA molecule we can cut it up into many small fragments by using restriction enzymes and then we can analyze and study and manipulate and amplify all these different types of fragments."}, {"title": "Introduction to Biotechnology.txt", "text": "In fact, we can use these fragments to essentially sequence DNA molecules and that leads us directly into factor number two."}, {"title": "Introduction to Biotechnology.txt", "text": "So we are now able to actually determine exactly what the sequence of nucleotides is in any DNA molecule."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, how is that useful in itself?"}, {"title": "Introduction to Biotechnology.txt", "text": "Well, if we want to study a specific gene we have to know what the sequence of nucleotides is in that gene."}, {"title": "Introduction to Biotechnology.txt", "text": "And by using a specific method that we're going to focus on in a future lecture, we can basically determine what the sequence of nucleotides is in any gene."}, {"title": "Introduction to Biotechnology.txt", "text": "And once we know what the sequence of nucleotides in that DNA is we can then determine what the corresponding sequence in the RNA will be."}, {"title": "Introduction to Biotechnology.txt", "text": "And we can use that and the genetic code to basically determine what the structure and the sequence of the protein is that is encoded by that gene."}, {"title": "Introduction to Biotechnology.txt", "text": "So this allows us to basically study how gene expression takes place and how we synthesize and which proteins we actually synthesize."}, {"title": "Introduction to Biotechnology.txt", "text": "Now this also leads us into factor number three."}, {"title": "Introduction to Biotechnology.txt", "text": "So now that we know what the specific nucleotide sequence of that DNA molecule is we can now synthesize that DNA molecule from scratch in the laboratory by using a method known as solid state method."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, once we synthesize that DNA molecule of interest, what do we do next?"}, {"title": "Introduction to Biotechnology.txt", "text": "Well, that leads us into factor number four."}, {"title": "Introduction to Biotechnology.txt", "text": "We have a process known as the polymerase chain reaction or simply PCR that allows us to amplify a single DNA molecule."}, {"title": "Introduction to Biotechnology.txt", "text": "That is, make many, many copies of that single molecule that we want to study."}, {"title": "Introduction to Biotechnology.txt", "text": "In fact, PCR allows us to make millions and billions of these copies from a single individual DNA molecule."}, {"title": "Introduction to Biotechnology.txt", "text": "So if we synthesize that fragment of DNA by using this solid state method we can then amplify the DNA and produce many, many copies of that DNA molecule."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, earlier I said that biotechnology can be used in forensic science."}, {"title": "Introduction to Biotechnology.txt", "text": "For example, let's suppose at some crime scene we find a single follicle of hair."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, we can extract DNA from that hair follicle and then we can amplify that single DNA strand by using the polymerase chain reaction to produce many of these DNA molecules that we now have at our disposal."}, {"title": "Introduction to Biotechnology.txt", "text": "And we can take these DNA molecules and we can essentially match them up to the DNA found in individuals in our computer database."}, {"title": "Introduction to Biotechnology.txt", "text": "And that allows us to basically determine exactly what individual was present at that particular crime scene and that can give us insight into whether or not that individual actually committed the crime."}, {"title": "Introduction to Biotechnology.txt", "text": "Now, factor number five is if we have a collection of different types of DNA molecules or RNA molecules we can use a specific method or two methods."}, {"title": "Introduction to Biotechnology.txt", "text": "We have southern blotting and we have northern blotting to basically determine exactly what the DNA molecule of interest within that mixture is."}, {"title": "Introduction to Biotechnology.txt", "text": "And this process is very similar to the process of Western blotting that we spoke about when we discuss proteins, their purification and their structure, and finally, computers."}, {"title": "Introduction to Biotechnology.txt", "text": "So the fact that we now have computers gives us an ability to basically store and catalog and quickly find any DNA sequence or any RNA sequence that we want to find."}, {"title": "Introduction to Biotechnology.txt", "text": "For example, in the human genome, we have over 3 billion nucleotides, and that's many, many, many nucleotides."}, {"title": "Introduction to Biotechnology.txt", "text": "You can imagine trying to write down all the billions of nucleotides on paper if we didn't actually have computers."}, {"title": "Introduction to Biotechnology.txt", "text": "But because we have computers, we have a very quick and a very efficient way of storing and accessing all the data that we collect over the years."}, {"title": "Introduction to Biotechnology.txt", "text": "And so, for example, if we find that particular DNA molecule at the crime scene, we can then use the computer to essentially match it up with the DNA in that particular individual."}, {"title": "Introduction to Biotechnology.txt", "text": "And this gives us a very quick and effective way to basically finding who committed that crime."}, {"title": "Introduction to Biotechnology.txt", "text": "And computers are used in a variety of different ways."}, {"title": "Introduction to Biotechnology.txt", "text": "So these are the six factors that essentially gave rise and made biotechnology possible."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So let's suppose we have a beaker."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And in that beaker, we have a mixture of a single type of enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And now we begin to add the substrate that the enzyme actually catalyzes."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "What will begin to take place?"}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Well, initially, this is the reaction that we're going to see take place."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So basically, on the reactant side, we have the enzyme by itself, we have the substrate by itself, and then a reaction takes place that has a raid constant of K one."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And this reaction basically is the reaction in which the substrate actually goes on and binds onto the active side of that enzyme to form the intermediate molecule, the enzyme substrate complex."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, once we form the enzyme substrate complex, one of two things can take place."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Either that substrate can actually dissociate from the active side before it is actually transformed into that product, and this reaction simply means we dissociate the complex back into the enzyme and the substrate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And the rate constant for this backward reaction is given by K minus one."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "But the other thing that can take place, and this is ultimately what we want to study in this lecture, is this reaction here."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And in this reaction, that enzyme, when the substrate is inside the active side, the enzyme will catalyze the transformation of the substrate into the product and we form our product and the product dissociates from the active side."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And the rate constant of this reaction is given by k two."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, let's focus on just this reaction here."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So in this reaction, we essentially have a certain rate law."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And the rate law, the expression that describes the rate at which this reaction takes place is given by this equation here."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So the V knot, the rate at which the enzyme catalyzes this reaction, is equal to the product of the rate constant, k two, and the concentration of the enzyme substrate complex Es."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So this is the equation that describes the rate at some concentration of Es."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, what exactly is the equation that gives us the maximum velocity, the maximum rate v max of that particular enzyme?"}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Well, to find what the maximum rate is V max, we have to basically assume that all the enzymes, all the initial enzymes that we begin with, contain all the active sites that are completely filled with the substrate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So when all the active sites are occupied by the substrate, what that basically means is the enzyme substrate complex concentration, Es, is equal to the initial total concentration of that enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So to see what we mean by that, let's take a look at the following diagram."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So let's suppose initially inside Arabica, before we added the substrate, we contained three of these identical enzymes."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So we have the red enzymes and we have the active side."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So the total concentration is three."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, once we add, let's say, three blue substrate molecules into the mixture, those molecules will bind onto the active side."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And once all the active sides are completely filled."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "This is when the enzyme mixture is operating at a maximum velocity, at a maximum rate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And in this moment in time, the concentration of the enzyme substrate complex, which is this here, is equal to the initial total concentration of that enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So three is equal to three."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So we can basically transform this equation to give us the maximum velocity, the maximum rate of that enzyme mixture simply by replacing the enzyme substrate concentration with the e total concentration."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And this is given by this equation here."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So once again, when all the active sides are filled, the reaction is said to be operating at a maximum velocity, at a maximum rate given by V max."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And we can simply transform this equation into this equation by changing this concentration to the total enzyme concentration."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And what this basically is telling us is all the active sites on all the enzymes are filled with that substrate molecule and therefore we are at a maximum operating rate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, how exactly can we actually physiologically interpret the VMAX value?"}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Well, the VMAX, the maximum rate of the enzyme, describes the highest number of substrate molecules that can be transformed into product molecules over a given time period when all the active sites are saturated are occupied with that substrate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "That is the meaning of VMAX."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, if we take the following equation and we solve for the rate constant of this reaction, K two, we get the following equation."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So K two, the rate constant of this reaction here is equal to V max divided by E total."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And this has an important physiological meaning."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "This K two is also known as K cat and this is given the name of the turnover number of the enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So what exactly is the physiological meaning of the turnover number K two of an enzyme?"}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Well, the turnover number tells us the maximum number of the substrate molecules that are transformed into the product molecules by a single active side per given unit of time."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So basically, let's suppose we have a single particular type of enzyme that we're studying and this is our enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "It could be any type of enzyme found inside our body."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So the enzyme, it's active side."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So these are the substrate molecules and these are the product molecules."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "What the turnover value tells us what the turnover number tells us is the total number of substrate molecules that can be transformed into the product molecules per unit time, for example, per second, when only a single active site, a single enzyme is actually being used."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, to demonstrate how this actually works and how we can calculate the K two value, let's take a look at the following hypothetical example."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So let's suppose we have the beaker."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Inside that beaker we have a mixture of some particular type of enzyme and the concentration, a total of that enzyme inside the mixture is given to us to be 0.1 molar now, let's suppose that experimentally, we calculate the V max value of that particular enzyme to be 60,000 molar per second."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So at this concentration, when all the active sites of that enzyme mixture are filled with the substrate, we know that the maximum rate of the reaction is 60,000 molar every single second."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So what that basically means is 60,000 of the substrate molecules are transformed into product every single second, when all the active sites are actually occupied, are actually saturated with that subtra."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "This is what 60,000 molar per second actually tells us."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So to calculate K two, also known as Kcat, the turnover number, we simply take the VMAX."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So 60,000 molar per second, and we divide it by the total number of enzymes that we have inside our mixture."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And what we ultimately get is 600,000 seconds to the negative one."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And what this describes is it tells us that a single enzyme and its single active side can basically transform 600,000 substrate molecules into 600,000 product molecules every single second."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And this is actually a description of a specific type of enzyme, one of the quickest enzymes found in our body, carbonic anhydrate."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So remember, carbonic anhydrates is that enzyme found inside the red blood cells, which essentially allows us to actually transform the non polar carbon dioxide molecule into the polar bicarbonate ion."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And that's how we can store the carbon dioxide inside our blood and transport it from the cells and tissues and to the lungs in our body."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So carbonic anhydrase has this turnover number."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "It is able to actually use a single active site, a single enzyme, a single carbonic."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And hydrate can transform this many substrate molecules, CO2 molecules, into the product bicarbonate every single second."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And this makes sense because our tissues and cells produce a very, very large number of CO2 molecules."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And so to effectively get rid of all those CO2 molecules, our body has to have a very effective and a very efficient enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, to compare carbonic and hydrates to another enzyme, let's, for example, talk about DNA polymerase one."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, DNA polymerase one has a turnover number of about 15."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And so what that means is only 15 of the substrate molecules are transformed into the product molecules by DNA polymerase one every single second."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So now the fact that carbonic anhydrase has a much higher rate than DNA polymerase one makes sense because DNA polymerase one is actually used in a very important process where we cannot make any mistakes because DNA polymerase one is used to replicate DNA molecules."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And that's a very important process."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So DNA polymerase one has to be very careful in how it actually catalyzes that particular reaction."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And so logically, it makes sense that DNA polymerase one has a lower turnover rate than carbonic and hydrase because all carbonic and hydrase has to do is take all those CO2 molecules produced by all the cells in our body and transform it into a bicarbonate molecule."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So that we can actually store and dissolve that bicarbonate the CO2 molecule in our blood."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "Now, the final thing that I'd like to discuss is what we get if we take the reciprocal of the turnover number."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So it turns out that if we take the K two value and we simply take the reciprocate, so we take one divided by Kcat, what that gives us is the time period that it takes a single active site of a single enzyme to actually transform a single substrate molecule into a single product."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So taking the reciprocal of the turnover number gives us the time it takes to transform one substrate into one product."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "And so if we use this example, for instance, we get one divided by 600,000 seconds to negative one, and we see that the units are seconds because this comes on top."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So what this means is 1.67 times ten to negative six of a second is the time it takes for this enzyme."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "In this particular case, it was carbonic and hydrase to basically transform a single substrate molecule into a single product."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So the turnover number and the VMAX are very important indicators of how enzymes actually act on some particular reaction."}, {"title": "Maximal Velocity and Turnover Number of Enzymes .txt", "text": "So these values can be used to describe how the rate of the enzyme or how the enzyme actually affects the rate of that particular reaction."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "On the molecular level."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "The way that atoms and molecules interact with one another is via chemical bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, from chemistry and from physics, we know that there are many types of chemical bonds that exist in nature."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "But all of these chemical bonds have the same thing in common."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "They are all electric in nature."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So all chemical bonds exist because of the existence of charge on different atoms and different molecules."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So, for example, if we have two atoms that are distance D apart and these atoms are stationary and atom one has a partial positive charge, and atom two has a partial negative charge, then these two atoms will attract each other as a result of that attractive electric force, now, because these are assumed to be stationary, that force is electrostatic."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And the equation that gives us the magnitude of that electrostatic force is Coulomb's equation."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So the electrostatic force between the two charges is equal to So the numerator is the product of K. A constant."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Q one, the charge of atom one and q two, the charge of atom two."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And the denominator is simply the square, the distance between the center of masses of those two charges."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So we see that the larger the charge is, the greater the numerator is and the greater the tractive force is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And likewise, the smaller our separation distance is, the closer our two charges are, the smaller our denominator is and the greater the electrostatic force is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, the thing about electric force is it's not only attractive in nature, but it can also be repulsive in nature."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "For instance, if we have two light charges."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So either two opposite, two positive charges or two negative charges."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "In both of these cases, the electrostatic force is repulsive in nature."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so, in this case, the two atoms will tend to move apart from one another."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So unlike gravity, unlike the gravitational force, the electric force that essentially holds and allows the interaction between atoms and molecules is both attractive and, in some cases, repulsive in nature, depending on the type of charges that are found in close proximity."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And all the different types of bonds we're going to discuss in this lecture are electric in nature."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So we have two categories of bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "We have intramolecular bonds and we have inter molecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Intramolecular bonds are the bonds that hold the atoms together within a given molecule."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And intermolecular bonds are those bonds that hold atoms together on different molecules."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And intramlecular bonds are, on average, on a one to one individual basis, stronger than intermolecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So let's discuss the three types of intramlecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So we have non polar covalent, polar covalent and ionic bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Let's begin by defining what a covalent bond is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "A covalent bond is a bond in which we have the sharing of electrons."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "If the sharing is equal between two atoms, we have a non polar covalent."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "If the sharing is not equal, if it's slanted to one side, then we have a polar covalent bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So let's suppose we're considering the following molecule."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "In this biological molecule that exists on DNA molecules and RNA molecules, this guanine molecule, we have four types of atoms that are arranged to form the molecule."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "We have h atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "We have n atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "We have carbon atoms, and we have an oxygen atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And all these atoms are held together by two types of intramolecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "We have non polar Covalent and polar Covalent."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, let's suppose we examine the bond between this carbon and this carbon."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "These two carbons are the same exact atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "They have the same exact electronegativity value."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And that means they will pull the electrons equally."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so they will have an equal distribution of electrons between these two atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so what that means is there will be a net charge of zero on this carbon and this carbon."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so there will be no electric dipole moment that exists between these two carbons."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And in that case, because we have an equal sharing of electrons, this is a nonpolar Covalent bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, Covalent bonds can be double bonds, single bonds or triple bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "A double bond simply means we have more electron density between the two atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so the two atoms will be closer together."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And because the atoms are closer together, that force will be larger."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And that's exactly why double bonds are stronger than single bonds and triple bonds are stronger than double bonds or single bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So in this case, we have a double non polar Covalent bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, what about a polar Covalent bond?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So let's suppose we examine this oxygen and this carbon."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So what can we say about this double bond here?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, oxygen is not the same atom as carbon."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And oxygen is more electronegative than carbon."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And that means it will have a stronger force for those electrons."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "It will pull the electrons closer to that oxygen."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so the oxygen will develop a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "That carbon will develop a partial positive charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And now we have a separation of charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And that will create an electric dipole moment that will point from the carbon to that oxygen."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And because we have the existence of an electronipolnom, that will create a polar Covalent bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So a polar Covalent bond is a bond that exists between two different atoms that have two different electronegativity values."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Another polar bond is this bond here."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "The nitrogen is more electronegative than our hydrogen, and so it will pull the electron density closer, developing a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "It will take away the electrons from H, and the H will develop a partial positive charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so this is another example of an electric dipole moment, a polar Covalent bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So the electric dipole moment here will point in this direction."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, the final type of intramlecular bond that is not found in this guanine molecule is an ionic bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And one example of an ionic bond is in a sodium chloride molecule."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So in a single sodium chloride molecule, we have one ionic bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, what happens is, because we have two different atoms, and because one of these atoms is so much more electronegative than the other atom, because chloride is so much more electronegative, it will pull that electron completely onto that chloride atom."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so we basically have no sharing of electrons because that same electron ends up entirely on that chloride."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so the chloride develops a full negative charge and a sodium develops a full positive charge because it becomes deficient, it doesn't contain that electron."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So because now we have the separation of two full charges, we're going to have an electric force that will exist between these two full charges."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so this is what an ionic bond is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So in some cases, one atom is so much more electronegative than a second atom because and so it pulls that electron density completely to one side, and that develops a full positive charge on this, a full positive charge on this, a full negative charge on that."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so we have a separation of two of these full charges, and that will create a force we call Dionic force, or Dionic bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So three types of intramolecular bonds that hold the atoms in a given molecule together."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now in biochemistry."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "The chemical bonds we have to really be familiar with are the intermolecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Because even though the intermolecular bonds aren't as strong as the intramolecular bonds are on a one to one basis because usually we have so many of these intermolecular bonds involved in any given reaction these intermolecular bonds end up playing a very important role in actually determining what the pathway of a reaction is and what the structure of a final molecule is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "For example, in proteins and in DNA, it's the inter molecular bonds that basically allow that three dimensional structure to actually exist in the first place."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And we'll see exactly what we mean by that in future lectures."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So let's discuss two important types of inter molecular bonds that you should be familiar with in your study of biochemistry."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So we have hydrogen bonds and London dispersion forces."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So a hydrogen bond is a specific type of a dipole dipole interaction, dipole dipole bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "In fact, hydrogen bonds are the strongest type of intermolecular bonds, as we'll see in just a moment."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So when we examine our DNA structure, we see that along our bases, on opposite strands of DNA, we have these bases that interact with one another via hydrogen bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So one of these bases is guanine."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Two other bases are adenine and thymine."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And adenine and thymine interact with one another via these hydrogen bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, in a hydrogen bond, a hydrogen atom is shared by two electronegative atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So what exactly do we mean by that?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So let's go back to this molecule."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So, in this molecule, we spoke about polar Covalent bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Here, we're also going to have polar Covalent bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So because the oxygen is more electronegative than the carbon this carbon will develop a partial positive charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "This oxygen will develop a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "By the same reasoning this will develop a partial negative charge and this also develops a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "This has a partial positive charge, this has a partial positive charge and this nitrogen will have a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So we have a partial positive charge here and right next to it on the other molecule we have a partial negative charge on the nitrogen."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so we have the existence of these two partial charges that are opposite in nature and that will be an attractive force."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And this bond is known as the hydrogen bond because this hydrogen atom is being shared by these two electronegative atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Likewise, because we have a partial positive charge on this H atom it is being shared by these two electronegative atoms namely the nitrogen and our oxygen."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So that is what a hydrogen bond is."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "A hydrogen bond exists between two different groups of atoms that have a permanent dipole moment."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So what that means is there's a permanent dipole moment right here and there's also permanent dipole moment right over, let's say right over here."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so these two permanent dipole moments interact with one another and they form a bond."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, why is a hydrogen bond the most stable, the strongest type of inter molecular bond?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Well, that's because hydrogen is the smallest nucleus that exists in nature and it's such a small atom that the H atom can get very close to this atom and this atom."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so what that means is because the distance between the two charges is so small that force is relatively large and that's exactly why hydrogen bonds are the strongest type of intermolecular bonds."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now, another terminology that you have to be familiar with in your study of biochemistry is what it means for a group of atoms to be an H bond donor and what it means to be an Hbond acceptor."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So if we examine the following interaction this group of atoms is our H bond donor and this is the Hbond acceptor."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "This is the H bond donor and this is the H bond acceptor."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So an Hbond donor is basically that group of atoms that contains the intramolecular bond between the electronegative atom and that H atom."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So this if we zoom in on just this diagram this is our intramolecular bond that exists between these two atoms."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so this is the H bond donor and the other atom that contains that partial negative charge is the H bond acceptor."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "It can basically bond with this partially positive charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now the other type of intermolecular bond that you have to be familiar with in your study of biochemistry are the London Dispersion forces."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Now in biochemistry sometimes the London Dispersion forces are also called Van der Valve forces."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So in biochemistry, if somebody ever tells you or refers to the Vanderbilts forces, they are probably referring to the London dispersion forces."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "The reason this is technically incorrect is because actually, all intermolecular bonds are technically vanderball's forces."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "But sometimes in biochemistry, they use these two terms interchangeably."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So, what exactly is a London dispersion force?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Well, it's an electric force that exists between two groups of atoms that have instantaneous dipole moments."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So, what exactly do we mean by that?"}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "Well, if we examine the electron density around atoms, the electron density isn't static."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "It fluctuates."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "It changes over time."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So, for example, if we have molecule one and molecule two that both consist of these carbon atoms, so we have two carbon atoms bonded, two carbon atoms bonded at one moment in time."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "This could be the electron density."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And because we have symmetry, we will not have a dipole moment."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "But at the next moment in time, the electron density of this can change to this, because the electrons are continually fluctuating over time."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "So if some of these electrons fluctuate to this side, that will give this carbon a partial positive charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "This carbon a partial negative charge."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And so an instantaneous dipole moment will exist that will point from this side to this side."}, {"title": "Intramolecular and Intermolecular Forces .txt", "text": "And because there are more electrons on this side, that will basically repel the electrons on this adjacent carbon on the second molecule pushing."}, {"title": "Spermatogenesis.txt", "text": "In humans, the specialized organs involved in reproduction are known as the gonads and the male gonads are known as testes."}, {"title": "Spermatogenesis.txt", "text": "Inside testes are these specialized tubules known as feminine philosopubials."}, {"title": "Spermatogenesis.txt", "text": "And inside the seminar philosopubials is where the sperm cells are actually formed and the process by which the sperm cells are formed inside the seminar philosopubials of the testes is known as spermatogenesis."}, {"title": "Spermatogenesis.txt", "text": "And this will be the focus of this lecture."}, {"title": "Spermatogenesis.txt", "text": "So let's begin by taking a cross section of the male gonads artistes."}, {"title": "Spermatogenesis.txt", "text": "We get the following diagram."}, {"title": "Spermatogenesis.txt", "text": "Now, these brown convolute tubules are the seminiprilly's tubules."}, {"title": "Spermatogenesis.txt", "text": "And notice that these seminar philosophy tubules eventually converge and form this highly convoluted structure known as the epididymis."}, {"title": "Spermatogenesis.txt", "text": "Now, before we discuss what the function of the epididymus is, let's discuss what the function of the seminar fields tubule is and what the structure of the tubule looks like."}, {"title": "Spermatogenesis.txt", "text": "So if we take a single seminiphers tubule and we take a cross section and we zoom in on that cross section, we get the following diagram."}, {"title": "Spermatogenesis.txt", "text": "So we have the internal cavity, the lumen of the seminphilus tubule and this red portion is the wall of the seminaries seminipherous tubule."}, {"title": "Spermatogenesis.txt", "text": "Now, if we further zoom in on a portion of the wall, we get the following diagram."}, {"title": "Spermatogenesis.txt", "text": "And this is the diagram that describes the process of spermatogenesis, how sperm cells are actually formed."}, {"title": "Spermatogenesis.txt", "text": "So the red portion is the wall of the seminefriendly stewart."}, {"title": "Spermatogenesis.txt", "text": "This is the basement membrane and this is the interstitulum."}, {"title": "Spermatogenesis.txt", "text": "It's the interstitial space."}, {"title": "Spermatogenesis.txt", "text": "Now, inside the interstitial space we have blood capillaries and we also have these cells known as Ladic cells."}, {"title": "Spermatogenesis.txt", "text": "Now, what Ladic cells do is they produce and release a special type of hormone known as testosterone."}, {"title": "Spermatogenesis.txt", "text": "And what testosterone does is it stimulates the stem cell, the precursor stem cell known as spermatogonium, to differentiate into a diploid cell known as the primary spermatocide."}, {"title": "Spermatogenesis.txt", "text": "So deep inside the wall of our seminar phil's tubule are the stem cells of the male gonas known as spermatogonium."}, {"title": "Spermatogenesis.txt", "text": "Now, spermatogonium are diploid cells and that means in humans the chromosome number of spermatogonium is 46."}, {"title": "Spermatogenesis.txt", "text": "So when lathic cells produce our testosterone, it stimulates the spermatogonium to differentiate into the primary spermatocyte, also a diploid cell."}, {"title": "Spermatogenesis.txt", "text": "So the primary spermatocyte also contains 46 chromosomes."}, {"title": "Spermatogenesis.txt", "text": "Now, the primary spermatocide can now undergo meiosis one."}, {"title": "Spermatogenesis.txt", "text": "And what undergoes meiosis one?"}, {"title": "Spermatogenesis.txt", "text": "It produces these two haploid cells."}, {"title": "Spermatogenesis.txt", "text": "And that means they have 23 chromosomes, half of the chromosome number of the primary spermatocides."}, {"title": "Spermatogenesis.txt", "text": "And so these two cells are known as the secondary spermatocides."}, {"title": "Spermatogenesis.txt", "text": "Each of these secondary spermatocides shown here can now undergo meiosis too."}, {"title": "Spermatogenesis.txt", "text": "And each one of these cells produces haploid cells known as spermatid."}, {"title": "Spermatogenesis.txt", "text": "So overall, we have four spermatids produced from one primary spermatocide."}, {"title": "Spermatogenesis.txt", "text": "And so we'll see four of these sperm cells produced at the end because these spermatids, with the help of these nourishing cells known as sirtoli cells, showed in green, eventually differentiate into our sperm."}, {"title": "Spermatogenesis.txt", "text": "Cell."}, {"title": "Spermatogenesis.txt", "text": "So these spermatids, when they interact with the surtoli cells the surtoli cells not only give the cells the proper nutrients but the surtole cells also faggot phagocytes."}, {"title": "Spermatogenesis.txt", "text": "They remove the cytoplasm from our spermatid to produce the sperm cell."}, {"title": "Spermatogenesis.txt", "text": "And we'll discuss what the structure is of the sperm cell in just a moment."}, {"title": "Spermatogenesis.txt", "text": "Once the sperm cells are actually formed they are released into the lumen, the cavity of the seminar's tubule."}, {"title": "Spermatogenesis.txt", "text": "And now the sperm cells can travel along the lumen of the seminar philosophy tubule and eventually they end up in the epididymus."}, {"title": "Spermatogenesis.txt", "text": "And once inside the epididymus this is where they mature into sperm cells that look like this."}, {"title": "Spermatogenesis.txt", "text": "And this is also where our sperm cells are stored before they're released the outside environment."}, {"title": "Spermatogenesis.txt", "text": "So in the epididymus the sperm cells not only mature into cells that look like this but the epididymis also serves to store those sperm cells before being released to the outside environment."}, {"title": "Spermatogenesis.txt", "text": "Now let's take a look at the structure of the mature sperm cell."}, {"title": "Spermatogenesis.txt", "text": "So we have a head, we have a midsection and we have a tail."}, {"title": "Spermatogenesis.txt", "text": "Now the head consists of the nucleus that contains a haploid number of chromosomes."}, {"title": "Spermatogenesis.txt", "text": "So in males, in male humans that's 23 chromosomes."}, {"title": "Spermatogenesis.txt", "text": "We also have the red section that is basically known as the acrosome."}, {"title": "Spermatogenesis.txt", "text": "This is a golgi apparatus that is capable of releasing special digestive enzymes that are needed to penetrate the xcel to produce the zygote."}, {"title": "Spermatogenesis.txt", "text": "So when the sperm cell combines with the excel for the sperm cell to get into our xcel it must use the digestive enzymes found inside the acrosome, the rest section to basically digest and penetrate the membrane of that egg cell."}, {"title": "Spermatogenesis.txt", "text": "Now within the midsection we have these green organelles known as mitochondria."}, {"title": "Spermatogenesis.txt", "text": "And these mitochondria are needed to produce ATP because the ATP is needed by the tail."}, {"title": "Spermatogenesis.txt", "text": "The tail consists of a flagellum that is needed for locomotion."}, {"title": "Spermatogenesis.txt", "text": "The flagellum basically allows the cell to actually move from point A to point B along these tubules, along these canals."}, {"title": "Spermatogenesis.txt", "text": "So once again we see that inside the male gonas our testes, we have these tubules known as seminiplus tubules."}, {"title": "Spermatogenesis.txt", "text": "And inside the wall of the semiiflose tubules we have the sperm cells being produced in a process known as spermatogenesis."}, {"title": "Spermatogenesis.txt", "text": "So we have Ladic cells that produce testosterone that stimulates the differentiation of spermatogonium into primary spermatocides."}, {"title": "Spermatogenesis.txt", "text": "And then with the help of these saratoga cells that provide the nutrients and also remove the cytoplasm, the primary spermatocides eventually differentiate and produce these sperm cells that move into the epididymis."}, {"title": "Spermatogenesis.txt", "text": "And inside the epididymis they mature into mature sperm cells and they are stored inside the epididymis until they are released to the outside environment."}, {"title": "Pleiotropy and Epistasis .txt", "text": "From genetics, we know that a gene is nothing more than the sequence of nucleotides found on our DNA."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And these genes basically code for specific types of proteins."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And once the proteins are produced, the proteins can either interact with other genes or the proteins can be used to basically produce some type of trait to express some type of phenotype characteristics of the adult individual."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, in this lecture, we're going to focus on two important phenomenon that exists in genetics."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We're going to discuss a concept, a phenomenon known as playotropy, and we're also going to look at episodes."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So let's begin by describing what playotropy is."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So playotropy is the process by which a pair of alleles on a single locus on some homologous chromosome affects the expression of more than one type of trait, of many different types of traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And to see exactly what we mean by that, let's consider albino individuals."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So, in albino individuals, it's a single pair of jeans at some particular locus that actually affects the expression of three different types of characteristics, of three different types of phenotype traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So, number one, lack of pigment hair, lack of pigment in the hair."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Number two, lack of pigment in the eyes."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And number three, lack of pigment in the skin."}, {"title": "Pleiotropy and Epistasis .txt", "text": "These three different types of phenotype traits are expressed as a result of a single locus."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Remember, in any diploid organism, such as humans, every single chromosome comes with a homologous pair."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So in this particular case, we have this chromosome, number one, and this is the homologous chromosome to this chromosome, number one."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And because they're homologous, what that means is they carry similar genes that code for the same exact trait or traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And in this particular case, we have three different traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we have allele number one shown in red, and allele number two, also shown in red."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And it's the pair of alleles found at this particular locus."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So this is the locust."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Locus is simply the location on our chromosome pair."}, {"title": "Pleiotropy and Epistasis .txt", "text": "It's this single locus that affects the expression of many different types of traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And that's exactly what play atrophy is."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So a single gene or a pair of genes on a single locus affects many different types of phenotype characteristics, and this is known as plyotropy."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, what about epistasis?"}, {"title": "Pleiotropy and Epistasis .txt", "text": "Well, in many cases, a gene creates a protein that goes on to a second gene, and that protein affects the expression of that second gene."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And this process can continue until some type of trait is actually expressed, and this is what we call epistasis."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So in many cases, a gene at one locus produces a protein that goes on to a second locus and affects the expression of that gene at that second locus."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And this is known as epistasis."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And an epistasis, two or more pairs of alleles at different loci basically affect a single trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So to see what we mean, let's take a look at the following example."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So this is a simple case of epistasis."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we have homologous chromosome pair number one."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we have gene number one, and it's homologous gene number two."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we have our set of alleles."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So these alleles basically express or produce some type of protein, and the protein goes on onto a second different locus."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So this is locus number one and this is a different locus number two."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And the protein goes on to the second locus and either inhibits or expresses the protein that is coded by these purple genes here."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So allele pair number one, allele pair number two at a different locus."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And so now the protein produced can either go on and either inhibit or express other alleles, or it can go on to actually express that single trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So this is what we mean by epistasis in plyotropy."}, {"title": "Pleiotropy and Epistasis .txt", "text": "It's a single locus, a single set of allele pair that basically expresses many different types of traits."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But an epistasis, it's the interaction between different allele pairs at different loci that ultimately produces or expresses or controls the expression of a single trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, recall in our discussion on embryological development and embryology, we said that when the zygote is formed, the zygote begins to develop into the adult organism."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And when the zygote undergoes embryological development, this is a very important process that takes place because during embryological development we have one gene can interact with the second gene, which interacts with a third gene, and this process can continue until we express that particular type of trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, embryology is a rather complicated case because we have many, many, many different types of interactions."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We're going to look at a much simpler case in this lecture."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We're going to discuss how dogs basically pass down their coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So another relatively simple example of epistasis is the inheritance of coat colors in certain types of dogs."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So in certain dogs, we have two different allele pairs at two different low side that ultimately determine the expression of some particular color trait, the code color trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So to designate these different types of allele pairs, we're going to use the letter D to designate one allele pair and the letter B to designate the second allele pair."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So let's begin by supposing that we have a dog that is homozygous dominant."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So let's suppose our dog is homozygous dominant for our D gene."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And so we have uppercase D, uppercase D. In this particular case, what happens is we're going to have a dark coat color, but there are two possibilities."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We can either have a light brown color, so a chocolate color, or we can have a black color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we have a lighter coat and we have a darker coat."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, the chocolate coat or the black coat depends on the second gene type."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So if we have uppercase D, uppercase D, and we have, let's say, uppercase B, uppercase B."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So if we have a homozygous dominant for D, and we have a homozygous dominant for the B, then we're going to produce a black coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And likewise, if we have a homozygous dominant for D and a heterozygous four B, so at least one of it is dominant, we're still going to produce the color black."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But if we have a homozygous dominant and a homozygous recessive for the B gene, then we're going to produce a lighter color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We're going to produce a brown or chocolate coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And the same thing is true for the heterozygous if we have a heterozygous for our D gene."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So if at least one of these is a dominant gene, then we're going to produce a darker coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And the options are either chocolate or a black coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And once again, if we have heterozygous and a homozygous recessive, then we're going to produce a chocolate color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But if we have a heterozygous and either this one or this one, so let's suppose this one."}, {"title": "Pleiotropy and Epistasis .txt", "text": "If we have these two, then we produce a black coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "If we have this and this, then we produce a black coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So we see that different types of possibilities create different types of coat colors."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Now, in this particular case, so we see that if we have either a homozygous dominant or a heterozygous for the Z gene, we're always going to produce a dark coat color, either black or chocolate."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And these depends on the second type of gene."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But if we have a homozygous recessive for the D gene so if both of these alleles on this homologous chromosome pair are lowercase DS, if they're recessive, then it doesn't matter what the second type of gene phenotype is, we're always going to produce a light coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "We're going to produce the yellow coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So if both of these D genes are recessive, if they're lowercase DS, no matter what we're going to have in this case, we're going to inhibit the production of this."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And so we're going to get a light yellow coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But if it's either homozygous dominant or heterozygous for D, then because we have the presence of at least one uppercase D, that means we're going to have a darker color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And the type or the shade of the dark color depends on if we have at least one of these uppercase bees."}, {"title": "Pleiotropy and Epistasis .txt", "text": "If we don't have an uppercase bees on either one of these two chromosomes, we produce a chocolate color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But if we have at least one uppercase B, so here or here, then we produce a black coat color."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So this is an example of epistasis."}, {"title": "Pleiotropy and Epistasis .txt", "text": "Why?"}, {"title": "Pleiotropy and Epistasis .txt", "text": "Well, because we have an interaction of at least two different pairs of alleles at two different loci that ultimately affect a single trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "And in this particular case, the trait is the color of that dog's coat."}, {"title": "Pleiotropy and Epistasis .txt", "text": "So once again, epistasis is when two or more pairs of alleles at different loci interact with one another to basically produce some type of gene or some type of trait."}, {"title": "Pleiotropy and Epistasis .txt", "text": "But plenty of people is basically the process by which a single locus, a single pair of alleles on a single locus of a homologous chromosome pair basically expresses many different types of traits, phenotype traits, as we discuss in this particular case."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "B lymphocytes or simply B cells are the white blood cells that make up the humoral immunity of our immune system."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And what that means is it's the B lymphocytes that produce the antibodies and also store the antibodies in specialized cells in case reinfection ever takes place."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "The question is what exactly is the mechanism of action of B lymphocytes sides?"}, {"title": "Mechanism of B-lymphocytes .txt", "text": "How exactly do B lymphocytes engage pathogens?"}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And how exactly do B lymphocytes protect and defend the cells of our body from these pathogenic invasions?"}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So let's begin by discussing what the structure of a B lymphocyte is."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So here we have a B lymphocyte and notice that the B lymphocyte contains these receptors on its membrane and they're known as B cell receptors."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So let's suppose we have a pathogen that makes their way into our body and that pathogen one way or another will release antigens."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now these antigens can either float around our blood, our lymph or our tissue."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Or the antigens can be picked up by some other type of white blood cell."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "For example a dendritic cell or a macrophage."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now let's suppose our antigen is picked up by the macrophage."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "What the macrophage will do is it will display that antigen bound to a special type of protein complex on the membrane of the macrophage."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And the protein complex is known as the major histocompatibility class two complex."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And this is shown in this diagram."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now anytime we have an antigen in our body either actually floating around in our body or bound to some other type of leukocide we're going to have a specific B lymphocide that has the B cell receptors that can bind to that particular and that specific pathogenic antigen."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So the B lymphocyte can either pick up these antigens found floating around our system or it can actually also grab the antigen off of our macrophage or some other type of leukocytes."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So the entire point of a B lymphocyte is to collect these antigens found inside our body and these antigens came from some type of pathogen."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "For example a bacterial cell."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "The next question is what happens once our antigen is bound onto the B cell receptor of our B cell?"}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Well, a process known as cell mediated endocytosis begins to take place."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And what this process does is it invaginates our cell membrane and it forms this vesicle that is brought into the cytoplasm of our cell as shown in this diagram."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So the antigen shown in red binds onto the cell receptor of the B cell and then that initiates the cell mediated endocytosis process and that ultimately forms that internal vesicle."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And now the antigen is found inside this vesicle of arocytoplasm."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now the cell also has lysosomes and these lysosomes are shown in green and they confuse with this vesicle."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And these lysosomes release digestive enzymes that can proteolytically break down our antigen."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So the antigen begins to break down and a small portion of that antigen known as the antigenic determinant or the epitope is taking and placed on the same type of protein complex that was found on the macrophage MHC class two major histocompatibility complex, class two."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So we have the antigen, we have our MHC class two complex on our B cell."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "What happens next?"}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Well, what happens next is for any type of mechanism, for any type of defensive mechanism to actually take place, our B cell must react, must interact with our T cell, our T lymphocyte."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So a special type of T lymphocyte known as the helper T cell that contains the complementary T cell receptor, complementary to this particular section of our antigen and MHC class two complex."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And also the helper T cell must have the CD four glycoprotein to actually be able to bind, interact with the section of our B cell."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So here we have the B lymphocyte that essentially contains the antigen bound to the MHC class two complex."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So if we have a nearby helper T cell that contains not only the complementary T cell receptor and this CD four, but also this CD four glycoprotein, only then can this binding process takes place."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And once this binding process takes place between the B lymphocyte and our helper T cell, now we begin to initiate different types of defensive responses."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "What happens is the helper T cell begins to release lymphocines or lymphocons."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And what these chemicals do is they basically initiate the process of cloning."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So this B cell begins to clone itself and when it clones itself, it produces identical cells, identical B cells that contain the same exact B cell receptor."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And what that means is these cloned cells can then go on and find the same exact antigens floating around in our body."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now, what it also does is it induces the process of differentiation."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Some of the clone B cells begin to differentiate into plasma cells as well as into memory B cells, the specialized versions of our B lymphocytes."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now, what the plasma cells do is they begin to produce plasma soluble and mobile versions of these B cell receptors that can bind onto antigens."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And what these are is our antibodies that we spoke of earlier."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So antibodies are soluble and mobile versions of these B cell receptors that are found on the membrane of the B lymphocyte."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And so what these plasma cells do is they contain highly extensive endoplasmic reticulum that can basically produce many, many of these antibodies."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And then these antibodies can move within our blood system, our lymph system and our tissue and bind onto that antigen and elicit some type of response labeled that antigen for destruction by our immune system."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "Now, finally, these chemicals can also induce the differentiation of B lymphocytes into memory B cells."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "And memory B cells, instead of producing our antibodies, they store a copy of the antibody in case reinfection by that same pathogenic antigen ever takes place."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "So it's, if the body is ever reinfected by that same pathogen."}, {"title": "Mechanism of B-lymphocytes .txt", "text": "It's the memory b cells that will have a copy of that antibody and which will be able to recognize those cells immediately and essentially label them for destruction by our immune system."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The next section of the nephron that we're going to focus on is the Loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, if we take a look at our nephron and we zoom in on this Ushaped."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Structure, well, this will give us our Loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And the first thing to notice about the loop of Henley is that it's located inside the medulla portion of the kidney."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So recall that the medulla portion is the lower portion of the kidney, while the cortex is the upper portion."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So the upper portion contains the glomerolus, the Bowman's capsule, the proximal and the distal convoluted tubule, while the medulla portion, this section of the kidney, contains our Loop of Henley as well as our collecting duct."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, the second thing to notice about the loop of Henley is that around the Loop of Henley, it contains a network of blood vessels, a network of capillaries known as the vasarcta."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And the vasarecta functions to absorb the electrolytes and nutrients that are reabsorbed from the loop of Henley and back into our body."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, the final thing to notice about the loop of Henley is that we can divide the loop of Henley into three sections."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, as the filter travels down the tubule of the Loop of Henley, this segment is known as the descending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "At the bottom, the filter basically changes direction and begins to travel upward."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And this segment is known as the thin ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The thin part simply means the size of our epithelial cells within this section are small."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "These cells are thin, they're relatively small, while this is our thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And thick means our size of the cells is relatively large."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The epithelial cells are relatively thick."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, the reason we divide the Loop of Henley into these three segments is because each one of these sections carries out its own unique function."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, before we examine the individual function of these three segments, let's discuss what the overall function of the Loop of Henley is."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, the loop of Henley utilizes a system known as the countercurrent multiply system."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And what that system does is it increases the amount of solute, it increases the concentration of the ions found within our tissue surrounding our Loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And the tissue surrounding the loop of Henley is known as the insertuum."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So it utilizes the countercurrent multiplier system to create a concentration gradient found inside the interstituum."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And what that ultimately does is it basically allows our Loop of Henley to absorb more water, and allows the nephron overall to absorb more water."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And this concentrates our urine that is produced by the nephron."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And at the same time, it utilizes as little energy as possible."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So the only time we actually use any energy within our Loop of Henley is within the thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And we'll see why energy is used in this segment in just a moment."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So what exactly is the meaning of the countercurrent multiply system."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Well, the countercurrent simply means that along the descending loop of Henley, the filter travels downward, but along our ascending loop of Henley, the filter travels upward."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So we have a counter current."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The two currents move in opposite direction."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, multiplier means the loop of Henley multiplies the amount of water."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "It increases the amount of water that is passively absorbed back into our body from the loop of Henley, as well as from other parts of our nephron, such as the collecting duct."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, to fully understand what the system is and how the loop of Henley actually creates this concentration gradient between the surrounding tissue and the lumen of our loop of Henley, let's begin with our thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So we're essentially going to work backwards."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, as I mentioned earlier, the thick ascending loop of Henley contains epithelial cells that are relatively thick, relatively large."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "It contains large, simple squamous epithelial cells."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, if we take a small section of our thick ascending loop of Henley, we basically get the following diagram."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So these are the large, simple squamous epithelial cells."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, as we see on the diagram, the membrane of these cells contains specialized proteins that are responsible for using ATP molecules, energy molecules, to establish a gradient inside our interstituum, between the interstituum and the inside the lumen of our loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So let's discuss how this is actually achieved."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, let's begin on the basil lateral side of our cell."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The basil lateral side of the cell is the side that points that faces our basement membrane, found in the interstituum of the surrounding thick loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So this membrane contains sodium, potassium, Atpas pumps, and these utilize ATP molecules, energy molecules to basically move sodium ions against their electrochemical gradient."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So three sodium ions are basically pumped from the inside of the cell to the outside of the cell."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "At the same time, two potassium ions are pumped from the outside to the inside of the cell."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And what this ultimately does is it establishes a gradient for sodium."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So inside the cell, we have less sodium than on the outside."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And so what happens on the apical side of our cell?"}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The apical side is the side that points towards the lumen of the thick loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The inside of the tubule, we have these passive co transport proteins that allow the movement of the ions down their electrochemical gradient."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, because we established a sodium concentration gradient in which we have less sodium inside, the sodium will move down its electrochemical gradient from the outside to the inside of the cell."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And at the same time, because this is a co transport protein membrane, it will allow the movement of other ions as well."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So for every one sodium that is moved inside the cell down the electrochemical gradient, our single potassium will be moved and two chlorides will also be moved."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So let's take a look at the following diagram which summarizes what takes place within the thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So what it does is it uses ATP to establish an electrochemical gradient that allows the movement of sodium, potassium and chloride from the lumen, from the lumen of aristic ascending lupifamily into the cells, and eventually out of the basil lateral side and into the interstituum of our loop of Henley into the surrounding tissue."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And this concentrates increases the solute concentration found in the interstituent."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "In fact, as we go down along the medulla, we have an increasing concentration of the solute of the sodium and chloride as we go lower and lower."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And we'll see why that's important in just a moment."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, between our cells, we have Thai junctions."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And these tight junctions prevent the leaking or the movement of water from the lumen and into our interstituum."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So no water is actually absorbed and no water actually flows into our thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The thick loop of Henley is impermeable to water."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, by the way, because we essentially increase the concentration of our interstituum found in the mid dull of the kidney."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "What that means is we increase the hemotic pressure in the interstituum, and we'll see why that's important in just a moment."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So let's move on to our descending loop of Henley, which is this section here."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, at the top of our descending loop of Henley, the inside filtrate is isotonic with respect to our interstituent."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, what exactly will happen as the filter travels downward?"}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, the epithelial cells of the descending loop of Henley are permeable to water."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So they allow the passive movement of water across the membrane of the descending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "However, the cells are impermeable to ions, so the ions such as sodium and chloride do not flow across the membrane in the descending loop of Penne."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, as the filtrate moves down, because the membrane of the descending loop of Penne is permeable of water, that means it will either flow out of the tubule or into the tubule."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The question is, where exactly will it flow?"}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Well, let's go back to the thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Recall that the thick ascending loop of Henley, what it basically did is it created a hypertonic environment in the surrounding tissue, in the interstituum."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "That means within the interstituum surrounding our descending loop of Henley, we have a high concentration of solute as compared to the inside."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And because water always travels from a low solute concentration to a high solute concentration, water will passively move from the lumen from the inside of the descending loop of Penalty and to the outside."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So at the top, our filtrate is isotonic with respect to our surrounding tissue."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "But as the water continually flows out and out and out, eventually at the bottom of our descending loop of Henley, because so much water left our tubule, the inside of our tubule will become hypertonic with respect to the surrounding tissue."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And this leads directly to the thin ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, before we go on to the thin ascending loop of Henley, let's mention the following things."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So previously I said that the function of the loop of Henley is to ultimately allow the nephron to absorb more water."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And it absorbs more water via passive diffusion without actually using any energy."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So the thick ascending loop of Henley uses energy to establish an electrochemical gradient, so that the water inside the descending loop of penalty flows out of the tubule without actually using any ATP molecules."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And that only happens when the water moves down its gradient from a low solute concentration to a high solute concentration."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, let's move on to the thin ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, if we look at the following diagram, this is the thin ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And unlike our epithelial cells in the descending loop of Henley, the cells here are impermeable to water, but they are permeable to sodium and chloride ions."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So the question is, in what direction will the sodium and chloride ions within the thin ascending loop of Henley actually travel?"}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Well, recall that as the filtered travels down the descending loop of Henley, the inside becomes more concentrated, so the relative amount of solutes inside our filtrate increases."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And at the bottom of our loop, we have a hypertonic environment."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Hypertonic with respect to our interstitium, we have a high concentration of sodium and chloride."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And because our cells within our thin ascending lupinly allow the movement of sodium and chloride passively, these sodium and chloride ions will move down their electrochemical gradient from a hypertonic environment, from where we have a high concentration of solute, to a low where we have a lower concentration."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So within a thin ascending lupa fennelly, the chloride and sodium ions will once again move passively without using any energy to the interstituent."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "Now, as we'll see in the next lecture, when we discuss our collecting duct, what the loop of Henley does is it increases the concentration of solute inside the surrounding tissue."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And that allows water to be reabsorbed not only in the descending loop of Henley, but also in the collecting duct, the final tubial portion of our nephron."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, once again, let's summarize our discussion."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So, the loop of hemle is this Ushaped structure that is found inside the medulla portion of the kidney."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And it uses a countercurrent multiplier system."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "It uses this system in which the filter travels downward here, but upward here, to multiply to increase the amount of water that is reabsorbed back by our body from the filtrate."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "At the same time, it concentrates the urine in the collecting duck."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And this basically is done without using too much energy."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "The only place we actually use energy is in the thick ascending loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So within the thick ascending loop of Henley, we establish an electrochemical gradient by using ATP."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And then in the descending loop of Henley, we utilize that electrochemical gradient to passively move water out of our tubial."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And as a result of all that water moving out of our tubule, we concentrate our filtrate towards the bottom of the loop of Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "And that's exactly why, in the thin, ascending loop of Henley, the sodium and chloride even further move to the outside, concentrating the outside even more."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "So this is a function of the lupus Henley."}, {"title": "Countercurrent Multiplier System and Loop of Henle.txt", "text": "It ultimately concentrates the medulla, the interstituum found in the medulla of our kidney."}, {"title": "Polymerase Chain Reaction.txt", "text": "Suppose we have a certain segment of a DNA molecule, a gene, for example, that we want to amplify."}, {"title": "Polymerase Chain Reaction.txt", "text": "And to amplify means to make many identical copies of."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, the question is, how can we go about amplifying that gene of interest?"}, {"title": "Polymerase Chain Reaction.txt", "text": "Well, one way that we spoke about earlier is to basically take that gene to integrate that gene into a bacteria plasmid, to place that recombinant plasmid into a bacterial cell, and then to allow that bacterial cell to divide many, many times and eventually we form many copies of that gene of interest."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, the problem with that method is it's not only time consuming and not only is it ineffective, but it also limits the size of that gene that we can actually use."}, {"title": "Polymerase Chain Reaction.txt", "text": "A much more effective and a much more efficient and accurate method is the polymerase chain reaction, or PCR."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, the polymerase chain reaction allows us to amplify a certain gene, a certain sequence of DNA, very quickly."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we can produce millions or even billions of copies of a single segment of DNA that we're actually interested in."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, let's begin by discussing what the ingredients are to this reaction."}, {"title": "Polymerase Chain Reaction.txt", "text": "What is it that we need to actually carry out a successful polymerase chain reaction?"}, {"title": "Polymerase Chain Reaction.txt", "text": "So we have four important ingredients."}, {"title": "Polymerase Chain Reaction.txt", "text": "Number one, we actually need that segment of DNA, the double stranded DNA that we want to amplify, that we want to replicate."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we have to begin with a certain target DNA molecule that contains that sequence, that gene that we want to amplify."}, {"title": "Polymerase Chain Reaction.txt", "text": "Number two, we need a pair of DNA primer."}, {"title": "Polymerase Chain Reaction.txt", "text": "So what is a DNA primer?"}, {"title": "Polymerase Chain Reaction.txt", "text": "Well, remember, a DNA primer is a relatively short sequence of DNA, so ranges from about 20 to 30 nucleotides."}, {"title": "Polymerase Chain Reaction.txt", "text": "And what this is used for is to initiate the process of DNA synthesis, DNA replication."}, {"title": "Polymerase Chain Reaction.txt", "text": "Number three, we need heat resistant DNA polymerase."}, {"title": "Polymerase Chain Reaction.txt", "text": "So the reason we need a heat resistant one is because we're going to carry out the reaction at a relatively high temperature."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, a DNA polymerase is needed because that's the protein complex that moves along that DNA and replicates that DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "And number four, we actually need the four different types of deoxyribonucleocide triphosphate."}, {"title": "Polymerase Chain Reaction.txt", "text": "So remember, we have adenine, guanine, we also have cytosine and thymine."}, {"title": "Polymerase Chain Reaction.txt", "text": "We need these four ingredients to actually produce that sequence of DNA that we want to amplify."}, {"title": "Polymerase Chain Reaction.txt", "text": "So these are the four main ingredients."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, the next question is what exactly are the steps and how many steps are there within a single cycle of PCR?"}, {"title": "Polymerase Chain Reaction.txt", "text": "So basically, if we take a single PCR cycle, we can break that cycle down into three different steps."}, {"title": "Polymerase Chain Reaction.txt", "text": "So in one PCR cycle, we have three different steps."}, {"title": "Polymerase Chain Reaction.txt", "text": "Step number one, we call DNA strand separation."}, {"title": "Polymerase Chain Reaction.txt", "text": "Step number two is the hybridization of the DNA primers onto that DNA that we want to replicate."}, {"title": "Polymerase Chain Reaction.txt", "text": "And number three is the actual DNA replication, the DNA synthesis process."}, {"title": "Polymerase Chain Reaction.txt", "text": "So this is one cycle of PCR and we'll see that in just a moment."}, {"title": "Polymerase Chain Reaction.txt", "text": "There are many of these cycles that actually take place to produce the many copies of that single DNA segment that we're interested in."}, {"title": "Polymerase Chain Reaction.txt", "text": "So let's basically break down what these three steps actually involved."}, {"title": "Polymerase Chain Reaction.txt", "text": "And let's begin with step number one, the strand separation."}, {"title": "Polymerase Chain Reaction.txt", "text": "So suppose we have a beaker and inside that closed beaker we basically have all these different ingredients inside a solution."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we basically have the target DNA molecule that we want to replicate, we have the pairs of DNA primers, we have the heat resistant DNA polymerase and we also have the different types of deoxyribonucleotide triphosphate."}, {"title": "Polymerase Chain Reaction.txt", "text": "So let's begin with step one."}, {"title": "Polymerase Chain Reaction.txt", "text": "In step one, what we actually want to do is we want to increase the temperature so that we reach a temperature where the hydrogen bonds will break between those two DNA strands."}, {"title": "Polymerase Chain Reaction.txt", "text": "So what we want to do is we want to separate the two strands of DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "So let's suppose this is the DNA molecule, our target DNA molecule, and this intersection is basically the target sequence."}, {"title": "Polymerase Chain Reaction.txt", "text": "It's the sequence of nucleotides that we want to replicate."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now these parts are basically known as the flanking sequence."}, {"title": "Polymerase Chain Reaction.txt", "text": "And the reason they're called flanking sequence is because they're found right next to the target sequence."}, {"title": "Polymerase Chain Reaction.txt", "text": "And those primers are actually going to bind to these flanking sequences as we'll see in just a moment."}, {"title": "Polymerase Chain Reaction.txt", "text": "So in step number one, we want to increase the temperature of that solution in which this DNA molecule is found to about 95 degrees Celsius for about 15 seconds."}, {"title": "Polymerase Chain Reaction.txt", "text": "And what this does is it breaks those electrostatic bonds, those hydrogen bonds that exist between those two strands of DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "And what we have is we have a separation, we have the breaking of these bonds and so the separation of these two individual strands of DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "So after step one, we now have this picture as shown in this diagram."}, {"title": "Polymerase Chain Reaction.txt", "text": "So these two strands have now separated."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now once we separate the two strands, we begin decreasing the temperature of that solution."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we cool the solution to about 54 degrees Celsius."}, {"title": "Polymerase Chain Reaction.txt", "text": "And the reason we cool it to that specific temperature is because at that temperature, that is when those DNA primers will begin to bind onto the flanking sequence."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, because we're going to have so many DNA primers moving about between this region that will keep these two single strands of DNA from forming those bonds and reforming that double stranded helix formation."}, {"title": "Polymerase Chain Reaction.txt", "text": "So in step number two, the solution is cooled to about 54 degrees Celsius and the DNA primers are added."}, {"title": "Polymerase Chain Reaction.txt", "text": "So they're basically floating around."}, {"title": "Polymerase Chain Reaction.txt", "text": "And once we cool our solution to that temperature, those DNA primers are now at an optimal temperature where they can begin binding onto the flanking sequences."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now the question is where exactly will these DNA primers actually bind to?"}, {"title": "Polymerase Chain Reaction.txt", "text": "Well, the sequence of the DNA primers are complementary to this flanking sequence and this flanking sequence here."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so what we see is one of the primers that has a complementary sequence to this one binds onto this end and the other one binds onto the opposite end of this complementary single strand of DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now the reason this binds at the three end is because the DNA polymerase can only form the single strand of DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "Colin can only elongate that DNA in the five to three direction."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so that primer must form at the five end."}, {"title": "Polymerase Chain Reaction.txt", "text": "So it actually forms at the three end of this DNA molecule so that we have a five M that begins on this side."}, {"title": "Polymerase Chain Reaction.txt", "text": "And likewise the other DNA primer binds until the three end of the complementary DNA molecule so that it forms at the five end."}, {"title": "Polymerase Chain Reaction.txt", "text": "And in the next step, when we add the DNA polymerase, the DNA polymerase can bind onto this section, this section, and can basically elongate that DNA molecule."}, {"title": "Polymerase Chain Reaction.txt", "text": "So one DNA primer binds to the three end of one strand and the other primer binds to the three end of the complementary strand."}, {"title": "Polymerase Chain Reaction.txt", "text": "So now we increase the temperature to about 74 degrees Celsius or 72 degrees Celsius."}, {"title": "Polymerase Chain Reaction.txt", "text": "And the reason we increase it to 72 degrees Celsius is because that is the optimal temperature of the heat resistant DNA polymerase molecule."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we have the deoxyribonucleocide triphosphates and we have that heat resistant DNA polymerase that are found in solution and which are swimming around this DNA molecule."}, {"title": "Polymerase Chain Reaction.txt", "text": "And once we increase the temperature to 72 degrees Celsius, it's then that the DNA polymerase will bind onto the DNA and will begin adding those deoxyribonucleotide triphostate molecules and will begin to synthesize elongate that DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so at the end of step number three, what we have formed is two identical copies of that DNA that we begin with."}, {"title": "Polymerase Chain Reaction.txt", "text": "So after one cycle, we amplify the number to two."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now this is only one cycle of PCR if two cycles take place."}, {"title": "Polymerase Chain Reaction.txt", "text": "So let's suppose this is cycle number one."}, {"title": "Polymerase Chain Reaction.txt", "text": "And now that we're in this position, we allow cycle number two to take place because now we have two DNA molecules and at one we begin with two."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so after two cycles, each one of these will be amplified to two."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we have two form from this, two form from this."}, {"title": "Polymerase Chain Reaction.txt", "text": "So after two cycles of PCR, we're going to have a total of four individual copies of that DNA."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we see that after three cycles we're going to have two times two times two."}, {"title": "Polymerase Chain Reaction.txt", "text": "So eight."}, {"title": "Polymerase Chain Reaction.txt", "text": "After four cycles we're going to have two times two times two, times two, so 16."}, {"title": "Polymerase Chain Reaction.txt", "text": "And this process continues."}, {"title": "Polymerase Chain Reaction.txt", "text": "And the formula, the equation that gives us the total number of copies made after N cycles is two to the N power."}, {"title": "Polymerase Chain Reaction.txt", "text": "So for example, if we have two cycles, two to the two is four copies."}, {"title": "Polymerase Chain Reaction.txt", "text": "If we have three cycles, two to the eight is eight copies."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so forth."}, {"title": "Polymerase Chain Reaction.txt", "text": "Now, about 20 to 30 of these cycles can take place within an hour."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we see that after an hour, we can form anywhere from millions to billions of copies of a single DNA segment."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we see that the polymerase chain reaction is very effective and very efficient in actually forming those copies and amplifying the DNA molecule that we're interested in."}, {"title": "Polymerase Chain Reaction.txt", "text": "And one other important property of the polymerase chain reaction is the fact that it takes within a given beaker, within a given closed container."}, {"title": "Polymerase Chain Reaction.txt", "text": "So what that means is after the first cycle takes place, we don't actually have to add anything into that mixture because the mixture has all the ingredients from the beginning."}, {"title": "Polymerase Chain Reaction.txt", "text": "So after one cycle takes place, all we have to do is we have to bump up the temperature back to 95 degrees Celsius to restart cycle number two."}, {"title": "Polymerase Chain Reaction.txt", "text": "So what that means is if cycle number one took place and we form these two double stranded DNA molecules, all we have to do to restart the cycle is to increase the temperature to 95, and then these two DNA will begin separation."}, {"title": "Polymerase Chain Reaction.txt", "text": "And then all we have to do is change the temperature to 54."}, {"title": "Polymerase Chain Reaction.txt", "text": "So cool the solution to go to step number two of cycle two, and then to get to step three, we have to bump the temperature back up to 72 Celsius to basically make sure that DNA synthesis takes place."}, {"title": "Polymerase Chain Reaction.txt", "text": "So we see that PCR is a very easy reaction to actually control."}, {"title": "Polymerase Chain Reaction.txt", "text": "All we have to do is we have a closed container and all the proper ingredients, and then we simply change the temperatures to basically ensure that the cycles continue right after the other."}, {"title": "Polymerase Chain Reaction.txt", "text": "And so the PCR method is a much more effective method than actually using bacterial cells to replicate to amplify the genes of interest."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "A punant square, as we'll see in just a moment, is actually a tool that is used in genetics."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And it helps scientists uncover the potential possibilities of the genotypes of the offspring that are formed in some given mating process, in some given crossing process."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So when we cross two individuals or when we cross two organisms, that simply means we mate those two organisms to produce some offspring."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And what the Ponnet square allows us to do is it allows us to basically uncover the type of genes that will be found within that given individual."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, before we actually examine what the Ponnet square is and how we can use it and what information it provides us with, let's actually discuss four important terms that we must know whenever dealing with pundit squares."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have something called heterozygous and something called homozygous."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We also have something called a genotype and something called a phenotype."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, before we look at these terms, let's actually recall the following fact."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "In any diploid organism, if we examine a somatic cell of a diploid organism, we'll see that for every chromosome in that somatic cell, there is always a homologous chromosome."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So two homologous chromosomes basically are chromosomes that not only have the same type of size, shape and structure, but also carry genes that code for proteins that express the same type of trade."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, to see what we mean, let's take a look at the following homologous pair."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, we have two chromosomes which are said to be homologous with respect to one another."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, along this chromosome, we have many genes."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We can have thousands of different genes."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "But in this diagram, we only have four different types of gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We have a purple gene or a dark purple gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We have a green gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We have a light purple gene and a red gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And each one of these genes codes for some type of protein or proteins that help express some type of trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "For example, let's say the purple gene codes for a protein that expresses the height of that organism."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We can say the green gene creates a protein or codes for protein that expresses the color of the seed."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Let's suppose our organism RP plants, the organisms that Gregor Mendel actually worked on."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, this gene codes for some other protein for a third trait, and this codes for yet another protein for another trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, notice that there are essentially homologous genes on the second homologous chromosome, we have a purple gene adjacent to this one, a green gene adjacent to this one, and so forth."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And these genes, these pairs of genes, or homologous genes, are also known as alleles."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And what alleles are they're basically genes found on the two different homologous chromosomes that code for proteins that express that same type of trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So these two genes, the purple genes, are alleles because they code for proteins that express that same high trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "These two are also alleles because they code for genes that code for another trait, let's say, the color of the seed and so forth."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, what exactly do we mean by a heterozygous organism?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, an organism is heterozygous if one of these genes in the pair of alleles is a dominant gene for that given trait, and the other one is a recessive one."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, what do we mean by dominant, and what do we mean by recessive?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, remember, according to the law of dominance, or Mendel's law of Dominance, the dominant gene codes for protein that inhibits the expression of that recessive gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And so the recessive gene is never actually shown in the phenotype of that individual, and we'll see what that means in just a moment."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, an individual or organism is said to be heterozygous for a given trait if one of the alleles is dominant while the other one is recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, usually, an uppercase letter is used to designate the dominant gene, and the lowercase letter is used to designate the recessive gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Let's suppose we're dealing with these two genes, the alleles that are shown in purple."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Let's suppose on chromosome number one, this chromosome, this gene is a dominant gene, and this is a recessive gene."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And the way that we describe this situation here without actually drawing out these chromosomes is by using the following symbolism."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, the uppercase T basically describes this gene that is dominant for that trait, the height trade."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And since we're talking about height, we use T to designate tall."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So uppercase T is tall, and lowercase T is short."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So uppercase T basically means it codes for proteins that expresses the tallness trait, while the lowercase T codes for the proteins that expresses the shortness trait in that particular Pplant organism."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have uppercase T, lowercase T, and this is how we describe this particular homologous chromosome with these corresponding alleles, these corresponding genes."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, upper case T represents dominant gene for that high trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Lower case T represents recessive gene for that trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, this is what we call a genotype."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "The genotype of an individual or organism is simply the genetic makeup of that individual."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "It tells the types of genes found in that organism."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And what this genotype tells us is, for this particular organism, one of the homologous chromosomes will contain a gene that is dominant, and the other one will contain a gene that is recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And what this tells us is the type of phenotype of that individual."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, the genotype is the genetic makeup of that individual, but the phenotype is actually what that organism will look like."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "It's the organism's visual appearance, physical appearance."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So the phenotype, on the other hand, describes what the organism actually looks like, the physical appearance of that organism."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And because upper case T is dominant over lower case T, what that means is this particular individual, this particular plant, will, in fact, be tall, because the dominant trait always inhibits that recessive trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, what about homozygous?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "What does it mean for individual or organism to be homozygous for some given trait?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Well, there are two possibilities for this type of genotype we have an individual organism is said to be homozygous one or two cases."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So either both of those alleles are actually dominant or both of those alleles are actually recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "In the case that they're both dominant, this is known as homozygous dominant."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "In the case they're both recessive, that is known as homozygous recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So this is the genotype of the homozygous dominant and this is the genotype of the homozygous recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, what is the phenotype in this case?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Well, because we have two of these genes both of these genes code for proteins that express the tall height this will be a tall individual or a tall plant and that will be the phenotype the physical appearance, on the other hand, lowercase T's because we don't have any dominant trait both of these traits are recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "That means that individual, in this particular case that plant will in fact be short."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So this phenotype or this genotype basically produces a phenotype in which that p plant will actually be short."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, the question is we see that the genotype tells us what the phenotype of that individual or organism is but is the opposite true?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Can we know what the genotype is if we know what the phenotype is?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And the answer is not always knowing."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "The phenotype does not always tell us what the genotype of that organism is."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "To determine what the genotype is, we actually have to conduct experiments, and usually the tools that we use to help us determine what the potential possibilities are for the genotype of any offspring."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "When we conduct a mating process, this tool is known as a Punnett square."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, what exactly does a Punnett square tell us?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Well, the Punnett square tells us the potential genotypes of that offspring in any given mating process, in any given crossing process."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So to see what a punitive square actually looks like let's take a look at the following cross let's suppose we have one parent that is homozygous dominant and the other parent is homozygous recessive so we're mating these two individuals or these two plants or these two organisms in the following way."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, before they actually mate, what must take place?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Well, they have to produce gametes and gametes are sex cells."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So let's suppose this is the male parent."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "They have to produce the sperm cells."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "This is the female parent."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "They have to produce the xcels because for fertilization to actually take place, we have to have a sperm cell combined with the xcel to reform that diploid number of chromosomes to basically form that zygote."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, we know from meiosis that during the process of meiosis when we form the gametes we have the law of segregation that is observed and what that means is the chromosomes, the homologous chromosomes actually separate."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "They segregate during gamete formation."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And so, even though this is the genotype of that parent number one, before the mating process takes place, these two chromosomes, these two chromosomes actually have to segregate, separate during the process of meiosis."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And so we form these individual gamete cells that contain only one of the pair of homologous chromosomes."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And that is how we show it in the following Punnett square."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have this T in its own cell, in its own compartment, and the second T also in its own cell in its own compartment."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And the same thing is true for that other parent that is homozygous recessive."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have lowercase, lowercase T. And then we have gamete formation."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "We have these X cells that are formed."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And so we have lowercase T, lowercase T. Now, we know when fertilization takes place to form the offspring, to form that zygote, the two cells actually fuse to basically form a single cell, a zygote that contains a diploid number of organisms."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have a haploid number, a haploid number."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "They fuse to form a diploid, and these chromosomes combine."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, the question is, what exactly are the possibilities of the offspring?"}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Well, basically, we can have this cell combined with this cell to form the following cell that contains upper case T that came from parent one and lower case T that came from parent one."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Or we can also have this T combined with this T to form this cell, this T combined with this T to form this cell and this T to combine with this T to form this cell."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we have a total of four different potential possibilities of the offspring."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And because these processes, these fusion processes are arbitrary, they're random, there is basically a 25% chance that each of these will actually take place."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, in this particular case, and in fact, whenever we mate a homozygous dominant with a homozygous recessive, we always get the following punished square, where each one of these are essentially identical."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So in this particular case, it really doesn't matter which one of these we choose."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "The phenotype and the genotype will be exactly the same."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So in this case, when we make, let's say, a tall plant with a short plant, all of these offspring will always be tall."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And that's because we have the dominant trait that masks or inhibits that recessive trait."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So, once again, to summarize, during gamete formation, the pair of alleles must separate, must segregate in accordance with the law of segregation, to form the sperm cells, the male gamuts and the XLS, the female gammates."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, the sperm cell eventually combines with the XL in an arbitrary process."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "What that means is this combining with this is just as likely that this combines with this, or this combines with this, or this combines with this."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And so each one of these possibilities is 25%."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "Now, in this particular case, because of the two types of individuals we combine all these offspring will look exactly the same."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "They have the same exact phenotype, and they will have the same exact genotype."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And in the next several lectures, we're going to examine many more examples where we're combining different types of organisms, different from what we actually did here."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "So we see that what a Punnett square actually is."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "It's the really useful tool that is used by scientists in genetics to basically determine the potential possibilities of the genotype of that offspring."}, {"title": "Genotypes, Phenotypes and Punnett square .txt", "text": "And once the genotype is known, we basically know what that phenotype will be for that particular organism, what that organism will actually look like physically."}, {"title": "Haldane Effect .txt", "text": "Previously, we focused on the Bore effect and we said the Bore effect tells us that the concentration of carbon dioxide and H plus ions in the blood affects hemoglobin's affinity for oxygen."}, {"title": "Haldane Effect .txt", "text": "And what the Bore effect ultimately does is it increases the amount of oxygen that can be absorbed by the exercising tissue and it also increases the amount of oxygen that can be absorbed by the blood from the alveoli of our lungs."}, {"title": "Haldane Effect .txt", "text": "Now, another equally important effect is known as the halding effect."}, {"title": "Haldane Effect .txt", "text": "And the Held in effect is really the opposite, the reverse of the Bore effect."}, {"title": "Haldane Effect .txt", "text": "So remember, the Bore effect talks about how the concentration of CO2 and hydrogen affect hemoglobin's affinity for oxygen."}, {"title": "Haldane Effect .txt", "text": "But what the helldon effect does is it takes the opposite perspective."}, {"title": "Haldane Effect .txt", "text": "It talks about how the concentration of oxygen inside the red blood cell, inside our blood actually affects hemoglobin's affinity for carbon dioxide and H plus ions."}, {"title": "Haldane Effect .txt", "text": "Now, why is the Haldane effect actually important?"}, {"title": "Haldane Effect .txt", "text": "Well, as we'll see in just a moment, the Held in effect actually promotes it increases the amount of carbon dioxide that can be released by the exercising tissue to the blood."}, {"title": "Haldane Effect .txt", "text": "And at the same time, it also increases the number of CO2 molecules that can be absorbed by the alveoli of the lungs from the blood plasma."}, {"title": "Haldane Effect .txt", "text": "And to see what the Halin effect is and how it achieves this, let's begin by taking a look at the following diagram."}, {"title": "Haldane Effect .txt", "text": "So let's suppose I'm moving my arm back and forth."}, {"title": "Haldane Effect .txt", "text": "And as I move my arm back and forth, the muscle tissue begins to contract and ATP molecules are being produced by those muscle cells."}, {"title": "Haldane Effect .txt", "text": "So this is let's suppose that muscle cell and this is the nearby capillary that carries the red blood cells."}, {"title": "Haldane Effect .txt", "text": "Now, as these cells are exercising, they require a greater number of oxygen molecules to produce the ATP."}, {"title": "Haldane Effect .txt", "text": "And so inside the red blood cells, the Bore effect takes place."}, {"title": "Haldane Effect .txt", "text": "That causes hemoglobin to actually unload and release the oxygen which then travels into those exercising cells inside the cells in a process called aerobic cellular respiration."}, {"title": "Haldane Effect .txt", "text": "We produce the energy ATP molecules."}, {"title": "Haldane Effect .txt", "text": "Now, these ATP molecules are used for muscle contraction, for the actin contraction."}, {"title": "Haldane Effect .txt", "text": "But the CO2 molecules, a byproduct, are produced and these cannot be used in any useful way."}, {"title": "Haldane Effect .txt", "text": "And so the CO2 molecules are expelled from the cell and they enter the blood plasma of the capillary, the nearby capillary."}, {"title": "Haldane Effect .txt", "text": "Now, because carbon dioxide is nonpolar, only a very small portion, about 5%, will actually remain dissolved in the blood plasma."}, {"title": "Haldane Effect .txt", "text": "The majority of it, the rest of it will enter the cytoplasm of the red blood cell."}, {"title": "Haldane Effect .txt", "text": "Now, once inside the red blood cell, what we have to do is we have to convert the carbon dioxide, a non polar molecule, into a polar form, namely the bicarbonate."}, {"title": "Haldane Effect .txt", "text": "And that's because we want to be able to dissolve the carbon dioxide in the blood."}, {"title": "Haldane Effect .txt", "text": "So the majority of the carbon dioxide in the red blood cell will follow this reaction pathway."}, {"title": "Haldane Effect .txt", "text": "So a special enzyme we call carbonic anhydrase will combine carbon dioxide and water to form the carbonic acid molecule."}, {"title": "Haldane Effect .txt", "text": "And then the carbonic acid being a good acid, it will dissociate into H plus ions and the bicarbonate ions."}, {"title": "Haldane Effect .txt", "text": "And this is where the halding effect takes place."}, {"title": "Haldane Effect .txt", "text": "So according to the halding effect, if we decrease the concentration of oxygen in the red blood cell, so the amount of oxygen decreases because it travels into the tissue that exercising tissue."}, {"title": "Haldane Effect .txt", "text": "And so as this basically decreases, that increases the affinity of hemoglobin for the H plus ions."}, {"title": "Haldane Effect .txt", "text": "Now if we increase hemoglobin's affinity for H plus ions, what that means is the hemoglobin will begin to bind the H plus ions."}, {"title": "Haldane Effect .txt", "text": "And so the concentration of these free H plus ions will begin to decrease because they will begin to bind to the hemoglobin."}, {"title": "Haldane Effect .txt", "text": "Now what will happen as we decrease this H plus concentration?"}, {"title": "Haldane Effect .txt", "text": "Well, by Laceyre's principle, if we decrease the product concentration, that will shift the equilibrium toward the right side, toward the product side."}, {"title": "Haldane Effect .txt", "text": "And what that means is, as hemoglobin is binding H plus ions, we're going to ultimately produce even more of the bicarbonate ions."}, {"title": "Haldane Effect .txt", "text": "And it's these bicarbonate ions that are basically the polar form of these CO2 molecules."}, {"title": "Haldane Effect .txt", "text": "And so ultimately, the Halden effect basically increases the number of bicarbonate ions that we can store and dissolve in the blood plasma next to the exercising tissue."}, {"title": "Haldane Effect .txt", "text": "So once again, the held in effect, the fact that as we decrease the concentration of oxygen inside the red blood cell as it leaves and enters our tissue cell, that increases hemoglobin's affinity to bind H plus ions."}, {"title": "Haldane Effect .txt", "text": "So this is what the Haldane effect tells us."}, {"title": "Haldane Effect .txt", "text": "And what the halding effect does is it basically shifts the equilibrium to the right side, so it's the bicarbonate side."}, {"title": "Haldane Effect .txt", "text": "And that increases the number of CO2 molecules in this form that we can store and dissolve in the blood plasma of the nearby capillary."}, {"title": "Haldane Effect .txt", "text": "Now we can also represent this effect graphically."}, {"title": "Haldane Effect .txt", "text": "So let's take a look at the following graph."}, {"title": "Haldane Effect .txt", "text": "The y axis is basically the CO2 content in the blood, dissolved in the blood."}, {"title": "Haldane Effect .txt", "text": "And the x axis is the partial pressure of the carbon dioxide in that region in the blood."}, {"title": "Haldane Effect .txt", "text": "Now this relatively straight line, the black curve, basically describes how much carbon dioxide we can fit, we can dissolve inside the blood at some given partial pressure of carbon dioxide."}, {"title": "Haldane Effect .txt", "text": "And notice as we decrease the concentration of oxygen inside the red blood cell, the Halden effect basically causes a leftward shift in this curve."}, {"title": "Haldane Effect .txt", "text": "And so the curve moves into the blue position."}, {"title": "Haldane Effect .txt", "text": "Now why is that?"}, {"title": "Haldane Effect .txt", "text": "Well, let's suppose that this is the partial pressure of carbon dioxide inside the exercising tissue."}, {"title": "Haldane Effect .txt", "text": "And so we draw a straight line going upward."}, {"title": "Haldane Effect .txt", "text": "Now in this particular case, this line basically did not take into consideration the halding effect."}, {"title": "Haldane Effect .txt", "text": "And according to this line, we can only fit this amount of CO2 inside our blood."}, {"title": "Haldane Effect .txt", "text": "But if we do take the held in effect into consideration, because we do decrease the oxygen content in our blood next to the exercising tissue, that shifts the curve this way to the left."}, {"title": "Haldane Effect .txt", "text": "And so the new Y coordinate is this value here."}, {"title": "Haldane Effect .txt", "text": "And notice that what that means is as the oxygen decreases, we can actually store even more carbon dioxide inside our blood because of what we discussed just a moment ago."}, {"title": "Haldane Effect .txt", "text": "So we see that a drop in the oxygen in the red blood cells next to the exercising tissue actually causes a leftward shift in the curve, which means more carbon dioxide can ultimately be stored inside the blood."}, {"title": "Haldane Effect .txt", "text": "And so the tissues will release more of the carbon dioxide because we can fit more of it into that blood plasma."}, {"title": "Haldane Effect .txt", "text": "Now, we can also use the halding effect to basically describe how the alveoli of the lungs are able to absorb more carbon dioxide from the blood plasma."}, {"title": "Haldane Effect .txt", "text": "So the Held in effect can also be used to explain how oxygen concentration affects carbon dioxide unloading into the alveoli of the lung."}, {"title": "Haldane Effect .txt", "text": "So let's take a look at the following diagram."}, {"title": "Haldane Effect .txt", "text": "So, as always, we have the red blood cell, and this is the alveolus of our lung."}, {"title": "Haldane Effect .txt", "text": "Now, what's happening inside our lungs?"}, {"title": "Haldane Effect .txt", "text": "Well, inside our lungs, the oxygen is moving down its concentration gradient from the alveolus and into the red blood cell."}, {"title": "Haldane Effect .txt", "text": "Now, by the Haldane effect, so again, we have this Haldane effect taking place."}, {"title": "Haldane Effect .txt", "text": "And by this Haldane effect, because we increase the concentration of oxygen inside our red blood cell, we decrease hemoglobin's ability to bind carbon dioxide and H plus ions."}, {"title": "Haldane Effect .txt", "text": "So as O two binds to hemoglobin, it basically decreases hemoglobin's affinity for H plus and CO2."}, {"title": "Haldane Effect .txt", "text": "So these two molecules are now released."}, {"title": "Haldane Effect .txt", "text": "Now, as we release carbon dioxide, the carbon dioxide will begin to dissolve and eventually will leave the red blood cell and into the alveolis."}, {"title": "Haldane Effect .txt", "text": "Now, the hemoglobin also releases the H plus ions, which bind onto the hemoglobin in this area."}, {"title": "Haldane Effect .txt", "text": "What happens to the H plus ions is they essentially recombine with the bicarbonate ions that came from the blood plasma."}, {"title": "Haldane Effect .txt", "text": "Remember, these bicarbonate ions dissolve cells into the blood plasma."}, {"title": "Haldane Effect .txt", "text": "At the same time, we have the chloride ions going into the red blood cell."}, {"title": "Haldane Effect .txt", "text": "That's known as the chloride shift."}, {"title": "Haldane Effect .txt", "text": "And in here, the opposite takes place."}, {"title": "Haldane Effect .txt", "text": "These basically move into the cell."}, {"title": "Haldane Effect .txt", "text": "Chloride ions leave the cell, and this recombines with the H plus to reform the carbonic acid."}, {"title": "Haldane Effect .txt", "text": "And then that basically breaks down into carbon dioxide."}, {"title": "Haldane Effect .txt", "text": "And the carbon dioxide then leaves the cell and it enters the alveolus."}, {"title": "Haldane Effect .txt", "text": "And so we see that the halding effect basically promotes the amount of CO2 that can be absorbed by the alveolus."}, {"title": "Haldane Effect .txt", "text": "So the red blood cells near the lungs filled with oxygen."}, {"title": "Haldane Effect .txt", "text": "The rise in oxygen causes them to bind to hemoglobin, which in turn decreases hemoglobin's affinity for carbon dioxide and H plus ions."}, {"title": "Haldane Effect .txt", "text": "And this stimulates the unloading of CO2 and H plus ions from the hemoglobin and eventually from the lungs and then enters the alveolus."}, {"title": "Haldane Effect .txt", "text": "And then we expel them in the process of exhalation."}, {"title": "Haldane Effect .txt", "text": "Now, we can also look at this graphically, but now we're going to see a rightward shift and not a leftward shift."}, {"title": "Haldane Effect .txt", "text": "So once again, the Y axis is the constant of CO2 in the blood."}, {"title": "Haldane Effect .txt", "text": "The x axis is the partial pressure of that CO2."}, {"title": "Haldane Effect .txt", "text": "And now the partial pressure of CO2 will be smaller than in this case."}, {"title": "Haldane Effect .txt", "text": "So we're going to be farther to the left side along the curve because in the lungs we have a lower CO2 concentration than in the tissues."}, {"title": "Haldane Effect .txt", "text": "And so now we're somewhere here."}, {"title": "Haldane Effect .txt", "text": "Now an increase in the oxygen content in our red blood cell next to the lungs means we have a rightward shift in our curve."}, {"title": "Haldane Effect .txt", "text": "So the black curve now shifts this way."}, {"title": "Haldane Effect .txt", "text": "And what that means is before this is how much CO2 was actually stored in the blood."}, {"title": "Haldane Effect .txt", "text": "But now this is how much CO2 can be stored in the blood."}, {"title": "Haldane Effect .txt", "text": "So we have less CO2 that can be stored and dissolved in the blood."}, {"title": "Haldane Effect .txt", "text": "Now, if we can dissolve CO2 in the blood, where can the CO2 go?"}, {"title": "Haldane Effect .txt", "text": "Well, the only place it can actually go is into the alveoli of the lungs."}, {"title": "Haldane Effect .txt", "text": "And that's exactly what happens."}, {"title": "Haldane Effect .txt", "text": "As it moves into the alveoli."}, {"title": "Haldane Effect .txt", "text": "We have the pressure difference that accepts spells that CO2 to the outside environment."}, {"title": "Haldane Effect .txt", "text": "And this is what the Haldane effect is."}, {"title": "Haldane Effect .txt", "text": "The Haldane effect promotes the release of CO2 from the tissue to the blood and also promotes the release of CO2 from the blood and to the alveoli of the lungs."}, {"title": "Apoptosis.txt", "text": "Apatosis, also known as programmed cell death, is a process that takes place not only in the cells of our own body, but also the cells of other organisms as well."}, {"title": "Apoptosis.txt", "text": "Now, what exactly is apatosis?"}, {"title": "Apoptosis.txt", "text": "Why does apatosis actually take place and how does apatosis actually take place?"}, {"title": "Apoptosis.txt", "text": "These are the questions we're going to address in this lecture."}, {"title": "Apoptosis.txt", "text": "Let's begin with the what."}, {"title": "Apoptosis.txt", "text": "So what exactly is apatosis?"}, {"title": "Apoptosis.txt", "text": "Well, it's a process, a natural process that takes place inside our own cells."}, {"title": "Apoptosis.txt", "text": "And if the cell actually commits to apatosis, what it does is it will follow a series of reactions that will eventually kill that cell off."}, {"title": "Apoptosis.txt", "text": "So in a way, apatosis is cell suicide."}, {"title": "Apoptosis.txt", "text": "Now the next question is why in a world would a cell actually want to kill itself off?"}, {"title": "Apoptosis.txt", "text": "Why would a cell want to commit suicide?"}, {"title": "Apoptosis.txt", "text": "Well, one of two reasons as it turns out."}, {"title": "Apoptosis.txt", "text": "Apatosis is a normal process during embryological development and it's also normal process during the development of our immune system."}, {"title": "Apoptosis.txt", "text": "So what exactly do we mean?"}, {"title": "Apoptosis.txt", "text": "Well, when the embryo is developing inside the uterus of the mother to actually form the fingers on the hand and the toes on the feet, apertosis must take place naturally between the regions on the fingers to actually form the fingers."}, {"title": "Apoptosis.txt", "text": "So the reason we go from this to this is because of apertosis that takes place during normal embryological development."}, {"title": "Apoptosis.txt", "text": "Now, what about development of our immune system?"}, {"title": "Apoptosis.txt", "text": "Well, remember, T cells, also known as T lymphocytes, mature and develop inside the thiamis."}, {"title": "Apoptosis.txt", "text": "So what happens inside the thiamis, which is an organ found in this section of the body inside the thiamis, those T lymphocytes are tested against self antigens."}, {"title": "Apoptosis.txt", "text": "Remember, self antigens are proteins found on the healthy cells of our body."}, {"title": "Apoptosis.txt", "text": "And if those T lymphocytes bind onto these healthy self antigens, then the binding process will initiate apatosis and those T cells will be killed off."}, {"title": "Apoptosis.txt", "text": "The reason is if the T cells actually bind onto cell antigens, that means those T lymphocytes will begin to kill off the healthy cells of our body."}, {"title": "Apoptosis.txt", "text": "And we don't want this."}, {"title": "Apoptosis.txt", "text": "We don't want to cause a condition known as autoimmunity."}, {"title": "Apoptosis.txt", "text": "And so what happens in the thiamine?"}, {"title": "Apoptosis.txt", "text": "We eliminate those T cells, these immunologically, insufficient T cells, by the process of apatosis."}, {"title": "Apoptosis.txt", "text": "So we see that apatosis is a normal process that takes place in development of the organ systems and the structures of our body."}, {"title": "Apoptosis.txt", "text": "Now, reason number two is basically to prevent from that cell harming other cells of our body."}, {"title": "Apoptosis.txt", "text": "So to destroy dangerous agents that can harm the healthy cells of our body, for example, cancer cells, infected cells or any type of damaged cell will undergo apatosis to kill itself off."}, {"title": "Apoptosis.txt", "text": "So this is why what about how how does apatosis actually take place?"}, {"title": "Apoptosis.txt", "text": "Well, there are three very common mechanisms by which apatosis takes place."}, {"title": "Apoptosis.txt", "text": "Mechanism number one is called intrinsic pathway."}, {"title": "Apoptosis.txt", "text": "Mechanism number two is called the extrinsic pathway."}, {"title": "Apoptosis.txt", "text": "And mechanism Three involves a molecule known as apatosis inducing factor, or AIF."}, {"title": "Apoptosis.txt", "text": "So let's begin with the intrinsic pathway."}, {"title": "Apoptosis.txt", "text": "So in this mechanism, the process of cell death initiates inside the cell itself."}, {"title": "Apoptosis.txt", "text": "In fact, it initiates inside the mitochondria, as we'll see in just a moment."}, {"title": "Apoptosis.txt", "text": "So let's suppose the cell is damaged in some way or form because remember, a damaged cell will undergo apatosis."}, {"title": "Apoptosis.txt", "text": "So if the cell is damaged, what happens is the following takes place."}, {"title": "Apoptosis.txt", "text": "So let's suppose we're inside the mitochondria."}, {"title": "Apoptosis.txt", "text": "This is the outer membrane of the mitochondria."}, {"title": "Apoptosis.txt", "text": "This is the inner membrane of the mitochondria."}, {"title": "Apoptosis.txt", "text": "Along the inner membrane, we have these proteins known as cytochrome C, which are shown in red and on the outer membrane of the mitochondria."}, {"title": "Apoptosis.txt", "text": "In healthy cells, we have a special type of protein known as BCL Two."}, {"title": "Apoptosis.txt", "text": "Now, BCL Two, what it does is it basically inhibits the process of apoptosis from actually taking place."}, {"title": "Apoptosis.txt", "text": "But if the cell is damaged in some way or form, what happens is another type of protein is produced and released and this protein is known as Bax."}, {"title": "Apoptosis.txt", "text": "Bax shown in purple."}, {"title": "Apoptosis.txt", "text": "So what happens is, once the cell is actually damaged back, bax moves on onto the cell membrane of the mitochondria and attaches next to this BCL Two protein."}, {"title": "Apoptosis.txt", "text": "Now, what Bax does is it prevents the BCL Two protein from inhibiting apatosis."}, {"title": "Apoptosis.txt", "text": "And Bax also punctures the membrane of the mitochondria."}, {"title": "Apoptosis.txt", "text": "So it creates holes inside the outer membrane."}, {"title": "Apoptosis.txt", "text": "And what happens is, once the holes are created, cytochrome C detaches from the membrane of the inner mitochondria and move to the outside of that mitochondria into the cytoplasm."}, {"title": "Apoptosis.txt", "text": "Now, once inside the cytoplasm, so these are the cytochrom C molecules."}, {"title": "Apoptosis.txt", "text": "The cytochrome C attaches to another type of protein known as apaf One."}, {"title": "Apoptosis.txt", "text": "And once they attach, they form a special structure known as apotheosome."}, {"title": "Apoptosis.txt", "text": "Now, what apothesome does is it basically goes on and activates a special type of protease protein known as Caspase Nine."}, {"title": "Apoptosis.txt", "text": "And by activating Caspase Nine, we form a complex known as the active Cast Space Nine complex."}, {"title": "Apoptosis.txt", "text": "And what this complex does is it moves around the organelles of our bot, of the organelles of that cell, and they break down those organelles and eventually they break down the DNA inside that cell."}, {"title": "Apoptosis.txt", "text": "And that causes the death of that cell."}, {"title": "Apoptosis.txt", "text": "And once the cell actually dies off, some type of phagocytic cell, for example, a macrophage, swims by and engulfs that cell."}, {"title": "Apoptosis.txt", "text": "And so this is one mechanism by which this process of apatosis takes place and involves this special type of active protein known as Cat Space Nine."}, {"title": "Apoptosis.txt", "text": "Now, this entire process takes place inside that cell."}, {"title": "Apoptosis.txt", "text": "It initiates and takes place inside the cell."}, {"title": "Apoptosis.txt", "text": "What about the extrinsic pathway?"}, {"title": "Apoptosis.txt", "text": "Well, the major difference between the intrinsic and the extrinsic pathway is the origin in the extrinsic pathway is outside of the cell."}, {"title": "Apoptosis.txt", "text": "So in this mechanism, the signal molecules are originating outside of the cell."}, {"title": "Apoptosis.txt", "text": "And they stimulate that cell to commit suicide inside that cell."}, {"title": "Apoptosis.txt", "text": "So it begins on the outside, but then it takes place."}, {"title": "Apoptosis.txt", "text": "Apatosis takes place on the inside."}, {"title": "Apoptosis.txt", "text": "So healthy cells contain special integral membrane proteins known as deaf receptors and that can bind complementary molecules known as deaf activators."}, {"title": "Apoptosis.txt", "text": "So, to see what we mean, let's take a look at the following molecules."}, {"title": "Apoptosis.txt", "text": "So, let's suppose this blue cell is our infected cell."}, {"title": "Apoptosis.txt", "text": "And that infected cell has a special membrane protein known as the death receptor."}, {"title": "Apoptosis.txt", "text": "And this is some other type of cell."}, {"title": "Apoptosis.txt", "text": "Let's suppose it's some type of immune cell."}, {"title": "Apoptosis.txt", "text": "For example, the cytotoxic T cell."}, {"title": "Apoptosis.txt", "text": "Now, the cytotoxic T cell has a special membrane protein known as the death activator."}, {"title": "Apoptosis.txt", "text": "And so what happens is, when they actually bind on the outside, that will initiate some type of internal process that will activate a cast based protein."}, {"title": "Apoptosis.txt", "text": "But this cast based protein is slightly different than caspase nine."}, {"title": "Apoptosis.txt", "text": "We call it caspase eight, but it's still protease."}, {"title": "Apoptosis.txt", "text": "And what that means is once we activate the cat space nine inside the cell, that cat space I'm sorry, cat space eight."}, {"title": "Apoptosis.txt", "text": "Once we activate the cat space eight, it will go on to basically destroy the organelles and the structures inside the cell as well as the DNA inside the nucleus of that cell."}, {"title": "Apoptosis.txt", "text": "And that will eventually lead to the death of that cell."}, {"title": "Apoptosis.txt", "text": "And once the cell dies, once again, a macrophage or another phagocytic cell can swim by engulf that dead cell."}, {"title": "Apoptosis.txt", "text": "And that will prevent that infected cell from actually destroying other healthy cells of our body."}, {"title": "Apoptosis.txt", "text": "Now, what about the final mechanism?"}, {"title": "Apoptosis.txt", "text": "So, notice, in the intrinsic pathway and the extrinsic pathway, we both used a category of protease proteins known as caspase."}, {"title": "Apoptosis.txt", "text": "The major difference between the final mechanism and these two mechanisms is that this does not actually include a caspase protein."}, {"title": "Apoptosis.txt", "text": "It includes its own molecule known as apatosis inducing factor or AIF."}, {"title": "Apoptosis.txt", "text": "So the final mechanism of apatosis involves using apatosis inducing factor AIF to actually initiate the process of apatosis."}, {"title": "Apoptosis.txt", "text": "This process does not use cast spaces."}, {"title": "Apoptosis.txt", "text": "So what exactly happens?"}, {"title": "Apoptosis.txt", "text": "Well, AIF basically is located inside the intermembrane space between the two membranes of the mitochondria."}, {"title": "Apoptosis.txt", "text": "And if the cell is actually damaged in some way, what happens is this AIF molecule is released from the mitochondria, it travels into the cytoplasm and then it moves into the nucleus of that cell."}, {"title": "Apoptosis.txt", "text": "It binds on to the DNA of that cell and ultimately destroys that DNA and that causes the death of that cell."}, {"title": "Apoptosis.txt", "text": "So ultimately, this is basically done by cells such as neurons."}, {"title": "Apoptosis.txt", "text": "So nerve cells in our body can commit apoptosis via this process by using the apatosis inducing factors."}, {"title": "Apoptosis.txt", "text": "So these are the three common methods by which our cells can naturally commit cell suicide, a process known as apatosis."}, {"title": "ATP-ADP Translocase.txt", "text": "The major function of the electron transport chain is to actually generate these highenergy ATP molecules via oxidative phosphorylation of ADP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "And this takes place on the electron transport chain of the inner mitochondrial membrane."}, {"title": "ATP-ADP Translocase.txt", "text": "And what this basically means is for the electron transport chain to actually take place and take place effectively and efficiently inside the matrix of the mitochondria we must have a high enough level of ADP molecules because the electron transport chain more specifically ATP synthase of the electron transport chain actually generates those ATP molecules by using the ADP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "So for the electron transport chain to be effective, ATP levels in the mitochondrial membrane must be appropriately high to ensure that complex five ATP synthase of the electron transport chain can actually use the proton motive force that is generated by complexes one, three and four to generate those ATP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, it also actually means that once we form these ATP molecules, we don't want to keep those ATP molecules in the matrix of the mitochondria."}, {"title": "ATP-ADP Translocase.txt", "text": "We want to actually move those ATP molecules out of the matrix and into the cytoplasm of the cell so that the ATP can become readily available to actually power all the different types of biological processes that exist within the cytoplasm of the cell."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, the problem with actually transporting ADP and ATP molecules across the inner mitochondrial membrane is the membrane is impermeable to these two molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "Why?"}, {"title": "ATP-ADP Translocase.txt", "text": "Well, because ADP contains the charge of negative three while ATP contained the charge of negative four."}, {"title": "ATP-ADP Translocase.txt", "text": "So both of these molecules are highly charged species."}, {"title": "ATP-ADP Translocase.txt", "text": "And what that means is they can't simply diffuse across the inner membrane of the mitochondria and their movement across the inner membrane of the mitochondria basically depends on the existence of a special type of antiporter transport system and exchange protein molecule known as ATP ATP translocase."}, {"title": "ATP-ADP Translocase.txt", "text": "And what this molecule does is it basically catalyzes the movement."}, {"title": "ATP-ADP Translocase.txt", "text": "It couples the import of the ATP into the matrix to the export of the ATP out of that matrix."}, {"title": "ATP-ADP Translocase.txt", "text": "And this is the neck reaction that is catalyzed by ATP ADP trams locates."}, {"title": "ATP-ADP Translocase.txt", "text": "So within the matrix of the mitochondria, we essentially generate these ATP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "And that means we use up the ADP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "So we want to actually move the ATP out of the matrix while at the same time we want to bring ADP from the cytoplasm into the matrix."}, {"title": "ATP-ADP Translocase.txt", "text": "So at the same time that the ATP moves out of the matrix into the cytoplasm, the ADP is brought from the cytoplasm and into the matrix so that oxidative asphorylation of the ADP can take place along the electron transport chain found on the inner membrane of the mitochondria."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, before we actually take a look at the mechanism by which ATP ADP translocase actually functions, let's discuss what the structure of ATP ADP translocase actually is."}, {"title": "ATP-ADP Translocase.txt", "text": "Well, this is a homodymer molecule and what that means is it consists of two identical polypeptide chains and each one of these identical polypeptide chains consist of six alpha helices that span the membrane."}, {"title": "ATP-ADP Translocase.txt", "text": "And these two identical polypeptide subunits basically work together to create this conformation in which we have a binding pocket that can bind ATP and ATP."}, {"title": "ATP-ADP Translocase.txt", "text": "And this binding pocket actually alternates between facing the matrix side and facing the cytoplasmic side, as we'll see in just a moment."}, {"title": "ATP-ADP Translocase.txt", "text": "So because along the inner membrane of the mitochondria, we have the electron transport chain which actually functions to generate these ATP molecules from ADP molecules, we might imagine that the inner mitochondrial membrane contains a relatively high concentration of this specific translocase."}, {"title": "ATP-ADP Translocase.txt", "text": "And that's exactly right."}, {"title": "ATP-ADP Translocase.txt", "text": "So about 15% of the protein content of the inner mitochondrial membrane consists of ATP ADP Trams LoCASE."}, {"title": "ATP-ADP Translocase.txt", "text": "So now let's take a look at the following mechanism by which the ATP ADP translocase actually moves these two molecules across the inner mitochondrial membrane."}, {"title": "ATP-ADP Translocase.txt", "text": "And let's begin with this diagram here."}, {"title": "ATP-ADP Translocase.txt", "text": "So we have the inner mitochondrial membrane, the matrix side, and the intermembrane size, also known as the cytoplasm side."}, {"title": "ATP-ADP Translocase.txt", "text": "So basically, in step one, the binding pocket that is formed by these two polypeptide chains that make up the ATP ADP translocase is open to the cytoplasm side."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, this molecule with a negative three charge, that's the ADP."}, {"title": "ATP-ADP Translocase.txt", "text": "And it moves into this pocket."}, {"title": "ATP-ADP Translocase.txt", "text": "And once it moves into the pocket, it creates a conformational change that essentially stimulates a process we call aversion."}, {"title": "ATP-ADP Translocase.txt", "text": "And in this process, the binding pocket basically everts."}, {"title": "ATP-ADP Translocase.txt", "text": "And now it faces not the cytoplasm side, but the matrix side."}, {"title": "ATP-ADP Translocase.txt", "text": "So what that means is this ADP molecule can now move into the matrix of the mitochondria."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, once this ADP moves out of that binding pocket, an ATP shown in blue with a negative four charge can actually move into this pocket."}, {"title": "ATP-ADP Translocase.txt", "text": "Once it moves into the pocket, another aversion takes place opposite to the one that took place here."}, {"title": "ATP-ADP Translocase.txt", "text": "So now that the binding pocket faces the cytoplasm side and not the matrix side."}, {"title": "ATP-ADP Translocase.txt", "text": "So now, once this takes place, the ATP can leave this binding pocket into the intermembrane space and then move into the cytoplasm via a protein found on the outer membrane of the mitochondria known as the mitochondrial porin."}, {"title": "ATP-ADP Translocase.txt", "text": "And once we get to this stage, the cycle can basically repeat itself."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, one last thing I'd like to mention about the movement of these ADP ATP molecules is the following."}, {"title": "ATP-ADP Translocase.txt", "text": "Remember that because the electron transport chain actually generates an electrochemical gradient for the protons, what that does is it creates a net positive charge on the outside portion of the inner membrane and a negative charge on the inner portion of the inner mitochondrial membrane."}, {"title": "ATP-ADP Translocase.txt", "text": "Now, ATP molecules have a greater charge than ADP molecules."}, {"title": "ATP-ADP Translocase.txt", "text": "ATP have a net charge of negative four, while ATP have a net charge of negative three."}, {"title": "ATP-ADP Translocase.txt", "text": "And so what that means is because the ATP have a greater negative charge, that greater negative charge on the ATP will promote the movement of these more negatively charged molecules onto the side of the membrane that contains a positive charge."}, {"title": "ATP-ADP Translocase.txt", "text": "And that's the side of plasmic side."}, {"title": "ATP-ADP Translocase.txt", "text": "So what that implies is the greater negative charge on the ATP molecules actually promotes the movement of these ATP across the inter mitochondrial membrane onto this intermembrane side because it's the side that contains a greater concentration of protons."}, {"title": "ATP-ADP Translocase.txt", "text": "So that means it has a greater positive charge."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The citric acid cycle is a very important process inside our cells because it's how we're able to actually metabolize fuel molecules."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "It's how we can break down glucose molecules and amino acids and fats to form high energy ATP molecules."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "On top of that, as we'll see in a future lecture, the citric acid cycle is also actually used to synthesize many types of building block molecules used by ourselves."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, there are three ways by which we can actually regulate the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The first method is what we discussed previously."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "It's by regulating pyruvate decarboxylation."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So remember that inside the cytoplasm, glucose molecules undergo glycolysis to form pyruvate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And in the presence of oxygen, the pyruvate moves into the matrix of the mitochondria, where we undergo pyruvate to carboxylation."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And what this produces is acetocoenzyme A."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, once this step takes place, it's an irreversible step that commits the glucose derivative, the CETO coenzyme A to undergoing the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Or in some cases, we can actually use it to form fat molecules, as we'll discuss in a future electron."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "But basically, by regulating this step, we call pyruvate carboxylation."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "By either turning it on or off, we can regulate the rate of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, that's the first process of regulation."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The other two methods by which we can regulate the rate of the citric acid cycle is by regulating the steps of the citric acid cycle itself."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So, out of the eight steps of the citric acid cycle, two of these steps are oxidative decarboxylation steps."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And both of these steps are controlled by allosteric enzymes."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So step three and step four are the two oxidative decarboxylation steps."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And the enzymes that regulate these two steps are allosteric enzymes which, as we'll see in just a moment, are actually regulated by specific types of allosteric effective molecules."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So the citric acid cycle has two regulatory points that are used to control its rate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And both of these points are allosteric enzymes used by the steps of the citric acid cycle, the TCA cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So let's quickly remember the eight different steps."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In step one, we take the four carbon oxaloacetate, combined with the acetyl group of acetoco enzyme A to form a six carbon molecule known as citrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The citrate is then transformed into isocytrate, another six carbon molecule, which is basically an isomer to citrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The isocitrate that undergoes step three, that is catalyzed by an allosteric enzyme known as isocytrate, dehydrogenase, and that produces alpha key to glutarate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The alpha key to glutrate, then catalyzed by an enzyme known as alpha key to glutarate, dehydrogenase undergoes step four and other oxidative decarboxylation step to produce a C four molecule, a four carbon molecule known as succinl coenzyme A."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And in the next series of steps so in this step, we transform the succinct coenzyme a into succinate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "succin is then transformed into fumarrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Fumarate is then transformed into the lisomer of malate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Malate is then transformed back into oxyacetate and this step basically repeats itself."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And these are the two important points that we have to focus on."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "These are the allosteric enzymes that our cells can actually use to regulate the rate at which the citric acid cycle takes place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so to begin, let's focus on step three that is catalyzed by the allosteric enzyme isocitrate dehydrogenase."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So we can break down step three into two steps."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "We have three A and three B."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In three A we have the oxidation reduction step."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "This basically takes place or the isocytrate is oxidized into an intermediate oxylociate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In the process, we reduce the NAD plus coenzyme into NADH and the NADH can then be used by the electron transport chain as we'll discuss in the future lecture."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In the second step three B, the oxylote undergoes a decreboxylation step in which we release a carbon dioxide and we produce a five carbon molecule alpha ketoglutrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, let's imagine inside our cell we want to produce ATP molecules."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So we have a low energy charge value, we don't have enough ATP and so we want to make sure, or the cell wants to make sure that the citric acid cycle takes place at a high rate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And what the cell does is to make sure the rate is high is it stimulates the isocitrate dehydrogenase."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So the isocitrate dehydrogenase, being an allosteric enzyme, contains allosteric regulatory sites and an allosteric activator molecule, ADP adenosine diphostate, will go on and bind onto special location on the enzyme isocitrate dehydrogenase."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And once it binds, it increases its affinity for the substrate molecule isocitrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And this isocitrate dehydrogenase will bind the isocitrate and the NAD plus more readily and that will increase the rate at which this reaction actually takes place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And that will increase the rate at which the overall citric acid cycle will actually take place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So when the cell needs to produce energy molecules, it has a low content of ATP."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "ATP will bind onto a regulatory side of the isocitrate dehydrogenase enzyme."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "This will increase the affinity of the enzyme for the substrate isocytrade, which will increase the rate of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, conversely, what happens if we have plenty of ATP inside our cells so we have a high energy charge value and a cell doesn't want to actually use energy to produce these ATP molecules and so it wants to decrease the rate at which the citric acid cycle takes place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And now what happens?"}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Instead of having allosteric activators, we have allosteric inhibitors that will bind onto isocitrate dehydrogenates and decrease its affinity for the isocitrate molecule."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In fact, what will happen is the ATP molecules themselves will bind onto special region of ISOC citrate dehydrogenase and that will decrease the rate at which it will actually take place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "On top of that, we also have NADH that will bind onto a special site of the isocitrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "It will kick off the NAD plus."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And if there is no NAD plus bound to the isocitrate dehydrogenase enzyme."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "If the NADH is bound instead of the NAD plus step three A cannot take place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so because that happens, because the NADH kicks off, the NAD plus the isocytrate dehydrogenase enzyme cannot carry out its function."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So we see that if we have high levels of ATP, a high energy charge value, we will not need to generate any more ATP."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In fact, ATP will act as an allosteric inhibitor of isocytrade dehydrogenase, and that will decrease the affinity for the substrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In addition, the NADH will kick off the NAD plus that is needed for step three A to take place, and that will inhibit the activity of ISOC citrate dehydrogenase, decrease the rate at which this step actually takes place, and that will decrease the rate of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So let's take a look at the following diagram to see exactly what we mean."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So the Pyruvate is transformed into acetyl coenzyme A via pyruvate carboxylation."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The citrate then is produced."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And once the citrate is produced, it is isomerized into isocitrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "The isocitrate is then transformed into alpha key to gluterate by the activity of isocytrade dehydrogenase."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, if we want to produce more ATP molecules, we want to increase the rate of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So ATP produces a positive feedback loop that essentially increases the activity of this isoctrade dehydrogenase enzyme."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "But if we have plenty of ATP inside our body, the cell must signal somehow for the citric acid cycle to actually decrease its activity."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In fact, it also has to signal for glycolysis to actually decrease its activity."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so what happens is ACP and NADH act as allosteric inhibitors."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "They bind to isocitrate dehydrogenase, and they turn off the activity of this enzyme."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so what that means is we cannot transform the isocitrate to alpha ketogrutrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so what happens once we turn off enzyme three?"}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "There is a build up of isocitrate, and Isacitrate is pretty much at equilibrium with citrate because this reaction is essentially at equilibrium."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so the isocitrate, once there's a build up of isocitrate, there will also be a build up of the citrate molecule."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And the citrate molecule, as it builds up, it moves into the cytoplasm of our cells from the matrix of the mitochondria."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And in the cytoplasm, if you remember back to regulation of glycolysis, the citrate actually inhibits a specific type of enzyme in glycolysis, which inhibits the rate at which glycolysis decreases the rate at which glycolysis actually takes place."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And the citrate can actually be used to form fat molecules, as we'll discuss in the future lecture."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, let's move on to step four."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Step four is the second oxidative decarboxylation step of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And this is catalyzed by alpha ketoglutrade dehydrogenase, also an allosteric enzyme."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So remember back to our discussion that this is actually step four."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In step four, we take the alpha key to gluterate produced in step three, and we basically kick off a carbon dioxide molecule and replace it with coenzyme A to form submit coenzyme A, we also oxidize the alpha ketoglutrate and reduce the NAD plus into NADH."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And here's our carbon dioxide molecule."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So alpha ketoglutrade catalyzes the second oxidative decarboxylation step."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, if we have a high energy charge value inside our cells, so we have plenty of ATP molecules to go around and we don't want to produce any more ATP molecules, we see that ATP, as well as these two molecules produced, will act as allosteric inhibitors."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So ATP, as well as succinctoenzyme A and NADH will basically act as allosteric inhibitors, binding them to special regulatory sites of this alpha keyoglutrade dehydrogenous enzyme and that will inhibit its activity."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And so when we have plenty of ATP, the rate of the citric acid cycle is basically decreased."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "By inhibiting the activity of these two enzymes, we have isocytrate dehydrogenase, step three and alpha key to gluterate dehydrogenase."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "Now, in the case of inhibiting enzyme four of step four, we essentially increase the build up of the alpha ketoglutrate."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "And when we increase the concentration of alpha ketoglutrate, we can actually use the access alpha ketoglutrate to produce specific types of amino acids, as we'll discuss in the future lecture."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In fact, we can also produce specific types of purine nitrogenous bases."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So we see that the citric acid cycle is in fact regulated very closely by our cells."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "So we have these three different places where we can regulate the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "We can regulate it right here, so pyruvate decarboxylation, or we can regulate it at step three or step four of the citric acid cycle."}, {"title": "Regulation of Citric Acid Cycle .txt", "text": "In either case, we decrease the rate at which the citric acid cycle takes place because we don't want to produce any more ATP molecules."}, {"title": "Meiosis II .txt", "text": "Meiosis is a type of cell division that consists of two stages."}, {"title": "Meiosis II .txt", "text": "We have meiosis one and meiosis two."}, {"title": "Meiosis II .txt", "text": "Now, previously, we discussed meiosis one, and we said that in meiosis one, the cell undergoes a genetic recombination process known as crossing over."}, {"title": "Meiosis II .txt", "text": "And the cell basically produces or divides into two genetically different habits, applooid cells."}, {"title": "Meiosis II .txt", "text": "So what that means is the following."}, {"title": "Meiosis II .txt", "text": "So this diagram generalizes the process of meiosis one."}, {"title": "Meiosis II .txt", "text": "So let's suppose we begin with a cell that consists of a single pair of homologous chromosomes shown in the following diagram."}, {"title": "Meiosis II .txt", "text": "So we have pair one or chromosome one and chromosome two."}, {"title": "Meiosis II .txt", "text": "So during ProPhase one of meiosis, this homologous pair undergoes the process of crossing over, and we basically form these recombinant chromosomes."}, {"title": "Meiosis II .txt", "text": "And what that basically means is each one of these chromatids are genetically different than the other one."}, {"title": "Meiosis II .txt", "text": "And then the following processes."}, {"title": "Meiosis II .txt", "text": "So, we have metaphase one, anaphase one, telephase one, and cytokinesis of meiosis one basically lead to our division of our cell into these two genetically different haploid cells."}, {"title": "Meiosis II .txt", "text": "Now, haploid means that whatever number of chromosomes we begin with, originally, these cells will have half of that number."}, {"title": "Meiosis II .txt", "text": "So in this case, we begin with one two chromosomes."}, {"title": "Meiosis II .txt", "text": "So that means we'll have half of that."}, {"title": "Meiosis II .txt", "text": "So this will have one chromosome, and this will have one chromosome."}, {"title": "Meiosis II .txt", "text": "But notice, each one of these chromosomes still consists of two individual chromatids that are genetically different than the other one."}, {"title": "Meiosis II .txt", "text": "So basically, in humans, we begin with 46 chromosomes."}, {"title": "Meiosis II .txt", "text": "So each one of these cells will contain only 23 chromosomes."}, {"title": "Meiosis II .txt", "text": "Now let's move on to the second stage of meiosis, known as meiosis II."}, {"title": "Meiosis II .txt", "text": "And just like mitosis and meiosis one are broken down into four stages."}, {"title": "Meiosis II .txt", "text": "Meiosis two can also be broken down into four stages or phases."}, {"title": "Meiosis II .txt", "text": "We have ProPhase II, metaphase II, anaphase II, and telephase two."}, {"title": "Meiosis II .txt", "text": "And we also have the process of cytokinesis, which is actually the separation of the cytoplasm and the cell membrane."}, {"title": "Meiosis II .txt", "text": "Now, the phases of meiosis two are actually very similar to the phases of mitosis II."}, {"title": "Meiosis II .txt", "text": "So if you can remember what mitosis is, you can remember what meiosis two is."}, {"title": "Meiosis II .txt", "text": "But there are important differences, as we'll see in just a moment."}, {"title": "Meiosis II .txt", "text": "So let's begin with ProPhase."}, {"title": "Meiosis II .txt", "text": "Now, the first difference between meiosis two and mitosis is that in mitosis one cell begins our division."}, {"title": "Meiosis II .txt", "text": "But in mitosis two, these two cells produced in meiosis one each basically undergo their own meiosis two process."}, {"title": "Meiosis II .txt", "text": "So we have these two genetically different haploid cells, as shown that each contain its own chromosome, as shown in the following diagram."}, {"title": "Meiosis II .txt", "text": "So basically, in ProPhase one, our centrioles begin to move to opposite ends."}, {"title": "Meiosis II .txt", "text": "And as they move to opposite ends, they begin to form our spindle apparatus, our spinal fibers that extend towards our chromosome, as shown in the following diagram."}, {"title": "Meiosis II .txt", "text": "So let's move on to metaphase two."}, {"title": "Meiosis II .txt", "text": "In metaphase II, the spindle fibers formed from our centrioles, which are now found on opposite ends of the cell, basically grab our chromosome as a kinetic core region on the centromere."}, {"title": "Meiosis II .txt", "text": "And that is shown in the following diagram."}, {"title": "Meiosis II .txt", "text": "And once they grab it, they align the chromosomes at the center of the cell at our equator, as shown in the following diagram."}, {"title": "Meiosis II .txt", "text": "So in metaphase the spindle fibers attached to the kinetic cores of each chromosome and align the chromosomes along the center of our cell."}, {"title": "Meiosis II .txt", "text": "Now let's move on to anaphase two."}, {"title": "Meiosis II .txt", "text": "In anaphase two, once again, we have the process of this junction."}, {"title": "Meiosis II .txt", "text": "What happens is our spindle fibers begin to basically contract, and they move or separate our two chromatids within our chromosome."}, {"title": "Meiosis II .txt", "text": "So the spindle fibers pull on the chromosome from both ends, separating the chromatids."}, {"title": "Meiosis II .txt", "text": "And notice that unlike an anaphase of mitosis, where we have genetically identical chromatids, in anaphase II of meiosis, these two chromatids are genetically different."}, {"title": "Meiosis II .txt", "text": "So this chromatid here is different than this chromatid, and this chromatid is different than this chromatid."}, {"title": "Meiosis II .txt", "text": "And this is one important difference between meiosis two and mitosis."}, {"title": "Meiosis II .txt", "text": "And finally, let's move on to telephase."}, {"title": "Meiosis II .txt", "text": "So, in telephase two, the chromatids are now found at opposite poles, at opposite ends of our cell, and the nuclear membrane begins to reform around those chromatids, around our set of chromatids."}, {"title": "Meiosis II .txt", "text": "In this case, we only have one of these chromatids."}, {"title": "Meiosis II .txt", "text": "But in eukaryotic, in human cells, we have 23 of these chromatids."}, {"title": "Meiosis II .txt", "text": "So basically, these chromatids are different from one another."}, {"title": "Meiosis II .txt", "text": "And that's exactly why, when cytokinesis actually takes place, each one of these haploid cells will be different from one another because they will have different genetic information."}, {"title": "Meiosis II .txt", "text": "So cytokinesis of each cell begins to take place, and then we basically separate our cell membrane, and we separate the cytoplasm and the organelles, and we form these two individual, distinct cells."}, {"title": "Meiosis II .txt", "text": "And because we have two cells undergoing this process, at the end, we form four individual and genetically different haploid cells."}, {"title": "Meiosis II .txt", "text": "So notice we begin with one, two chromosomes."}, {"title": "Meiosis II .txt", "text": "So that means we're only going to have one chromosome because these are haploid cells."}, {"title": "Meiosis II .txt", "text": "So in humans, if we have 46 of these chromosomes, that means each one of these cells will contain only 23 chromatids, which are now known as chromosomes."}, {"title": "Meiosis II .txt", "text": "So basically, let's recap what the entire purpose of meiosis is."}, {"title": "Meiosis II .txt", "text": "So meiosis is a type of cell division in which our beginning cell, the parent cell, known as argumetocide, basically divides into four distinct and genetically different haploid cells."}, {"title": "Meiosis II .txt", "text": "So basically, the underlying process that takes place in meiosis one is the crossing over process, in which we basically cross over our genetic information."}, {"title": "Meiosis II .txt", "text": "We exchange our genetic information, and that allows us to produce, ultimately, these four different haploid cells that each have their own genetic information."}, {"title": "Meiosis II .txt", "text": "So at the end of meiosis, a single gametocide forms for genetically distinct haploid cells."}, {"title": "Meiosis II .txt", "text": "In humans, these cells contain 23 chromatids, which are now known as chromosomes."}, {"title": "Meiosis II .txt", "text": "So the genetic recombination that occurs in meiosis One and the random segregation that takes place in Meiosis One and Two that basically allows and provides our cell with the genetic diversity."}, {"title": "Meiosis II .txt", "text": "Meaning these cells are different from one another."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "When we eat carbohydrates, these carbohydrates begin the process of digestion and breakdown in our mouth."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So in the mouth, we release a special type of digestive enzyme known as salivary amylase."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And what salivary amylase does is it breaks down the carbohydrates into smaller polysaccharides."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, eventually, those polysaccharides will travel through the pharynx, through the esophagus, through the stomach, and will enter our small intestine."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, in the small intestine, we have a special type of digestive enzyme that is more powerful than salivary amylase."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And this digestive enzyme is known as pancreatic amylase that is produced by the pancreas."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, pancreatic amylase breaks down the polysaccharide into disaccharides."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And those disaccharides consist of only two monomers of sugar."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, our cells cannot actually absorb disaccharides."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "They're simply too large."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So what happens is on the membrane of our anterocytes, the cells in our small test, and we have specialized types of digestive enzymes that can break down disaccharides into their individual monomers."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, the membrane of our anterocy is known as a Brush Water because it consists of microvilli."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So this is a single cell found in the small intestine."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "This is known as an anteraside."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And on the apical side of the cell, apical simply means it faces the lumen cavity of the small intestine."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "We have these hair like protrusions, these hair like projections known as microvilli."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And these microvilli together are known as the Brush Water."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And they contain these digestive enzymes that can break down disaccharides into their individual sugars."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, the three most common disaccharides in the human body are maltose, sucrose, and lactose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, maltose is basically obtained by the digestion of the carbohydrate we call starch."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So our body breaks down starch into maltose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And maltose consists of two glucose molecules that are attached via an alpha one four glycocitic bond."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And the enzyme found on the Brush border that breaks down Maltose into two glucose molecules is known as maltase."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, for sucrose, sucrose consists of our glucose and fructose attached via an alphagly acidic bond."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And the digestive enzyme at the Brush Water that breaks down our sucrose is known as sucrase."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And finally, lactose consist of galactose and glucose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And the enzyme that breaks down lactose is known as lactase."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "It is also found on the Brush border attached to the membrane on the apical side of our entericide."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So to summarize what we just said, let's take a look at the following diagram."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So, we eat the carbohydrates, such as starch in the mouth."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Salivary amylase breaks down the carbohydrates very large molecules into polysaccharides, smaller ones."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "These polysaccharides ultimately end up in the lumen of the small intestine, where our pancreatic amylase breaks down the polysaccharide into disaccharides, our maltose, sucrose and lactose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, Maltose is broken down at the Brush border into two glucose molecules."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Sucrose is broken down at the Brush border by sucrase into fructose and glucose, while lactose is broken down by lactase into galactose and glucose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Also at the brush border."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, the reason we have to break down the carbohydrates ultimately into their individual monumeric constituents is because the intricacies, the cells of the small intestine, can only absorb these monomers."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "That means it cannot absorb disaccharides because they're simply too big."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So we have to break down the disaccharides into our individual monomers."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, the question is, once we actually break down the disaccharides into glucose, galactose and fructose on the microvilli at the brush border of anterocytes, what exactly takes place then?"}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "How exactly do we transport the glucose, galactose and fructose into the cytoplasm of entericides?"}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So we have two modes of transportation."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So fructose follows one pathway, while our glucose and galactose follows a different pathway."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So basically, glucose and galactose interrogates via sodium linked secondary active transport."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And what that means is we actually have to use ATP to create a certain electrochemical gradient of sodium."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And then as sodium moves down its electrochemical gradient, it will move the galactose and glucose along with it."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "This is what we mean by sodium linked secondary active transport, and we'll see exactly what that looks like in just a moment."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "On the other hand, fructose can easily pass across the cell membrane by using a special type of integral protein that allows the passive diffusion of fructose into the cytoplasm of the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So fructose can easily move into the cell via an integral protein, and it doesn't actually use any ATP molecules."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And once fructose is inside the cytoplasm, the majority of the fructose is broken down into glucose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, what about glucose and galactose?"}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, before glucose and galactose can actually move into the cytoplasm of the cell, and by the way, this is our single antarocyte, before they move into the cytoplasm, something has to happen on the other side of the membrane."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "This other side is known as the basil lateral side, or the basal side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Remember, this side is the apical side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "It points towards the lumen of the small intestine."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And the other side is the basil lateral side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "It points towards our blood vessels."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So on the basil lateral side, we have an important type of transport protein known as sodium, potassium, Atpas."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And this is basically a pump that hydrolyzes uses ATP, transforms it into ATP, and at the same time, it pumps three sodium ions against its electrochemical gradient out of the cell to the basilateral side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "At the same time, it pumps two potassium into the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And over time, this establishes an electrochemical gradient inside the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So that means inside the cell, we have a low concentration of sodium."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And on the outside, we have a higher amount of sodium."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So that means because we have a higher amount of sodium on the lumen side, the sodium will travel into the cell via this special type of co transporter protein."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "The reason it's called a co transporter is because as the sodium moves down its electrochemical gradient that was established by this ATPA pump the glucose or galactose is brought in with the movement of this sodium."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So as the sodium moves in, the glucose and galactose also moves in via this same cotransport of protein."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, as soon as glucose, galactose and fructose is inside the cell, they can then diffuse via passive diffusion, passive transport via special type of protein that is found on the basil lateral side shown in green."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And the glucose, galactose and fructose will ultimately be transported into our blood vessels that are found very close to the basil lateral side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And these blood vessels will basically carry these molecules, these sugars, via the portal vein into our liver."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And inside the liver, the glucose will be transformed into glycogen and will be stored in liver cells as well as muscle cells."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So once again, let's summarize what we just said."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So in diagram one, we basically have these special proteolytic digestive enzymes found on the brush water of the anterocy on the apical side, on the apical membrane that break down our disaccharides into their individual monosaccharide form."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Then what happens is on the basilateral side, we have specialized types of sodium, potassium, Atpas pumps that establish an electrochemical gradient by using ATP molecules."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So we create a lower concentration of sodium inside the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, we have specialized types of cotransport or protein membrane protein molecules that are found on the apical side that allow the movement of sodium into the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "At the same time, glucose and galactose also travels into the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, fructose, on the other hand, doesn't actually use this same system."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "It doesn't use ATP and it enters the cell via a different type of integral protein that basically allows for passive transport."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So not using any ATP molecule, but when fructose is inside, the majority of fructose is transformed into glucose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "And in part five, we basically have fructose, glucose and galactose then leave the cell via passive transport on the basil lateral side."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So this membrane doesn't actually use any ATP molecules, any ATP energy molecules, and eventually they enter the blood vessel, they enter our hepatic vein and then they basically travel into our liver where the liver stores the glucose in the form of glycogen, which is basically the carbohydrate that is stored inside our cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "The polysaccharide that is stored inside the cell."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, I should mention that this protein here is known as a HEXOS co transporter protein."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "The HEXOS simply means that it transports six membrane sugars, for example, the galactose and glucose."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "Now, our fructose is a five membered sugar."}, {"title": "Absorption of Carbohydrates by Small Intestine.txt", "text": "So that means this co transporter will not be able to transfer the fructose because it's a five membered sugar."}, {"title": "Salting Out.txt", "text": "So in our discussion on cellfactionation, we mentioned eight different types of methods that we can use to basically purify proteins, to isolate proteins from a mixture of different types of protein."}, {"title": "Salting Out.txt", "text": "So in this lecture, we're going to focus on one of those methods."}, {"title": "Salting Out.txt", "text": "We're going to discuss salting out."}, {"title": "Salting Out.txt", "text": "So we're going to see what salting out is, what property of proteins it uses, and then we're going to look at a specific example when we can use salting out efficiently."}, {"title": "Salting Out.txt", "text": "So let's begin by discussing what a protein is."}, {"title": "Salting Out.txt", "text": "So proteins are these sequences of amino acids."}, {"title": "Salting Out.txt", "text": "And inside our body, the proteins are composed of 20 different types of amino acids."}, {"title": "Salting Out.txt", "text": "Now, some of these amino acids are hydrophobic, some of them are hydrophilic."}, {"title": "Salting Out.txt", "text": "And when you place the protein into an aqueous solution, it's the hydrophilic amino acids that will be found on the surface interacting with the polar water molecules, forming hydrogen bonds, while the hydrophobic amino acids will be found inside that protein in the core."}, {"title": "Salting Out.txt", "text": "So we're basically going to get the following diagram."}, {"title": "Salting Out.txt", "text": "So this is our protein."}, {"title": "Salting Out.txt", "text": "The protein core consists of a non polar section, while the surface of the protein consists of the blue section that is basically the hydrophilic section."}, {"title": "Salting Out.txt", "text": "The hydrophilic amino acids and these water molecules will form hydrogen bonds with those hydrophilic amino acids found on the surface of that protein molecule."}, {"title": "Salting Out.txt", "text": "Now, the extent to which a given protein is soluble in water basically depends on the number of hydrophilic amino acids that are found on the surface of that protein and generally on that protein."}, {"title": "Salting Out.txt", "text": "So let's suppose we have a beaker, and in that beaker, we have pure water."}, {"title": "Salting Out.txt", "text": "And to the pure water, we add one type of protein."}, {"title": "Salting Out.txt", "text": "Now, when we add that protein to our water, the protein will dissolve."}, {"title": "Salting Out.txt", "text": "And what we'll get is the following situation."}, {"title": "Salting Out.txt", "text": "So let's suppose we have the water."}, {"title": "Salting Out.txt", "text": "We place the protein molecules into our water, and what will happen is these protein molecules will exist as individual entities."}, {"title": "Salting Out.txt", "text": "They will not be combined."}, {"title": "Salting Out.txt", "text": "They will exist as individual molecules."}, {"title": "Salting Out.txt", "text": "And that's because inside that pure water, we have enough water molecules to basically surround the hydrophilic section of our protein and stabilize that protein structure via hydrogen bonds."}, {"title": "Salting Out.txt", "text": "So we see in pure water, we have plenty of water molecules present that can interact with the charge and hydrophilic sections, hydrophilic amino acids of that protein."}, {"title": "Salting Out.txt", "text": "Now, what we want to basically ask right now is what happens when we add salt into our pure water solution that contains dissolved protein molecules?"}, {"title": "Salting Out.txt", "text": "So we can add, for example, sodium chloride."}, {"title": "Salting Out.txt", "text": "We can add another type of salt, for example, ammonium sulfate, as we'll see in just a moment."}, {"title": "Salting Out.txt", "text": "So as soon as we begin to add our salt, what will begin to happen is the solubility of that protein in the water will begin to decrease."}, {"title": "Salting Out.txt", "text": "And not only that, if we continue adding more salt, eventually we're going to reach a certain specific concentration of salt."}, {"title": "Salting Out.txt", "text": "And in that value, what happens is that protein will become insoluble in that solution."}, {"title": "Salting Out.txt", "text": "And that means the protein will begin to precipitate out of the solution."}, {"title": "Salting Out.txt", "text": "It will crystallize and form the solid state."}, {"title": "Salting Out.txt", "text": "And this is what we call salting out."}, {"title": "Salting Out.txt", "text": "So we know what salting out is, but why does it actually take place?"}, {"title": "Salting Out.txt", "text": "Well, to see why it takes place, let's take a look at the following picture."}, {"title": "Salting Out.txt", "text": "So, let's suppose we begin to add our sodium chloride molecules."}, {"title": "Salting Out.txt", "text": "As soon as we add the sodium chloride molecules, the ionic bond holding the sodium chloride will break."}, {"title": "Salting Out.txt", "text": "And what happens is, when we dissociate the two atoms, they will form ions."}, {"title": "Salting Out.txt", "text": "So we're going to have a bunch of positively charged sodium ions and a bunch of negatively charged chloride ions floating around in our aqueous solution."}, {"title": "Salting Out.txt", "text": "Now, because we don't increase or decrease the amount of water molecules present inside our mixture, what that means is the number of hydrogen bonds that are available to interact with the hydrophilic amino acids of the protein will decrease."}, {"title": "Salting Out.txt", "text": "And if we decrease the amount of stabilizing hydrogen bonds interacting with our protein, that will destabilize the structure of these individual proteins."}, {"title": "Salting Out.txt", "text": "And what that means is, if we destabilize the structure of these individual molecules, they will begin to aggregate."}, {"title": "Salting Out.txt", "text": "And that's because by aggregating, by interacting between the non polar sections of these amino acids, that will in turn, stabilize the structure of this entire aggregate molecule."}, {"title": "Salting Out.txt", "text": "And so we see that as we add the salt into our mixture, because some of those water molecules that were interacting with the protein before are now forming hydrogen bonds with these ions, dissolved ions, we have less H bonds to basically stabilize the protein."}, {"title": "Salting Out.txt", "text": "And so the protein begins to aggregate, and by aggregating, it stabilizes the protein structure, because it decreases the amount of surface area that is exposed to that water."}, {"title": "Salting Out.txt", "text": "So before, the entire surface area of these proteins were exposed, but now only these sections are exposed, and this section here is not exposed to the water."}, {"title": "Salting Out.txt", "text": "And so what that means is it accommodates that decrease in hydrogen bonds that results as a result of the addition of that salt into our mixture."}, {"title": "Salting Out.txt", "text": "So when we add salt, the charged ions interact with water."}, {"title": "Salting Out.txt", "text": "And this means that there are less solvent water molecules to interact with the protein."}, {"title": "Salting Out.txt", "text": "And as a result, to stabilize that structure, protein molecules begin to aggregate."}, {"title": "Salting Out.txt", "text": "And that is what causes precipitation crystallization out of the solution."}, {"title": "Salting Out.txt", "text": "And this is known as salting out."}, {"title": "Salting Out.txt", "text": "So an application of salting out is basically purification."}, {"title": "Salting Out.txt", "text": "So purifying our proteins, as we'll see in just a moment."}, {"title": "Salting Out.txt", "text": "Now, this can be done because different proteins are composed of different amino acids, and different amino acids contain different hydrophilic and hydrophobic nature."}, {"title": "Salting Out.txt", "text": "So, because proteins consist of different variation of amino acids, they have different solubilities in water."}, {"title": "Salting Out.txt", "text": "And that means the salt concentration at which protein salt out will differ from one protein to another."}, {"title": "Salting Out.txt", "text": "And so if we have two different proteins in, let's say, an Aqueous solution, and those two different proteins have a big variation in their salt concentration at which they salt out, we can basically purify them and separate them by using the salting out method."}, {"title": "Salting Out.txt", "text": "So let's see exactly what we mean."}, {"title": "Salting Out.txt", "text": "So salting out can be used to isolate a protein of interest from a mixture of different proteins."}, {"title": "Salting Out.txt", "text": "And in our example, we're going to look at a mixture of two proteins."}, {"title": "Salting Out.txt", "text": "So one of these proteins is a blood clotting protein known as fibrinogen."}, {"title": "Salting Out.txt", "text": "And another protein is serum albumin."}, {"title": "Salting Out.txt", "text": "And this is a protein that carries lipids, for example, fatty acids and cholesterol inside our blood plasma."}, {"title": "Salting Out.txt", "text": "Now, for fibrinogen, which is shown in green, this protein requires a concentration of 0.8 molar of ammonium sulfate to basically precipitate."}, {"title": "Salting Out.txt", "text": "But this requires three times this concentration, so 2.4 molar."}, {"title": "Salting Out.txt", "text": "And because we have such a drastic difference between their solubilities and their salt concentration values, we can basically apply this salting out procedure to isolate this protein out of our mixture."}, {"title": "Salting Out.txt", "text": "So before we add the salt, we pretty much have this situation as described here."}, {"title": "Salting Out.txt", "text": "We have these fibrinogens shown in green and the serum albumin shown in purple, that are basically existing as individual entities."}, {"title": "Salting Out.txt", "text": "But as we begin to add that salt, and as we add 0.8 molar of ammonium sulfate, the green fibrinogen begins to aggregate because that stabilizes that structure."}, {"title": "Salting Out.txt", "text": "And so this begins to precipitate and crystallize."}, {"title": "Salting Out.txt", "text": "But what happens to this one?"}, {"title": "Salting Out.txt", "text": "Well, nothing, because it requires 2.4 molar to actually precipitate."}, {"title": "Salting Out.txt", "text": "And so while this one will crystallize, the albumin will not crystallize."}, {"title": "Salting Out.txt", "text": "And what we can do now is apply another method, another technique that we're going to focus on in the next lecture, known as dialysis."}, {"title": "Salting Out.txt", "text": "And if we apply dialysis to this particular case, we can basically separate and isolate that fibrinogen from the mixture of this serum albumin."}, {"title": "Salting Out.txt", "text": "And at that particular point in time, we now have two different beakers."}, {"title": "Salting Out.txt", "text": "One contains one of these enzymes, one of these proteins fibonaccin, and the other one contains the other one albumin."}, {"title": "Salting Out.txt", "text": "So salting out basically uses the property of protein we call solubility."}, {"title": "Salting Out.txt", "text": "So because different proteins require different salt concentrations to basically precipitate, we can use this property of proteins to basically isolate and purify our mixture of proteins, as we saw in this particular A case."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Glycogen metabolism involves two important processes."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "We have the synthesis of glycogen from glucose molecules glycogenesis and we also have the breakdown of glycogen into glucose glycogen degradation."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, these two processes never take place at the same exact moment in time inside our cells."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "In fact, the cells of our body have a mechanism in place that helps regulate these processes in a reciprocal fashion."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And what that basically means is when one process is on, the other process must be off."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "For instance, if our body for our cells are breaking down glycogen to glucose the process of glycogen synthesis will be turned off."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, what exactly is this process of reciprocal regulation and how does it actually take place?"}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So let's begin by imagining that our body is either exercising or our body is fasting."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "In either case, the blood glucose levels in our body will decrease."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And when our blood concentration of glucose basically decreases what that means is our liver cells will begin to break down glycogen to glucose and release that glucose into the blood and that will help maintain a correct concentration of glucose in our blood."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "At the same time, for instance, if we're exercising our skeletal muscles will begin to break down glycogen to glucose and use that glucose to form the energy ATP molecules needed to carry out the proper voluntary motions that are required for that particular exercise."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So basically during these circumstances our body wants to break down glycogen to glucose but at the same time it wants to stop the process of the synthesis of glycogen glycogenesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So this is a signal transduction pathway that essentially allows us to carry out these two processes to turn on glycogen breakout and turn off glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So let's imagine where in our liver cell so we have glucagon and to a very small extent epinephrine are the primary messengers that bind to these receptor molecules on liver cells."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And once the glucagon binds onto the glucogon receptor it basically stimulates the GDP to leave and a GTP to enter this green g protein."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And that stimulates the g protein to dissociate and go on and bind to adenylate cyclase, another membrane bound protein."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Once bound, it stimulates adenylate cyclase to begin creating secondary messenger molecules."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So it transforms ATP into cyclic amp."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now it's the cyclic Amp that acts as a secondary messenger."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "It goes on and binds onto regulatory sites of protein kinase A and that activates it by allowing the catalytic sites or the catalytic units to actually dissociate from that regulatory site from that regulatory subunits."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And so that activates protein kinase A."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And protein kinase A actually does two important things."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Number one is it creates a pathway that activates glycogen breakdown and it also creates a pathway that essentially deactivates glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So let's begin by focusing on this pathway here."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So protein kinase A in the active form goes on and phosphorylates an enzyme called phosphorylase kinase and that transforms it into the active form."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, phosphoralase kinase in the active form goes on to activate phosphorate, phosphorase B and that transforms it into the much more active phosphorase A."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Remember, phosphorase A exists predominantly in the relaxed state and so it's fully active."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And it's phosphorase A that is responsible for actually initiating the process of glycogen breakdown."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So this allows, let's say, the liver cell to actually break down the glycogen into glucose molecules and then release the glucose into the blood plasma to help regulate the concentration of glucose in our blood during times of fasting or exercise."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "At the same exact time, the PKA also actually phosphorylates glycogen synthase A and that transforms it into the act from the active form into the inactive form, glycogen synthase B."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Remember, it's glycogen synthase that initiates the elongation of glycogen."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "It builds the glycogen molecules."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And so by inactivating this molecule, we stop glycogen synthesis from actually taking place."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So this is what we mean by a reciprocal pathway."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "One of them is turned off or one of them is turned on, but the other one is turned off."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So when we're fasting or when we're exercising, the blood glucose levels are low."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And in this particular case, we're going to basically initiate a signal transduction pathway that activates PKA."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And it's the PKA that is responsible for actually initiating the breakdown of glycogen and at the same time stopping or turning off glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, let's suppose our body is at rest or our body just ate a meal that is rich in carbohydrate molecules."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "In this particular case, what our body will want to do is it will want the skeleton muscle cells to begin rebuilding the glycogen, to actually replenish the glycogen storage in our cells."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And the liver cells will want to uptake some of that glucose from the blood and transform the glucose into glycogen."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And in this particular case, our body would want to actually stop the breakdown of glycogen while at the same time turning on the process of glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And the enzyme that basically plays a key role in this process is known as protein phosphatase One or simply PP One."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So what happens when our cells need to regenerate glycogen supplies?"}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Well, an enzyme called protein phosphatase One, PP One, stimulates glycogenesis, the building of glycogen from glucose and turns off glycogen breakdown."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, how does it actually achieve this?"}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Well, protein phosphatase One basically activates this molecule back to this molecule."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Remember, a phosphatase is something that defosphorylates a target enzyme and PP One defosphorylates the glycogen synthase back to glycogen synthase A and that activates this molecule."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And that in turn allows the process of glycogen synthesis to actually take place at the same exact time."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Protein phosphatase One also defosphorylates this molecule, inactivating it, and the defuse formulates this molecule also inactivating it."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And so this process, the process of synthesizing glycogen is initiated."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "But the process that leads to the glycogen breakdown basically stops."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now let's go back to this particular case for just a moment."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So let's suppose we have low blood glucose levels because of either exercise or fasting."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "What our body will want to do is stimulate the process of glycogen breakdown and stop the process of glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And what that means is in this particular case our body must also be able to regulate the protein phosphatase one."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "It basically wants to be able to stop the activity of protein phosphatase one when we want to break down glycogen and when we want to stop glycogen synthesis."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So let's focus on the structure of protein phosphatase one."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So this is protein phosphatase one and in the active form, protein phosphatase one PP one is attached to a regulatory subunit and that regulatory subunit basically allows the PP one to actually interact with the glycogen and the target enzymes and target proteins."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Now, when this signal transduction pathway is activated and we want to basically turn on glycogen breakdown and turn off glycogen synthesis, what the PKA also does is the following two things."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "Number one, PKA goes on and phosphorylates the regulatory section of this molecule."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And once phosphorylating that and once it phosphorylates that regulatory section, the PP one actually dissociates."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And as soon as that PP one dissociates, it's no longer as active."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "In this particular case, at the same exact time, the PKA alsophosphorylates an inhibitory protein molecule."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So this is our inhibitory protein molecule in the form that is not attracted to the PP one."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "But once it phosphorylates it, this becomes attracted to the PP one and it goes on and binds unto protein phosphatase one."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And once these two things take place, once the regulatory subune dissociates from PP one and once the phosphorylated inhibitory molecule binds onto protein phosphatase one it puts it into the fully inactive form."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So basically PKA doesn't only inactivate glycogen synthase A, it also actually inactivates the protein phosphatase one."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And that's what allows this signal transduction pathway to actually turn off the process of glycogen synthesis while at the same time turning on the process of glycogen breakdown."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "So once again, when glycogen metabolism takes place inside our cells, our cells basically separate these two processes."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "When one takes place, the other one does not take place and vice versa."}, {"title": "Reciprocal Regulation of Glycogen Metabolism.txt", "text": "And this is a signal transduction pathway that allows our liver cells and skeletal muscle cells and other cells to basically capture pariosis reciprocal mechanism."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "One particularly pathogenic agent that infects our body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "More specifically, our immune system is a type of virus known as the human immunodeficiency virus or simply HIV."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now transmitted through bodily fluids such as blood and semen."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "What this virus does is it infects special wide blood cells, special lymphocytes of that our immune system and transforms these healthy lymphocytes into virus producing cells that ultimately lose all their functionality as immune cells, they lose their ability to defend our body from infections and from invading pathogens."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And this greatly weakens our immune system and leads to a medical condition known as Acquired Immune Deficiency Syndrome or simply AIDS."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, AIDS is not the same thing as HIV."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "HIV is that pathogenic agent that eventually leads to AIDS."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So this is the cause and this is the effect."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So don't use these two terms interchangeably."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "They are not the same exact thing, but they are related."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "One causes the other."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, let's discuss the mechanism by which HIV actually invades the wide blood cells of our body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And let's begin by examining the structure of an HIV agent."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So this is what HIV looks like."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We basically have this membrane shown in pink and on the membrane we have these embedded glycoproteins."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, we have different types of glycoproteins."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "The two glycoproteins we're going to focus on in this lecture is a glycoprotein called GP 120 and glycoprotein called GP 41."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So GP 120 is positioned on top of GP 41."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, GP 120 is actually used to bind onto receptors on the target cell's membrane and GP 41 is used to stimulate the process of fusion of the membrane of the virus and the membrane of the target cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, inside this membrane we have the protein capsule shown in brown and inside that protein capsite we have the contents of that virus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We have the genetic information, the RNA shown in red and we have two very important types of protein enzymes."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "One known as integrates."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Let's suppose that's the blue one, that's the green one, and the other one is known as reverse transcriptase."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Let's suppose that is our blue one and we'll discuss what their function is in just a moment."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So basically, the GP 120 glycoprotein of HIV binds to a specific glycoprotein receptor found on membrane of immune cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And this special type of glycoprotein is called CD four glycoprotein."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So HIV contains a glycoprotein, the GP 120, that can bind onto the CD four protein of immune cells are white blood cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, recall from our discussion on white blood cells and specifically on T lymphocytes, we said that one of the specialized types of T lymphocytes that contains a CD four glycoprotein are the helper T cells of our adaptive, our acquired immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So recall that helper T cells are CD four positive cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And what that means is these HIV agents will be able to bind and will be able to attack these helper T cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So these are the helper T cells that HIV actually attacks."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So let's take a look at the following diagram."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We have the HIV agent that uses the GP 120 glycoprotein to bind onto the CD four Glycoprotein of this healthy helper T cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, inside the helper T cell, we have these different types of organelles."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we only show the nucleus and we show our endoplasmic reticulum."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "This is the rough endoplasm reticulum that synthesizes our proteins."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And we have the genome, the DNA of that helper T cell inside the nucleus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, once this binding process takes place, what happens next is the GP 41 Glycoprotein."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "The other glycoprotein attached to GP 120 and to the membrane of our virus, initiates or stimulates the cell mediated endocytotic process."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "This is the process by which the membrane of the virus fuses with the membrane of the cell and that essentially dumps all the viral contents into the cytoplasm of our cell, as shown in this diagram."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we have the fusion of the membrane in tank of the virus and the membrane in blue of that helper T cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And so this is what happens."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We have the blue section and we have the fused pink section and the protein capsule along with the contents are now found inside the cytoplasm of our cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So what happens next?"}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Well, HIV is a type of virus known as a retrovirus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, what exactly is a retrovirus?"}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Well, a retrovirus is a virus that contains RNA molecules as well as a special enzyme that catalyzes the formation of viral DNA from that viral RNA."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So that's why we have reverse transcriptase because it synthesizes our nucleotides in the opposite direction to what is normally seen in nature."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Normally we synthesize DNA to RNA, but in this case it goes from RNA to DNA in the opposite process."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So HIV is a retrovirus, which means it has an enzyme called reverse transcriptase that can form viral DNA from the viral RNA."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So these blue molecules, once inside the cytoplasm attached to the red RNA molecules and they begin to synthesize the viral DNA."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, once the viral DNA is synthesized, it moves into the nucleus of that helper T cell and an enzyme known as Integrase, shown in green, basically binds onto that DNA of that cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "It clips it and opens it at a certain position and it inserts, it incorporates that viral DNA into that original genome, original DNA of the helper T cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And now this is an infected helper T cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So notice in this case, this was purely brown."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "But now a small piece of that viral DNA shown in red has been integrated with that genome of our helper T cell."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, now that we have incorporated the viral DNA into our DNA of the cell, when that DNA is used to synthesize mRNA, we're going to synthesize viral mRNA to produce viral proteins."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And in this manner we transform our helper T cell into a factory that produces viral proteins and viral RNA molecules that ultimately causes the cell to lyse."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And when it licenses, when it breaks open it releases many, many HIV agents that go on to essentially infect other helper T cells of our body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And in this method, what HIV does is it essentially destroys our population of helper T cells in our body and that weakens our immune system and leads to the Choired Immune Deficiency Syndrome."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And because we have the acquired Immune Deficiency Syndrome we have a very, very weak immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Any type of infection that enters our body can essentially kill us off."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And that includes the common cold."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So it's not the actual HIV that virus that kills us but it's what it does that ultimately kills us."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "It's the fact that we create a very weak or the virus creates a very weak immune system and any infection whatsoever can essentially kill us off."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, the next question is what's the big deal about these helper T cells?"}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Why is it that when these helper T cells are destroyed our immune system becomes so weak?"}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we have many, many different types of white blood cells in our body and helper T cells are only one of these different types of white blood cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So what exactly makes the helper T cells so special?"}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Well, it turns out that helper T cells are the cells that oversee all the different types of processes that take place inside our immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And they essentially allow that immune system to function effectively and efficiently."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And although they do not attack pathogens directly what they do is they bind onto T lymphocytes and they induce the differentiation of these T lymphocytes into other specialized white blood cells such as cytotoxic t cells that are important in fighting off infections and infected cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "They also bind onto B lymphocytes and that induces the differentiation of these B cells into plasma cells that are needed to produce antibodies floating in our blood."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And they also induce differentiation into memory B cells that store the antibodies in case we are ever reinfected with that same pathogen."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, these helper T cells also release special chemicals called cytokines."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And these cytokines not only induce wide blood cell differentiation but they also stimulate the cells of our innate immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "These are our macrophages, neutrophils, basafils and other wide blood cells of our innate immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we see that by destroying the population of our helper T cells what HIV actually does is it severely weakens not only our adaptive, our acquired immune system but also our innate immune system."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And as a result, most individuals infected with HIV die not from the virus itself but from other infections that infect our bodies such as the common cold, pneumonia, the flu or even cancer."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And because our body cannot actually defend itself because our immune system is weakened that is why we actually die."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we die because of our body's inability to mount a proper immune response as a result of the Choir Immune Deficiency Syndrome or AIDS."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, the final thing I'd like to briefly discuss is the stages that the person goes through when they are infected with HIV."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So there are three stages."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We have the early stage, we have the middle stage, and we also have the late stage, which is a stage when the person is set to have AIDS."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So early stage lasts about two weeks."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And this is when the person actually feels sick."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "This is when the person experiences flulike symptoms."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "For example, they have a high fever, they have different types of body aches, they have headaches."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And this is when inside the block there's a high level of these viral agents, the HIV agent."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So basically the individual experiences flulike symptoms, fever, aches and so forth and has a high level of virus in the body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Now, the middle stage is the stage when the person doesn't actually experience any symptoms."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So you have no way of actually knowing whether or not you are carrying the virus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "The only way that you can know is if you go get tested."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And that's because this is the stage when the body begins to produce antibodies."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So we have antibodies floating in our blood that are specific to this virus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And these antibodies can be used to detect that virus in our body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So middle stage can last from several months to several years."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So no visible symptoms, low levels of that virus."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "We have the presence of these antibodies and we have a very slow but very continual decline in the population of our helper T cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "So during the middle stage, the HIV continually but slowly begins to kill off these helper T cells."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And the final stage, the late stage, this is when we actually are diagnosed with Acquired Immune Deficiency Syndrome."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "This is when our HIV begins to kill off the helper T cells at a very high rate and the population of helper T cells drops to very low amount."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And what that means is this is when our innate and acquired immune systems are weakened to the point where if any infection takes place, such as the common cold, flu, pneumonia, we essentially will die because of our body's inability to create to mount some type of defensive response."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And this is when the person can also develop cancer."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And that's because our immune system loses its ability to fight off cancer."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "Because if we can't produce cytotoxic T cells and because if we can't release cytokines that influence natural killer cells, we don't have any cells that can destroy our cancer cells of the body."}, {"title": "HIV, AIDS, and Helper T-Cells .txt", "text": "And that's why we ultimately develop cancer when we are at the late stage, when we have the Choir Immune Deficiency Syndrome."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So far in our discussion on carbohydrate molecules, we focus on the open chain form of sugar."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So if we're examining, let's say, glucose, the open chain form of glucose looks like this."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And if we're examining, let's say, fructose, well, then the fructose open chain form looks like this."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, although the open chain form of sugar molecules does exist to a very a small extent inside our body, these open chain sugar molecules actually undergo a cyclic reaction to form ring structures."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Why?"}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Well, because the ring structure of the sugar molecule is lower in energy and more stable than its open chain counterpart."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, what exactly is this reaction that takes place that allows that less stable or higher in energy open chain form to transform into the more stable, lower in energy ring structure form?"}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Well, what this reaction is is basically a reaction between a nucleophile and an electrophile."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "The nuclear file in this case is an alcohol group on the sugar molecule, while the electrophile is the carbon of the carbonyl."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And that can be either an aldehyde or a ketone, depending if we're looking at aldos or ketosis."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So if we have an aldehyde group on that sugar molecule, well, then it reacts with an alcohol group on that same sugar molecule to form a hemicata."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And likewise, if we have a ketone instead of the aldehyde, that ketone will act as the electrophile reacting with the nucleophile, one of the hydroxyl groups on that sugar molecule, to form a hemiketel."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So let's begin by focusing on aldohexos."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And the aldohexos that we're going to use as our prototypical example is glucose, more specifically, the D glucose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So remember, the de glucose simply means this blue hydroxyl group found on the last stereogenic carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Carbon number five points to the right side and not to the left side."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, what basically happens is an intramolecular nucleophilic reaction takes place in which the hydroxyl group, the oxygen of the hydroxyl group found on the fifth carbon, basically attacks nucleophilically, the carbon of this carbonyl that is part of this aldehyde group, and we form this bond."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And that bond is shown in purple here as well as here."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, why did I draw two different molecules, A and B?"}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Well, because if we examine this reaction, this oxygen can either attack the carbon from the top or from the bottom."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And because it has the option of attacking it from these two sides, we form two different isomers."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So isomer A and isomer B."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, isomer A is known as the Beta d glucopyronose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "We call this a pyrenose, because it is a six membered ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Inside the ring, we have six different atoms."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So we have carbon one, carbon two, carbon three, carbon four, carbon five, and this oxygen."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And that's why we call it a pyrenose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "The glucose simply means we begin with the deglucose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So this is the ring form of that glucose molecule."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, what is the meaning of the beta."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Well, if we examine this carbon number one, the beta simply means that the hydroxyl group of this carbon number one, known as the anumeric carbon, points in the same direction as this group here that is bound onto carbon number five."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So this entire ch two oh group points in the same direction, so up as this hydroxyl group."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And when they point in the same direction, that type of sugar is known as the beta anemer, because this carbon here, carbon number one, is known as the anomeric carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, on the other hand, if this nucleophile attacks from the other side, we're going to form the other animal known as the alpha animal, and this is known as alpha dlucopyrenose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, notice in this particular case, this hydroxyl group points in the opposite direction with respect to this entire group here, that points up."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So this points down and this points up."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, when we discussed the open chain form of sugar molecules, we said that it's the fissure projection that is used to basically describe the three dimensional arrangement of the atoms, the stereo chemistry of the atoms in that sugar molecule."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Likewise, when we're describing the ring structures of sugar molecules, to basically describe the stereochemistry of the ring structure in that sugar molecule, we use the Horworth projection."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And these are examples of Horworth projections."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so in the Horworth projection, what we have is these thick bonds are the bonds that are coming out of the board."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So these bonds here are coming out of the board and they're essentially perpendicular to the plane of the board."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So these atoms here are basically coming out of the board."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so what that means is, for instance, this hydroxyl group points upward and this hydrogen group points downward."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So we see for our D glucose molecule, which is an example of an aldo HEXOS."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "HEXOS means we have 123456 carbon atoms, and aldo means we have the aldehyde group on that first carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So for D glucose, an example of an aldo HEXOS, the hydroxyl group on the fifth carbon, this blue hydroxyl group on the fifth carbon basically attacks the carbon number one of this carbonyl group that is part of that aldehyde."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And we form a mixture of two types of isomers."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And these isomers are known as animals."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So animals are isomers that differ in this first area, genic carbon, in the arrangement of atoms on this first stereogenic carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So we have the alpha and the beta animal."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "The alpha animal means that the hydroxyl group on the first carbon points in the opposite direction with respect to this group here, which is shown here, while the beta anamar, these two groups, point in the same exact direction."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, inside our body, about two thirds exist in this beta form, one third exists in this alpha form."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And a very, very small amount, less than 1%, actually exists in this deglucose open chain form."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, as I mentioned, just a moment ago, we have the fissure projections that are basically used to describe the stereo chemistry, the arrangement and the three dimensional position of atoms for the open chain forms."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "On the other hand, we have the Holworth projections, which are used to describe the stereo chemistry of the cyclic sugars."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And these are examples of the Holworth projections."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now let's take a look at another type of sugar molecules."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So, remember, we have aldo hexosis, and we also have sugar molecules that contain ketone groups, and these are known as ketosis."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So let's take a look at a specific example of a keto hexose, basically a six carbon sugar molecule that contains a ketone group."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And the example we're going to look at is defractose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So, in defuctose, we also have 123456 carbon atoms, just like in this particular case."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "But instead of having the aldehyde, we have this ketone group."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so now what takes place is this hydroxyl group on the fifth carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So this hydroxyl group on the fifth carbon here reacted with the first carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "But in this case, this hydroxyl on the fifth carbon will react with the carbon that is number two, because this is the carbon of the carbonyl that will act as the electrophile."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so now, instead of forming a six member ring, instead of forming the pyramids, we're going to form a fewer nose, and this is a five membered ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Why?"}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Well, because we're going to have bond number one, bond number two, three, four, and bond number five."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And that means we're going to have five atoms and five bonds inside our ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And just like in this particular case, we can attack from the top or from the bottom here."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "We can also attack from the top or the bottom."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so we also formed the alpha and the beta animals."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So we have the alpha D fructopiornos, and the beta, D fructo."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Furnos."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "In the alpha case, this group points in the opposite direction as this group."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "In the beta case, this hydroxyl group points in the same direction as this group here."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So for D fructose, an example of a keto HEXOS, the hydroxyl group of the fifth carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So carbon number five, this hydroxyl acts as a nucleophile, attacks the carbon of the carbonyl, which happens to be carbon number two, not carbon number one."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And so in this case, we form the five member ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And that's why we call these furnose furnishes."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, what I haven't actually shown is a second type of reaction can actually take place."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So in the case of the defurctose, in the case of all keto hexosis, actually, we can also have under certain circumstances, we can have the hydroxyl group on the 6th carbon attack the carbon of the carbonyl nucleophilically."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And if this hydroxyl group on the 6th carbon attacks this carbon, instead of forming our five member ring, we're going to form a six membered ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So for deflectose, a second reaction can take place in the second reaction, not shown on the board, the hydroxyl of the six carbon."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "This one will react with the Ketone group carbon number two, nucleophilically, to form a five membrane ring."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And this Fructose molecule is known as Fructopyrenose."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So Fructose a furnace simply means five membrane ring, and Pyrenose is in this case, means six membrane."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And just like we have the alpha and the beta animals, we can also form the alpha and the beta anomers of Fructopyranos."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So basically, the takeaway point from this lesson is the fact that inside our body, the open chain form of sugars does not actually predominate."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "It's the ring structure, the ring form that predominates because it's the ring form that is lower in energy and thermodynamically more stable than that open chain form."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "Now, what I haven't mentioned also is the fact that ribose sugar molecules, which are actually examples of pentosis, so hexoses contain six sugars, but pentosis, like ribose contain five sugars."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And pentosis, like ribose are important because they're constituents of nucleic acids, DNA molecules and RNA molecules."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "And just like hexosis, Aldo, HEXOS and Ketohexos pentosis, five member sugars like riboses, also exist predominantly in their ring form, more specifically in the five membered ring form."}, {"title": "Cyclic Form of Carbohydrates .txt", "text": "So ribose molecules, when they undergo this intramolecular reaction, they form a five member ring, just like this defructose does."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "The citric acid cycle is a very important cycle because it's the center of aerobic respiration."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "It's basically the cycle where all our fuel molecules, the carbonbased fuel molecules, such as amino acids and fat molecules and glucose molecules, actually end up going."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And this is where we extract the high energy electrons from these carbon fuel molecules and use those electrons on the electron transport chain to actually generate the high energy ATP molecules that are needed by the cell to carry out many different types of processes, such as contraction of our skeleton muscle cells."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, because the citric acid cycle is so important, we actually have to regulate this citric acid cycle."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We have to closely monitor its activity, in fact, even before the citric acid cycle actually begins."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "One point of regulation of the citric acid cycle is by regulating Pyruvate decarboxylation because remember, Pyruvate decarboxylation must take place before the citric acid cycle actually begins."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So in the cytoplasm of our cells, the glucose is transformed into Pyruvate via glycolysis."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And under certain circumstances, the Pyruvate can even be transformed back into glucose."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, if we have plenty of oxygen in our cell and our cell wants to produce ATP molecules, the Pyruvate will enter the matrix of the mitochondria."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And in the matrix, the Pyruvate will be transformed via an irreversible step into acetyl coenzyme A."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And what this step does is it commits the CETL coenzyme A, the derivative of Pyruvate, into one of two different pathways."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We either commit the CETL coenzyme A to undergo the TCA cycle, the citric acid cycle, or also known as trichrobicylic acid cycle to generate those NADH molecules and fadh two molecules to basically form ATP via the electron transport chain."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Or under other conditions, the CETO cola enzyme A can be committed to a second pathway that produces lipids."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And we'll talk more about that in a future lecture."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So we see that the Pyruvate decarboxylation process is a very important step, very crucial step in glucose metabolism because it essentially commits that glucose derivative molecule, the Pyruvate, into carrying out the citric acid cycle or in some cases, lipid synthesis."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, one way by which the cells can actually regulate this pathway is by regulating the enzyme that catalyzes this step."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So remember, Pyruvate decryptoxylation is regulated by an enzyme complex known as Pyruvate dehydrogenase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And this actually consists of three different types of proteins, three different types of enzymes."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We have e one, e two and E three."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, E One is also known as Pyruvate dehydrogenase, e Two is also known as dihydrolypoil acetyl, trans acetylase, and E Three is known as Dihydrolypoil dehydrogenase."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And these three enzymes are found within this complex and they catalyze different steps of Pyruvate degreeboxylation."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, let's suppose in our cell we have plenty of ATP molecules."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And if we have plenty of ATP molecules, that basically means we're going to have plenty of intermediate molecules that are used to actually produce those ATPs."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So we're going to have high levels of NADH and acetylcoenzyme A."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And under such conditions, the CETO coenzyme A will act as an allosteric inhibitor."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "It will bind onto the e two component of this complex and that will inhibit the activity of that complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Likewise, NADH is also an Alstairic inhibitor to the complex because it binds onto the e three location of the complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Also in activating its ability to actually catalyze this pyruvate decreboxylation step."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, in addition to these regulatory pathways in eukaryotic cells, such as the cells of our body, we also have another important regulatory method."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We actually use a type of covalent modification, namely for sporulation, to actually regulate the activity of this complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So in eukaryotic cells, Pyruvate dehydrogenase complex is controlled via phosphorylation, a form of covalent modification."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So let's study this diagram for just a moment."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So this is our Pyruvate dehydrogenase complex in its active form."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And notice it is not phosphorylated."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "But under certain conditions we have a kinase that is actually attached onto the e two component of the complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "This kinase is stimulated and we'll see what stimulates it."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "In just a moment, it is stimulated to transfer a phosphoryl group from ADP from ATP onto the e one component of the complex and that essentially forms this phosphorylated state and that inactivates the activity of e one."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So remember, the e one component of the complex actually catalyzes step one and step two of Pyruvate decarboxylation."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "It essentially stimulates the e one, stimulates oxidative decarboxylation of Pyruvate into that acetyl component to ultimately form that acetyl coenzyme A."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, once we form this phosphorylated state, it is no longer active."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "But under certain circumstances we can inactivate the kinase and activate another molecule known as a phosphatase."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So remember, phosphatase is our enzymes that reverse the effects of kinases."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "They can use water to hydrolyze those bonds, releasing that inorganic phosphate and reforming this initial state of the molecule."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And so in this state, the enzyme is active and can catalyze Pyruvate decarboxylation."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So we see that the complex basically moves back and forth between the active and the inactive state."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And this is the major method by which the cells of our body actually regulate pyruvate carboxylation and in turn regulate the citric acid cycle."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, what types of conditions actually favor this state and what types of conditions actually favor this state?"}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So let's suppose we're in a skeleton muscle cell and in that skeleton muscle cells we are at a resting condition."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So what that means is we're not contracting those skeleton muscle cells and so they're not using ATCP molecules to actually generate those contractions of the actin mice and filaments."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And under such conditions we're going to build up our ATP concentration."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We're going to have a high energy charge value."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Remember, the energy charge basically tells us the relative concentration of ATP."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And if the energy charge is high, we're going to have a high concentration of ATP in our cell."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, if we have plenty of ATP molecules, we're also going to have plenty of intermediate molecules that help us produce those ATPs."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So things like NADH and acetylco enzyme A will also have a high concentration in the cell under resting conditions."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And because under resting conditions we don't actually want to produce any more ATP molecules from the glucose, we want to conserve that glucose."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "What our cells will do is they will actually inactivate Pyruvate decarboxylation."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "How?"}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Well, these acetylco enzymes A, the NADH molecules and the ATP molecules can actually stimulate the kinase attached onto the E two to phosphorylate the E one component of the complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And what that does is it transforms the molecule from the active state into the inactive state."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And now Pyruvate decarboxylation will not take place."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And that means we will conserve the glucose molecules in our body and we will not produce any more ATP molecules."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So once again, to summarize, let's take a look at this diagram."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So in the mitochondrial matrix, we have Pyruvate, which is transformed into acetyl coenzyme A via Pyruvate dehydrogenase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And this is the committed step."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Once we form acetyl coenzyme A, it will be fed into the citric acid cycle where we produce the Nadhs and Fadh twos."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And those high energy electrons on these molecules will move onto the electron transport chain on the inner membrane of the mitochondria to form those high energy ATP molecules."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "But under resting conditions, we don't want to generate these ATP molecules because we already have lots of these ATP molecules to begin with."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And so we want to turn off this pathway."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And one way by which we turn off this pathway is by inhibiting Pyruvate dehydrogenase complex from committing this molecule into the citric acid cycle."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So we see that the kinase phosphorylates this, inactivates this enzyme and that prevents this reactor from actually taking place."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, let's suppose we switch the argument."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Let's suppose now our cells are contracting."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And if the cells are contracting, we are using up ATP molecules and our energy charge value in the cell will drop."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And if the energy charge value drops, we're going to have a relatively high concentration of molecules such as ADP."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And the ADP adenine diphosphate will actually go on and inhibit the activity of kinase."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "In addition, Pyruvate will also inhibit the activity of kinase."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And the kinase found on the E two component will no longer phosphorylate that Pyruvate dehydrogenase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, just because we're no longer phosphorylating this molecule doesn't actually mean the molecule will spontaneously go back into this state."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "We actually have to activate the phosphatase."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, what activates the phosphatase to reverse these effects of the kinase?"}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Well, it's the calcium."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So remember in contracting muscles, when we contract our skeleton muscles, what happens is the calcium that is stored in the sarcoplasm reticulum will be released into the cytoplasm and the calcium is not only used to actually contract those actin myosin filaments."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "But the calcium is also used by this enzyme here."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "When there is a rise in calcium concentrations in the cytoplasm of the skeleton muscle cells, there's also rise in calcium levels in the matrix of the mitochondria."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And that calcium will go on and stimulate the phosphatase to actually defosphorylate this molecule, use a water molecule to hydrolyze this bond, releasing that inorganic orthophosphate and activating our Pyruvate dehydrogenase complex and that will stimulate this process."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "It will basically continually transform the Pyruvate into acetyl coenzyme A and that will commit the molecule to undergoing the citric acid cycle which is ultimately used to generate ATP molecules along the proteins of the inner mitochondria, along that electron transport chain."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So this is how we basically inhibit or activate the activity of Pyruvate dehydrogenase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, the final thing that I'd like to focus on is how there are certain cells of our body which also respond to hormones."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And these hormones essentially stimulate or in some cases don't stimulate the activity of Pyruvate dehydrogenase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So let's focus on epinephrine and insulin."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So, epinephrine is basically released by our body when we're on this stressful situation."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So for instance, when we're trying to run away from some type of scary animal, for instance a bear, and as we're running away, we want to produce lots of ATP molecules to allow the skeleton muscle to actually contract."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And what will begin to happen is the epinephrine molecules will bind until liver cells that will initiate a specific type of signal transduction pathway."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So remember that epinephrine binds unto the beta anginergic receptor of liver cells and that stimulates epinephrine signaling and that ultimately produces a calcium ions and the rise in calcium inside the cell."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "What that basically does is it stimulates the phosphatase molecule and the phosphatase basically hydrolyzes this bond and transforms the inactive molecule into its active state."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And once this is activated, we'll produce plenty of acetyl coenzyme A molecules needed to produce ACP, so we can continue running away from that scary animal, our bear."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, insulin."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So following a meal that's let's suppose rich in carbohydrates, we're going to see that our blood glucose level will rise and liver cells and other cells of the body will try to maintain that glucose level."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So liver cells will respond to insulin by basically activating that phosphatase and activating this Pyruvate dehydrogynase complex."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "So that ultimately all those glucose molecules that are absorbed by the liver cells can be transformed into acetyl coenzyme A."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "And we can produce those ATP molecules."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Now, in other cells of the body, for instance adipose cells, so fast cells, the insulin can also affect these fast cells to actually indirectly stimulate the phosphatase to activate the Pyruvate dehydrogenase complex, to actually produce many more of these acetyl coenzymes A."}, {"title": "Regulation of Pyruvate Decarboxylation .txt", "text": "Because in these fast cells, the acetyl coenzyme A are precursor molecules that are used to actually synthesize lipid molecules."}, {"title": "Introduction to Embryological Development.txt", "text": "During the process of fertilization the xcel fuses with the sperm cell to produce a single diploid, unspecialized cell we call the zygote."}, {"title": "Introduction to Embryological Development.txt", "text": "Now, from one perspective, there's nothing too special about the zygote."}, {"title": "Introduction to Embryological Development.txt", "text": "The zygote is simply a single cell that contains a single nucleus."}, {"title": "Introduction to Embryological Development.txt", "text": "It contains organelles swimming around in the cytoplasm and it also contains the cell membrane that encloses all the organelles and the cytoplasm."}, {"title": "Introduction to Embryological Development.txt", "text": "But from another perspective, the zygote is a very, very special cell."}, {"title": "Introduction to Embryological Development.txt", "text": "And that's because following the formation of the zygote the zygote somehow knows to begin a set of very, very complicated and very intricate processes we call embryological development that allows the zygote to actually eventually develop into the highly specialized and highly complex tissues and organs and systems found within the human body."}, {"title": "Introduction to Embryological Development.txt", "text": "Such as, for example, the cardiovascular system that consists of the hearth and the blood vessels the nervous system that consists of the brain and the spinal cord as well as the other ganglia found in the body."}, {"title": "Introduction to Embryological Development.txt", "text": "It also creates the bone, the kidneys, the pancreas, the liver and many other organs of our body."}, {"title": "Introduction to Embryological Development.txt", "text": "So the question we want to address in this lecture is what exactly allows embryological development to actually take place in the first place?"}, {"title": "Introduction to Embryological Development.txt", "text": "So as it turns out, there are four individual processes that have to work together for embaloglogical development to actually take place the way that it does in our body."}, {"title": "Introduction to Embryological Development.txt", "text": "So these four processes includes cell proliferation, cell growth, cell differentiation and morphogenesis."}, {"title": "Introduction to Embryological Development.txt", "text": "So let's begin with cell proliferation."}, {"title": "Introduction to Embryological Development.txt", "text": "So we know that we begin with a single zygote, a single cell."}, {"title": "Introduction to Embryological Development.txt", "text": "But eventually our body consists of billions of different cells."}, {"title": "Introduction to Embryological Development.txt", "text": "So what cell proliferation means is the zygote, to go from one cell to billions of cells must actually divide via mitosis and cytokinesis."}, {"title": "Introduction to Embryological Development.txt", "text": "So the single cell zygold undergoes mitosis and cytokinesis many, many times until it forms the billions of cells that are found in the adult human organism."}, {"title": "Introduction to Embryological Development.txt", "text": "So we begin with one cell."}, {"title": "Introduction to Embryological Development.txt", "text": "We have one cycle of mitosis."}, {"title": "Introduction to Embryological Development.txt", "text": "We produce two cells."}, {"title": "Introduction to Embryological Development.txt", "text": "Then each of these cells divide."}, {"title": "Introduction to Embryological Development.txt", "text": "We produce four cells and this continues many times until we form the billions of cells found in the dull organism."}, {"title": "Introduction to Embryological Development.txt", "text": "Now, of course, we know that this process all by itself is not enough to actually produce the organism."}, {"title": "Introduction to Embryological Development.txt", "text": "And that's because human beings, for example are not simply a collection of billions of cells not organized in any way."}, {"title": "Introduction to Embryological Development.txt", "text": "We know that we have different types of cells."}, {"title": "Introduction to Embryological Development.txt", "text": "We know that we have different sizes of cells."}, {"title": "Introduction to Embryological Development.txt", "text": "We know that the cells must somehow organize themselves into these highly specialized organs and tissues and systems that carry out specific functions."}, {"title": "Introduction to Embryological Development.txt", "text": "So this process by itself is not alone."}, {"title": "Introduction to Embryological Development.txt", "text": "We also have these other three processes that also take place."}, {"title": "Introduction to Embryological Development.txt", "text": "So cell proliferation increases the number of cells but cell growth actually increases the size of that cell."}, {"title": "Introduction to Embryological Development.txt", "text": "So any given cell could, for example, build more organelles."}, {"title": "Introduction to Embryological Development.txt", "text": "It could build a larger membrane."}, {"title": "Introduction to Embryological Development.txt", "text": "It could also develop more cytoplasm and as a result it will grow in size."}, {"title": "Introduction to Embryological Development.txt", "text": "And so we have a smaller cell but eventually it becomes a larger cell."}, {"title": "Introduction to Embryological Development.txt", "text": "So we have an increase in the number of cells and an increase in the size of that cell because we know in our body we have different sizes and different types of cells."}, {"title": "Introduction to Embryological Development.txt", "text": "Now, what about morphogenesis?"}, {"title": "Introduction to Embryological Development.txt", "text": "Well, morphogenesis is the process by which these single individual cells actually aggregate."}, {"title": "Introduction to Embryological Development.txt", "text": "They organize themselves in a special manner by moving around to produce the many tissues, the organs and the systems of our body."}, {"title": "Introduction to Embryological Development.txt", "text": "For example, if we take a look at the female reproductive system we have different organs involved in the system."}, {"title": "Introduction to Embryological Development.txt", "text": "For example, we have the ovary, we have the fallopian tube."}, {"title": "Introduction to Embryological Development.txt", "text": "We have the uterus and other organs not shown in this diagram."}, {"title": "Introduction to Embryological Development.txt", "text": "And this process by which we have the heap of cells, unorganized heap of cells eventually organize itself into these structures."}, {"title": "Introduction to Embryological Development.txt", "text": "This process is known as morphogenesis."}, {"title": "Introduction to Embryological Development.txt", "text": "Now, cell proliferation, cell growth and morphogenesis is not enough."}, {"title": "Introduction to Embryological Development.txt", "text": "And that's because if we examine, for example the female reproductive system we know that somehow this collection of cells that creates the Ovaries knows its function."}, {"title": "Introduction to Embryological Development.txt", "text": "What the Ovary does is it helps develop that primary follicle into a secondary follicle and the follicle eventually ruptures releasing that xcel, the secondary OASI into another structure known as the fallopian tube."}, {"title": "Introduction to Embryological Development.txt", "text": "And the fallopian tube somehow knows to carry this xcel along the canal where fertilization takes place in this section."}, {"title": "Introduction to Embryological Development.txt", "text": "And then that zygo travels into the uterus and inside the uterus we have that endometrium that the zygote implants into."}, {"title": "Introduction to Embryological Development.txt", "text": "And so the uterus functions to actually provide the nutrition that is needed for that zygote to actually grow."}, {"title": "Introduction to Embryological Development.txt", "text": "So the question is how exactly do these collection of cells know to carry out a specific type of function?"}, {"title": "Introduction to Embryological Development.txt", "text": "Well, this is because of a process known as cell differentiation."}, {"title": "Introduction to Embryological Development.txt", "text": "And what cell differentiation is?"}, {"title": "Introduction to Embryological Development.txt", "text": "It's when a single precursor stem cell basically divides and produces differentiates into many different types of cells."}, {"title": "Introduction to Embryological Development.txt", "text": "And a great example of this differentiation process is our immune system."}, {"title": "Introduction to Embryological Development.txt", "text": "We know that our immune system consists of many different types of cells that have not only different structures and different sizes but also have their own unique function."}, {"title": "Introduction to Embryological Development.txt", "text": "So we have this single stem cell known as the hematopoietic stem cell that produces red blood cells and white blood cells."}, {"title": "Introduction to Embryological Development.txt", "text": "And we have many different types of white blood cells."}, {"title": "Introduction to Embryological Development.txt", "text": "For example, we have macrophages which are these large cells that engulf pathogenic agents and break down those pathogenic agents."}, {"title": "Introduction to Embryological Development.txt", "text": "But macrophages are not the only wide blood cells."}, {"title": "Introduction to Embryological Development.txt", "text": "We also have slightly smaller neutrophils that can also engulf these pathogenic agents."}, {"title": "Introduction to Embryological Development.txt", "text": "We also have natural killer cells that can find infected cells and cancer cells and destroy those cells."}, {"title": "Introduction to Embryological Development.txt", "text": "We also have other cells."}, {"title": "Introduction to Embryological Development.txt", "text": "We have dendritic cells and mass cells which are part of the innate immune system."}, {"title": "Introduction to Embryological Development.txt", "text": "And we have the T lymphocytes and the B lymphocytes as well as basic films and he hasn't phils."}, {"title": "Introduction to Embryological Development.txt", "text": "And in fact, the B lymphocytes and T lymphocytes can even further differentiate into other cells."}, {"title": "Introduction to Embryological Development.txt", "text": "So the B lymphocytes produce the plasma cells and the memory B cells T lymphocytes produce the helper T cells, the memory T cells, cytotoxic T cells and so forth."}, {"title": "Introduction to Embryological Development.txt", "text": "So this process by which a single stem cell somehow divides and produces these specialized cells that carry out a special type of function and eventually organize themselves into this conglomerate these structures we call organs that carry out highly specific and complex functions."}, {"title": "Introduction to Embryological Development.txt", "text": "This process is known as cell differentiation."}, {"title": "Introduction to Embryological Development.txt", "text": "And we need all these four processes cell proliferation, cell growth, morphogenesis and cell differentiation for embryological development to actually take place."}, {"title": "Introduction to Embryological Development.txt", "text": "So in the next several lectures as we continue our discussion on embryological development, let's keep these four processes in mind because they have to work together on a continual basis for embryological development to actually take place."}, {"title": "Introduction to Embryological Development.txt", "text": "For that zygote to eventually develop into the human organism that contains highly specialized organs, tissues and systems that carry out specific types of functions and allow the organism to actually live and survive."}, {"title": "Law of Segregation.txt", "text": "Previously we discussed a very important experiment that was conducted by Gregor Mendel which basically gave rise to the law of dominance, the principle of dominance."}, {"title": "Law of Segregation.txt", "text": "So let's briefly recall what this experiment was."}, {"title": "Law of Segregation.txt", "text": "Let's summarize this experiment."}, {"title": "Law of Segregation.txt", "text": "So what Gregor Mendel did was he crossed a true breeding tall plant with a true breeding short plant."}, {"title": "Law of Segregation.txt", "text": "And every time he tried this experiment he always saw that the f one generation offspring was always tall."}, {"title": "Law of Segregation.txt", "text": "In fact, every time he tried to experiment with other traits he got the same exact result."}, {"title": "Law of Segregation.txt", "text": "He saw that the f one generation offspring always resembled one of the parents and never the other parent."}, {"title": "Law of Segregation.txt", "text": "Now because of this result he posed he asked the following question what exactly happens to the trait for shortness, for the short height within this offspring?"}, {"title": "Law of Segregation.txt", "text": "Does this f one generation offspring lose the trait that gives it the shortness quality?"}, {"title": "Law of Segregation.txt", "text": "Well, to answer that question, what he did was he took the f one generation offspring and he made it it with itself to produce the f two generation offspring."}, {"title": "Law of Segregation.txt", "text": "And what he saw was that although about 75% of the f two offspring were in fact tall the remaining 25 were actually short."}, {"title": "Law of Segregation.txt", "text": "And that meant that this tall f one generation offspring had that shore trait in it all along."}, {"title": "Law of Segregation.txt", "text": "But it was being inhibited, it wasn't actually being expressed."}, {"title": "Law of Segregation.txt", "text": "So because of that, what he proposed was that each one of these plants contain two hereditary factors that code for that given trait."}, {"title": "Law of Segregation.txt", "text": "In this case for that given height."}, {"title": "Law of Segregation.txt", "text": "And nowadays we know that these two hereditary factors are simply the genes found on homologous chromosomes and we'll see exactly what that means in just a moment."}, {"title": "Law of Segregation.txt", "text": "So basically he argued that because this tall f one generation offspring contains that short trade but the short trade is not being expressed."}, {"title": "Law of Segregation.txt", "text": "That means the tall trade is actually dominant over that short trade which is said to be recessive."}, {"title": "Law of Segregation.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Law of Segregation.txt", "text": "So this is the tall true breeding plant."}, {"title": "Law of Segregation.txt", "text": "And what that means is it contains two genes that are both essentially tall."}, {"title": "Law of Segregation.txt", "text": "So we have uppercase T. So we have uppercase dark purple tea and uppercase light purple tea."}, {"title": "Law of Segregation.txt", "text": "Now in this case we have a short plant that is true breeding which means both of these genes are lowercase T and that means they're short, they're recessive."}, {"title": "Law of Segregation.txt", "text": "And so let's suppose we have a red color and we have the orange color for the second lowercase T. Now this is called the law of Dominance."}, {"title": "Law of Segregation.txt", "text": "What he proposed next was the principle of segregation, also became known as the law of segregation or Mendel's law of Segregation."}, {"title": "Law of Segregation.txt", "text": "Now, what he argued was that whenever the gametes are formed before we actually have the mating process take place, the two genes that code for that same trait."}, {"title": "Law of Segregation.txt", "text": "In this case, the height behave like particles and actually separate."}, {"title": "Law of Segregation.txt", "text": "During the process of gamete formation."}, {"title": "Law of Segregation.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Law of Segregation.txt", "text": "So, before they can combine to actually form the offspring, both of these must actually segregate."}, {"title": "Law of Segregation.txt", "text": "They must separate into different compartments into different cells."}, {"title": "Law of Segregation.txt", "text": "For this particular case, we have the dark purple tea going to its own cell, and a light purple tea also go into its own cell."}, {"title": "Law of Segregation.txt", "text": "And so let's suppose this is the male parent."}, {"title": "Law of Segregation.txt", "text": "So this is the male gametes."}, {"title": "Law of Segregation.txt", "text": "The same thing happens here."}, {"title": "Law of Segregation.txt", "text": "Let's say this is the female parent."}, {"title": "Law of Segregation.txt", "text": "So they separate."}, {"title": "Law of Segregation.txt", "text": "They segregate into these individual compartments, individual cells."}, {"title": "Law of Segregation.txt", "text": "Let's call these the female gannettes."}, {"title": "Law of Segregation.txt", "text": "And notice that this means that the gammies are sex cells."}, {"title": "Law of Segregation.txt", "text": "These sex cells right here are formed and only contain one copy of the pair of genes."}, {"title": "Law of Segregation.txt", "text": "So this is the pair of genes."}, {"title": "Law of Segregation.txt", "text": "But each one of these game needs contain a single."}, {"title": "Law of Segregation.txt", "text": "Copy of that pair of genes and notice we actually have no mixing between the genes."}, {"title": "Law of Segregation.txt", "text": "These genes are separate entities, and they separate into these different compartments."}, {"title": "Law of Segregation.txt", "text": "And this separation process that takes place when we actually form the gametes is known as law of segregation."}, {"title": "Law of Segregation.txt", "text": "So this idea that the two hereditary factors our genes for any given trait, in this case, our heights segregate from one another during gammy formation became known as Mendel's law of segregation."}, {"title": "Law of Segregation.txt", "text": "Now, the amazing thing about this discovery was this was basically discovered at the time when we knew nothing about meiosis or Mitosis."}, {"title": "Law of Segregation.txt", "text": "So even though at the time when mendel made the discovery, we knew what gametes were and we knew that gametes must fertilize to form the Zygote."}, {"title": "Law of Segregation.txt", "text": "We knew nothing about how Meiosis takes place and so we knew nothing about how the gametes are actually formed."}, {"title": "Law of Segregation.txt", "text": "So although this was actually correct, it wasn't exactly correct."}, {"title": "Law of Segregation.txt", "text": "Because we knew nothing about meiosis."}, {"title": "Law of Segregation.txt", "text": "So now let's actually try to combine the concept of meiosis with the principle of segregation."}, {"title": "Law of Segregation.txt", "text": "So basically, nowadays we know that segregation is a direct result of the separation of the homologous chromosomes."}, {"title": "Law of Segregation.txt", "text": "That contain the two genes, those two hereditary factors which takes place during the process of meiosis."}, {"title": "Law of Segregation.txt", "text": "So let's basically tweak this slightly to see how it actually takes place."}, {"title": "Law of Segregation.txt", "text": "So let's suppose we have parent number one."}, {"title": "Law of Segregation.txt", "text": "This is parent number one."}, {"title": "Law of Segregation.txt", "text": "And this is parent number two."}, {"title": "Law of Segregation.txt", "text": "So what exactly does the cell look like inside the toll parent?"}, {"title": "Law of Segregation.txt", "text": "The true breeding parent, number one."}, {"title": "Law of Segregation.txt", "text": "So, basically, we have a pair of homologous chromosomes."}, {"title": "Law of Segregation.txt", "text": "Chromosome number one is homologous to chromosome number two."}, {"title": "Law of Segregation.txt", "text": "And what that means is the genes found on this chromosomes are basically homologous."}, {"title": "Law of Segregation.txt", "text": "They code."}, {"title": "Law of Segregation.txt", "text": "For that Same Train that Are Found On this."}, {"title": "Law of Segregation.txt", "text": "So If This Chromosome Carries, let's Say, the Dark Purple Uppercase T, then this One Homologous To It carries The Uppercase Light Purple T. Now, During The Process Of Meiosis, we have replication taking place."}, {"title": "Law of Segregation.txt", "text": "And each one of these are replicated to produce cystochromatids here and cystochromatids here."}, {"title": "Law of Segregation.txt", "text": "So these two are identical?"}, {"title": "Law of Segregation.txt", "text": "These two are identical."}, {"title": "Law of Segregation.txt", "text": "But these are homologous with respect to one another."}, {"title": "Law of Segregation.txt", "text": "Next meiosis one takes."}, {"title": "Law of Segregation.txt", "text": "Place."}, {"title": "Law of Segregation.txt", "text": "And when meiosis one takes place, these are basically pulled to opposite sides to form the two different cells."}, {"title": "Law of Segregation.txt", "text": "And we form the following cells."}, {"title": "Law of Segregation.txt", "text": "And when meiosis two takes place, then these are separated, these cystochromats that are separated, and we form the following four gametes of parent one."}, {"title": "Law of Segregation.txt", "text": "And the same exact thing takes place with parent number two."}, {"title": "Law of Segregation.txt", "text": "Except here we have these two homologous chromosomes that contain genes that code for the short trait."}, {"title": "Law of Segregation.txt", "text": "So we have the lowercase red tea and the lowercase orange tea."}, {"title": "Law of Segregation.txt", "text": "And so we have replication taking place to form these two pairs that now consists of identical fistochromatids then these separate toposite sides, then these separate to form the following four gametes."}, {"title": "Law of Segregation.txt", "text": "And now that we form these two gametes, let's imagine this is the male."}, {"title": "Law of Segregation.txt", "text": "This is the female."}, {"title": "Law of Segregation.txt", "text": "One of the male has to combine with one of the female to basically form that final product that final offspring, the f one generation."}, {"title": "Law of Segregation.txt", "text": "So let's suppose that the upper case t that is light purple mixes with the lowercase t that is red."}, {"title": "Law of Segregation.txt", "text": "So we have the mixing process take place and we form the following zygote."}, {"title": "Law of Segregation.txt", "text": "That eventually gives rise to this f one generation offspring."}, {"title": "Law of Segregation.txt", "text": "And so we have uppercase T, lowercase T. We basically have the following third case."}, {"title": "Law of Segregation.txt", "text": "And since the toll trade is dominant over that short trade, we have the fact that no matter which one of these possibilities we actually obtain, we always get the same exact result."}, {"title": "Law of Segregation.txt", "text": "Because uppercase t is domino or lowercase T, we get the fact that this will always resemble this parent and never this."}, {"title": "Law of Segregation.txt", "text": "Parent."}, {"title": "Law of Segregation.txt", "text": "So notice in this particular example, this t could have mixed with this t to produce possibility one."}, {"title": "Law of Segregation.txt", "text": "Or this t could have mixed with this t to produce possibility two."}, {"title": "Law of Segregation.txt", "text": "Or this could have mixed with this to."}, {"title": "Law of Segregation.txt", "text": "Produce possibility three, which we got in this case, or this t could have mixed with this to produce possibility four."}, {"title": "Law of Segregation.txt", "text": "And we have the same exact proportions, the same exact possibilities when these are mixed."}, {"title": "Law of Segregation.txt", "text": "So basically, this is what we call the law of segregation, and it takes place as a result of meiosis."}, {"title": "Law of Segregation.txt", "text": "So during the process of meiosis, those homologous chromosomes that contain the genes, that code for any given trade."}, {"title": "Law of Segregation.txt", "text": "Basically separate from one another into their identical compartments, into their identical gametes, into to their identical selves."}, {"title": "Law of Segregation.txt", "text": "And this is what we know as the principle or the law of segregation."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Within the cells of our body, the PH ranges from about six eight to about seven four."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So based on that information, we can say that the average PH of our cells is around seven."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, the question is, why exactly do the cells in our body spend so much energy trying to maintain a constant PH of seven?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "And more specifically, how exactly does change, changing the PH inside our cells effect the many different types of biological processes and reactions that take place within those cells?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, what we're going to focus on in this lecture is how increasing the PH inside our nucleus of the cell actually changes the structure of the DNA, how it affects the double helix structure of the DNA, the formation of the double helix."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So let's begin by looking at the following diagram that basically describes the relationship between the PH change and the structure of our DNA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So the x axis is the intracellular PH, the PH inside the cell."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And as we go from left to right, the PH increases."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, the y axis describes the percentage of the DNA molecules that exist in their double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So what exactly does this graph actually tell us?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, we see that at a PH of seven, at a normal PH of seven, all the DNA molecules, 100% of the DNA molecules in the nucleus, exist in their double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, as we begin to add a few drops of hydroxide ions, we begin to increase our PH."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, initially, what happens to our percentage of those molecules that exist in their double helix form?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, initially the slope is essentially flat."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So what that means, the slope is essentially zero."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And initially, changing the PH doesn't really change the amount of DNA molecules that exist in their double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "But as we approach a PH of nine, what we see happen is the slope becomes much more steep and much more negative."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so what that means is between the nine and ten PH values, a small change in the PH in the x value creates a very large change in the y value."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so the majority of those DNA molecules actually break down and associate into their single strand form between the PH nine and PH ten between this range."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And by the time we get to a PH of ten, we see that less than 10% of those DNA molecules inside the nucleus actually exist in their double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we see that by increasing the PH or decreasing the PH, which is not shown in this diagram, our DNA molecules begin to break down into their single strand form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "The question is why?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Why does this actually take place?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "And how does the PH actually affect that structure of the DNA molecule?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "So let's begin by recalling what Ka and PKA is with respect to some hypothetical acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So let's suppose we have the following acid and we know that the acid dissociates into the H plus ion and its conjugate base."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now from basic chemistry we know that the equilibrium constant expression for this particular reaction is given by this equation."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So the ka, the acid dissociation constant ka is equal to the product of the concentration of these two products divided by the concentration of this acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now what exactly does the Ka tell us about the acid?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, the ka is nothing but a ratio between the concentration of the products and the concentration of the reactants."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So the greater the ka is, the greater our numerator is and the more products we form and if we form more products, if we form more H plus ion that means the acid is a much stronger acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so we can say that a higher ka value means more of these H plus ions are produced."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And the stronger the acid is and the stronger the acid is, the more likely it will dissociate and give off and donate that H plus ion."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now normally in chemistry instead of using ka to basically describe the strength of that acid, we use something else called the PKA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And the relation between PKA and Ka is given by this equation."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So PKA is equal to the negative log of the ka."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So from this relation we see that the greater the ka value is, the smaller the PKA is."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And likewise the smaller the K is, the greater the PKA is."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we see that the greater the Ka is, the smaller the PKA is."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And the better that acid is, the more likely that it will donate that H plus ion."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And likewise the smaller our Ka is, the larger the PKA is and the less likely our acid will actually donate that H plus ion."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So a smaller PKA means the acid is strong and it will be very likely to donate that H plus ion."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So that is what we mean by the PKA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "The PKA basically used to describe the strength of that acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now what are the acids that exist within our DNA?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, if we actually examine the bases within our double helix structure, some of the bases can act as acids."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So let's take a look at Guanine for example."}, {"title": "pH disrupts double helix of DNA.txt", "text": "This hydrogen attached to this nitrogen can actually act as an acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And what that means is at a certain particular PH it will begin to dissociate and give off that age."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And when it dissociates it forms the depronative version of Guanine in which this age has been removed."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And the two electrons in that covalent bond have now gone on to that nitrogen."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so we produce a negative charge here and a positive charge here."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And this is basically equivalent to this equation here, where the H is this H here and the A is this entire molecule here and the Ha is this molecule here."}, {"title": "pH disrupts double helix of DNA.txt", "text": "But for this particular reaction the PKA is equal to 9.7."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now what 9.7 means is it's a relatively large value, it's relatively positive."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so, this isn't a very good acid."}, {"title": "pH disrupts double helix of DNA.txt", "text": "But if the PH is driven high enough, it will become a good acid in a sense that it will readily dissociate and give off that H atom."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, why is that a problem?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, that's a problem because this H atom actually associates with the other complementary base to form a hydrogen bond."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And the hydrogen bonds within our DNA hold the two strands of DNA together."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, before we examine that in more detail, let's answer the following question."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, what can we say about guanine, when the PH inside our nucleus of the cell is equal to the PKA of the guanine molecule?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, let's suppose, we look at the following curve."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And along the curve, if we examine the PH of PKA of 9.7."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, if we're somewhere here, we see that the majority of these DNA molecules have dissociated."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Why?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, to answer this question, let's actually said these two equal to each other."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we know that the PH of our solution is equal to PKA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, PKA is equal to this equation negative log of ka, and ka is equal to the ratio of these two."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so, if we plug in the right side into the ka here on the right side of this equation, we basically get this."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, negative log of ka, and ka is equal to this ratio."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, we replace ka with this ratio."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, what is the PH?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, PH by definition is equal to the negative log of the concentration of the hydrogen ions."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, we replace PH with this."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, algebraically, we see that on both sides we have a negative."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so we multiply both sides by negative one to cancel that negative."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And we also see on both sides we have the lock function."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, if we raise both of these to the power of ten, or actually if we do this, we see that the log will basically cancel out."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so, all we get is this concentration of the hydrogen ion is equal to the ratio of these two guys."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so, we see that the negatives cancel and the logs cancel and we're simply left with this relationship."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, the concentration of our hydrogen ion, this is equal to the product of the concentration of the H plus ion and the a divided by the concentration of ha."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, the H plus appears on both sides."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so, we can cancel that out."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And then, if we bring this side to the left, this denominator to the left side, we get the following equality."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, we see that when the PH is equal to the PKA, when the PH of our solution inside the cell is equal to 9.7."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So, somewhere about here, we see that the concentration of the ha is equal to the concentration of the a."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, what is ha in this case?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, H A we said is the guanine."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And our a is basically this deproynated guanine."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we see that at a PH of 9.7."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So this is about 9.7."}, {"title": "pH disrupts double helix of DNA.txt", "text": "We see that exactly half of the guanine molecules within the DNA are going to be deprotonated."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, why is that bad?"}, {"title": "pH disrupts double helix of DNA.txt", "text": "Well, that's bad because there is this hydrogen bond that exists between this age atom and this nitrogen atom of the complementary base cytosine."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And if we remove this age then we basically disrupt that hydrogen bond."}, {"title": "pH disrupts double helix of DNA.txt", "text": "The hydrogen bond cannot form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "In fact, we have a negative charge here and a partially negative charge here and those two like charges will basically repel one another."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so what happens is they will begin to dissociate."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And that's exactly why at around this range we see a tremendous decrease in the number of DNA molecules that exist in a double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Because around this PH, half of these guanine have lost their age and have been deprotonated."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, they cannot form those stabilizing hydrogen bonds."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So when the PH of the cell equals the PKA of guanine, so when the PH is 9.7, the concentration of the protonated guanine will equal to the concentration of deprotonated guanine."}, {"title": "pH disrupts double helix of DNA.txt", "text": "That is exactly half of the guanine bases will be deprotonated."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, that's a problem because guanine participates in hydrogen bonds which are responsible for holding the two strands of DNA together."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And as we increase the PH, we basically decrease the amount of h bonds because we decrease the number of h atoms on the guanine and that destabilizes that entire double helix structure of DNA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "And so within this range we see this very drastic decrease in the number of DNA molecules that exist in a double helix form because all those guanian molecules lose that h atom."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we see within this range we have a very, very drastic change in the y value in the percent of those DNA molecules that exist in a double helix form."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So we see that this is precisely why the cells of our body spend so much energy trying to maintain a constant PH value."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Because decreasing or increasing the PH will affect all the different types of biological processes that take place inside our cells."}, {"title": "pH disrupts double helix of DNA.txt", "text": "Now, by the way, in this case, in this example, we focus on increasing our PH."}, {"title": "pH disrupts double helix of DNA.txt", "text": "But the same effect or similar effect is seen if we decrease the PH."}, {"title": "pH disrupts double helix of DNA.txt", "text": "If we decrease the PH, then what we end up doing is we end up protonating, some of those atoms that are involved in forming hydrogen bonds and that also disrupts our bonding between the two strands of DNA."}, {"title": "pH disrupts double helix of DNA.txt", "text": "So not only will increasing the PH disrupt the double structure of the DNA, but also decreasing the PH will have the same, similar effect on the structure of the DNA."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Previously, we discussed 15 of the 20 amino acids that make up the proteins found in the human body."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So we spoke about the eight hydrophobic amino acids."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "We spoke about the five polar but uncharged amino acids, and we also discussed the two special cases, proline and glycine."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now let's discuss the five remaining amino acids."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And the special thing about these these five remaining amino acids is they all contain a full charge on their side chain groups at the normal physiological PH."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And that's exactly what makes them very highly hydrophilic, because they have that full charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, Lysine, Arginine, and histidine are basic amino acids."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is their side chain groups at the normal physiological PH bears a full positive charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "On the other hand, aspartate and glutamate are the two acidic amino acids."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is their side chains bear full negative charge at the normal physiological PH of around seven."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So let's begin with Lysine."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, Lysine contains the following relatively long side chain group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So we have 1234 of these carbon atoms, and each one of these carbon atom has two h atoms."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, at the terminal end of the side group, we have a primary amino group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is we have a nitrogen that is bound to a single carbon, as shown in the following diagram."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, all of these Lysine amino acids at the normal physiological PH of around seven have a full positive charge on that nitrogen."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And that's because to actually deprotonate our nitrogen, we really have to increase our PH."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "We have to make it basic, because the PKA value of this nitrogen is ten."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Remember, what the PKA means is if the PH is equal to the PKA, then that is the point at which half of these molecules are deprotonated and half of them are protonated."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So if we're below the PKA of ten at the physiological PH of seven, that means all of these Lysine amino acids will be protein."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "It will have a full positive charge on the nitrogen."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "That's exactly what makes Lysine a basic amino acid."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "It has a full positive charge on that side chain group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, let's move on to Arginine."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Arginine, just like Lysine, also contains this relatively long side chain group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "But instead of having this primary amino group, the group here is known as the guanidinium group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And the guanidinium group has an even higher PKA value."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "This is equal to a PKA of 12.5."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is all of these side chain groups, for all of these arginine at the normal physiological PH of seven, will be protein, will have a full positive charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, unlike in this case, in this case, the positive charge is delocalized among different atoms, and that stabilizes this molecule."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So this molecule is, in fact, resonant stabilized."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And finally, let's look at histidine."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, we saw that Lysine and Arginine are always positively charged at the physiological PH of around seven."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "The thing about histidine is, even though it is basic, it bears a full positive charge on that side chain group."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "It can also sometimes be neutral at the physiological PH of around seven."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "That's because, unlike in this case, in this case, the PKA value here is around six."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is histidine can exist in his protonated or deprotonated state at a neutral PH."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And this really depends on what the local environment is and what the local conditions are around this amino acid."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, this group here is known as the immediazel group, and it has a PKA of 6.0."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, which one of these atoms will gain that H atom and be protonated?"}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Well, it's this nitrogen here."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So at the physiological PH, this is the nitrogen that can be protonated."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And so when this is protonated, we basically gain a positive charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And that positive charge can be delocalized among this region here."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So if this gains an H atom, then what happens is this is delocalized among these two atoms, and there will be a positive charge that is delocalized."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And so this is also resonant stabilized, just like the argument, because this is essentially an aromatic ring."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, the thing about histidine, because it contains a lower PKA, and because it can be protonated or deprotonated at the physiological PH, this is a very common amino acid that exists in the active sites of enzymes."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Remember, an enzyme is a biological catalyst that speeds up different reactions, and the active side is the location on that enzyme where that reaction actually takes place."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So histidine is very commonly found in the active sites of many different enzymes, as we'll see in our study of biochemistry."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So we have Lysine and Arginine, which are always positively charged on their side chain groups at the physiological PH of seven, histidine, which is also basic, like Lysine, Arginine."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "But the thing about HistoGene is it can either be positively charged or neutral at the normal physiological PH."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, let's move on to the two acidic amino acids, aspartate and glutamate."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So what do we mean by acidic amino acids?"}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Well, acidic simply means that the side chain groups will have a full negative charge at the normal physiological PH, and that's because the PKA value of the side chains will be relatively low, will be below seven."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So if we examine the PKA value of the side chain groups in Aspartate and Glutamate, the PKA value is 4.1."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And what that means is, below 4.1, these groups are very likely to be protonated."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "But above 4.1, these groups are very likely to be deprotonated."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And so at a physiological PH of around seven, these two groups will exist in their deprotonated state."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And these two groups are known as the carboxylate ion groups."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And so they will bear a full negative charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And that full negative charge will be delocalized among these two electronegative oxygen atoms."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And that will be a stabilizing effect now, the only difference between these two amino acids is in this particular case, we have an extra carbon."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "In this case, we have one less carbon, as in this case."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, when we are below the PTA value of 4.7, or actually, when we are below the PH value of 4.7, these are going to be protonated."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "Now, when this is protonated, we no longer call it aspartate."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "We call it aspartic acid."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So aspartate refers to our amino acid form that exists in the physiological PH of around seven."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So this, in its deprotonated form, is known as aspartate."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "But if we protonate this, then it's called aspartic acid."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And likewise, in its deprotonated state, we call it glutamate."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "But in its protonated state, we call it glutamic acid."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "So these are the two acidic amino acid acids, while the other two, or the other three, are basic amino acids."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "And once again, these five amino acids are very highly hydrophobic because they bear a full charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "In this case, it's a full positive charge."}, {"title": "Basic and Acidic Amino Acids .txt", "text": "In this case, it's a full negative charge."}, {"title": "Respiration in the Lungs .txt", "text": "Our lungs are the primary organs of our respiratory system and they function in the process of breathing."}, {"title": "Respiration in the Lungs .txt", "text": "Now, breathing is a simple process of inhaling oxygen and exhaling carbon dioxide."}, {"title": "Respiration in the Lungs .txt", "text": "And breathing is also known as ventilation or respiration."}, {"title": "Respiration in the Lungs .txt", "text": "Now, this respiration process is not the same thing as cellular respiration that takes place within the individual cells of our body."}, {"title": "Respiration in the Lungs .txt", "text": "Cellular respiration is when our cell uses oxygen to produce ATP and produces carbon dioxide as a byproduct."}, {"title": "Respiration in the Lungs .txt", "text": "But respiration is simply the breathing process, the process by which we inhale oxygen and we exhale."}, {"title": "Respiration in the Lungs .txt", "text": "We expel our carbon dioxide."}, {"title": "Respiration in the Lungs .txt", "text": "So our lungs are specialized organs that are responsible for carrying out this process of breathing."}, {"title": "Respiration in the Lungs .txt", "text": "So inside our lung, inside the lungs, we have many tiny microscopic, specialized saclike structures we call alveoli."}, {"title": "Respiration in the Lungs .txt", "text": "And these alveoli are specialized in exchanging oxygen for carbon dioxide."}, {"title": "Respiration in the Lungs .txt", "text": "And the lungs ultimately expelled that carbon dioxide to the outside of our body, to the outside environment."}, {"title": "Respiration in the Lungs .txt", "text": "Now, the question we're going to explore and answer in this lecture is how the process of breathing, how the process of ventilation actually takes place inside our lungs."}, {"title": "Respiration in the Lungs .txt", "text": "So we're going to describe the mechanism by which ventilation is carried out inside human lungs."}, {"title": "Respiration in the Lungs .txt", "text": "Now, let's begin by breaking down the process of ventilation into two stages, into two processes."}, {"title": "Respiration in the Lungs .txt", "text": "We have the process of inhalation and the process of exhalation."}, {"title": "Respiration in the Lungs .txt", "text": "And these two processes are actually opposite with respect to one another."}, {"title": "Respiration in the Lungs .txt", "text": "Inhalation is when we bring air into the lungs."}, {"title": "Respiration in the Lungs .txt", "text": "And exhalation is the process by which we expel the air from the lungs into the outside environment."}, {"title": "Respiration in the Lungs .txt", "text": "And more specifically, inhalation, we bring in oxygen and exhalation we expel, we remove the carbon dioxide that is produced inside our cells as a result of a byproduct of, let's say, cellular respiration, which once again, is not the same thing as respiration breathing that we're focusing on in this lecture."}, {"title": "Respiration in the Lungs .txt", "text": "So let's begin by describing how inhalation is carried out by the lungs."}, {"title": "Respiration in the Lungs .txt", "text": "So let's take a look at the following diagram."}, {"title": "Respiration in the Lungs .txt", "text": "Now, in this diagram, we have our respiratory system."}, {"title": "Respiration in the Lungs .txt", "text": "We have the windpipe, also known as the trachea, which by furcates at the bottom, it breaks down, it splits into the right bronchi and the left bronchi."}, {"title": "Respiration in the Lungs .txt", "text": "And these bronchi connect to the right and our left lung."}, {"title": "Respiration in the Lungs .txt", "text": "So the right lung and our left lung."}, {"title": "Respiration in the Lungs .txt", "text": "Now remember, the lungs are actually enclosed in a double layer structure known as our pleura."}, {"title": "Respiration in the Lungs .txt", "text": "So the outer membrane of the pleura is known as the parietal pleura."}, {"title": "Respiration in the Lungs .txt", "text": "And the inner membrane of the pleura is known as the visceral pleura."}, {"title": "Respiration in the Lungs .txt", "text": "And in between these two membranes, we have the space we call intraplural space, or our intraplural cavity."}, {"title": "Respiration in the Lungs .txt", "text": "And inside this cavity, we basically have a special type of fluid that decreases the friction that exists as a result of that process of breathing."}, {"title": "Respiration in the Lungs .txt", "text": "Now, these structures are basically the ribs and this is our ribcage."}, {"title": "Respiration in the Lungs .txt", "text": "Now, in between the ribs, we have these red portions, and that is the external intercostal muscle, a type of skeletal muscle."}, {"title": "Respiration in the Lungs .txt", "text": "And beneath the lungs, we have another type of skeletal muscle we call the diaphragm."}, {"title": "Respiration in the Lungs .txt", "text": "The diaphragm is basically a dome shaped skeletal muscle that is found below the lungs and which separates the thoracic cavity, the chest cavity, where the lungs are found, and our abdominal cavity, which is found beneath our diaphragm."}, {"title": "Respiration in the Lungs .txt", "text": "So let's describe how inhalation actually takes place."}, {"title": "Respiration in the Lungs .txt", "text": "So the diaphragm, as well as these external intercostal muscles found between our ribs, begin to actually use ATP and contract."}, {"title": "Respiration in the Lungs .txt", "text": "So the process of inhalation is an active process because it requires using ATP for muscle contraction."}, {"title": "Respiration in the Lungs .txt", "text": "Now, as the diaphragm begins to contract, it begins to flatten out."}, {"title": "Respiration in the Lungs .txt", "text": "So it moves in the following general direction."}, {"title": "Respiration in the Lungs .txt", "text": "Now, the diaphragm is actually connected to the chest cavity, our thoracic cavity."}, {"title": "Respiration in the Lungs .txt", "text": "And as the diaphragm flattens down, it increases the space inside our chest cavity."}, {"title": "Respiration in the Lungs .txt", "text": "It increases the volume inside that chest cavity."}, {"title": "Respiration in the Lungs .txt", "text": "Now, as the external intercostal muscles contract, they also increase the space inside our chest cavity."}, {"title": "Respiration in the Lungs .txt", "text": "And that's because as these muscles contract, they essentially increase our rib cage size."}, {"title": "Respiration in the Lungs .txt", "text": "They move the ribcage outward, and that increases the overall space inside our thoracic cavity, inside the chest cavity."}, {"title": "Respiration in the Lungs .txt", "text": "Now, in the same time that the space inside the chest cavity increases, what also increases is the space inside the intraplural space."}, {"title": "Respiration in the Lungs .txt", "text": "So the volume inside this entire region that is found between the parietal and the visceral plural, basically increases."}, {"title": "Respiration in the Lungs .txt", "text": "Now, let's recall Boils Law."}, {"title": "Respiration in the Lungs .txt", "text": "We know that in physics, boyle's Law describes the relationship between volume and pressure when the temperature is held constant."}, {"title": "Respiration in the Lungs .txt", "text": "And because our body is at a constant temperature of 36.7 degrees Celsius, we can assume that this obeys Boil Law, meaning the temperature is constant."}, {"title": "Respiration in the Lungs .txt", "text": "Now, Boyle's Law tells us that the pressure multiplied by the volume is equal to a constant value."}, {"title": "Respiration in the Lungs .txt", "text": "And that gives us an inverse relationship between pressure and volume."}, {"title": "Respiration in the Lungs .txt", "text": "So as the volume increases inside the intraplural space, by Boils Law, the pressure must decrease."}, {"title": "Respiration in the Lungs .txt", "text": "Now, what exactly is the pressure inside the lungs?"}, {"title": "Respiration in the Lungs .txt", "text": "Well, the pressure inside this space of our lungs is known as the intrapulmonary pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And the intrapulmonary pressure is the same as the atmospheric pressure because the lungs are actually exposed to our environment."}, {"title": "Respiration in the Lungs .txt", "text": "And what that means is, inside our lungs, if the pressure outside the body is, let's say, one atmospheric pressure, then the pressure inside the lungs is also one ATM."}, {"title": "Respiration in the Lungs .txt", "text": "Now, as our diaphragm flattens down and as the ribcage increases, that increases the volume inside the intraplural space, and that decreases the pressure inside that space."}, {"title": "Respiration in the Lungs .txt", "text": "And eventually, the pressure inside the space will basically decrease to a point where it will be lower than the pressure inside our lungs than atmospheric pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And at this point, there exists a pressure gradient, a difference in pressure, such that inside the intraplural space, we have a low pressure and in the outside of our body and inside the lungs, we have a higher pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And at that particular point, when the intralural space has a pressure that is lower than the pressure inside the intrapulmonary area, then our air will begin to move down its gradient, down the pressure gradient from a high pressure to a low pressure."}, {"title": "Respiration in the Lungs .txt", "text": "So, in the same exact way that a marker or any other mass will always move down its potential gradient, gravitational potential gradient, from a high potential to a low potential, molecules, air molecules will also always move from a higher pressure to a low pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And that's exactly why when the diaphragm flattens down and when the external intercoastal muscles contract and expand the ribcage, that increases the volume and decreases the pressure inside the intraplural space."}, {"title": "Respiration in the Lungs .txt", "text": "And that creates a pressure difference, also known as a pressure differential or negative pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And now our air molecules move from a high pressure from the outside to the inside into our lungs."}, {"title": "Respiration in the Lungs .txt", "text": "Now, actually, I don't like using this term called negative pressure because it's misleading."}, {"title": "Respiration in the Lungs .txt", "text": "We know from physics that pressure is simply the force that molecules exert on a certain area."}, {"title": "Respiration in the Lungs .txt", "text": "Now, if we are inside a container and inside that container we have no molecules, then the absolute pressure inside that container is zero."}, {"title": "Respiration in the Lungs .txt", "text": "Now, what exactly is negative pressure?"}, {"title": "Respiration in the Lungs .txt", "text": "Well, negative pressure means inside our container we must have negative number of molecules."}, {"title": "Respiration in the Lungs .txt", "text": "And of course, that's impossible."}, {"title": "Respiration in the Lungs .txt", "text": "How can we have a negative number of molecules inside a container?"}, {"title": "Respiration in the Lungs .txt", "text": "The smallest number of molecules that we can have inside a container is zero."}, {"title": "Respiration in the Lungs .txt", "text": "In that case, we have a vacuum and our pressure is zero."}, {"title": "Respiration in the Lungs .txt", "text": "But we can never actually have negative pressure."}, {"title": "Respiration in the Lungs .txt", "text": "Now, technically, what they mean when they say negative pressure is a negative pressure difference and what a negative pressure difference is, when we subtract the high pressure and the low pressure, we get a negative value because the change in pressure values is a negative quantity."}, {"title": "Respiration in the Lungs .txt", "text": "So you should be careful in using this term negative pressure because negative pressure doesn't make sense."}, {"title": "Respiration in the Lungs .txt", "text": "But negative pressure difference does, in fact, make sense."}, {"title": "Respiration in the Lungs .txt", "text": "So let's take a look at the following diagram, which describes what I just discussed."}, {"title": "Respiration in the Lungs .txt", "text": "So this diagram describes the curve for Boils Law."}, {"title": "Respiration in the Lungs .txt", "text": "So the y axis is the pressure inside the intraplural space and the x axis is the volume inside that intraplural space."}, {"title": "Respiration in the Lungs .txt", "text": "And this curve describes Boils Law PV multiplied by constant, where v is the volume is equal to a constant, where vs the volume, and p is our pressure."}, {"title": "Respiration in the Lungs .txt", "text": "So when we essentially inhale the diaphragm flattens down, the ribcage expands as a result of the external intercostal muscles contracting."}, {"title": "Respiration in the Lungs .txt", "text": "And we basically move down the following curve from the initial point where we're fully relaxed to this final point on the curve where we're fully contracted."}, {"title": "Respiration in the Lungs .txt", "text": "So fully relaxed and fully contracted."}, {"title": "Respiration in the Lungs .txt", "text": "Now, as we move down the volume inside the space increases and that decreases the pressure inside the intraplural space."}, {"title": "Respiration in the Lungs .txt", "text": "Eventually, the pressure at the end of the contraction is less than the atmospheric pressure that is given by the following blue line."}, {"title": "Respiration in the Lungs .txt", "text": "At that point, we have this difference in pressure known as the pressure difference or the negative pressure difference."}, {"title": "Respiration in the Lungs .txt", "text": "And that creates that pressure gradient that is needed to actually allow the movement of the air from the outside environment and into our lungs."}, {"title": "Respiration in the Lungs .txt", "text": "At this point, air rushes into the lungs and inhalation actually takes place."}, {"title": "Respiration in the Lungs .txt", "text": "And once again, inhalation is an active process."}, {"title": "Respiration in the Lungs .txt", "text": "It needs ATP because our muscles need ATP to actually contract."}, {"title": "Respiration in the Lungs .txt", "text": "Now, once the lungs are filled with air, the individual alveoli of the lungs essentially exchange the carbon dioxide and oxygen."}, {"title": "Respiration in the Lungs .txt", "text": "We take an oxygen into the capillaries of our body and we expel our carbon dioxide from the capillaries and to our lungs, eventually expelling them to the outside."}, {"title": "Respiration in the Lungs .txt", "text": "Now, once we exchange the oxygen for carbon dioxide, how exactly does exhalation actually take place?"}, {"title": "Respiration in the Lungs .txt", "text": "Well, once we're at this stage, what happens is the diaphragm and these intercoastal, external intercostal muscles begin to relax."}, {"title": "Respiration in the Lungs .txt", "text": "And as they begin to relax, we're essentially moving in the opposite direction along the following curve."}, {"title": "Respiration in the Lungs .txt", "text": "So the diaphragm begins to recreate the following dome shape and that pushes on our cavity and it pushes on the space inside."}, {"title": "Respiration in the Lungs .txt", "text": "And the Rift cage, as it basically decreases in size, it also forces our volume inside the intraplural space to decrease."}, {"title": "Respiration in the Lungs .txt", "text": "And by Boils law, when we decrease our volume, we increase our pressure as long as the temperature is allowed to be constant."}, {"title": "Respiration in the Lungs .txt", "text": "And so what happens is, because the pressure inside our intraplural space drops, eventually the pressure inside the intraplural space at the end of that relaxation where when we're at this point, the pressure inside the intraplural space will be greater than the pressure outside of our environment so outside of the body and inside the lung."}, {"title": "Respiration in the Lungs .txt", "text": "And in that case, that pressure gradient will force the air to move from the lungs to the outside."}, {"title": "Respiration in the Lungs .txt", "text": "And at that point, these two quantities are switched."}, {"title": "Respiration in the Lungs .txt", "text": "So when we're exhaling, the pressure inside the intraplural space is greater than the pressure in the outside environment, our atmosphere pressure."}, {"title": "Respiration in the Lungs .txt", "text": "And so at that point, when we're right here, we have exhalation taking place."}, {"title": "Respiration in the Lungs .txt", "text": "So this is the process by which our lungs carry out the process of breathing."}, {"title": "Respiration in the Lungs .txt", "text": "This is the mechanism by which the lungs carry out the process of breathing."}, {"title": "Activation of Fatty Acids .txt", "text": "So we know that triglycerides are fuel molecules."}, {"title": "Activation of Fatty Acids .txt", "text": "But before the cells of our body can actually use the potential energy that is stored in the chemical bonds of triglyceride molecules, the triglyceride molecules have to undergo three important processes, three important stages."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, in the previous lecture, we discussed stage one, and we said that in stage one, the adipose cells that store the triglycerides actually have to release those fatty acids."}, {"title": "Activation of Fatty Acids .txt", "text": "So they essentially break down and mobilize the triglycerides into free floating fatty acids and glycerol molecules and then release the fatty acids into the blood plasma of our body."}, {"title": "Activation of Fatty Acids .txt", "text": "And once inside the blood plasma, a carrier protein molecule known as serum albumin picks up these fatty acids and then brings them to target cells."}, {"title": "Activation of Fatty Acids .txt", "text": "So let's suppose we have some type of target cell, let's say a muscle cell, and this is a cell membrane of that target cell."}, {"title": "Activation of Fatty Acids .txt", "text": "So in stage two, once the fatty acids are brought into the cytoplasm of that target cell, that cell needs to activate the fatty acids and then transport the fatty acids into the matrix of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "Why is it the matrix?"}, {"title": "Activation of Fatty Acids .txt", "text": "Well, because in stage three, within the matrix, those fatty acids are actually broken down into acetyl coenzyme A molecules."}, {"title": "Activation of Fatty Acids .txt", "text": "And then these acetyl coenzyme A molecules are fed into the citric acid cycle and that helps the cell generate ATP molecules."}, {"title": "Activation of Fatty Acids .txt", "text": "So what I'd like to focus on in this lecture is stage two."}, {"title": "Activation of Fatty Acids .txt", "text": "So the activation of the fatty acids and the subsequent transport into the matrix of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "So, as we go through the following text, let's use this diagram as our reference."}, {"title": "Activation of Fatty Acids .txt", "text": "So let's suppose the fatty acid makes its way into the cytoplasm of the target cell."}, {"title": "Activation of Fatty Acids .txt", "text": "What happens next?"}, {"title": "Activation of Fatty Acids .txt", "text": "Well, the first thing that has to happen is a special type of enzyme found on the outer membrane of the mitochondria known as fatty acidicinase, or sometimes acyl coenzyme synthetase, has to actually activate the fatty acid."}, {"title": "Activation of Fatty Acids .txt", "text": "And it activates the fatty acid by ultimately creating a thio ester bond between the sulfur atom on the coenzyme molecule and the carbon atom on that fatty acid."}, {"title": "Activation of Fatty Acids .txt", "text": "So in a two step process, the enzyme fatty acid thy kinase catalyzed the formation of a thyroid bond between the carboxyl group of the fatty acid and the sulfur group of that coenzyme aid."}, {"title": "Activation of Fatty Acids .txt", "text": "So let's take a look at this two step process and let's begin with step one."}, {"title": "Activation of Fatty Acids .txt", "text": "So, in step one, we actually use an ATP molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "And what this enzyme does is the enzyme catalyze the transfer of an adenosine monophosphate group from the ATP and onto this fatty acid."}, {"title": "Activation of Fatty Acids .txt", "text": "And that generates an intermediate molecule known as acyl adenylate."}, {"title": "Activation of Fatty Acids .txt", "text": "In the process, it also releases a Pyrophosphate."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, this Pyrophosphate here actually plays a very important role in this reaction."}, {"title": "Activation of Fatty Acids .txt", "text": "What's its role?"}, {"title": "Activation of Fatty Acids .txt", "text": "Well, basically, inside a cytoplasm, we also have an enzyme known as Pyrophosphatase."}, {"title": "Activation of Fatty Acids .txt", "text": "And what Pyrophosphatase does is it acts on the pyrophosphate."}, {"title": "Activation of Fatty Acids .txt", "text": "It essentially hydrolizes the bond in the Pyrophosphate."}, {"title": "Activation of Fatty Acids .txt", "text": "And that generates two orthophosphate molecules."}, {"title": "Activation of Fatty Acids .txt", "text": "And this hydrolysis of the Pyrophosphate that is produced in step one basically makes this reaction product favored."}, {"title": "Activation of Fatty Acids .txt", "text": "It drives this reaction forward."}, {"title": "Activation of Fatty Acids .txt", "text": "So in the first step, an ATP molecule is used to transfer AMT onto the fatty acid."}, {"title": "Activation of Fatty Acids .txt", "text": "This releases a Pyrophosphate molecule, which subsequently hydrolyzes into orthophosphate, and this drives the reaction forward."}, {"title": "Activation of Fatty Acids .txt", "text": "That's why this step here is important."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, once we form the acoladenolate, it then acts as a reactive molecule in step two."}, {"title": "Activation of Fatty Acids .txt", "text": "And in step two, this entire fatty acid is actually bound onto the active side of the enzyme."}, {"title": "Activation of Fatty Acids .txt", "text": "And then a coenzyme molecule comes in and acts as a nucleophile and attacks the carbon."}, {"title": "Activation of Fatty Acids .txt", "text": "And it forms a thiolacid bond between this sulf hydro group of the coenzyme and this carbon here."}, {"title": "Activation of Fatty Acids .txt", "text": "And that generates the acyl coenzyme A molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "In the process, it also displaces and kicks off that adenosine monophosphate molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "So if we sum up these reactions, this will be the net reaction that we have."}, {"title": "Activation of Fatty Acids .txt", "text": "On the reactant side, we have that incoming fatty acid, an ATP molecule that is used here."}, {"title": "Activation of Fatty Acids .txt", "text": "We have the coenzyme A that is used here."}, {"title": "Activation of Fatty Acids .txt", "text": "And then we have a water molecule that is used in this hydrolysis reaction."}, {"title": "Activation of Fatty Acids .txt", "text": "On the product side, we have this acyl coenzyme A molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "We have the amp molecule, two orthophosphates, and then we have the two H plus ions."}, {"title": "Activation of Fatty Acids .txt", "text": "And notice this molecule doesn't actually show up because it acts as an intermediate."}, {"title": "Activation of Fatty Acids .txt", "text": "When we sum up these molecules, these two molecules actually cancel out."}, {"title": "Activation of Fatty Acids .txt", "text": "And so that intermediate will not appear in this overall net reaction."}, {"title": "Activation of Fatty Acids .txt", "text": "So this is basically a two step process in which the cells basically activate the fatty acid molecule and prepared for transfer into the matrix of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, once we form that acyl coenzyme A, the next step is to basically transfer or the next step is to transport it into the matrix of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, before the acyl coenzyme A molecule can actually be transferred, it has to be converted into another molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "And an important molecule that is used in this step is carnitine."}, {"title": "Activation of Fatty Acids .txt", "text": "So carnitine is essentially made from two different amino acids, and it's an alcohol molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "More specifically, it's a zvitorion alcohol molecule."}, {"title": "Activation of Fatty Acids .txt", "text": "And that means it contains a positive charge on one side and a negative charge on the other side."}, {"title": "Activation of Fatty Acids .txt", "text": "So this is what carnitine actually looks like."}, {"title": "Activation of Fatty Acids .txt", "text": "And what the carnitine does is it reacts with the acyl coenzyme A and it kicks off that coenzyme A component, and the carnitine basically replaces that coenzyme A."}, {"title": "Activation of Fatty Acids .txt", "text": "And what happens is we have a bond that is formed between this carbon and this oxygen on the carbonsine."}, {"title": "Activation of Fatty Acids .txt", "text": "So the carbonne contains a negative charge on the carboxylate group, a positive charge on this quarterinary nitrogen, and we also have this alcohol group."}, {"title": "Activation of Fatty Acids .txt", "text": "And the oxygen of the alcohol forms a bond with the carbon of this carbonyl group of the Acyl coenzyme A."}, {"title": "Activation of Fatty Acids .txt", "text": "And so we kick off that coenzyme A, and we form a molecule known as Acyl carnitine."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, this particular reaction is actually catalyzed by an enzyme found on the outer membrane of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "So just like fatty acetikinase, it's found on the outer membrane of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "This enzyme known as carnitine Acyl transferates one, is also found on the outer membrane of the mitochondria, and it catalyzes the formation of the Acyl carnatine."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, why do we need to form Acyl carnitine?"}, {"title": "Activation of Fatty Acids .txt", "text": "Well, because we have an enzyme found on the inner membrane of the mitochondria known as translocase."}, {"title": "Activation of Fatty Acids .txt", "text": "And this is this enzyme shown in orange."}, {"title": "Activation of Fatty Acids .txt", "text": "And this translocase allows the movement of asyl carnitine molecules across the inner membrane of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "So we form the Acyl carnitine to actually be able to shuttle that molecule into the matrix of the mitochondria."}, {"title": "Activation of Fatty Acids .txt", "text": "So we see that once activated, the fatty acid must be transported into the matrix via the transport protein known as translocase."}, {"title": "Activation of Fatty Acids .txt", "text": "And to do this, the Acyl coenzyme A must first react with carnitine to actually form Acyl carnitine."}, {"title": "Activation of Fatty Acids .txt", "text": "And the enzyme that catalyze this death is known as carnitine Acyl transfer ace one."}, {"title": "Activation of Fatty Acids .txt", "text": "Now, once we form the acyl carnitine molecule, it then moves into the matrix via the translocase."}, {"title": "Activation of Fatty Acids .txt", "text": "And once inside the matrix, we actually have the opposite reaction taking place that took place here."}, {"title": "Activation of Fatty Acids .txt", "text": "So we essentially want to replace that carnitine with a coenzyme A."}, {"title": "Activation of Fatty Acids .txt", "text": "And so we have another enzyme, a different enzyme known as carnitine."}, {"title": "Activation of Fatty Acids .txt", "text": "Acyl transfers two that essentially catalyze the transfer of a coenzyme component onto that Acyl molecule and that displaces the carnitine and kicks that carnitine off."}, {"title": "Activation of Fatty Acids .txt", "text": "And in the final step, the carnitine is basically shuttled back into the cytoplasm via that same translocase."}, {"title": "Activation of Fatty Acids .txt", "text": "So we have an exchange taking place for every Acyl carnitine molecule that moves in."}, {"title": "Activation of Fatty Acids .txt", "text": "We have a carotene molecule that moves out, and those Carnine molecules essentially go back into the cytoplasm because the carnitine molecules are used by this particular step in the formation of Acyl carnitine from Acyl co enzyme A."}, {"title": "Activation of Fatty Acids .txt", "text": "So this is basically the process by which that particular target cell that accepts the fatty acids is able to actually activate the fatty acids and then bring those fatty acids into the matrix of the mitochondria."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits (Part II) .txt", "text": "Showed was that this pedigree does in fact describe a disease that could potentially be autosomal dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits (Part II) .txt", "text": "Because everything, as I just showed you, works out."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits (Part II) .txt", "text": "But previously, we showed that although it can't, it can be autosomal dominant, it is not sex linked dominant and it is not sex linked recessive."}, {"title": "Asexual Reproduction .txt", "text": "Organisms reproduce in one of two ways to form our offspring."}, {"title": "Asexual Reproduction .txt", "text": "So one type of reproduction that humans and other animals undergo is known as sexual reproduction."}, {"title": "Asexual Reproduction .txt", "text": "And in sexual reproduction, we combine the DNA, the genetic information from the male parent and a female parent to produce an organism who is genetic information is unique."}, {"title": "Asexual Reproduction .txt", "text": "It's different than either one of the parents."}, {"title": "Asexual Reproduction .txt", "text": "And that's because sexual reproduction involves a type of cell division known as meiosis."}, {"title": "Asexual Reproduction .txt", "text": "And meiosis basically scrambles the genetic information and diversifies the genetic information of the offspring."}, {"title": "Asexual Reproduction .txt", "text": "Now, other organisms, and this includes both unicellular as well as multicellular organisms, undergo a second method of reproduction known as asexual reproduction."}, {"title": "Asexual Reproduction .txt", "text": "In asexual reproduction, the offspring that is produced contained genetic information that came directly from a single parent cell."}, {"title": "Asexual Reproduction .txt", "text": "And that's exactly why, for the most part, the offspring have the same exact genetic information as our parent sell."}, {"title": "Asexual Reproduction .txt", "text": "Now, there are four major types of asexual reproduction processes that we're going to discuss in this lecture."}, {"title": "Asexual Reproduction .txt", "text": "We're going to examine budding, binary fission regeneration as well as parthenogenesis."}, {"title": "Asexual Reproduction .txt", "text": "And let's begin by briefly discussing the process of budding."}, {"title": "Asexual Reproduction .txt", "text": "So budding is one form of asexual reproduction in which we replicate the genetic information, the DNA of the parent cell, and then we enclose that DNA into a small portion of the cytoplasm in the cell membrane that came from the original parent cell."}, {"title": "Asexual Reproduction .txt", "text": "And that's exactly why the daughter cell that we produce as a result of budding is much smaller in size but contains the same exact genetic information as our parent cell."}, {"title": "Asexual Reproduction .txt", "text": "So basically, we begin with the parent cell."}, {"title": "Asexual Reproduction .txt", "text": "The genetic information of the parent cell shown in blue, begins to replicate itself and that is shown in green."}, {"title": "Asexual Reproduction .txt", "text": "So green is the replicated DNA."}, {"title": "Asexual Reproduction .txt", "text": "Eventually, our replicated DNA will be enclosed in a small portion of the cytoplasm that will bud off and form this small daughter cell."}, {"title": "Asexual Reproduction .txt", "text": "Eventually, of course, this small daughter cell will grow in size and eventually will be the same size as this parent organism."}, {"title": "Asexual Reproduction .txt", "text": "Now, unicellular as well as multicellular organisms undergo the process of budding."}, {"title": "Asexual Reproduction .txt", "text": "One common example of a unicellular eukaryotic organism is the yeast cell, while an example of a multicellular organism that undergoes the process of budding is the hydra."}, {"title": "Asexual Reproduction .txt", "text": "Now, let's move on to the second type of asexual reproduction known as binary fission."}, {"title": "Asexual Reproduction .txt", "text": "So binary fission is the asexual reproduction that bacterial cells as well as other prokaryotic cells actually undergo."}, {"title": "Asexual Reproduction .txt", "text": "So what happens is inside the bacterial cell we have circular DNA, and the circular DNA basically begins to replicate itself."}, {"title": "Asexual Reproduction .txt", "text": "As that takes place, the original DNA shown in blue and the replicated DNA shown in green attached to different positions on the cell membrane."}, {"title": "Asexual Reproduction .txt", "text": "At the same time, the cell begins to expand and the cell begins to grow."}, {"title": "Asexual Reproduction .txt", "text": "Eventually, once we replicate our DNA, the cell basically divides into equal size daughter cells as shown in the following diagram."}, {"title": "Asexual Reproduction .txt", "text": "So budding basically involves producing two cells that are unequal in size."}, {"title": "Asexual Reproduction .txt", "text": "But binary fission involves producing two cells that contain the same exact amount of cytoplasm and therefore are the same exact in size."}, {"title": "Asexual Reproduction .txt", "text": "Now let's move on to the process of regeneration."}, {"title": "Asexual Reproduction .txt", "text": "So regeneration is a type of process in which our organism can actually regrow certain body parts."}, {"title": "Asexual Reproduction .txt", "text": "Now, although regeneration occurs mostly in lower level organisms, it also can take place in higher level organisms."}, {"title": "Asexual Reproduction .txt", "text": "And regeneration basically involves the cell division known as mitosis, in which a cell reproduces into two identical cells that contain the same exact genetic information."}, {"title": "Asexual Reproduction .txt", "text": "For instance, sea stars can basically regrow arms, arrow lizards can regrow their tails, and humans have the ability to regrow their livers to a certain extent."}, {"title": "Asexual Reproduction .txt", "text": "And these are examples of organisms undergoing regeneration."}, {"title": "Asexual Reproduction .txt", "text": "And now let's move on to the final type of asexual production known as parthenogenesis."}, {"title": "Asexual Reproduction .txt", "text": "So in humans, as well as other organisms, what happens is the sperm cell basically combines with the egg."}, {"title": "Asexual Reproduction .txt", "text": "And the sperm and the egg are both haploid with respect to their chromosome number."}, {"title": "Asexual Reproduction .txt", "text": "And when they combine, they form the diploid zygote."}, {"title": "Asexual Reproduction .txt", "text": "And the diploid zygote eventually grows into the organism, into the human, or into some other animal."}, {"title": "Asexual Reproduction .txt", "text": "Now, what parthenogenesis is is the following."}, {"title": "Asexual Reproduction .txt", "text": "Parthenogenesis is the process by which an unfertilized egg, which is haploid with respect to its chromosome number, develops by itself into the organism."}, {"title": "Asexual Reproduction .txt", "text": "And that means the organism will have a haploid number of chromosomes."}, {"title": "Asexual Reproduction .txt", "text": "Now, certain organisms can actually restore the chromosome number to the chromosome number of the parents, but this only happens in certain organisms."}, {"title": "Asexual Reproduction .txt", "text": "And one example of an organism that undergoes the process of parthenogenesis are bees."}, {"title": "Asexual Reproduction .txt", "text": "Other examples of other insects that undergo parthenogenesis are ants."}, {"title": "Asexual Reproduction .txt", "text": "So basically, budding binary fission and regeneration are three types of asexual reproduction processes that produce offspring cells that contain the same exact genetic information as the parent cell."}, {"title": "Asexual Reproduction .txt", "text": "But parthenogenesis is a type of asexual reproduction in which we produce the offspring that does not necessarily have the same genetic information as the parent cell."}, {"title": "Asexual Reproduction .txt", "text": "Because in the case of parsonagenesis, if we begin with a diploid number and we go to a haploid number, that means the genetic information will be different in the two types of cells."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "The process of transcription involves the production of RNA molecules from DNA molecules."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And what this process actually involves is the passing down of the genetic information from the DNA to the RNA molecules."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And it's the RNA molecules that are directly involved in the process of protein synthesis that takes place in the science of our cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, one important type of RNA molecule is known as messenger RNA or mRNA."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And it's the mRNA that actually serves as the template for protein synthesis that takes place in the ribosomes in the cytoplasm of our cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, before our messenger RNA actually leaves the nucleus and enters the cytoplasm where it attaches to the ribosomes and undergoes protein synthesis, our messenger RNA has to undergo several important types of modifications several important types of post transcriptional processes."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, within the nucleus of our cell we produce a molecule known as the precursor mRNA."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So the mRNA that is formed directly following the process of transcription before any type of post transcriptional modification actually took place is known as the precursor mRNA or simply as the mRNA or the pre mRNA."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So this is the mRNA that has not yet undergone the necessary modification processes that are needed for the molecule to exit the nucleus and enter the cytoplasm."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And there are three important types of post transcriptional modifications."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So we have the addition of the five guanosine triphosphate cap, we have the polyadenylation of the three N tail and we have the splicing of our axons and the removal of our introns."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So let's take a look at each one of these post transcriptional modifications of the mRNA and see what they are and why they actually take place."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And let's begin with the addition of the five and guanosine triphosphate cap."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So within the nucleus of the cell, before our pre mRNA actually leaves the nucleus the five end of the precursor mRNA is altered by the attachment or the addition of a guanacine nucleotide via a special type of bond, a special type of linkage known as the five to five triphosphate linkage."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And following the additional detachment of this cap the guanacine nucleotide is also altered in several ways."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "One of the ways in which the guanacinucleotide is altered is by the methylation of the seven position to form the seven methyl guanosine nucleotide."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So this type of five guanosine triphosphate cap is shown in the diagram."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So let's pretend that this is the five end of our premna that is synthesized directly following the process of transcription."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So basically what we do is we add this guanacine nucleotide via the following triphosphate bond."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "The reason it's called a triphosphate bond or a triphosphate linkage is because we have one, two, three phosphorus atoms."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And the reason it's called a five to five triphosphate linkage is because that linkage is between the fifth carbon on this sugar and the fifth carbon on this ribosugar."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So this is the five guanosine triphosphate cap."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, the question is why exactly should we add this cap to our pre mRNA molecule?"}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "What is the function of this cap?"}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Well, basically one important function of this cap is to protect our mRNA from the degradation that could take place during the process of translation, during the process of protein synthesis."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And not only that, this addition of the five cap also basically gives our mRNA the ability to leave our nucleus through the nuclear pores and enter the cytoplasm of our cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So it also stabilizes the mRNA molecule and AIDS in transport across the nuclear membrane of the nucleus of the cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now let's move on to the second type of process, second type of post transcriptional modification that takes place in the nucleus known as the poly and ventilation of the three and tail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So before the nucleus or before the pre mRNA actually leaves our nucleus, our tail has to actually be removed."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So a small section of the tail of the premna is removed and instead we add many adenosine nucleotides."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And this tail, this three and tail is now known as the polyatail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So in this type of post transcriptional modification the three end of the precursor mRNA is removed and a series of adenosine nucleotides are added."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And therefore the three end tail that contains the many adenosine nucleotides is known as the polyadenosine tail or the polyadenine tail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, just as the five cap adds the ability to resist different types of degradation in the cytoplasm and gives our mRNA stability, the polyatail also provides the mRNA with stability and keeps the tail from degrading in the cytoplasm of the cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And it also AIDS in the transport of our mRNA from the nucleus to the side of plasma of our cell."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So basically what happens is if this is our mRNA molecule, if this is the premRNA molecule and this is the five end and this is the three end, what happens is a small section of the three end of the pre mRNA is cleaved, is removed and then we add a bunch of adenosine phosphates."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "How many?"}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Well, anywhere from 200 to 250 adenosine molecules."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Adenosine nucleotides are added to our tail, to our end and that's exactly why it's known as the polya or the poly adenosine tail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now let's move on to the final type of post transcriptional modification and this is known as the process of splicing."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So we remove regions known as the introns and we combine the regions known as the axons."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So not all regions of the premrname molecule code for our protein or proteins."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Those regions that do code for the proteins are known as exons and those regions that do not code for the protein are known as introns."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And so special types of enzymes that together are known as the splicosome basically remove our introns and split together or combine or glue our exons and we form the final mRNA molecules."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So basically to see what we mean, let's take a look at the following diagram."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So let's suppose this is our precursor mRNA that now contains the polyatail that is shown here and it also contains the five guanosine triphosphate cap."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, before our pre mRNA actually becomes the mRNA and is able to leave the nucleus, the final process that has to take place is the following."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So, the molecule contains sections known as exons."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And these are the sections that actually carry the genetic code that codes for our protein."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "It also contains these introns which are sections that do not code for any type of protein."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So what must take place in the nucleus is a certain set of proteins known as the splicosome has to remove these introns and basically splice together or combine our exons."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So these three sections are removed and we basically splice together these four exon sections including the polyatail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And so we form the following molecule as shown."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So it also should contain our polyatail."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "So once all these processes actually take place, once we add the five cap, once we add our tail that contains the polyadeny nucleotides, and once we splice together the exons and remove the introns, only then does our pre mRNA molecule become the mRNA molecule."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "And only then can the messenger RNA actually exit the nucleus into the cytoplasm and undergo protein synthesis and be used by the ribosomes to synthesize our proteins."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "Now, the entire purpose of adding this five cap and the polya tail is to basically give our mRNA molecule the ability to resist degradation by different types of enzymes and different types of proteins."}, {"title": "Post-transcriptional modifications of mRNA.txt", "text": "It also gives our mRNA molecule the ability to basically travel from the nuclear and into the cytoplasm of our cell."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Biochemistry is the study of the chemistry of the many different types of biological reactions and biological processes that take place in nature."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, the majority of the different types of biological reactions that exist in nature for example, in our body and inside the cells of our body, they exist in water."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So water is the natural solvent."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "It's the solvent that allows all these different types of biological reactions to actually take place in the first place."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And because of the properties of water, as we'll see, in just a moment we'll see what these properties are."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "The fact that water is a solvent allows those reactions to follow a certain pathway."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And water also actually helps determine what the final structure is of these biological molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "For example, one biochemical process in our body, inside the cells of our body, is the biosynthesis of proteins."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And as a result of the properties of water, that protein is able to actually obtain its final three dimensional shape."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And we'll discuss that in much more detail in a future lecture."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "In this lecture, we're going to focus on two important properties of water, and we're going to see how these two properties lead to an effect known as the hydrophobic effect."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So let's begin by discussing property number one, the fact that water is a polar molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "It contains an electric dipole moment."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, a single water molecule consists of three individual atoms."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "We have the central oxygen atom, which is a large molecule, and the two tiny H atoms found on a side."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Water is not a linear molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "It has a bench shape."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And what that means is these bonds create a certain angle that is not 180 degrees."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So notice the bench shape of the H 20 molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, oxygen is much more electronegative than either of these h atoms."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And because of that, oxygen is able to pull that electron density away from these two H atoms."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And because it is much more likely that electron density will be found around the oxygen than around the h atoms, and at any given moment in time, that oxygen atom will have a partial negative charge, and the two h atoms will be deficient of the electron density, and so they will have a partial positive charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, from physics, we know that whenever we have the separation of two opposite charges, whenever a positive charge is separated from a negative charge by a certain distance, there will exist an electric dipole moment as a result of that separation of charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So what does that mean about this water molecule here?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So basically, we have this partial positive charge that is a certain distance, this distance here, away from this partial negative charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so from physics, we know there will be an electric dipole moment that will exist and will point in the following general direction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Likewise, we have a separation of charge between these two charges."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so there will be an electric dipole moment that points in this direction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So what that means is we have these two electric dipole moments that point this way."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And if we add up these two vectors, then the net result will be a vector, an electric dipole moment that will point beginning here and will point this way, as shown by the following green arrow."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So this green arrow basically describes the direction of our net electric dipole moment of this water molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So the fact that water is polar simply means it has an electric dipole moment."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And what that means is there is an unequal and asymmetric distribution of electron density."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And that gives the oxygen a partial negative charge and these h atoms a partial positive charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, let's move on to the second property of water, its ability to basically form strong intermolecular bonds with other water molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And as we'll see in just a moment, with other polar molecules as well."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So let's suppose we have several water molecules that are in close proximity."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "How exactly will these water molecules actually orient themselves with respect to one another?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And how will they interact with one another?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Well, as a result of the fact that water is polar, it will have a partial positive charge on the oxygen."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so we draw the oxygen with a blue sphere."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So the blue sphere basically designates our partially negative oxygen, while these red spheres designate the partially positive h atoms."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so if we have these 123456 water molecules in close proximity, they will orient themselves with respect to one another in such a way to basically maximize the amount of electric interactions."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "They're actually electromagnetic, but we can say electric interactions between the different atoms on different molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So because these h atoms have a partially positive charge, they will be attracted to the partially negative oxygen atoms."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so if we look at these two water molecules, for example, this H atom of this water molecule will try to get as close as possible to this partially negative oxygen atom."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this bond is known as an intermolecular bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, the specific type of intermolecular bond in this case is a hydrogen bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So anytime we have the H atom bonding with some type of negative charge that is a hydrogen bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, what's so special about a hydrogen bond?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Well, a hydrogen bond is a very strong inter molecular bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And that's because of the tiny size of that H atom."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So remember, h atoms are the smallest types of atoms in nature."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "The smallest type of nucleus is the nucleus of an h atom."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so what that means is this H atom, because it's so small, it can actually get very close to that oxygen atom."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And if it gets very close, the distance decreases."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And we know that our electric force is directly or inversely proportional to the square of the distance between our two charges."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so because the distance here will be so small."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "If the distance is small, the force will become large."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And if the force is large, this interaction is very strong."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this type of interaction between the H atom of one water molecule and the oxygen atom of another water molecule is known as a hydrogen bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So, once again, water molecules interact strongly with other water molecules via electrical forces or, to be more specific, electromagnetic forces."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, the small size of the positively charged hydrogen atom of one molecule, for example, let's say this molecule allows it to get very close to the negatively charged oxygen of another molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "For example, this molecule right here, the small size of this allows it to get very close to this oxygen."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this small distance basically means we have a very strong interaction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this type of strong intermolecular interaction, or intermolecular bond, is known as a hydrogen bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So we see the fact that water is a polar molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And because it consists of these very tiny H atoms, we form these very strong intermolecular bonds, known as hydrogen bonds, when many of these water molecules actually are found in close proximity."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, these two properties lead directly into something called the hydrophobic effect."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So the hydrophobic effect is a manifestation of these two properties, as we'll see in just a moment."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And the hydrophobic effect plays an important role in the field of biochemistry."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So let's suppose we take water molecules and we place some type of polar substance into the water molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "For example, sodium chloride."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, sodium chloride is polar because it consists of an ionic bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And an ionic bond is basically a bond in which we have an unequal distribution of charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So one of the atoms, namely the chloride, is more electronegative, so it will have that full negative charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "But the sodium is not very electronegative, and it will give away those electrons, and so it will have a positive charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so if we place the sodium chloride into water, that sodium chloride will separate, that ionic bond will break, but many of these hydrogen bonds will form, and that will be a favorable reaction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so that's exactly why, if we take a polar molecule or a polar substance and place it into water, the water will be able to dissociate and dissolve that substance because of these hydrogen bonds."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So, due to the high polarity of water and its ability to hydrogen bond, water can readily dissolve other polar substances."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "For instance, by adding sodium chloride into water, we break the ionic bond between sodium and the chloride, and we form many individual hydrogen bonds."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this is a very favorable reaction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "For example, let's say we form 12345 of these hydrogen bonds between sodium and water, and we form all these bonds between chloride and water."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So even though we break that sodium chloride bond, we form many of these hydrogen bonds, and that is overall a favorable reaction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So notice that because the sodium loses that electron it gains a full positive charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so all these oxygen atoms of the water molecules orient themselves in a line in such a way so that the oxygen is in close proximity with the sodium."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And if we examine the chloride, because the chloride gained that electron it took away from the sodium, it has a full negative charge."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so now all the h atoms will orient themselves and will become very close with that chloride and that will form all these stabilizing hydrogen bonds."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, we know that polar dissolves polar as a result of this."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "But what happens if we take water and we place a single non polar molecule into that water?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "What exactly will happen then?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Well, non polar substances basically have very little or no polarity."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And what that means is non polar substances have a symmetric distribution of charge and so they will not show an electric dipole nomin like water does."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So non polar substances have no polarity and do not interact favorably with water because if they don't have an unequal separation of charge, that means they cannot form these relatively strong hydrogen bonds."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so if we take a single non polar molecule and we place it into water, what will happen is all these water molecules will essentially form a cage around the non polar molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And that is not a stabilizing effect because all these water molecules will essentially be fixed."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "They will be trapped around that non polar molecule and these water molecules will not be able to interact favorably with other water molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So when a non polar substance is added to water, the water molecules form a cage around that non polar molecule as shown in this diagram."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "This is not a favorable effect because it limits those water molecules, it traps those water molecules around the non polar substance and it limits the amount of hydrogen bonds that can form between these water molecules and that is not a favorable effect."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Now, what happens if instead of taking one nonpolar substance we take two nonpolar molecules and place it into our water?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "What will happen now?"}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Well, the same exact thing will happen at first."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "Initially what happens is once we place the two non polar molecules into water, those water molecules will form a cage effect."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "They will become trapped around the nonpolar substance and that is not a favorable process."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So what actually happens is these two non polar molecules will aggregate."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "They will essentially combine and form bonds."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And the reason for that is when this process takes place we basically decrease the number of trap molecules found around the non polar substance."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So in this particular case, we have 123-456-7891 thousand and 1112, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So we have 22 of these water molecules that are trapped around these nonpolar molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And because they are trapped, they cannot interact via these hydrogen bonds with other water molecules."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "But if these two non polar substances actually aggregate together, they will decrease the amount of surface area around this entire molecule."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And instead of having these 22 water molecules that are trapped we only have 123-45-6789 of these water molecules that will be trapped."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And that is a favorable reaction because we basically decrease the amount of we decrease the amount of water molecules that are trapped."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And so we increase the amount of water molecules that can actually form those hydrogen bonds that are stabilizing."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this interaction between the non polar molecules in a polar solvent such as water is known as a hydrophobic interaction."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this effect is known as the hydrophobic effect."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And it is a result of the fact that water is a polar molecule and it forms these strong intermolecular bonds we call hydrogen in bond."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "So once again, if two or more non polar molecules are added into water, our solvent, the non polar molecules, will aggregate together."}, {"title": "Properties of Water and Hydrophobic Effect .txt", "text": "And this is favorable because it releases those trap molecules."}, {"title": "Dialysis.txt", "text": "Surrounding every single cell of our body, we have a special membrane, a phospholipid bilayer membrane known as a semipermeable membrane."}, {"title": "Dialysis.txt", "text": "So what that basically means is it allows the movement of certain molecules, but at the same time, it prevents the movement of other molecules across that cell membrane."}, {"title": "Dialysis.txt", "text": "For example, polar molecules that have charged and large molecules cannot pass across the cell membrane without using a special type of protein transport molecule."}, {"title": "Dialysis.txt", "text": "Now, in the same analogous way, we can also build a semipermeable membrane, and we can use the semipermeable membrane in a process known as dialysis."}, {"title": "Dialysis.txt", "text": "So dialysis is a process by which we can purify proteins by using a semipermeable membrane."}, {"title": "Dialysis.txt", "text": "So let's see exactly what we mean by taking a look at the following three diagrams."}, {"title": "Dialysis.txt", "text": "So, let's begin with diagram A."}, {"title": "Dialysis.txt", "text": "In diagram A, we have this beaker that contains pure water, and we also have the bag."}, {"title": "Dialysis.txt", "text": "Now, the bag is enclosed in a semipermeable membrane."}, {"title": "Dialysis.txt", "text": "So we have these tiny pores inside our bag."}, {"title": "Dialysis.txt", "text": "And these tiny pores allow the movement of very small molecules and ions, but prevent the movement of large molecules such as protein."}, {"title": "Dialysis.txt", "text": "So, inside the bag, we have this solution, where we have these protein molecules shown in purple, and these very tiny molecules shown in red."}, {"title": "Dialysis.txt", "text": "So the membrane can be, for example, composed of cellulose, and it contains very tiny pores."}, {"title": "Dialysis.txt", "text": "Now, what happens if we take this bag?"}, {"title": "Dialysis.txt", "text": "We're going to call our dialysis bag and place it into our solution of pure water."}, {"title": "Dialysis.txt", "text": "Well, at the instant we place it inside, nothing will happen."}, {"title": "Dialysis.txt", "text": "But what will happen over time?"}, {"title": "Dialysis.txt", "text": "Well, to answer this question, we're going to use the second law of thermodynamics, the law of entropy."}, {"title": "Dialysis.txt", "text": "So the second law of thermodynamics tells us that when given a chance to, energy will disperse to larger volume of space."}, {"title": "Dialysis.txt", "text": "So what that means is if we have localized energy that is closed in a very small localized region, and then we open up the space, that energy will disperse and spread out throughout the entire region of space."}, {"title": "Dialysis.txt", "text": "Now, because molecules carry energy, we can say the same thing about molecules."}, {"title": "Dialysis.txt", "text": "If we have molecules localized and trapped in a very small region of space, and then we open up that volume, those molecules will begin to move and disperse and spread out throughout that region of space."}, {"title": "Dialysis.txt", "text": "So what we see will happen is, over time, according to the second law of thermodynamics, those molecules that carry energy that can actually pass across these tiny pores in the membrane, will in fact pass across."}, {"title": "Dialysis.txt", "text": "And so that over time, this entire region of space that contains the water molecules also will contain these tiny red molecules, as shown in the following diagram."}, {"title": "Dialysis.txt", "text": "So this is dictated, this must happen by the second law of thermodynamics."}, {"title": "Dialysis.txt", "text": "So over time, almost all of these red molecules, the majority of these molecules in our dialysis bag, will essentially move out of our protein mixture."}, {"title": "Dialysis.txt", "text": "So over time, the majority of the small molecules, the ions, for example, will pass through the semipermeal membrane and out of the bag."}, {"title": "Dialysis.txt", "text": "So energy will disperse because all these molecules carry energy."}, {"title": "Dialysis.txt", "text": "In this case, all the molecules were localized in the bag."}, {"title": "Dialysis.txt", "text": "So all the energy that the molecules carry was localized in the bag."}, {"title": "Dialysis.txt", "text": "But now the molecules are dispersed, and so the energy is also dispersed throughout this larger region of space."}, {"title": "Dialysis.txt", "text": "Now, the protein molecules, even though they want to leave that bag, cannot leave that bag because of that physical barrier."}, {"title": "Dialysis.txt", "text": "They are simply too large to pass across those tiny pores in that semipermeable membrane."}, {"title": "Dialysis.txt", "text": "And so when we actually take out that bag, after the process, inside the bag, we're going to have very, very little of those tiny molecules."}, {"title": "Dialysis.txt", "text": "And so this means we're going to have a much pure sample of our protein than before."}, {"title": "Dialysis.txt", "text": "So this is the process of dialysis."}, {"title": "Dialysis.txt", "text": "And dialysis basically allows us to purify a protein mixture that contains these very tiny non protein substances, for example, ions and other tiny molecules."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "The cell theory is a set of principles that defines what it means for an organism to be a living organism."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, the cell theory states that the basic unit of life is a cell and all living organisms consist of one or more cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "It also states that cells arise from other preexisting cells and this means that living cells can replicate and reproduce to form other cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, the focus of this lecture will be viruses."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And viruses are basically small agents that infect other cells and this includes animal cells, plant cells as well as all different types of other cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, viruses do not actually satisfy the cell theory."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "For example, as we'll see in just a moment viruses cannot actually replicate and reproduce on their own."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And that means viruses are not considered living organisms."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "They are non living."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, although viruses can come in many different forms and shapes and types all viruses contain nucleic acids, either RNA or DNA."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "But viruses never contain both RNA and DNA."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "They only contain one or the other."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Viruses also contain a protein covering that is found outside the nucleic acid, inside the viruses."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this protein covering is known as a capsid."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, some viruses also contain another covering that is made of lipids and this is known as the lipid envelope."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And the lipid envelope actually comes from other living cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, the lipid envelope doesn't actually only act in protecting the cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "It also serves as an attachment."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "It basically allows the virus to attach onto living cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So the lipid code can have receptor proteins that can recognize and bind to other living cells and in fact, those living cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, as I mentioned earlier viruses cannot actually reproduce on their own and this is because they did not contain the proper machinery to actually reproduce and create the molecules needed for reproduction and division."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "For example, viruses do not have ribosomes and that means they cannot themselves produce proteins."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "However, instead of actually replicating and dividing on their own our viruses can actually infect living cells and use the machinery, the organelles of the living cells to actually reproduce and divide and form other viruses."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So one very common example of a virus, one very common type of a virus is a bacteriophage."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And a bacteriophage is a virus that only targets and infects bacterial cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So basically, the structure of our bacteriophage looks something like this."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "We have our nucleic acids, either DNA or RNA, found inside the protein capsule."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "This is the protein capsule also known as the head of our bacteria phage."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "We also have a protein midsection as well as the protein tail."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And in order to actually attach the virus onto the cell membrane of the bacteria, this tail, the bottom portion of the tail, actually has to attach to the proper receptor on the cell membrane of that bacteria."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And once our attachment actually takes place so following attachment, our bacteria phase injects the nucleic acid, either DNA or RNA, never both into the cytoplasm of the cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And within a short period of time the cell begins to basically translate and synthesize the proteins encoded by the viral nucleic acid."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, the bacteria phage usually undergoes a pathway, a cycle known as the Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "But other types of bacteria exist that can or other types of viruses exist that can also undergo the lysogenic cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So when the virus enters the cell there are two types of pathways that can be taken by that virus."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "We have the lytic cycle, the lytic pathway, as well as our lysogenic cycle lysogenic pathway."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So let's begin by discussing the lytic cycle which is basically followed by our bacteria phages viruses that infect bacterial cells."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So under this pathway, as soon as the virus actually injects itself into the cell or injects the nucleic acid into that cell, in the case of the bacteriophage, the bacteria phage only actually injects the nucleic acid into the cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "It leaves the protein tail, the protein midsection and the protein capsule outside of that cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So under this pathway, as soon as the virus is inside the cell it directs the cell to synthesize new viruses by using the host cell's machinery."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this includes the nucleus, it includes the endoplasm reticulum, it includes our ribosomes."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So for example, ribosomes synthesize the protein coating our capsid and the viral nucleic acids are essentially replicated and placed inside those protein capsids."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Eventually, Aracell basically fills up with these new viruses and eventually the pressure, as a result of the many different viruses inside the cell causes our cell to actually burst open."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this process is known as lysing."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And that's exactly why this is known as the Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, once our cell license, it releases all these new viruses and these viruses that are found outside the whole cell are known as virants."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, another method by which our cell can basically release the viruses onto the outside of the cell is by undergoing a type of process that looks like exocytosis, basically using the cell membrane to take our viruses and bring them outside of that cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, the period between when our virus actually infects the cell and right before the cell lysis is known as the latent period."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this diagram basically describes the process by which the bacteria phase undergoes our Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So in step one, our bacteria or our virus approaches the cell membrane of our bacterial cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So we have the cell membrane, we have the bacteria phage."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So our bottom portion of our tail protein of this bacteriophage attaches itself onto the proper receptor region on that cell membrane."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "At that point, this capsid essentially injects that nucleic acid into that cell through the midsection and this tail section."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So this entire protein tail and caps in the midstation is left behind on the outside of that bacterial cell while this nucleic acid, either DNA or RNA found in the capsid is injected entirely into that bacterial cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now in step three we have the assembling process."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So now the cell has been infected and the cell is in the latent period."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So basically the cell is producing many new viruses as shown in the following diagram."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And in the final step, because we have so many different viruses, that increases the pressure and causes the cell to actually burst open and light."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And at this point the cell basically dies releasing all the new virus into the outside portion surrounding that cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this process is known as the Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, a different process that other types of viruses undergo is known as the lithogenic cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Under this pathway the viral DNA or RNA that enters that cell is basically incorporated into the host's genome, the host's DNA."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now certain viruses such as HIV do not contain DNA, they contain RNA and they also contain special types of enzymes known as reverse transcriptase."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And these enzymes basically reverse transcribe the RNA into DNA and then that DNA is integrated, is incorporated into the host cell genome, the host cell DNA."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now once integrated into our DNA of the host, the cell can basically live on and show no sign of actual infection."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "And this stage, this phase is known as the doorman period."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now of course eventually we can have some type of environmental factor that can cause the cell to basically undergo the Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "For example, UV radiation is one form of environmental factor that can basically take a cell under the lythogenic cycle and transform it into the lytic cycle, forced it to go into the lytic cycle and produce many different viruses and eventually lice."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So a cell whose genome contains a viral DNA section inside that cell is known as a provirus."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So these are the two types of cycles of pathways that can be followed by our cell once the virus actually ingests itself or injects the nucleic acid into that whole cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "A specific type of virus that only infects and targets bacterial cells is known as the bacteria phase and this usually undergoes the Litig cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "There are also different types of viruses."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "For example, the HIV virus, virus that doesn't only undergo the Litig cycle, it can also undergo the lysogenic cycle."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "In the lipogenic cycle the DNA of that virus is actually incorporated, it's integrated with the DNA of that whole cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Now, what exactly is the main difference between the Litig cycle and the lipogenic cycle?"}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Well, the Litig cycle isn't very useful because it actually kills off that whole cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "So once the cell dies, the virus does have to find other cells to actually infect."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "However, the lytogenic cycle is more useful because the virus doesn't actually directly and immediately kill off that cell."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "It incorporates, operates into the cell and can undergo the lytic cycle any time it wants to."}, {"title": "Viruses, Lytic Cycle and Lysogenic Cycle .txt", "text": "Basically when it is stressed by certain types of environmental factors such as for example, heat or UV radiation."}, {"title": "Autosomal Recessive Diseases.txt", "text": "As you might already know, a chromosome is nothing more than a collection of many different types of genes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And a gene is nothing more than a sequence of nucleotides that codes for some specific protein."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, proteins are very important macromolecules."}, {"title": "Autosomal Recessive Diseases.txt", "text": "They're used by the cells of our body for many different types of processes and many different types of reactions."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, there are many examples of different types of diseases that are a result of abnormalities that exist on either the genes of the chromosomes or the chromosomes themselves."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So in this lecture, we're going to focus on a specific type of genetic disease, genetic disorder known as autosomal recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, before we examine four specific examples of human autosomal recessive diseases, let's actually recall and define what we mean by an autosomal recessive disease in the first place."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Well, recall that in every single somatic cell of the human body, we have 23 pairs of homologous chromosomes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "One of these pairs is known as the sex chromosomes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So in males we have the X and the Y."}, {"title": "Autosomal Recessive Diseases.txt", "text": "In females, we have the X and the X sex chromosome."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And the other 22 pairs of homologous chromosomes are known as autosomes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And so what we mean by an autosomal recessive disease is that genetic abnormality exists on one of the genes or both of the genes on the autosomal homologous chromosome pair."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So this is a type of abnormality that exists on autosomes and not on sex chromosomes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So let's actually define what we mean by recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So a disease is said to be recessive if only the homozygous recessive individual, the homozygous recessive genotype actually creates that particular phenotype for that particular disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So a disease is autosomal recessive, if only the homozygous recessive individual for that particular trait expresses that phenotype for that disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And the genetic abnormality exists on the autosome and not on the sex chromosome."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So to see what we mean, let's take a look at the following three diagrams."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So we basically have an autosome on which both of these genes are fully functional and they're represented by uppercase DS."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So this is homozygous dominant, and a homozygous dominant individual will have a normal phenotype, and they will not be a carrier for that particular disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "In the case of the heterozygous individual, because we have at least one of these alleles, at least one of these genes on one of the autosomal chromosomes is normal uppercase D. This individual will have a normal phenotype because they will be able to express that particular protein that is needed for that cell."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, the other gene is abnormal, and that's why it's lowercase D, and that's why it is said to be a carrier of that disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, this is the only genotype that will actually express the disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And that's because both of these autosomes, both of these homologous chromosomes have a non functional gene that is given by lowercase D. And so they will not be able to produce that fully functional protein that is needed by the cell."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So now that we know what we mean by an Autosole and recessive disease, let's quickly look at four individual examples."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, we're not going to go into too much detail on each and every one of these diseases."}, {"title": "Autosomal Recessive Diseases.txt", "text": "We'll simply go into discuss briefly what they actually mean."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Let's begin with phenyl ketonuria."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So what exactly is PKU?"}, {"title": "Autosomal Recessive Diseases.txt", "text": "Well, under normal conditions, in individuals who are homozygous dominant or are heterozygous, they have this gene that codes for a special protein that breaks down the phenolamine amino acid into another amino acid known as tyrosine."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So let's suppose that inside the somatic cell of my body, I have this particular genotype."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So what that means is because I have at least one of these normal genes, that gene will be able to code for a special protein that breaks down that basically converts phenylalamine into tyrosine."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So every time I ingest the phenylalamine, my body, my cells will have this enzyme to convert it into tyrosine."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, in homozygous recessive individuals, however, they don't have that proper gene that is needed to form that enzyme."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And as a result, that enzyme will not be able to convert the phenoalamine into tyrosine."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And so instead of converting the phenolalanine into tyrosine, what our body will do is it will convert the phenylalanine into toxic substances."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And as a result, over time, the accumulation and the build up of the toxic substances will damage the central nervous system and that will lead to many different types of mental abnormalities and mental disabilities."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So this is what we mean by pheno keto Neuria."}, {"title": "Autosomal Recessive Diseases.txt", "text": "It's one example of a human autosomal recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now let's move on to sickle cell anemia."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, in sickle cell anemia, the individual once again is homozygous recessive."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And in this particular case, they basically have a non functional gene."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So basically, the gene codes for a protein that is not fully functional."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And this protein happens to be a protein that is very important in our body."}, {"title": "Autosomal Recessive Diseases.txt", "text": "This protein is hemoglobin."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So normally, hemoglobin binds oxygen in the lungs and it unloads that oxygen in the tissues of our body and then it returns back into our lungs to pick up more oxygen."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, in individuals with sickle cell anemia, what happens is the amino acid number six on the beta subunit chain."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Remember, hemoglobin consists of two alpha units and two beta units."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So in individuals with sickle cell anemia, the glutamic acid amino acid at position number six on the beta subunit hemoglobin is replaced by valium."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And what that does is it changes the hydrophobic properties of hemoglobin."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, that's not really a problem when the hemoglobin is bound to oxygen."}, {"title": "Autosomal Recessive Diseases.txt", "text": "But as soon as the hemoglobin unloads that oxygen in the tissues, what happens is the three dimensional shape of that hemoglobin changes as a result of that valine amino acid."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And so what happens is because the red blood cells are filled with these hemoglobin molecules."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And because these hemoglobin proteins change their shape, the entire red blood cell also changes its shape."}, {"title": "Autosomal Recessive Diseases.txt", "text": "It changes its shape from a biconcave shape to a sickle half moon shape."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, because of the shape, these red blood cells, the sickle red blood cells, can actually aggregate together and they can form clogs, clots inside the veins of our body because it's inside the veins that our red blood cells have unloaded that oxygen."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So the sickle cells slow down the blood flow in our veins and they can clog the veins of our body, leading to tissue damage which can be very, very painful."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Painful."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, let's move on to the third type of Autosole recessive disease found in humans known as cystic fibrosis."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So sickle cell anemia, by the way, is very prevalent in African American population."}, {"title": "Autosomal Recessive Diseases.txt", "text": "I believe one in one, two African Americans living in the US."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Are heterozygous for this particular disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "On the other hand, cystic fibrosis is much more prevalent in white individuals."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And in the US."}, {"title": "Autosomal Recessive Diseases.txt", "text": "One out of 20 White individuals are living with the heterozygous genotype for this particular condition."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So what exactly is cystic fibrosis?"}, {"title": "Autosomal Recessive Diseases.txt", "text": "So just like PKU and stickle cell anemia, cystic fibrosis is an autosomal recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So an individual will have the disease and will show it if they are homozygous recessive."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So people with this condition basically lack that proper gene that is needed to synthesize an important chloride ion channel because they have two of these recessive alleles on some autosomal homologous pair."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, as a result, there is an excessive build up of this very sticky, very thick and very viscous mucus that is found in the passageway of the lungs as well as in our liver, in our pancreas and in our small intestine."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So as a result of this thick mucus layer, our body cannot actually rid itself of this mucus layer properly."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And what happens is there is a build up of pathogenic agents in those mucous membranes."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Remember, the entire purpose of the mucous membranes in our lungs and other parts of our body is to trap pathogens and keep the pathogens from entering our body."}, {"title": "Autosomal Recessive Diseases.txt", "text": "But because of this thick layer of mucous membrane, as a result of cystic fibrosis, those bacterial ages and pathogens end up spending way too much time in the mucous membrane and that can basically create many different types of infections."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So our body's inability to rid itself of the mucus membrane can increase the rate of infection and lead to many other respiratory and digestive problems."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And finally, let's look at Tasax disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Taste sac disease is another example of the human, of a human autosomal recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So individuals with taste act disease typically begin showing symptoms by age one and usually die before age five."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So this is a very, very dangerous type of Autosole recessive disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "Now, these individuals, individuals that are homozygous recessive, basically are individuals that lack the gene that codes for a special enzyme that breaks down fats in the brain cells of our body."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And because those lipids, those fats, are not broken down properly, they basically build up, they accumulate in the lysosomes of our brain cells."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And that accumulation eventually leads to many different types of problems."}, {"title": "Autosomal Recessive Diseases.txt", "text": "For example, blindness as well as mental disabilities."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So we see that these different types of Autosole and recessive diseases are very, very dangerous."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And normally, Autosole and recessive diseases act very quickly."}, {"title": "Autosomal Recessive Diseases.txt", "text": "They usually act in the first few months or the first few years of our life, of that individual's life."}, {"title": "Autosomal Recessive Diseases.txt", "text": "So once again, for examples of auto soldier diseases are phenylketonurium, sickle cell anemia, cystic fibrosis and taste acts disease."}, {"title": "Autosomal Recessive Diseases.txt", "text": "And what each and every one of these diseases have in common is the only time they express rest of phenotype for that disease is when that individual has a homozygous recessive genotype for that particular trait."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Fatty acids, which contain an odd number of carbon atoms, are broken down in a very similar way to the ones that contain an even number of carbon atoms."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "The only difference is in the breakdown of fatty acids with an odd number of carbon atoms."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "One of the final products that we form is a molecule of three carbon molecule known as ProPanel coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So aside from generating the acetylco enzyme A molecules, we also generate proponel coenzyme A molecules."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So let's suppose we have an odd chain fatty acid that contains five carbon atoms."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we have carbon atom 1234 and five."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So once we activate this molecule and we transport into the matrix of the mitochondria, in the matrix, it undergoes a beta oxidation process in the same way that the even chain fatty acid undergoes a beta oxidation process."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, remember that in the even chain fatty acid breakdown, we generate acetyl coenzyme A molecules only."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And though the acetyl coenzyme A molecules are fed into the citric acid cycle to help generate, to help generate ATP molecules."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "But in the case of odd chain fatty acid breakdown, not only do we generate the acetyl coenzyme A, we also generate a proponel coenzyme A three carbon molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, what happens to this proponel coenzyme A?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "This will be the focus of this lecture."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So basically, inside the matrix of the mitochondria, the proponel Co enzyme A molecule undergoes a three step process."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And in this three step process, we transform the proponent Co enzyme A into a suckyl coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we see that the ultimate fate of this proponel coenzyme A that we produce in the oxidation, the breakdown of our chain fatty acids, is to form the substantial coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Why?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Well, because the succinct coenzyme A is an intermediate of the citric acid cycle."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we basically form the succinct coenzyme A, place it into the citric acid cycle, and that helps us generate ATP molecules that the cell can use for energy."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So what exactly is this three step process?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "This is what I'd like to focus on in this lecture."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And let's begin with step number one."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "In step number one, we basically want to transform this three carbon molecule, the proponental coenzyme A, into a four carbon molecule known as demethylmel coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And the enzyme that catalyzed this reaction is a carboxylase."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, anticurboxylase requires three things."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "It needs an energy source, it needs a carbon source, and it needs vitamin B molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "That vitamin B molecule is biotin."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, the energy source that this enzyme uses is ATP."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So it basically hydrolyzes that ATP to form ATP, and it uses the energy that is released to drive this reaction forward."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, the carbon source that it uses is bicarbonate."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "It uses a bicarbonate to basically take that carbon dioxide and place it onto the proponel coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And that helps us generate the methylmelanyl coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So it hydrolyzes."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "An ATP molecule takes that energy and uses that energy to basically help attach that carbon dioxide onto the ProPanel coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And this entire process requires a vitamin B twelve molecule, vitamin B seven, known as biotin."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So this carboxylase is known as ProPanel, COA carboxylase because this is a substrate of this reaction."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we have ProPanel coenzyme A. Carboxylase uses the biotin, it hydrolyzes an ATP, and that helps attach the carbon dioxide onto the ProPanel coenzyme at form the deisomer of methyl malno coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So the most important takeaway lesson from this particular step is to remember that the ProPanel coenzyme A carboxylase needs three things."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "An energy source, the ATP, it needs a carbon source, the bicarbonate, and it also requires a biotin molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, this is step number one."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "In step number two, we basically want to take this D methyl melanyl coenzyme A and transform it into the l isomer form."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we want to transform the Dmethylmel coenzyme into the l methylmelanyl coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Why?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Well, because the enzyme in the last third step of this process, it uses, it only uses the l isomer and not the deisomer."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So the enzyme that catalyzes step number two, the conversion of the deisomer into the l isomer is methylmalcoenzyme a racimase."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And so we transform the Dmethyl malnol coenzyme A in which we have this methyl group pointing out of the board into this l isomer form in which the methyl group is now pointing into the board."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And the reason is because the enzyme in the third step, the methyl malanyl coenzyme A mutase, only acts on the l isomer and not on the deisomer."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So let's move on to step number three."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, step number three is basically catalyzed by this methyl malnoco enzyme, a mutase."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And what it does is it catalyzes an intramolecular reaction, an intramolecular rearrangement reaction in which a group, namely this entire group, is transported from the carbon number two onto this methyl group in the process that exchanges an H atom, as we'll see in just a moment."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, just like in the case of this carboxylase, it requires biotin for its activity."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "In the case of this mutase, it requires vitamin B twelve."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "In fact, with that vitamin B twelve, this reaction would not actually take place."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So let's see exactly what we mean by an intramolecular rearrangement reaction that is catalyzed by this mutase."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And let's begin with this l isomer of methylmalcouncilma that we formed in step number two."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So this is our molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So this is carbon number one, carbon number two, and carbon number three."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And the ultimate goal is to take this entire group that is shown in blue and to move it from carbon number two onto this carbon that is part of this methyl group."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now, how exactly is this reaction actually catalyzed?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Well, that's where vitamin B twelve actually comes into play."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So part of that vitamin B twelve molecule is shown in this diagram and it contains a radical."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we have a single electron on this carbon."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now remember from organic chemistry that radicals are very reactive."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And what happens in this particular case is the vitamin B twelve is used by this mutase enzyme to help abstract an h atom from this methyl group."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we essentially take away this h atom, we take away the one electron with that h atom and we basically help form a sigma bond, a single bond between the H and the carbon as shown in this particular diagram."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And we also generate a radical species on this carbon."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And so we form this unstable reactive intermediate."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now in the next step, we basically want to take this entire group shown in blue and move it onto this carbon."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So what happens is this carbon along with one electron that is present in this sigma bond, goes away and moves onto this carbon to form a sigma bond between this carbon and this carbon."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "At the same time, one of the electrons in this bond that is broken remains on this carbon number two."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And so that is what we see in this diagram."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So this carbon number two is this carbon shown in this diagram that contains this single electron."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now in the final step, we basically want to regenerate this vitamin B twelve group."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And so what happens is one of these h ions along with one of the electrons moves on to form a sigma bond between this carbon and this h atom and we form this succinct coenzyme a."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And we regenerate that coenzyme the vitamin B twelve that is used by the methylmelanyl coenzyme A mutate."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So ultimately in step three, we transform the methylmalanal coenzyme a into sucl coenzyme A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And once we generate that succil coenzyme A, this can now go into the citric acid cycle to help generate ATP molecules."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So we see that anytime we have a fatty acid that contains an odd number of carbon atoms, it will undergo the beta oxidation process to ultimately generate acetyl coenzyme a molecules."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And this ProPanel coenzyme A molecule, these acetyl coenzyme A molecules are fed into the citric acid cycle directly."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "But this ProPanel coenzyme A has to undergo this three step process to help generate the suctional coenzyme A that now can be fed into the citric acid cycle."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now the last thing that I'd like to discuss is vitamin B twelve deficiency."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "What happens if an individual is vitamin B twelve deficient?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "For example, because of malnutrition?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "What exactly will happen?"}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Well, in an individual that is vitamin B twelve deficient, this reaction will not actually take place and will have a build up of this intermediate molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So because we have no vitamin B twelve in vitamin B twelve deficiency, this mutase will not be able to transform the lmethyl malnol coenzyme a into the suclaim A."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And that will essentially build up this lmethyl malnol coenzyme a."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And that particular individual will begin to excrete this molecule in the urine."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And so a physician can basically test the patient's urine and look for the buildup, look for the presence of this molecule."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "And if that's the case then that might be because of vitamin B twelve deficiency."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "Now in another case we can have a mutation, a deficiency in the mutase."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "So in an individual who is born with some type of genetic mutation in which this mutase is not active the same thing will happen."}, {"title": "Oxidation of Odd chain fatty acids .txt", "text": "If the mutase can not activate catalyze this reaction then we will not be able to transform the lmethylmel co enzyme into the succeed up of this intermediate inside that individual and that will be excreted via urine."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "In our discussion on cardiac muscle cells, we said that cardiac muscle cells have a slightly different action potential than do neurons."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is what we're going to focus on in this lecture."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "We're going to discuss the generation of an action potential in cardiac muscle cells."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, cardiac muscle cells are also known as cardiac myosides, where the word myocide simply we means a muscle cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, cardiac myocides can generate an action potential as a result of three things."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "They can either be stimulated by a neuron, they can either be stimulated by a nearby muscle cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So if a nearby muscle cell generates an action potential, that action potential can propagate two adjacent muscle cells as a result of the gap junctions found between cells."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And the third reason is something called myogenic activity."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So certain cardiac myosites can actually generate their own action potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "They can contract by themselves without actually any type of outside stimulus."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is known as myogenic activity."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, generally speaking, the action potential can be broken down into five phases."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this graph describes these five phases."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the y axis is the membrane voltage difference."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "It's the potential difference between the inside and outside of the membrane of the cardiac myocyte known as our sarcolema."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the sarcolema is another word for the membrane of a cardiac myocytes."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So basically, this is given in millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And as we go higher along the y axis, our voltage increases, it becomes more positive."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, the x axis is our time and that's given in milliseconds."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And as we go along the x axis in this direction, our time progresses, our time increases."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So we have the brown region, and that is phase four."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "The red region is phase zero."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "The purple region is phase one."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "The blue region is phase two, and the green region is phase number three."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So, before we actually examine each one of these phases, let's discuss what this dashed line is."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the dashed line basically is our threshold potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "This is basically the voltage difference that must exist across the membrane of the cell for our action potential to actually generate."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So if our stimulus does not reach this value, no action potential is generated."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But if the stimulus reaches or exceeds this value, our action potential is generated."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So let's begin by describing phase number four."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So phase number four is shown in brown."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And notice that this line has a constant slope of zero, and that means our membrane voltage is not changing."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "In fact, this is the voltage of the membrane when the cell is resting, when it's not generating any action potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this is known as the resting membrane potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the brown section describes the resting membrane potential of the cell for a typical cardiac myoside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "This is at around negative 90 millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, before we discuss anything else, let's discuss the relative concentrations of four different ions found on the inside and on the outside of the membrane."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So when the cell is resting, when it's not generating any action potential, that is, when we are at phase four, these are the relative concentrations."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So we have a higher concentration of sodium, calcium and chloride on the outside than on the inside portion of the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And we have a lower concentration of potassium on the outside than on the inside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And these are the relative concentrations given to us in millimolar."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So mm is Millimolar."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So basically, this cell membrane is impermeable to ions."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that's because these ions carry charge."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, if we have some type of protein channel that opens up inside our cell membrane, then our sodium or any other ion can move across the cell membrane and they will always move down their electrochemical gradient."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So, for example, if our sodium channels open up that carry sodium channels across the membrane, then the sodium channels will move down their electrochemical gradient from a higher concentration to a lower concentration from the outside to the inside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "The same thing is true for calcium."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "The same thing is true for these other two."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But for potassium, they will move in the opposite, because potassium has a higher concentration on the inside than on the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, when the cell is resting, our sodium as well as the calcium voltage gated channels are closed, but the potassium is able to actually leak into this or actually outside of the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And because our potassium can leak slightly to the outside of the cell, that's exactly why our membrane is negative on the inside than on the outside, because we have a leakage of these potassium to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that basically creates a slightly negative membrane potential on the inside of the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So phase four is the resting membrane potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now let's move on to phase zero."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Phase zero is shown by the red region."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So let's suppose we have some type of outside stimulus, either by a neuron or by an adjacent muscle cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Let's suppose the stimulus basically reaches the threshold potential of around negative 70 millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "If this takes place, then we have the opening of our sodium voltage gated channels down on the cell membrane."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So these voltage gated sodium channels are known as time dependent channels."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And what time dependent means is they only open for a very small fraction of a second and they close immediately afterwards."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So as soon as our threshold potential is reached, all these sodium voltage gated channels open up very quickly."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And because they open up so quickly, we have the movement of the sodium channels from the outside of the sodium ions from the outside to the inside, down their electrochemical gradient."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And as they move into the cell, they carry positive charge into the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And as they carry positive charge, that increases the positive charge on the inside of the cell compared to our outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So we see this increase as shown by this curve."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, when we reach about negative 40 millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "When it becomes greater than negative 40 millivolts, we also have the opening of these special Ltype calcium channels, and we'll see what those are in just a moment."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So as these sodium channels, as these sodium ions rush in, they create a positive charge on the inside and a negative charge on the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that's exactly why we have this positive charge and increase in our membrane voltage potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So we see that this will cause the movement of sodium ions into the cell, which will lead to the depolarization of that membrane."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So depolarization simply means our polarity of the cell membrane switches."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So at the resting membrane potential, we had an internal negative and an external positive."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But when we depolarize, the inside becomes positive."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So it goes from negative to positive, and the outside goes from positive to negative."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "That's what we mean by depolarization."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the red is our depolarization phase."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "That is phase zero."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So we also have the opening of Ltype calcium channels at about negative 40 millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, what exactly do we mean by Ltype calcium channels?"}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So that basically means long opening calcium channels."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So they open up slowly and they remain open."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And basically, this means we have a very slow and steady rate of calcium ions, and they slowly move from a higher concentration to a lower concentration from the outside to the inside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this is shown by this diagram."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this basically contributes to our increase in positive charge on the inside of our cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, eventually, we move on to phase number one."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is phase number one."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, just as quickly as these sodium voltage gated channels open, they close."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Remember, because they're time dependent, they are only open for a very small fraction of a second."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So as soon as we reach this highest point of positive 30 millivolts, these sodium voltage gated channels basically close very quickly."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And at the same time, potassium voltage gated channels begin to open."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But they begin to open very slowly."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And so this is described in the following diagram."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So notice that our sodium voltage gated channels, shown in red, basically close."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But the calcium voltage gated channels, the Ltype calcium channels, are still open."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So because they're open, we still have a movement of positive charge the calcium into the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "But now our potassium channels begin to open up, and we have a movement of potassium to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And so what that basically means is, because we have a movement of the potassium onto the outside, initially the movement of potassium to the outside is higher than the movement of calcium to the inside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And so we have this decrease in our membrane potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "It becomes more negative, slightly more negative."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "That is shown by phase one."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the movement of the positively charged ions out of the cell down their electrochemical gradient from a high concentration to a low concentration that causes the inside of the cell to basically become more negative."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, this continues to take place until we reach about zero millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "When we reach about zero millivolts, the rate of movement of our sodium, of the potassium to the outside is equal to the rate of movement of the calcium inside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And what that basically means, because our rates are equal, because we have the positively charged potassium leaving the cell, but we have the positively charged calcium entering the cell, and the rates are equal."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "That means the charge on the membrane will basically be the same for a short period of time."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this is shown by the phase number two, the blue region."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So once the cell reaches a voltage difference of about zero millivolts, the rate of influx of the calcium is equal to the rate of e flux."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "It leaves the cell of potassium, and this extends our depolarization period and is known as our plateau phase."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is our plateau phase because we essentially reach a point on the action potential where the membrane potential is not changing, it remains around zero millivolts."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, some people say that this is an extension of depolarization, because what depolarization does is it basically maintains a positive concentration on the inside of the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that's exactly what we see on this diagram."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "Now, other people say that this is our depolarization shown in red."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "This is our early repolarization, because repolarization means we're basically in the process of returning our membrane voltage to normal."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So some people say this is early repolarization, this is our plateau and this is our repolarization period."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is our repolarization when we basically return it back to when we return it back to normal."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And this is our depolarization, while other people say this entire section is our depolarization, because what this does is it maintains a positive concentration on the inside of the cell."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So in a way, we can imagine that what the plasto phase does is it extends the time of contraction."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "It extends the period of time where our inside of the cell is basically positive with respect to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is phase number two, our plateau phase."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And phase number three is this phase."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "This is known as our repolarization phase."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "This is when our calcium voltage gated channels essentially close, and that causes the opening of even more potassium voltage gated channels, and that creates a very high efflux of our potassium to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So our potassium rushes to the outside, and that causes the inside of the cell to basically become more negative, and eventually it returns to the resting membrane potential."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So as the calcium voltage gated channels begin to close, the influx of potassium exceeds the influx of calcium."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So the movement of potassium to the outside exceeds the movement of calcium to the inside, and that basically causes the opening of even more of these voltage gated potassium channels shown in green."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that causes the increase in the rate of movement of our potassium to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that causes the inside of the cell to become more negative because we have the movement of positive charge to the outside."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "And that basically continues until we reach our resting membrane potential, until we reach our phase number four, this brown section."}, {"title": "Action Potential of Cardiac Muscle .txt", "text": "So this is the action potential inside cardiac myocytes."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "One method by which we can control the activity of enzymes is via Allosteric Control."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "In Allosteric Control we have a special type of effective molecule or ion that can bind to the allosteric site of that enzyme to basically either inhibit it or activate it."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now Allosteric Control is not the only method by which we can actually regulate the activity of our enzymes."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Two other methods exist and these methods include proteolytic Activation or Proteolytic Cleavage, as well as reversible covalent modification."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And these are the two methods that we're going to focus on in this lecture."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So let's begin by defining and discussing Proteolytic Activation."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now a good quantity of the enzymes that are synthesized in living organisms, and this includes human beings, are synthesized in their inactive form and such inactive enzymes are known as zymogens or proenzymes."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, under the proper environmental conditions, our zymogens, the inactive enzymes can be transformed permanently and irreversibly into their active form by a process known as proteolytic cleavage."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So proteolytic cleavage simply means we have some other type of protein that cleaves bonds within that zymogen."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So this process involves the hydrolysis of one or several peptide bonds within that Zymogen enzyme."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now Proteolytic cleavage doesn't necessarily require ATP, a source of energy, and that means that proteolytic cleavage can take place outside of the cell."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now proteolytic cleavage is also a permanent and irreversible process and that basically means that it only occurs once in the life cycle of that enzyme."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, what are some examples of our body using Proteolytic Activation?"}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Well, the process of blood clotting is one example of a biological process that involves a series of proteolytic cleavages."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And we're going to discuss blood clotting in much more detail when we get into biochemistry."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Another example of enzymes that undergo proteolytic cleavage to basically activate themselves are digestive enzymes."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So to look at an example, let's focus on a specific type of enzyme known as Chimotrypsin."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So basically Chimetrypsin is a specific type of enzyme that is found in the small intestine and it plays a role in cleaving polypeptides in breaking them down so that we can ingest them into the cells of our body."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So one important digestive enzyme that is formed in its zymogen form in the pancreas of our body is known as a Chimotrypsinogen."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So Chimotripsynogen is a single polypeptide chain that is inactive."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So that is the Xymogen form."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And to actually activate our molecule, to activate our protein, another protein known as trypsin has to actually cleave or break a single peptide bond within that zymogen."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So we have a Chimotryptinogen that basically reacts with our trypsin and the trypsin essentially cleaves our polypeptide chain along a single polypept or along a single bond shown here."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And then we transform the Chimotryptin into the active enzyme known as Pychiamitrypsin."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And then when Pi Chimotrypsin reacts with another Pi Chimotrypsin, we cleave it at yet another location."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So basically, we remove two dipeptides from this location and this location and we form the final active molecule, our chimotryptin."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And then this chimetryptsin can basically react with polypeptides, cleave them at specific locations in the small intestine and then we can ingest those molecules into the cells of our body."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So this process is known as proteolytic cleavage or proteolytic activation."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now let's move on to reversible covalent modification."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So what exactly is reversible covalent modification?"}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Well, this is the process by which we essentially modified our enzymes in a reversible fashion."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "We basically add some type of group and then we can remove that same type of group."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, a significant number of enzymes are regulated by adding or removing some type of group."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And one very common type of group is our phosphoryl group."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So basically a group or a class of proteins that are responsible for phosphorylating adding these phosphoryl groups onto enzymes are known as protein kinases."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So protein kinase is catalyzed the addition of the phosphoryl group onto other enzymes."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now another class of enzymes known as protein phosphatases are basically responsible for catalyzing the removal of that phosphoryl group from our enzyme."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now the molecule that acts to basically donate that phosphoryl group is commonly our ATP."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So adenosine triphosphate, but other high energy molecules can also be used."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "It's just this ATP is the most common."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, what is an example of our protein kinase?"}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Well, one type of protein kinase is protein kinase A or PKA."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So PKA is an enzyme that phosphorylates proteins on specific amino acids along that polypeptide chain."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, when cyclic adenosine monophosphate allosterically activates PKA at a specific type of site on that PKA enzyme."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "PKA can then begin adding the phosphoryl group onto different types of enzymes using those ATP molecules."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And PKA is involved for example in synthesizing glucose so that we can use that glucose as an energy source."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "Now, one example of a protein phosphatase enzyme is pte N which stands for phosphatase and tense and homolog."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So it basically removes the phosphoro group via a process of hydrolysis off of a specific type of amino acid on our protein."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And this specific type of protein phosphatase plays a role in regulating the growth of our cells."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So it basically plays an important role in controlling cancer."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So basically, let's review what each type of our regulation method is."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So earlier we spoke about allosteric regulation and this basically involves the binding of some type of specific molecule onto the allosteric site of the enzyme to either activate it or deactivate it."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So we actually look at an allosteric regulation in this case."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So we said a specific type of effective molecule known as cyclic adenosine monophosphate has to actually bind to the PKA molecule protein Kindness A to actually activate that."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And this is our method of allosteric regulation."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So proteolytic AC cleavage was discussed in this section."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And it basically involves an irreversible process that usually does not require energy."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And what happens is Arozymogen inactive enzyme is transformed into its active via the process of hydrolysis of one or several peptide bonds."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "And the final method of regulation that we focused on was reversible covalent modification."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So, unlike proteolytic activation, this process is reversible, and it usually requires energy."}, {"title": "Proteolytic Cleavage and Reversible Covalent Modification .txt", "text": "So to basically phosphorylate some type of molecule, some type of protein, we have to use the ATP molecule."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Recombinant DNA technology basically gives us the ability to modify and change preexisting genes."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And by changing the sequences of nucleotides in the preexisting gene, we can in turn change what the sequence of amino acids is in the protein that is produced by that gene."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And in certain cases, by changing the sequence of amino acids, we create brand new proteins that can contain brand new functions."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So we see that recombinant DNA technology makes it possible to produce brand new proteins that have never been produced before, that contain brand new structures and have their own unique function."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And we can do this by basically modifying the preexisting genes, by changing the nucleotide sequence in those genes that encode for certain proteins."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, there are three types of modifications that we can commonly make to our gene."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "We can modify that gene by deleting a segment of DNA in that gene."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "We can modify a gene by inserting a segment into that gene, or we can modify it by substitution."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, in this lecture, we're going to focus on deletions and insertions."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "In the next lecture, we're going to discuss substitutions."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So let's begin with deletions."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, deletions can be broken down into two categories."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "We can delete very large segments of the gene, or we can delete smaller segments of the gene."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And these two categories basically require slightly different methods."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So let's begin with method number one, by which we essentially modify our plasmid by removing a large segment of DNA from that plasmid."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And the way that we carry out this process is so we take our plasmid."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So remember, the plasmid is this circular, double stranded DNA molecule."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And let's suppose we want to delete, we want to remove this entire chunk of DNA shown by purple."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So to remove this, all we really have to do is take those specific restriction enzymes that cleave at this position."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And this position, we mix it with this plasmid molecule that basically cleaves, removes this unwanted section, and then we can essentially purify and remove that unwanted section by some type of process."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "For example, gel electrophoresis."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And then we can add a DNA ligase molecule which will use ATP to basically create that phosphodiaste bond between this end and this end."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So at the end, we produce this new synthesized plasmid in which we removed, we deleted a large chunk of that DNA molecule, as shown in this diagram."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So we essentially removed this purple section from that plasmid."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And now we can basically take the plasmid, place it into our bacterial cell, and that bacterial cell can synthesize the gene that the plasmid actually codes for."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, let's suppose instead of removing a large segment of that gene, a large segment of this plasma, we want to remove a much smaller segment, as shown in the following diagram."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So instead of removing this segment, we only want to remove this small segment."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Well, the way that we carry out this process is almost like this process, but it has a slightly different case."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So what we have to use is something called an axonuclease."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So we take our restriction enzyme and in step one we basically add the restriction enzyme that also cleaves on this side and this side."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And so at the end, we basically produce the following linear DNA molecule."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And on both ends we basically contain those green sections that we want to remove."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So in the next step, we add a molecule we call an exonuclease."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And what an exonuclease does is it essentially removes these tiny portions at the end."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And once the exonuclease removes these two portions, we can remove that exonuclease, remove these two tiny portions and then add DNA ligase to basically create that phosphodiasta bond between these two ends that now don't have these green sections."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And so now we contain this new gene sequence, this new gene that now contains this new DNA sequence."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And now we can add it into our bacterial cells and once again it can synthesize the protein that the plasmid actually codes for."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So this is how we delete segments of DNA in our plasmid."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, what about if we want to insert a segment of DNA into our plasma?"}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "How can we go about inserting DNA segments?"}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Well, once again, let's suppose we have the following segment or the following plasma."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So on the plasmid we have this orange section that we essentially want to keep and we want to remove this brown section."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And then we want to insert a specific segment of DNA that we essentially synthesized in the laboratory."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, the method that we're going to use is known as the Cassette Mutagenesis method."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So a procedure called Cassette Mutagenesis can be used to insert specific segments of DNA into the plasmid known as cassettes."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So we essentially take our plasma and as always, we mix it with our restriction enzymes."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And these restriction enzymes basically cleave at position one and position two."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "So we basically produce these two fragments that differ by size."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And because they differ by size, and because we want to remove this fragment here, we can use some type of purification method, for example, gel electrophoresis, to remove this molecule here."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And so after the purification method, we have this molecule."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And now we can place our cassette, that newly synthesized DNA molecule that was created in the laboratory."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "We can basically make it in such a way that the ends contain the sticky ends, complementary ends, which can stick to the end of this initial orange strand of DNA."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And so now we mix it in the presence of once again, DNA lie gaze."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And the liegase will basically combine the complementary sequences of these two ends to these two ends."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And we form the following newly synthesized plasmid that contains this insertion, this cassette."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And now we can use this plasmid, place it inside a cell, and the cell can basically synthesize the protein that corresponds to the DNA sequence in this particular plasmid."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "Now, the final type of modification method is known as a base pair substitution."}, {"title": "Cassette Mutagenesis and Gene Deletions .txt", "text": "And we'll talk about that in the next lecture."}, {"title": "Structure of the Human Eye.txt", "text": "The human eye is a specialized type of structure that is capable accepting outside stimuli in the form of photons of light."}, {"title": "Structure of the Human Eye.txt", "text": "So basically, our human eye takes the energy that is stored in the photons of light and it transforms that energy into electrical signals which eventually end up in the human brain."}, {"title": "Structure of the Human Eye.txt", "text": "And the human brain uses those electrical signals to to create an image of our surroundings."}, {"title": "Structure of the Human Eye.txt", "text": "So let's begin by looking at the diagram of our eye."}, {"title": "Structure of the Human Eye.txt", "text": "So if we examine the eye from a side view and we take a cross section, we get the following diagram."}, {"title": "Structure of the Human Eye.txt", "text": "So let's go through each one of these individual structures of the eye and discuss what their function is."}, {"title": "Structure of the Human Eye.txt", "text": "And let's begin with the outside most portion of the eye known as the sclera."}, {"title": "Structure of the Human Eye.txt", "text": "So the square begins here, it extends all the way around the eye and ends here."}, {"title": "Structure of the Human Eye.txt", "text": "It's basically this inner white portion here."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the sclera basically takes up the majority of the outside portion of our eye."}, {"title": "Structure of the Human Eye.txt", "text": "It is not transparent and it's white."}, {"title": "Structure of the Human Eye.txt", "text": "So when we look in the mirror, the white portion we see is our sclera."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the sclera is composed of a protein known as collagen, as well as elastic fibers."}, {"title": "Structure of the Human Eye.txt", "text": "And the sclear serves a protective purpose."}, {"title": "Structure of the Human Eye.txt", "text": "It basically protects our eye from various forms of damage."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the next portion we're going to discuss is the cornea."}, {"title": "Structure of the Human Eye.txt", "text": "The cornea is the outside portion found in the front of the eye."}, {"title": "Structure of the Human Eye.txt", "text": "And unlike the sclera, the cornea is clear, it's transparent, and that means it absorbs very little of the light and it allows most of the light to actually pass through."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the cornea contains an index of refraction of about 1.4, which is much higher than the index of a fraction of air."}, {"title": "Structure of the Human Eye.txt", "text": "And because of this relatively large difference between the index of refraction of the air and the cornea, most of the bending of light in the eye actually takes place on an inside arneum."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the next portion I'd like to discuss is the chloroid."}, {"title": "Structure of the Human Eye.txt", "text": "Now the chloroid is basically the layer below the sclera."}, {"title": "Structure of the Human Eye.txt", "text": "So if the sclero is this white portion, the layer below that is our chloroid."}, {"title": "Structure of the Human Eye.txt", "text": "And the chloroid actually contains the vascular portion of the eye, the portion that contains our connective tissue."}, {"title": "Structure of the Human Eye.txt", "text": "So the chloroid is linked to our blood, and so the blood that carries our nutrients and oxygen, the nutrients and oxygen are supplied to the eye via our chloroids."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the next region is this anterior cavity."}, {"title": "Structure of the Human Eye.txt", "text": "So this anterior or frontal cavity of the eye contains a special type of fluid known as our aqueous humor."}, {"title": "Structure of the Human Eye.txt", "text": "And the aqueous humor consists predominantly of water, but it also consists of a low concentration of proteins as well as other things."}, {"title": "Structure of the Human Eye.txt", "text": "And the aqueous humor basically maintains the pressure inside this region inside the eye."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the ciliary body, which is this portion here, and this portion here, basically contains the ciliary processes which actually synthesize and secretes our aqueous humor, the fluid known as aqueous humor."}, {"title": "Structure of the Human Eye.txt", "text": "And they secrete that fluid through a canal known as the canal of schlem."}, {"title": "Structure of the Human Eye.txt", "text": "So we have this anterior cavity that contains our aqueous humor, that is a fluid that maintains that pressure inside this region of our eye."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the next portion is our pupil."}, {"title": "Structure of the Human Eye.txt", "text": "So the pupil is the opening of the eye."}, {"title": "Structure of the Human Eye.txt", "text": "The pupil is the opening that actually allows light to pass through this region and into this large cavity that contains another type of gellike fluid known as our vitreous humor."}, {"title": "Structure of the Human Eye.txt", "text": "So what exactly is this pupil?"}, {"title": "Structure of the Human Eye.txt", "text": "So the pupil is this opening that can actually be controlled by special types of smooth muscles."}, {"title": "Structure of the Human Eye.txt", "text": "So these smooth muscles are known as the iris."}, {"title": "Structure of the Human Eye.txt", "text": "So when we look into the mirror, the iris is the colored portion of the eye, while the square is the white portion of the eye."}, {"title": "Structure of the Human Eye.txt", "text": "And the iris consists of two types of smooth muscles."}, {"title": "Structure of the Human Eye.txt", "text": "We have circular smooth muscles and we have radial smooth muscles."}, {"title": "Structure of the Human Eye.txt", "text": "And both types of smooth muscles are controlled by the autonomic nervous system."}, {"title": "Structure of the Human Eye.txt", "text": "So let's discuss how this control actually takes place."}, {"title": "Structure of the Human Eye.txt", "text": "So let's suppose that we are inside a room that is dark."}, {"title": "Structure of the Human Eye.txt", "text": "So we have very little light inside that room."}, {"title": "Structure of the Human Eye.txt", "text": "So that means in order for us to actually see, we would want to open up the pupil so that more light goes inside our eye and that basically helps us see better."}, {"title": "Structure of the Human Eye.txt", "text": "And that's exactly what happens when we enter a room that contains very little light."}, {"title": "Structure of the Human Eye.txt", "text": "So the sympathetic nervous system of our autonomic nervous system."}, {"title": "Structure of the Human Eye.txt", "text": "So our sympathetic division of the autonomic nervous system innervates one type of smooth muscle inside the iris, known as the radial smooth muscle."}, {"title": "Structure of the Human Eye.txt", "text": "And when we are inside a dark room, so under very dark conditions, the sympathetic nervous system basically contracts the radial smooth muscle, which dilates or opens up our pupil."}, {"title": "Structure of the Human Eye.txt", "text": "So this iris basically contains the radial smooth muscle that contracts as a result of the sympathetic division of the autonomic nervous system and opens up our pupil."}, {"title": "Structure of the Human Eye.txt", "text": "And by opening up our pupil, that allows more light inside the eye and that allows us to see better in the dark."}, {"title": "Structure of the Human Eye.txt", "text": "Now, on the other hand, if we are in a room that contains lots of light, our parasympathetic nervous system that innervates the circular muscle, the circular muscles of our iris basically contract the circular muscle and that actually decreases the size of the pupil, decreases the size of the opening, and that allows less light inside our eye."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the next portion that I want to discuss is the lens."}, {"title": "Structure of the Human Eye.txt", "text": "So once the light hits our cornea, it basically bends and it enters the lens through our pupil."}, {"title": "Structure of the Human Eye.txt", "text": "Now, once it enters the lens, from physics we know that the lens is a convex lens and a convex lens basically diverges the rays of light."}, {"title": "Structure of the Human Eye.txt", "text": "So the lens of the eye is a convex lens that is used for fine tuning and focusing the light rays onto a special region at the back of the eye known as our retina."}, {"title": "Structure of the Human Eye.txt", "text": "Now, just like the pupil can basically be controlled, the length can also be controlled by a set of smooth muscles known as the ciliary muscles found inside our section shown here."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the ciliary muscles are controlled by the autonomic system."}, {"title": "Structure of the Human Eye.txt", "text": "And basically, by changing the shape of our lens, we're essentially changing the focal length of that lens."}, {"title": "Structure of the Human Eye.txt", "text": "And that allows us to focus our image onto our retina at the back of our eyes."}, {"title": "Structure of the Human Eye.txt", "text": "So remember, from physics, we should know that because the lens is a convex lens, that basically creates a real image found on the back of the eye on the retina."}, {"title": "Structure of the Human Eye.txt", "text": "And that image is upside down, it's inverted."}, {"title": "Structure of the Human Eye.txt", "text": "So actually, when the image is taken to the brain, the brain actually has to flip that image right side up."}, {"title": "Structure of the Human Eye.txt", "text": "And that's exactly why we see things the right way up, the right side up."}, {"title": "Structure of the Human Eye.txt", "text": "Now, let's discuss our retina."}, {"title": "Structure of the Human Eye.txt", "text": "So, the retina is basically this portion in the back of the eye, and the retina contains specialized types of cells known as the rods and cones."}, {"title": "Structure of the Human Eye.txt", "text": "Now, rods and cones contain special photochemicals that are capable of detecting our life, absorbing the photons of light."}, {"title": "Structure of the Human Eye.txt", "text": "And this photochemical is known as a pigment."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the rods contain a pigment known as rhodopsin."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the thing about radopsin is it can actually absorb all the wavelengths of visible light."}, {"title": "Structure of the Human Eye.txt", "text": "And that means our rods cannot actually distinguish the different colors."}, {"title": "Structure of the Human Eye.txt", "text": "On the other hand, we have three different types of cones, and each one of these different types of cones contains its own unique pigment that can basically absorb its own unique frequency of light, its own unique wavelength of light."}, {"title": "Structure of the Human Eye.txt", "text": "And so that means it's the cones and not the rods that are capable of distinguishing and producing the different colors that we actually see."}, {"title": "Structure of the Human Eye.txt", "text": "Now, what exactly happens when the photons of light hit our rods and cones?"}, {"title": "Structure of the Human Eye.txt", "text": "Well, when the photons of light actually hits these photochemicals known as our pigments, what basically happens is we have a conformational change taking place on the proteins inside the membrane of our cells."}, {"title": "Structure of the Human Eye.txt", "text": "And that basically increases or decreases the permeability of ions such as sodium ions."}, {"title": "Structure of the Human Eye.txt", "text": "So that can either depolarize or hyperpolarize our cell membrane and that can ultimately create our electrical signal, which will basically pass up to our brain through a nerve known as our optic nerve."}, {"title": "Structure of the Human Eye.txt", "text": "So once the photons of life hit the rods and cones, this causes conformational change."}, {"title": "Structure of the Human Eye.txt", "text": "So the change in our shape of the proteins found on the membranes of our cells, which leads to the production of an electrical signal that shovels up to the brain via our optic nerve."}, {"title": "Structure of the Human Eye.txt", "text": "So there are two types of cells that we have to be familiar with when we're talking about this transmission of electrical signals."}, {"title": "Structure of the Human Eye.txt", "text": "So once the light actually hits the rods and cones, that light is transformed into electrical signals that basically ends up on a cell known as a bipolar cell."}, {"title": "Structure of the Human Eye.txt", "text": "And the bipolar cell then passes down that signal to our retinal ganglion cells."}, {"title": "Structure of the Human Eye.txt", "text": "And those retinal ganglion cells, their exxons basically converge and meet and they form our optic nerve, which basically goes all the way up to the brain."}, {"title": "Structure of the Human Eye.txt", "text": "And inside the brain, those electrical signals are basically used to create an image that is right side up."}, {"title": "Structure of the Human Eye.txt", "text": "Now, the last portion I'd like to talk about is something called the phobia."}, {"title": "Structure of the Human Eye.txt", "text": "The phobia is basically a specialized, a localized region found on the retina."}, {"title": "Structure of the Human Eye.txt", "text": "And the phobia consists of predominantly cones."}, {"title": "Structure of the Human Eye.txt", "text": "So we have a very high concentration of cones in the fobia compared to our rods."}, {"title": "Structure of the Human Eye.txt", "text": "And that's exactly why on the fovia, we have the sharpest image being formed."}, {"title": "Structure of the Human Eye.txt", "text": "So the fovia is a part of the rectangle that forms the sharpest image because it contains a high concentration of cones compared to our rods."}, {"title": "Structure of ATCase .txt", "text": "Asperset transcarbomoliase or Atcase is this enzyme found side aristones that catalyzes the first step in the biosynthesis of perimeterinebased nucleuside triphosphate molecules such as CTP or citadine triphosphates."}, {"title": "Structure of ATCase .txt", "text": "And this enzyme is actually controlled by these CTP molecules because they can ultimately go back and bind onto special regulatory sites, allosteric sites found on the enzyme and that inhibits the activity of the enzyme."}, {"title": "Structure of ATCase .txt", "text": "And so that's why we call asparty transcarbomoylease an allosteric enzyme."}, {"title": "Structure of ATCase .txt", "text": "Now, what we want to focus on in this lecture is the actual structure of asperty transcarbomolise."}, {"title": "Structure of ATCase .txt", "text": "And then we want to discuss what happens to that structure of the enzyme once the substrate molecule actually binds onto the active side of the enzyme."}, {"title": "Structure of ATCase .txt", "text": "So let's begin by describing the structure."}, {"title": "Structure of ATCase .txt", "text": "Now, this enzyme has coordinate structure."}, {"title": "Structure of ATCase .txt", "text": "And what that means is it consists of multiple subunits."}, {"title": "Structure of ATCase .txt", "text": "And there are two types of multi subunit structures."}, {"title": "Structure of ATCase .txt", "text": "One of them we call a catalytic triumph."}, {"title": "Structure of ATCase .txt", "text": "And we call it catalytic because it contains the active sites."}, {"title": "Structure of ATCase .txt", "text": "The other one is called a regulatory dimer."}, {"title": "Structure of ATCase .txt", "text": "And we call this one regulatory because that's where that regulatory molecule binds to."}, {"title": "Structure of ATCase .txt", "text": "The CTP molecule binds to the regulatory dimer, as we'll see in the next lecture."}, {"title": "Structure of ATCase .txt", "text": "So each one of these catalytic trimers actually consists of three individual but identical catalytic chains."}, {"title": "Structure of ATCase .txt", "text": "And that's why we call it a trimmer."}, {"title": "Structure of ATCase .txt", "text": "So C three, where C stands for catalytic and three stands for trimer."}, {"title": "Structure of ATCase .txt", "text": "And we actually have two of these catalytic trimers."}, {"title": "Structure of ATCase .txt", "text": "So we have a total of two multiplied by three."}, {"title": "Structure of ATCase .txt", "text": "So six of these individual but identical catalytic chains."}, {"title": "Structure of ATCase .txt", "text": "On the other hand, we have three of these regulatory dimers."}, {"title": "Structure of ATCase .txt", "text": "And each dimer consists of two identical chains."}, {"title": "Structure of ATCase .txt", "text": "Two identical regulatory chains."}, {"title": "Structure of ATCase .txt", "text": "And so we also see that we have three times two."}, {"title": "Structure of ATCase .txt", "text": "So six of these regulatory chains."}, {"title": "Structure of ATCase .txt", "text": "So we have six catalytic chains."}, {"title": "Structure of ATCase .txt", "text": "We have six regulatory chains to make a total of twelve of these subunits that make up the coronary structure of aspartame transcarbolase."}, {"title": "Structure of ATCase .txt", "text": "And if we examine the three dimensional structure of this molecule from top to bottom, this is basically what we see."}, {"title": "Structure of ATCase .txt", "text": "So these red dimers are the regulatory dimers."}, {"title": "Structure of ATCase .txt", "text": "So each one of these dimers consists of 121212 of these regulatory chains."}, {"title": "Structure of ATCase .txt", "text": "And this entire orange structure constitutes a single catalytic primer."}, {"title": "Structure of ATCase .txt", "text": "So we have one, two, three of these orange subunits."}, {"title": "Structure of ATCase .txt", "text": "Each one of these orange subunits is a catalytic chain."}, {"title": "Structure of ATCase .txt", "text": "And three of these catalytic chains arranged in this triangular format make up that catalytic trimer."}, {"title": "Structure of ATCase .txt", "text": "Now, because we're examining the structure from top to bottom, the other trimer is hiding beneath this trimer."}, {"title": "Structure of ATCase .txt", "text": "So if we take this structure and flip it this way, we're going to see this on top."}, {"title": "Structure of ATCase .txt", "text": "And the other trimer is basically found on the bottom."}, {"title": "Structure of ATCase .txt", "text": "So we have a total of two catalytic primers and three of these dimers on the sides."}, {"title": "Structure of ATCase .txt", "text": "So we have this triangular form as shown in this diagram."}, {"title": "Structure of ATCase .txt", "text": "Now, the question is, what exactly is the interaction like between regulatory dimers and these catalytic triumphs?"}, {"title": "Structure of ATCase .txt", "text": "Well, it turns out that each one of the regulatory chains in each one of these dimers interacts with one of these catalytic chains in each one of these catalytic trimmers."}, {"title": "Structure of ATCase .txt", "text": "And this interaction is made better."}, {"title": "Structure of ATCase .txt", "text": "It is amplified by the presence of a metal atom, of a zinc metal atom."}, {"title": "Structure of ATCase .txt", "text": "So if we examine so let's take a look at one of these red structures."}, {"title": "Structure of ATCase .txt", "text": "Let's say we're examining this regulatory structure here."}, {"title": "Structure of ATCase .txt", "text": "So this is basically what we're going to see."}, {"title": "Structure of ATCase .txt", "text": "So we have a bunch of these beta chains."}, {"title": "Structure of ATCase .txt", "text": "We have some of these alpha chains."}, {"title": "Structure of ATCase .txt", "text": "And right about here at the interface between the red regulatory chain and this orange catalytic chain, we're going to find a zinc atom."}, {"title": "Structure of ATCase .txt", "text": "And that zinc atom interacts with the Sistine residues with four cysteine residues."}, {"title": "Structure of ATCase .txt", "text": "And that basically amplifies it makes better the interaction between the orange chain, the catalytic chain and the red chain that regulatory chain."}, {"title": "Structure of ATCase .txt", "text": "So each R regulatory subunit contains a zinc domain that contains the zinc metal atom that interacts with the C subunit, the catalytic subunit."}, {"title": "Structure of ATCase .txt", "text": "So again, each one of these red regulatory chains in the dimer interacts with one of these catalytic chains in that catalytic trimer via this metal atom that is present within the end portion, the interface section of each one of these regulatory chains."}, {"title": "Structure of ATCase .txt", "text": "Now, when scientists were basically studying this molecule, how exactly did they actually discover where the active side is found within this molecule?"}, {"title": "Structure of ATCase .txt", "text": "Well, instead of actually using the substrate molecules for this enzyme, they used an inhibitor, an irreversible inhibitor to this enzyme."}, {"title": "Structure of ATCase .txt", "text": "They synthesized an irreversible inhibitor that resembles the two substrate molecules of this particular enzyme."}, {"title": "Structure of ATCase .txt", "text": "So remember what Atcase actually does."}, {"title": "Structure of ATCase .txt", "text": "It catalyzes the conversion of a molecule called aspartate and a second molecule called carbomol phosphate."}, {"title": "Structure of ATCase .txt", "text": "So it combines these two molecules to form the end carbomol aspartate as well as a single orthophosphate molecule."}, {"title": "Structure of ATCase .txt", "text": "Now, what this molecule does is scientists created so scientists created this irreversible inhibitor, a bisubstrate analog known as the poly molecule which stands for and phosphor, acetyl, l, aspartate."}, {"title": "Structure of ATCase .txt", "text": "And the structure of this poly molecule resembles the intermediate molecule that is formed in the bisynthesis of the CTP molecule."}, {"title": "Structure of ATCase .txt", "text": "And this is what polar actually looks like."}, {"title": "Structure of ATCase .txt", "text": "So polar resembles an intermediate in the reaction pathway and is therefore a highly potent, a highly effective inhibitor."}, {"title": "Structure of ATCase .txt", "text": "It binds onto the active side because it resembles the bisepttrat analog that is formed as an intermediate in this particular reaction."}, {"title": "Structure of ATCase .txt", "text": "And so once it binds onto the active side, it binds irreversibly and it does not let go."}, {"title": "Structure of ATCase .txt", "text": "And that inhibits the activity of this enzyme."}, {"title": "Structure of ATCase .txt", "text": "Now, once we actually bind the polyme molecule to the active side, that also that not only tells us where the active side is found, but it can also be used to basically study what kind of structural changes actually take place within the enzyme."}, {"title": "Structure of ATCase .txt", "text": "As we'll see in just a moment."}, {"title": "Structure of ATCase .txt", "text": "Now, one thing I'd like to point out about the active side of the enzyme, wherever that active side is, we have these three negative charges on this polymolecule."}, {"title": "Structure of ATCase .txt", "text": "And the fact that we have three negative charges basically implies that inside the active side of this enzyme we'll find residues that contain positive charges."}, {"title": "Structure of ATCase .txt", "text": "So basically, those positive charges in the residue interact with the negative charges of this bi substrate analog molecule, the poly molecule."}, {"title": "Structure of ATCase .txt", "text": "So the next question is what exactly did scientists see when they mixed the poly with this enzyme?"}, {"title": "Structure of ATCase .txt", "text": "Well, what they saw was where that poly actually bound to was at the interface between any pair of these catalytic chains within that primer."}, {"title": "Structure of ATCase .txt", "text": "So the poly inhibitor binds onto a region located on the boundaries of each pair of catalytic subunits in any one of those catalytic trimmers."}, {"title": "Structure of ATCase .txt", "text": "And because we have three of these boundaries between the pairs in any given trimer, we see that we have three of these active sites in any trimer."}, {"title": "Structure of ATCase .txt", "text": "And because we have two triumphs, that implies we must have six active sites."}, {"title": "Structure of ATCase .txt", "text": "So we see that the quotinary structure of the ATCAs actually consists of six individual active sites."}, {"title": "Structure of ATCase .txt", "text": "And that means if all those active sites are occupied at some given moment in time, six of these reactions are taking place at the same exact moment in time."}, {"title": "Structure of ATCase .txt", "text": "So this is where poly so this is let's suppose the poly molecule, it binds onto this location, the first active side, this location, the second active side, and the third active side as well."}, {"title": "Structure of ATCase .txt", "text": "And of course, if we flip it this way, we're going to see the other catalytic trimmer and it also contains three of these active sites."}, {"title": "Structure of ATCase .txt", "text": "Now, the final question I'd like to explore is what did scientists actually see when that polymer molecule was bound onto the active side?"}, {"title": "Structure of ATCase .txt", "text": "What types of structural changes actually took place in the queen every structure of this atcase allosteric enzyme?"}, {"title": "Structure of ATCase .txt", "text": "Well, just like as we discussed in hemoglobin, when the oxygen molecules are not bound to the heme groups of hemoglobin, that hemoglobin molecule exists in the T state, in the ten state."}, {"title": "Structure of ATCase .txt", "text": "And what that means is the entire coronary structure is constrained."}, {"title": "Structure of ATCase .txt", "text": "And so the affinity of the heme groups for oxygen is very low."}, {"title": "Structure of ATCase .txt", "text": "And in the same analogous way, because this allosteric enzyme basically exhibits cooperativity."}, {"title": "Structure of ATCase .txt", "text": "It also exists in the T state as well as in the r state."}, {"title": "Structure of ATCase .txt", "text": "So when the polyme molecule E is absent from the environment, that means none of the active sites are actually occupied."}, {"title": "Structure of ATCase .txt", "text": "And so the entire coordinary structure of this enzyme will exist in the T state."}, {"title": "Structure of ATCase .txt", "text": "It will be very tense and very constrained."}, {"title": "Structure of ATCase .txt", "text": "And so that means the affinity of all the active sites for the substrate will be low."}, {"title": "Structure of ATCase .txt", "text": "And so it will display a low catalytic activity."}, {"title": "Structure of ATCase .txt", "text": "But as those substrate molecules and in this particular case, as the bi substrate analog, the polyp molecule begins to bind onto the active sites of the enzyme."}, {"title": "Structure of ATCase .txt", "text": "What begins to happen is the primers basically begin to move away from one another."}, {"title": "Structure of ATCase .txt", "text": "And as more and more active sites are filled, the trimmers move even farther."}, {"title": "Structure of ATCase .txt", "text": "And as they move, they rotate and they cause the dimers to also rotate and move."}, {"title": "Structure of ATCase .txt", "text": "And that creates a quarterly change in the quarterinary structure of that molecule."}, {"title": "Structure of ATCase .txt", "text": "And that causes it to basically go from the T state to the relaxed state."}, {"title": "Structure of ATCase .txt", "text": "It basically becomes less constrained, more relaxed, and the affinity of the active sides for the substrate molecule increases as this actually takes place."}, {"title": "Structure of ATCase .txt", "text": "So once again, as the substrate binds, in this case, as the poly inhibitor binds onto the active side, it causes the two trimmers to move farther apart and rotate, which in turn causes the regulatory subunits to also move."}, {"title": "Structure of ATCase .txt", "text": "And therefore, the entire structure seems to expand upon the binding of that substrate molecule to the active side."}, {"title": "Structure of ATCase .txt", "text": "And so as the active sides become filled, we see that the tank state, the T state, transitions into the r state, and the equilibrium basically shifts."}, {"title": "Structure of ATCase .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Structure of ATCase .txt", "text": "So we have this equilibrium that exists between the T state and the r state."}, {"title": "Structure of ATCase .txt", "text": "Now, before we add any polymolecules, when they are not present in the environment, in the absence of the polysubstrate or the actual substrate, the aspartate or the carbo moyl phosphate, the coronary structure exists in the T state."}, {"title": "Structure of ATCase .txt", "text": "And in this state, the enzyme has a low affinity for the subtract molecules and will display a low catalytic activity."}, {"title": "Structure of ATCase .txt", "text": "On the other hand, as we begin to add the polymer molecules, they begin to slowly add into the active sides found in those catalytic primers."}, {"title": "Structure of ATCase .txt", "text": "And as they begin to fill those active sides, what that does is it moves."}, {"title": "Structure of ATCase .txt", "text": "So this is one trimer."}, {"title": "Structure of ATCase .txt", "text": "This is a second trimer."}, {"title": "Structure of ATCase .txt", "text": "As the pilot begins to bind onto the trim or active sides, the entire trimmers begin to move apart."}, {"title": "Structure of ATCase .txt", "text": "As they move apart, they rotate, and they cause the movement of these regulatory sides."}, {"title": "Structure of ATCase .txt", "text": "And so the entire molecule basically expands."}, {"title": "Structure of ATCase .txt", "text": "It becomes more relaxed, so it becomes less constrained."}, {"title": "Structure of ATCase .txt", "text": "And what that means is the active sites of the other active sites, which are unoccupied will basically increase the affinity for the substrate molecule and they will be much more likely to actually bind onto those Units."}, {"title": "Structure of ATCase .txt", "text": "And what that means is, because we have more than one active site, those active sites will basically be able to interact with one another as a result of these structural changes that take place upon the binding of that substrate molecule to the active side of the enzyme."}, {"title": "Structure of ATCase .txt", "text": "substrate molecules."}, {"title": "Structure of ATCase .txt", "text": "And so ultimately, as more of the active sites become filled with those substrate molecules, the equilibrium basically shifts to the r state."}, {"title": "Structure of ATCase .txt", "text": "And what that means is at a high concentration of substrate, when most of the active sites will be filled by the substrate molecule, all the enzymes will exist predominantly in the r state."}, {"title": "Structure of ATCase .txt", "text": "But in the absence of the substrate molecule, when none of the active sites are filled by the substrate molecules, that means all the enzymes will predominate in the T state."}, {"title": "Structure of ATCase .txt", "text": "Now, the thing about the Rstate is the r state describes this relaxed state, relaxed structure where there is not too much constraint and so definitive of the active side for the substrate is high and that represents a high catalytic activity, a high catalytic rate."}, {"title": "Structure of ATCase .txt", "text": "Now, what we still haven't discussed is where the CTP actually binds to and how exactly does the binding of the CTP molecule to the regulatory dimer?"}, {"title": "Structure of ATCase .txt", "text": "That's where it binds to."}, {"title": "Structure of ATCase .txt", "text": "How exactly is the binding of the CTP onto these regulatory dimers actually inhibits affects the activity of that enzyme?"}, {"title": "Structure of ATCase .txt", "text": "This is what we actually want to focus on in the next lecture and we're also going to discuss what this molecule or how this molecule actually exhibits the process of cooperativity."}, {"title": "Structure of ATCase .txt", "text": "So remember, the reason this molecule exhibits cooperativity is because it consists of these twelve different sub."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "We know the cells of our body need to use ATP to actually carry out many different types of cell processes."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, one source of these ATP molecules are fatty acids."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, where the cells of our body actually obtained these fatty acids in the first place?"}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Well, the answer is simple from our diet."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "The majority of the fatty acids used by our body to actually generate ATP come from married diets."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "But the next question is, can the cells of our body actually synthesize their own fatty acid molecules from constituents?"}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And the answer is yes."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "In fact, this is exactly what happens when we eat one too many donuts."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So if we eat excess carbohydrates or protein, these molecules can actually be transformed into fatty acids, then stored as triglycerides in our adipose tissue."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "This process is what we call fatty acid synthesis."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So, fatty acid synthesis takes place predominantly in our liver cells, in hepatocytes, and to a smaller extent, it also takes place in lactating memory glands and an adipose tissue."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So, in the next several lectures, we're going to look at the details of this complicated process."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "But in this lecture, what I'd like to focus in is on seven important facts that you have to know about fatty acid synthesis."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So, fact number one, fatty acid synthesis takes place in the cytoplasm, and this is in contrast to the beta oxidation, the breakdown of fatty acids which takes place in the matrix of the mitochondria."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Fact number two in eukaryotic cells to cells in our own body, we actually have a single polypeptide chain, a single protein known as fatty acid synthase that catalyzes the elongation, the formation of fatty acid molecules."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And this fatty acid synthase actually contains seven different catalytic sites, which each carries out its own specific function, as we'll see in the next lecture."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, in addition to these seven catalytic sites on the fatty acid synthase, we also have a domain we call the Acyl carrier protein domain, or ACP domain."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And attached onto this acid carrier protein is a phosphopancy thion molecule, which is a vitamin B five derivative."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So, to see exactly what we mean, let's take a look at the following diagram."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So, we have the fatty acid synthase shown in red, and that contains seven catalytic sites which are not shown."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "In addition to those seven catalytic sites, we also have a domain we call the Acyl carrier protein domain."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And that's shown in green."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And attached onto this ACL carrier protein, is the vitamin B five derivative we call phosphopancythione."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, on the tip of this phosphopancythine is a sulfide hydro group."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And attached onto this sulfidel group is the next acetolico enzyme, a molecule that will be used to actually elongate that fatty acid chain."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So we see that fatty acid synthesis incorporates carbon atoms from acetylco enzyme A molecules onto that growing fatty acid chain."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And as we'll see in more detail, those acetyl Cozume molecules are attached onto this sulfidel group."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, the process by which we actually form fatty acids isn't a very energetically, favorable process."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "In fact, we have to use ATP molecules to carboxylate, and then the process of decarboxylation releases energy, and that helps drive the fatty acid synthesis process forward."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So we see that fatty acid synthesis is driven by the release of carbon dioxide molecules via a decarboxylation step."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, in addition to this decarboxylation step, we also have reduction steps."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And these reduction steps actually utilize reductant molecules."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And in the case of fatty acid synthesis, these are NADPH molecules."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "And a final thing you have to know about fatty acid synthesis is the following."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Fatty acid synthesis actually stops at the 16 carbon stage, the palmtate stage."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "So our fatty acid synthesis synthase will essentially stop the process of producing those fatty acids once we form a 16 carbon molecule."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "Now, once we form that 16 carbon molecule, we can actually elongate that 16 carbon molecule, or we can even add double bonds."}, {"title": "Introduction to Fatty Acid Synthesis .txt", "text": "But this happens at a different site in the cell, and it uses different enzymes that are not the same as the fatty acid synthase."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Aside from temperature and carbon dioxide."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Another fact that that influences and affects hemoglobin's ability to bind oxygen and therefore affects the oxygen hemoglobin dissociation curve is something known as two three bifoxoglycerate, or simply two, three BPG."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So two, three BPG is a three car carbon sugar that is an intermediate in the process of glycolysis."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So when we break down sugar, specifically glucose, into Pyruvate molecules to form ATP, in the process of cellular respiration, we essentially form the two three BPG as an intermediate."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, when our cells are exercising, when they have a relatively high rate of metabolism, they can produce an excess amount of two, three BPG."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And some of these two three BPG molecules can ultimately leave these exercising cells and enter the capillaries that are found next to these exercising cells."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And once the two three BPG molecules are inside the capillaries, they enter the red blood cells where we have the hemoglobin molecule."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So, these are the exercising cells that have a relatively high rate of metabolism found within our tissue."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, when we produce an excess amount of two three BPG, some of these molecules leave the cell and enter our matrix."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, what exactly does a two three BPG molecule actually look like?"}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Well, it looks something like this."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So we have one two three carbons, and we also have these two phosphate groups."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And as we'll see in just a moment, these two phosphate groups, because they have a negative charge, they play a crucial role in actually binding to our deoxyhemoglobin molecules."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So once our two three BPG molecules into the matrix, they're then diffused via the capillary wall and into the blood plasma found inside the capillary."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So this is our capillary, and inside the capillary, we have red blood cells."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Our erythrocytes death carry our hemoglobin proteins."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So within our red blood cell, we have many of these hemoglobin proteins as shown."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And if we zoom in on a single hemoglobin, this is what we're going to see."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So recall that our structure of hemoglobin contains four individual polypeptide subunits."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So we have alpha one and alpha two."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And we also have beta one and beta two subunit."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, each of these subunits contains a hein group shown in brown."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And that heme group is capable of binding a single diatomic oxygen molecule."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So once our two three BPG molecule enters the red blood cells, what exactly takes place?"}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Well, basically, some of these hemoglobin molecules inside our red blood cells, some of these hemoglobin proteins will not contain any oxygen and these are called deoxy hemoglobin proteins."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And the two three BPG molecules, these molecules will be able to bind to a cavity to a space found between the beta one and the beta two subunits of deoxyhemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So deoxy hemoglobin has a cavity between the two beta subunits to which the two three BPG can comfortably bond to via electrostatic forces."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So between the beta two and the beta one, we have residues."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "We have amino acids that contain side chains that have positive charge."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And these positively charged sections of beats of a beta two and beta one subunits can bond electrostatically to the negatively charged phosphate groups of 23 BPG."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And this space, this cavity inside the hemoglobin, only exists when no oxygen are actually bound to the heme groups found within our hemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So once again, note that 23 BPG can only bond to deoxiform of hemoglobin because when oxygen actually binds onto the hemoglobin, it creates a conformational change that squeezes in, that narrows in that space in the middle."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And so once oxygen is actually bound to the hemoglobin and that space closes in, and the two three BPG shown in purple can no longer actually bind onto our hemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So, once again, two three BPG only binds to deoxy hemoglobin proteins found within the red blood cells."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, once the two three BPG actually binds to our deoxy hemoglobin, it makes the protein much less likely to actually bind to other oxygen molecules."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And what that means is a high concentration of two three BPG inside the red blood cells shifts the entire oxygen hemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So, dissociation curve to the right."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And to see what we mean by that, let's take a look at the following diagram."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So, the Y axis is the percent saturation of hemoglobin, and we range from zero to 100%."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "The x axis is the partial pressure of our oxygen inside our tissue, exercising our tissue, and that is given to us in millimeters of mercury."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And so we begin at zero mmhg, and we end up at 100 hhmg."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So notice that this partial pressure corresponds to the partial pressure inside our lungs."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And this partial pressure of 40 mercury corresponds to the partial pressure inside the tissue of our body."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, the blue curve is the curve that describes our relationship when we don't have any two three BPG present inside our blood plasma."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "But when we have two three BPG present, the red curve is the curve that describes the relationship between our hemoglobin and the partial pressure of oxygen."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And notice that the red curve is shifted to the right of our blue curve."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And that's exactly what we mean by shifting the curve to the right side."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, why does this actually take place?"}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Well, let's take a look at our tissue partial pressure of 40 mercury."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So if we draw a vertical line and we find the corresponding Y coordinates, the Y points for the blue curve, when we don't have any two three BPG present in the red blood cells found inside the capillaries, we see that we have a percent equaling to about 70% saturation of hemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "But at the same exact partial pressure for our curve that contains the two three BPG, we have a value of about 60% saturation of hemoglobin."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And the fact that we have less saturation of hemoglobin in our red blood cells that contain the two three BPG."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "That basically means more of these hemoglobin molecules are not actually bound to the oxygen."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And so more oxygen is unloaded into the exercising cells of our tissue."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So when our metabolic rate inside the tissue increases, they require more oxygen to actually produce ATP."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And that's exactly why the two three DPG interests the red blood cells in the first place to stimulate our deoxy hemoglobin to not actually bind to the oxygen, so that more oxygen is allowed to travel into the cells of the exercising tissue."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So, once again, from the graph, we see that 23 BPG helps unload more oxygen into the metabolically active tissue."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "At a partial pressure of about 40 mercury, the red curve shows a smaller percent saturation, about 60%, compared to the blue curve, which shows about 70%."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And this implies that when 23 bifoxylglycerate is present, it is bound to deoxy hemoglobin, and it makes it much less likely to attach to oxygen."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "And so more oxygen actually unloads into those exercising tissues that have a high metabolic rate."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So we conclude that just like increasing the temperature and increasing the concentration of carbon dioxide inside our blood plasma shifts the entire curve to the right, so does increasing the concentration of two three BPG."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "Now, if we decrease the concentration of two three BPG, the red curve will essentially shift to the left side."}, {"title": "2,3 BPG and Hemoglobin.txt", "text": "So increasing two, three BPG shifted to the right, but decreasing it shifted in the opposite direction to the left side."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Enzymes are biological catalysts which basically act to speed up the reactions and processes that take place within living organisms for example, within the human body."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, enzymes have a very high specificity and what that basically means is enzymes react with a specific type of molecule or with a group of molecules that are close closely related."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, the molecules or molecule that reacts with our enzyme is known as the substrate."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And the substrate binds to a specific location on the enzyme known as the active site."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And the interaction between our enzyme and the substrate is electric in nature."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "The force involved is electric in nature."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, when the enzyme binds with our substrate this complex is known as the enzyme substrate complex."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So in most cases, for the enzyme to actually function effectively and efficiently another type of molecule, a non protein molecule, has to bind to our enzyme and this molecule is known as a Cofactor."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So Cofactors are non protein molecules that basically optimize the activity of our enzyme."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And Cofactors can be broken down into two categories."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we have our metal ions, which are basically inorganic cofactors and we have the coenzymes, which are the organic Cofactors."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And the coenzymes are usually vitamin derivatives."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we have two main types of coenzymes."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So coenzymes can be further subdivided into these two groups."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "We have the Co substrates, which are basically coenzymes that bind to our enzyme via loosely held bonds while our prosthetic group is basically the coenzyme that binds to the enzyme via tightly held bonds for example, Covalent bonds."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So let's discuss in more detail what the difference between these Cofactors are."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So metal ions include the minerals such as magnesium, zinc and potassium and so forth while our coenzymes are basically vitamin derivatives and this includes biotin and Thiamin Pyrophosphate."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, biotin is basically a water soluble B vitamin."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Specifically, it's the B seven vitamin while our Thiamine pyrophosphate is also a B vitamin derivative."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, our coenzymes can be subdivided into these two groups but what exactly is the major difference between these two groups?"}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "As discussed earlier?"}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we have the prosthetic group which basically bind tightly to the enzyme."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So these coenzymes bind tightly, usually via Covalent bonds to our enzyme and remain tightly bound during the reaction."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And during the reaction they are not actually changed."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And so following the reaction those coenzymes are regenerated and they remain unchanged."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "However, Co substrates bind to our enzyme via weak bonds and usually the Co substrates end up transferring one of the groups on that Co substrate on that coenzyme to our substrate."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So following our enzymeatic reaction these coenzymes, known as Co substrates usually change themselves."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And to actually regenerate that Co substrate we have to undergo some other type of reaction that usually involves energy."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, one example of a prosthetic group, basically a Co enzyme that tightly binds to our enzyme is the heme group."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And we'll talk more about the heme group when we discuss hemoglobin."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Hemoglobin is basically a biomolecule or protein that binds oxygen and carries oxygen to the different tissues found in our body."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now an example of a loosely health group that we're going to discuss is our coenzyme A which is basically a molecule that is involved in cellular respiration."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now an enzyme that is without its cofactor is known as the APO enzyme while the enzyme that has the cofactor bound to that enzyme is known as the hollow enzyme."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now the question still remains how exactly does the substrate actually bind to the active side of our enzyme?"}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we have two different models that basically describe two different ways by which our substrate can bind to our enzyme."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "We have the lock and key model as well as the induced fit model."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now the induced fit model is the model is the theory that basically is accepted nowadays while the lock and key model is the older model that is basically no longer really accepted."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And we'll see why that's the case in just a moment."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So let's begin with the locking key model."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "This model presumes that the enzymes active side is a perfect keyhole for our substrate which is basically the key."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So it states that the active side is a perfect fit for the substrate and neither the substrate nor the enzyme actually changes shape during our binding."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So this is basically the diagram that describes the locking key."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we can basically imagine that the enzyme has this active side that is a perfect fit for this substrate in the same way that our lock is a perfect fit for our key."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And when we place that key into our lock the key nor the lock actually changes in shape."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "They do not change in shape."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And so this is our lock and key model."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So the substrate shown in red fits perfectly into the active side of the enzyme and no change in structure actually takes place."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So this is our lock and key model."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now the more accepted model, what we think actually takes place on the molecular level between the substrate is the enzyme and the enzyme is described by the induced fit model or the induced fit theory."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So this is the much more accepted model."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "It states that the active side is not exactly a perfect fit."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "However, as the substrate basically goes into the active side what happens is the active side, the actual enzymes active side as well as the substrate itself actually change in shape ever so slightly to basically create that perfect fit."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And that makes sense because if we examine the subatomic level, if we examine the molecular level and we discuss the electric forces involved whenever we have the interaction between different molecules these electric attractive and repulsive forces will basically change the shape of the molecule just a little bit."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And this can be basically explained from a physics perspective."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So basically we can imagine our enzyme initially has a rectangular active side while our substrate is, let's say, some type of trapezoid."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "Now, when the trapezoid, the substrate shown a red actually goes into this rectangular active side."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "The rectangular active side changes in shape slightly and the trapezoid, we can imagine the trapezoid also changing in shape."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "For example, it is basically lengthened."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So we see that the substrate as well as our enzyme are not really perfect fits but when they interact within the active side, the enzyme as well as the substrate, they change in shape to basically create that perfect fit."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And this model is known as the induced fit model where the lock and key model basically states that the active size shape and our substrate shape does not actually change in shape in any way because they are essentially a perfect fit."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So this fits perfectly into the active side of the enzyme."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "So this theory doesn't really hold very much when you think about it from a physics perspective because we know from physics when our molecules interact because of the electrostatic forces, electromagnetic forces, whenever molecules are essentially approach one another there has to be some change in shape of those molecules as a result of those electric forces."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "And so the induced fit model is the model that is basically the accepted model nowadays."}, {"title": "Cofactors, Lock-and-Key and Induced Fit Model .txt", "text": "It describes Vibes, the way that our substrate interacts with our enzyme."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "Final step can actually take place, in which a water molecule can actually cleave this red bond."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "The high end energy thio esther bond between the sulfur and this carbon, and in the process, to stimulate the second step hydrolysis, this residue, the HistoGene 274, once again donates the H ion onto this oxygen, and that promotes the hydrolysis of the citral COA into that citrate molecule."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "So the citro Co enzyme A complex, is stabilized via these interactions shown in this region here."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "And in the final step, which is not shown in the diagram, we see that the Histidine 274 will act as an H plus donor, giving that H I onto this oxygen of the carbonyl group."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "And that will allow it will stimulate the hydrolysis of the red bond to ultimately form the citrate molecule and release that coenzyme A."}, {"title": "Step 1 of Citric Acid Cycle (Part II) .txt", "text": "So this is step number one of the citric acid cycle."}, {"title": "Oxidation of Fatty Acids .txt", "text": "In order for the cells of our body to actually be able to use the energy that is stored within the chemical bonds of triglyceride molecules, three things must actually take place."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Number one is the triglycerides must be broken down and mobilized into fatty acids within the fat cells of our body."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And once these fatty acids are mobilized, they travel into the bloodstream and then move into the cytoplasm of the target cell."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And once inside that target cell, the second thing that must happen is the fatty acid must be activated and it must be transported into the matrix of the mitochondria."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, the third thing that must happen is once that fatty acid is inside the matrix of the mitochondria of that target cell, the fatty acid must be broken down into acetyl coenzyme A molecules."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And this is what I'd like to focus on in this lecture."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So I'd like to focus on the degradation, the breakdown of fatty acids into acetylcoenzone A molecules as it takes place in the matrix of the mitochondria of the target cell."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So let's suppose our fatty acid, which is fully saturated and contains an even number of carbon atoms, actually makes its way into the matrix of the mitochondria of the target cell."}, {"title": "Oxidation of Fatty Acids .txt", "text": "What happens within the matrix?"}, {"title": "Oxidation of Fatty Acids .txt", "text": "Well, within the matrix, we basically have a series of four reactions that basically take place."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And these reactions ultimately shorten that carbon chain of the fatty acid by two, because they release an acetyl coenzyme a molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And this process will basically take place over and over and over until the entire fatty acid is actually broken down into these acetyl coenzyme A molecules."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And these acetyl coenzyme A molecules can then be fed into the citric acid cycle, which also takes place in the matrix of the mitochondria."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the citric acid cycle can actually help generate the high energy ATP molecules."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So once again, once the fully saturated fatty acid that contains an even number of carbon atoms makes its way into the matrix of the mitochondria in the acylcoemsi form and then undergoes a series of four reactions that ultimately shorten the carbon chain by two and release an acetylcoenzine a molecule and this process recurs within the matrix of the mitochondria."}, {"title": "Oxidation of Fatty Acids .txt", "text": "It takes place over and over and over until the fatty acid is fully broken down into these acetyl coenzyme a molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So what exactly are these four steps?"}, {"title": "Oxidation of Fatty Acids .txt", "text": "Well, step one is the oxidation step."}, {"title": "Oxidation of Fatty Acids .txt", "text": "It's an oxidation by specific type of molecule we call Fad, where Fad stands for Flavin adenine dinucleotide."}, {"title": "Oxidation of Fatty Acids .txt", "text": "The second step is a hydration step."}, {"title": "Oxidation of Fatty Acids .txt", "text": "The third step is another oxidation step, but now it is oxidized by NAD Plus."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the final step is a thiolytic cleavage bico enzyme, a molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So let's begin by focusing on the first step, the oxidation of flavin oxidation by flavin adenine dinucleotide."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So we begin with our fatty acid in the acyl coenzyme A form."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this is the activated form of the fatty acid and an enzyme known as acyl coenzyme adhdrogenase basically catalyzes the formation of a double bond between carbon two, the alpha carbon, and carbon three, the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So remember that this is the alpha carbon and this is the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And so we're forming a double bond of pi bond between the alpha and the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "In the process, we essentially oxidize this fatty acid chain."}, {"title": "Oxidation of Fatty Acids .txt", "text": "We remove two electrons and we place those two electrons onto this electron accepted a flavin adenine dinucleotide molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So we reduce the Fad into Fadh two."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And once we reduce the Fad into the Fadh Two, those two electrons are then transferred from the Fadh Two and onto another Flavon protein molecule known as the electron transferring flavor protein."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And that basically is the ETF that we have here."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So the two electrons are taken from that acetyl coenzyme A molecule and placed onto Fad to form the Fadh two."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Then those electrons move onto another flavor protein molecule, ETF electron transferring flavor protein."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Then those electrons move on to a different enzyme known as ETF dehydrone."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this basically contains sulfur ion groups or iron sulfur groups, and they can accept those electrons."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And finally, those electrons are ultimately transferred onto Ubiquinone, which is found on the inner membrane of the mitochondria, and that reduces that Ubiquinone into Ubiquinol."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the Ubiquinol can then transfer those two electrons onto the second proton pump found within the electron transport chain."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And that generates 1.5 ATP molecules."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So the Fadh Two that is produced in this oxidation step of the metabolism, the breakdown of the fatty acid, basically is used to form 1.5 ATP molecules."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So once again, in the first step, we have an oxidation reaction in which the acyl coenzyme A is oxidized into inoil coenzyme A with a trans double bond between the alpha and the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this molecule, the product molecule, is known as the trans delta two Enoil coenzyme A, where the delta two basically means we have a double bond between the second carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "That's why we have the second SuperScript, the two SuperScript, and the third carbon here."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And notice it's a trans, which means these two h atoms point along different directions."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, the electrons that are taken from the ACL coenzyme are transferred onto flavin adenine dinucleotide, and then it is reduced into Fadh two."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the enzyme that catalyze this reaction is the acyl coenzyme adhdrogenase."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, actually, we have three is design versions, three isozyme forms of acyl coenzyme Adhdrogenase."}, {"title": "Oxidation of Fatty Acids .txt", "text": "We have one that is known as the long chain, acyl coenzyme adhdrogenase."}, {"title": "Oxidation of Fatty Acids .txt", "text": "We have one that is called the medium chain and one that is called, that is called a short chain."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, the long chain basically acts on fatty acids that contain anywhere from twelve to 18 carbon atoms."}, {"title": "Oxidation of Fatty Acids .txt", "text": "The medium chain acts on fatty acids, which contain anywhere from four to 14 carbon atoms."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And we're only talking about even number of carbon atoms."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the short chain one acts on fatty acids that contain four or six carbon atoms."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So, as we discussed in this particular section, once the two electrons are transferred onto Fadh two, which is actually a prosthetic group found on this enzyme, the two electrons are then moved onto ETF, then onto an enzyme we call ETF dehydrogenase."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And then finally, they are used to actually reduce Ubiquinone into Ubiquinol."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And the Ubiquinol carries those two electrons onto the second proton pump found along the electron transport chain."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And so we see that the Fadh two that is produced in this oxidation step basically generates 1.5 ATP molecules along the protons, along the proteins of the electron transport chain, etc."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now let's move on to step two."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So step two is basically a hydration step, and it is catalyzed by an enzyme known as Enoil coenzyme hydrates."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So we take this same product molecule, TransDelta Two, inoil coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And now it acts as a reactant in this particular step."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this enzyme used the water molecule to basically attach a hydroxyl group onto carbon three, onto the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And so we transformed this double bond here into this alcohol group that is now attached onto the carbon, the third carbon, the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And notice that if we begin with the transversion, which we do in this particular case, this enzyme will act on the transversion and form the l isomer."}, {"title": "Oxidation of Fatty Acids .txt", "text": "If this was the cyst, the enol Co enzyme, hydrates would still be able to act on this CIS structure, but it would form the deisomer."}, {"title": "Oxidation of Fatty Acids .txt", "text": "But in this particular case, because we do have the trans, we're only going to form the l isomer of three hydroxy acyl coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, this is important because the enzyme that catalyze the third step only acts on the l molecule, the l isomer, not the deisomer."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So in the second step, we have the enzyme in oil, coenzyme A. hydratase adds a hydroxyl group onto the beta carbon, and this creates the l isomer version of hydroxy acyl coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now let's move on to the third step."}, {"title": "Oxidation of Fatty Acids .txt", "text": "In the third step, we have a second oxidation step actually taking place."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this was the first oxidation step, and this is the second oxidation step."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And in this particular case, the molecule that is basically abstracting those electrons is not Fad, but it's NAD plus."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So nicotine amide, adenine dinucleotide."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And so the NAD plus extracts two electrons as well as an H ion, and it forms the NADH."}, {"title": "Oxidation of Fatty Acids .txt", "text": "It also releases an H plus ion."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So essentially, the NADH molecule grabs this H atom along with the two electrons, and that releases the H plus ion, and that forms a double bond between this oxygen and this carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So we ultimately transform the alcohol group into a keto group that contains this carbonyl group shown here."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this molecule is known as the three keto, acyl coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So the third step is the second oxidation step in which the hydroxyl group on the third carbon, the beta carbon, is transformed into the keto group in the process that produces a nicotine amine adenine dinucleotide molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, the enzyme that basically catalyzed this step is the l three hydroxy acyl coenzyme A dehydronase."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And it only acts on the substrate molecule if it's the l isomer."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And that's why this step is so important."}, {"title": "Oxidation of Fatty Acids .txt", "text": "It has to form the l isomer and not the deisomer, because if this was the deisomer, this specific enzyme would not be able to actually bind that substrate molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, once we carry out the second oxidation step, this molecule is now ready to actually be cleaved."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So in the final step, we have a cleavage by coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So we have a second coenzyme A molecule that comes into the reaction and it uses its thyl group to actually cleave the bond between the second, the alpha carbon and the third carbon, the beta carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And because it's the thyl group of the coenzyme A that is acting as a nucleophile and cleaving that bond this cleavage is known as a Thiolytic cleavage of bico enzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, the enzyme that catalyzes the final step of this process is the beta keto thylase enzyme."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So in the final step, beta keto thylase catalyzes the cleavage of the sigma bond between the second carbon and the third carbon."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And so in this particular reaction, the molecule that is the nucleophile is another coenzyme A."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So the coenzyme A acts as a nuclear file and uses a thyl group to basically carry out this thylytic cleavage reaction."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, notice because the reaction took place on the beta carbon of the fatty acid and this was an oxidation reaction, we call this particular pathway the beta oxidation pathway."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So this series of four reactions that basically takes place over and over and over until that fully saturated fatty acid is completely converted into these acetyl coenzyme A molecules, is known as the beta oxidation pathway."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So once we actually generate those acetyl coenzyme A molecules, they are then fed into the citric acid cycle."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And in the next lecture, we're going to discuss how many ATP molecules are actually formed in this process."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So when this entire four step process actually takes place one time, we generate a single fadh two molecule and a single NADH molecule."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And these can then go on the electron transport chain to help generate ATP molecules, as we'll discuss in the next lecture."}, {"title": "Oxidation of Fatty Acids .txt", "text": "And we also generate the CETO coenzyme A product that now can enter the citric acid cycle."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Now, notice this other product that is formed in this step is different than this molecule that we began with."}, {"title": "Oxidation of Fatty Acids .txt", "text": "This molecule contain a certain number of carbon atoms, let's say, for instance, N number of carbon atoms."}, {"title": "Oxidation of Fatty Acids .txt", "text": "Then this product will be shortened by two."}, {"title": "Oxidation of Fatty Acids .txt", "text": "So it will contain N minus two numbers number of carbon atoms."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Inside our body, we have all these different types of processes which are catalyzed by enzymes."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So in order to actually study the behavior of enzymes and how they catalyze reactions, we have to study the rates of these enzymes and the rates at which they catalyze the reactions."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, one way in enzyme kinetics that we study the rates of reactions is by plot the following curve."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now on the curve, the y axis is the reaction velocity v knot of that particular enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And that's basically the rate at which the enzyme catalyzes its particular substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the x axis is the concentration of the substrate S that binds onto the active side of the enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So what we essentially do is we carry out an experiment."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So in the experiment, we have a beaker."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "In that beaker, we have the enzyme that we want to study."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, initially in the beaker, we don't have any concentration of substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so the concentration is zero."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And because no substrate is present in that beaker, no substrate will be bound onto the active side of the enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so the velocity, the rate of that enzyme will be zero."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so in trial one, point number one is zero."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, in trial two, we then add a certain amount of concentration of S, let's say this many S molecules, and then we measure that corresponding y value, that velocity of that enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so suppose we get the following value."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so this is data point number two, and now we add even more S concentration."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And let's say we add this quantity and that corresponds to this data point here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so we continue adding these data points."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And eventually, every single time we do this for any enzyme, this is the curve that we're going to obtain."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So notice what the blue curve tells us."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Initially, at the beginning, when we have relatively little amount of S in that mixture, this blue curve will resemble a straight line."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So from about here to about here, this blue curve looks like a straight line."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And what that basically means initially, when we add a small amount of concentration of S into our mixture, the rate, the velocity of that enzyme, the rate at which the enzyme catalyzes the reaction will be directly proportional."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we'll have a straight line with respect to that S, the concentration of substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "But as we continue increasing the concentration of S, we see that the slope begins to decrease and the curve begins to level off."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And eventually it approaches asymptotically the maximum velocity of that enzyme given by the red curve asymptotically means the blue curve never actually crosses that red line."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So that horizontal red line basically describes the maximum rate of activity of that enzyme at which the enzyme can actually operate on that substrate and transform it into some type of product."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "This is what the blue curve actually describes."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So to see this in equation form, let's take a look at the following equation."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "This equation basically describes what has taken place inside that beaker once we add the substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So initially we have the enzyme by itself and then we add the substrate and the substrate is also by itself."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "But then what begins to happen is the substrate begins to bind onto that enzymes active site and we form an intermediate molecule known as the enzyme substrate complex."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now going this way the rate constant is k one, but once we form some of this complex it begins to dissociate back into these two reactants and the rate constant of that reverse reaction is K minus one, at the same time some of that complex."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we now have the substrate inside the active side and the enzyme will begin to transform that substrate into the product and once we form the product, it will dissociate from the active side to basically form these final molecules, the product and the enzyme in its individual form."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now going this way the rate constant is k two and going in reverse, the rate constant is k minus two."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So this is the equation that basically describes what is taking place inside the beaker once we reach equilibrium, once we establish equilibrium."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now what we essentially want to do in this lecture is we want to derive the mathematical equation, the mathematical expression that basically describes this blue curve."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So can we derive such an equation?"}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the answer is yes."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "But before we actually begin our derivation, we want to simplify this equation."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So instead of using the equation that describes equilibrium, we're going to assume that we're essentially at the beginning of that equation."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So right at the start when the time is approximately equal to zero, and at this point in time the velocity of that enzyme is equal to v naught."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, another important point about the beginning of the reaction is right at the beginning of the reaction we have not yet formed a large amount of products."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So right at the beginning what happens is we have that enzyme that binds onto the substrate and this takes place relatively quickly."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so equilibrium is established here between these and this complex quickly because this takes place very quickly."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "But the enzyme basically converts that substrate into the product relatively slowly."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so at least initially at the beginning, we don't actually form a lot of the product."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So at a time of t approximately equal to zero, what that means is because we don't have a lot of product form, this reaction will take place at a very very low rate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so by approximating that we can essentially remove this entire equation and remove the k minus two term and that's because this reaction takes place at a negligible rate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So once again to simplify this equation here we can instead study the reaction at the beginning, that is when the time is approximately equal to zero, right at the beginning of that reaction."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "At that point in time, the rate V is equal to V Naught."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So at this moment in time, very little product P has actually formed."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so the reverse reaction of the formation of the product, this reaction here, becomes negligible, and we can basically remove that from our equation and this will simplify our equation and that will allow us to actually derive the equation that we're looking for."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So this is the equation that we want to use."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, what exactly is our starting point?"}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Well, the starting point is right here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we essentially begin by studying how that enzyme is functioning."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And to study how the enzyme functions, we have to actually look at the enzyme as it is down to that substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So in this particular case, so this is our starting point, and that's exactly where we get equation number one."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So equation number one basically gives us the rank law of this reaction here, as the enzyme actually has the substrate at the active side and it transforms it into the product."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so the rate law of this reaction is given by equation number one."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the rate of this, which is the V knot, remember, the Y axis here describes the rate at which the enzyme actually transforms the substrate that is bound to the active side."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so this V knot is the same V knot that we have along the Y axis here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So V Naught, the rate at which the substrate is transformed in the active side, is equal to the product of the rate constant K two of this reaction multiplied by the concentration of this molecule, the complex, this intermediate molecule, by the way, these are reactants, these are products."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And this is an intermediate molecule that exists between the reactants and the product."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, the problem with this equation is, remember, we ultimately want to basically derive a mathematical equation that describes this curve."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so what that means is, whatever this equation is, we have to be able to describe V Naught in terms of the concentration as of the substrate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And this equation has es."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And what that means is we can actually use this equation and we have to somehow replace the Es concentration with the S. And that's exactly what we're going to do in all these steps, as we'll see in just a moment."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So in the next step, we basically want to ask ourselves once we form this enzyme substrate complex."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Well, first of all, how do we form this enzyme substrate complex in the first place?"}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Well, to form this, we have to go in this direction."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And what's the rate law for the formation of this enzyme substrate complex?"}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Well, that is given by equation two."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the rate of formation of this enzyme substrate complex is equal to the product of the rate constant K one, and the concentrations of these two reactants, so E and S. Now, once we form the es."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "The Es can basically go in two different ways."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "It can either go on and form this product, which is basically this equation number one that we described here, or it can go back and reform these two reactants."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And equation three gives us the dissociation of that substrate from that enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the rate of dissociation of the enzyme substrate complex is equal to the product of the reverse reaction, k minus one multiplied by this quantity here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, our Es complex doesn't only dissociate going this way, there's also a probability that it will dissociate going this way."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so when it dissociates going this way, we have K two multiplied by the concentration of Es."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So this basically describes the entire rate of dissociation of the enzyme substrate complex."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So it can dissociate not only going this way, but also going this way."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And that's why we have these two summations."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we sum this with this and that gives us the rate at which our enzyme substrate complex actually breaks down."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So before we actually continue now, we have to make an important assumption."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the assumption that we make is that our reaction is at a steady state condition."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And what a steady state condition actually means, the intermediate that is involved in our reaction, the concentration of the intermediate, is not changing."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the only intermediate we have in our reaction is the enzyme substrate intermediate."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So what that means is the concentration of the enzyme substrate complex is not changing."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And what that implies is the only way that this concentration is not changing is if this reaction going this way if the formation of the enzyme substrate complex is equal to the dissociation of that enzyme substrate complex."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So assuming the steady state condition, the concentration of the enzyme substrate complex will remain constant."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And this means that the rate of formation of the enzyme substrate complex is the same of the rate as the rate of dissociation."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So equation number two is equal to equation number three because we make this assumption of a steady state condition."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So once again, a steady state condition means this concentration remains unchanged."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the only way that's true is if this K one reaction is equal to these two reactions here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the breaking is equal to the forming."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And so that's exactly what we do in this step."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "We essentially equate this equation to this equation here."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we have K one multiplied by these two concentrations is equal to K minus one multiplied by Es plus K two multiplied by Es."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Notice on the right side we have these two same terms and we can bring that out of our equation to get the following result."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And now we can basically bring all the concentrations to the left side and all the K values, the rate constants to the right side and we get this equation."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the product of the concentration of the enzyme in the substrate divided by the complex concentration is equal to K minus one plus K two divided by K one."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And instead of using these three rate constants, we basically set this ratio equal to a new ratio defined by uppercase K with the M subscript."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And this is known as the Michaelis constant."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the Makalis constant is actually a very important constant, as we'll see in the next lecture."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And the units of Michael's constant are concentration."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we'll talk much more about this in the next lecture and let's designate this as equation number four."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, if we take this new equation, this is equal to this and rearrange it and solve it for the concentration of the enzyme substrate complex, we get equation five."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So we essentially bring this to this side and we bring this to our denominator here, and we get equation five."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the concentration Es is equal to E multiplied by S divided by Km."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, for a moment, let's go back to that assumption that we made at the beginning."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "We said that we're looking at the reaction in its initial stages when the time is approximately equal to zero."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "Now, initially, when the time is approximately equal to zero, we have a lot of the substrate that hasn't actually bound onto the active side of the enzyme."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "And this means equation six."}, {"title": "Derivation of Michaelis-Menten Equation.txt", "text": "So the total substrate found inside our beaker is equal to the substrate that is not bound to the active side of the enzyme plus the substrate that is bound onto the active."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So as we discussed previously, many of the biological processes that exist in nature, for example, in the cells of our body, are catalyzed by enzymes."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So enzymes speed up the rates of chemical reactions and that essentially produces the same amount of product as without the enzyme, but it produces that product at a much higher rate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, the thing about that is we don't always want to produce some given product at a high rate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Sometimes we want to basically stop the production of a product because simply we have too much of that product inside our cell or inside the environment in the first place."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so what that means is for the biological systems, such as our cells, to actually function effectively and efficiently, they have to have a way of actually controlling and regulating the activity and the functionality of enzymes."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And one way by which we can actually control the activity of enzymes is by using these special molecules, and in some cases ions, to basically inhibit the activity of these enzymes."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And these are known as Enzymatic inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So once again, in order to function effectively, biological systems must be able to regulate and control the activity and the functionality of enzymes."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Special agents we call inhibitors can bind onto enzymes and inhibit or block their activity."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So there are two categories of inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "We have Irreversible inhibitors and we have Reversible inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So let's begin by briefly focusing on Irreversible inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So in Irreversible inhibition, that particular inhibitor basically binds onto the enzyme very tightly, very strongly."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "It binds so strongly that it's very unlikely that it's ever going to actually dissociate from that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So if we take a look in the following chemical reaction, we have the enzyme and our Irreversible inhibitor."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so because this is attracted very strongly to that enzyme, it will bind onto that enzyme, forming this product, this enzyme inhibitor complex."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And notice the arrow is much longer going this way than this way."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And what that means is the binding is essentially irreversible."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "The equilibrium lies very far to the right side of this chemical reaction."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now the majority of the time when this binding takes place between the Irreversible inhibitor and the enzyme, the binding is via covalent bonds."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "But sometimes we can also have non Covalent bonds."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So some inhibitors will bind to enzymes very tightly, either by covalent or non Covalent means."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once bound, they will not dissociate very easily from the enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And these inhibitors are known as Irreversible inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "They have a very high affinity for the enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So one very common misconception about Irreversible inhibition is that these inhibitors always bind Covalently by forming covalent bonds between the enzyme and the inhibitor."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that is simply not true."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "There are examples of molecules that inhibit Irreversibly, and yet they only form non covalent bonds."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So remember that the underlining, the defining point about Irreversible inhibitors is that they bind very strongly and so they will not let go of that enzyme very easily."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "That is what defines Irreversible inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once they bind, they change the confirmation."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so they essentially inhibit or block the activity of that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, there are many different examples of Irreversible inhibitors and three examples are listed on the board."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So we have nerve gas, we have penicillin, and we have aspirin."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And each one of these molecules basically binds to inhibits a specific type of enzyme found inside our body."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So let's begin with nerve gas."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Nerve gas is a very dangerous, very potent Irreversible inhibitor and it forms covalent bonds."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "It binds onto a special enzyme found inside the nervous system known as acetylcholine esterase."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So remember, acetylcholine esterase is an enzyme that breaks down the neurotransmitter acetylcholine that is used to basically communicate between nerve cells."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so by binding onto that enzyme, onto the acetylcholine estherase, it inhibits that enzyme from breaking down that neurotransmitter."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that essentially leads to the breakdown of the nervous system and that leads to death of that particular individual."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, what about penicillin?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So nerve gas kills off that individual, but penicillin actually saves that individual because, for example, if an individual has an infection by some type of bacterial agent, if we add penicillin into that individual, what penicillin does is it binds until special enzyme found in that bacterial cell that essentially is used by the bacterial cell to form the bacterial cell wall."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So that enzyme is known as transpeptidase."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So transpeptidase is an enzyme used by the bacterial cell to form the wall, the cell wall around that bacterial cell."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And penicillin binds onto transpeptidase and prevents it in, activates it, inhibits it, and prevents it from making that cell wall."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so the bacterial cell eventually dies off."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "What about Aspirin?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Well, Aspirin is once again an Irreversible inhibitor that binds until special enzyme known as cycloxycloxygenase."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So Aspirin binds until cycloxygenase, and it prevents that molecule from essentially stimulating the process of inflammation."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so that decreases pain, it basically makes headaches go away and so forth."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And each one of these are Irreversible inhibitors that modify the enzyme by binding covalently to that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now let's move on to reversible inhibitors."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So in reversible inhibition, we have these inhibitors that bind onto the enzyme, but they bind relatively weakly, and that means reversibly."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So we can easily change the conditions in the environment and that will essentially cause the dissociation of that inhibitor from that particular enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So the defining property of reversible inhibition is the ease with which the inhibitors can actually dissociate and break away from the enzyme under certain condition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And this is in contrast to Irreversible inhibitors that basically bind onto the enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once bound, they will not dissociate very easily."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, we can subdivide subcategorize reversible inhibition into three different types, and actually there are four, but in this lecture we're going to focus on three."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So we have competitive inhibition, we have uncompetitive inhibition, and we have non competitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "We also have something called mixed inhibition, but we're not going to focus on that in this lecture."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So let's begin with competitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So what exactly do we mean by competitive inhibition?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Well, in some cases, we have an inhibitor that actually resembles the substrate that binds onto the active side."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so what that means is the structure of that inhibitor is similar to the structure of that particular substrate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And because the structure resembles what that means is that inhibitor will bind to that same location where the substrate actually binds to."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so that's exactly why that inhibitor will compete with the substrate for that active site."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And we see in competitive inhibition that inhibitor binds onto that same active site that the substrate actually binds to."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So in this inhibition, the inhibitor molecule typically resembles that substrate and can therefore bind into the active side of that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once bound, the inhibitor prevents that substrate from actually occupying that active side."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, what competitive inhibition does, and we'll discuss this in much more detail in the next lecture, is it keeps the V max the same, so it keeps the maximum velocity of that enzyme the same, but it increases the parent Km value, it increases the mechaless constant, and we'll see exactly what that means and why."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "That's the case in the next lecture."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So let's take a look at the following diagram."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So we have the enzyme shown in blue."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "This is the active side of the enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "This is the inhibitor, and this is the substrate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Notice that they are very similar in their structure."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that's precisely why when we mix these three molecules, that inhibitor will bind onto the active site, forming the enzyme inhibitor mixture."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so this substrate will not bind onto that active site simply because there is no space to actually go into that active site."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, the question that you might ask is, why is it that the red molecule, the inhibitor, binds into the active side and not the green molecule, the substrate?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Well, because normally the affinity of that inhibitor for that active side is much higher than the affinity of that substrate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that's exactly why if given the chance to, if we mix these three molecules, because this has a much higher affinity for the active side than the substrate, this will be much more likely to actually bind into that active side to form that enzyme inhibitor mixture, enzyme inhibitor complex."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, the defining point about competitive inhibition that you should know is because that inhibitor binds into the active side the same region where the substrate actually binds to, we can actually kick off that inhibitor from the active side by increasing the concentration of the substrate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that's because when we increase the number of the green substrate molecules, there is much higher mathematical probability chance that the substrate will essentially collide with the active side and go into that active side."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So by increasing the concentration of the green molecules we increase the likelihood that the green molecules will collide with the active site to form the enzyme substrate complex."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that's exactly why if we increase the concentration of the substrate those green molecules will eventually outcompete these red inhibitor molecules and that will bring back the velocity of that velocity or the rate of that enzyme back to its normal value."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So once again, competitive inhibitors typically have a much higher thinly for the active side than natural substrate molecules."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "However, if we increase the concentration of the substrate the additional substrate can outcompete the inhibitor for the active side."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Therefore, increasing the substrate concentration can remove the effect of that competitive inhibitor that it has on that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And this is only true in competitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "It is not true in uncompetitive and it is not true in non competitive."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So if you're given a problem and you are told that by increasing the concentration you essentially remove that effect, you should know that that is competitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, what's one example of a molecule that acts as an inhibitor in the competitive inhibition fashion?"}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Well, inside our body, the cells have to be able to synthesize purine molecules and pyrimidine molecules because these are the molecules that are basically used to produce DNA molecules."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, one important enzyme in the biosynthesis of purines and pyramidines is known as Dihydropholate reductase."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And the substrate to this enzyme is dihydrophobate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, we also have this molecule known as methotrexate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And methotrexate is a competitive inhibitor to this substrate to this enzyme here."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "In fact, methotrexate is about 1000 times more likely to actually bind onto the active side of Dihydrofolate reductase than Dihydropholate itself."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And so that's exactly why it will be much more likely to bind to the active side than the substrate."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "But if we increase the concentration of the substrate that will essentially outcompete that inhibitor for the active side and that will bring back the rate of the enzyme back to normal."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, let's move on to uncompetitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Well, in some cases, we see that when that substrate actually binds onto the active side of the enzyme once the binding takes place, it creates conformational changes."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And sometimes in some enzymes that conformational change actually creates a brand new pocket, a brand new region of space that can now bind some type of inhibitor molecule."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And that inhibitor molecule can now bind into the space to form the enzyme substrate inhibitor complex."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once this complex is formed, that will essentially inhibit or block the activity of that enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And this type of inhibition is known as uncompetitive inhibition."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So in some cases, the binding and the substance to the active side changes the confirmation of the enzyme and creates a brand new pocket we call an allosteric side that was not previously there."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And this pocket is only created when the green substrate binds into the pocket of this blue enzyme."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "So before the binding took place, we did not have that allosteric site."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "But once the binding takes place, we create this pocket, the crevice, that can now bind some type of inhibitor molecule."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And if that red inhibitor molecule is in close proximity, it can bind onto that pocket."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And once it binds, it forms the enzyme substrate inhibitor complex."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "And notice that once the inhibitor is bound, it will basically prevent that green structure from exiting that active site, and that will will ultimately prevent that product from actually being formed."}, {"title": "Irreversible and Reversible Inhibition.txt", "text": "Now, as we'll see in the next lecture, and again, we'll discuss this in much more detail, and we'll see why this is the case in uncompetitive inhibition, the ven."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Previously, we introduced the concept of the active site and we said that all the different types of enzymes down inside our body and inside our cells have active sites."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So it turns out that just like all enzymes have similar properties, the active sites of enzymes also have important similar properties."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "We're going to discuss the six major properties of active sites."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And let's begin with property number one."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "The active side is that location."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "It's the three dimensional region found on that enzyme that is responsible for actually binding onto that substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So inside the active side so if this is our enzyme, this is our active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "This three dimensional crevice, the three dimensional crack in that enzyme is the active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this active side consists of the residues, those amino acids that are responsible for binding onto the substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And not only that, inside the active side, we also have these catalytic groups, these residues part of the enzyme that are responsible for actually catalyzing that particular reaction."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this leads us directly into property number two."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Active sites are responsible for stabilizing the transition state as well as forming and breaking the particular bonds involved in that chemical biological reaction."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So inside the active side, we have those residues responsible for actually stabilizing and lowering the energy of the transition state."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this is precisely what speeds up that particular reaction."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "In addition, we have those catalytic groups that are responsible for stimulating the breaking of bonds and the forming of bonds."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, property number three active sites create a microenvironment."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So if we look in the following diagram, we have this active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And what the active side does is when it actually binds onto that substrate, it essentially closes off ever so slightly and it creates this microenvironment that is predominantly nonpolar."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "In fact, the only time we're going to find water molecules inside the active side is when the water molecule is actually a participant or reactant in that particular chemical reaction."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Otherwise, we'll never find the water molecules inside the active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And that means the environment in the active side is non polar."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, what this microenvironment does is it brings the reactants very close together and it orients them in just the right orientation for that specific reaction to actually take place."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And what it also does is it decreases the likelihood that other reactions take place and that decreases the likelihood that unwanted products are actually formed."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So active sites typically create non polar microenvironments in which bonds can be formed and broken very easily."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And unless water actually participates as a reactant in that biological reaction, it is usually excluded from that microenvironment from that active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this also helps prevent unwanted reactions."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, property number four of active sites active sites actually only make up a very small portion, a very small component of that overall enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So even though the enzyme is usually relatively large."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "That active side is actually quite small compared to the overall structure and size of that particular enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "The question is why?"}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Well, if we examine the residues involved in the active side, those residues are usually found very far away, apart from one another on that primary sequence of the polypeptide chain."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And what that means is to bring those residues close together, that entire enzyme has to fold and form this particular three dimensional shape."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And to fold and bring those residues that are far apart close together, we have to fold different ways and many times to basically form the active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So it turns out the entire enzyme basically creates a scaffolding system that supports and stabilizes that small section, the active side that is actually used by the enzyme to catalyze that particular chemical reaction."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So the active side is much smaller than the actual size of the enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So the remaining portion of the enzyme acts to create, stabilize and support the active side by bringing the residues that are far apart closer together to basically catalyze the reaction and bind the substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, in addition, we can have other sites on the enzyme outside of the active side that also play an important role in actually regulating the functionality of that particular enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And these other sites are known as allosteric sites."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And we'll see many examples in the next several lectures or in future lectures."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, on top of that, these other portions of the enzyme can also interact with different types of components found in the cell."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "For example, we have a variety of different types of proteins and enzymes found in a cell membrane that actually bind onto that cell membrane."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And so these other sections of the enzyme can be responsible for actually adhering and binding onto the cell machinery."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "For example, the membrane of the cell."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, property number five of enzymes and the active sides of enzymes is that active sites typically bind substrates reversibly via non covalent forces."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So in property number one and two, we basically mentioned that inside the active side we have these special residues, the amino acids that contain the special side chain groups that are responsible for actually attaching and binding the substrate molecules."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And the binding that takes place takes place via non covalent interactions such as hydrogen bonds, such as hydrophobic interactions and vandervals forces."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So non covalent electric forces such as hydrogen bonds, Vanderwal's forces and the hydrophobic effect can all promote the reversible binding between the active side and the substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And what reversible binding basically means is once the substrate binds onto that active side and once we convert the substrate to the product, that product will essentially release itself and move away from the active site, it will not remain bound to that active site forever."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "That's what we mean by reversible binding."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now and this leads us directly into property six."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So recall from our discussion on non covalent interactions we said that for non covalent interactions to actually be strong enough and to actually be meaningful, the distance between our bonds, the distance between the molecules and atoms forming the bonds actually has to be short enough."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And so what that means is in order for the substrate to actually get close to the active side, to get close enough to form those meaningful non covalent bonds, the shape of that substrate has to be complementary to that shape of the active side of the enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And that leads us to property six active sites."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Active sites."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "This should be active sites where is my marker?"}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So this should be active sites have structures complementary to their corresponding substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So in order for the non covalent interactions between the residues of the active side of the enzyme and the substrate to be meaningful and strong enough for them to actually remain attached, the distance between them must be short enough."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this implies that the substrate must fit Snugly into the active side of that particular enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And this leads us into these two models."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So these two models are generally used to basically describe the way that the binding between the substrate and the active side of the enzyme actually takes place."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And although we still use the lock and key model, it's really the induced fifth model that describes more correctly the way that our binding takes place."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So let's begin by discussing what we mean by the lock and key model."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So lock and key simply means we have a key, we have a lock."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And essentially when we place the key into the lock, we know that the shapes are complementary and that's why we have a perfect fit between our lock and between our keys."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So in the lock and key model, the substrate fits precisely and perfectly into the active side due to their complementary shape."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So even before they actually bind, what this model tells us is the active side of the enzyme."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So the green structure is the enzyme, this is the active side and this is a substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And notice that before the binding actually takes place, this is complementary in structure to this active side."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And so when they fit, this simply moves into the active side and then they form those non covalent interactions."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "Now, according to our induced fit model, the active side of that enzyme is not exactly complementary to our substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "But when the binding actually takes place, the enzyme actually conforms to the structure of that substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And so the enzyme's active side basically changes shape ever so slightly."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "It induces the shape."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And then once the binding takes place, the active side basically conforms and takes the complementary shape of that particular substrate molecule."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So in the induced fit model, the shape of the enzymes active side is not exactly complementary."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "However, upon binding of the substrate to the active side, the binding causes the active side to become complementary to that substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So what the induced fifth model basically tells us is when the binding takes place, the active side of that enzyme and the substrate itself actually change shape ever so slightly, and they both conform into the shape in which each one is complementary to the other."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "So the substrate becomes complementary the active side, and the active side becomes complementary to that particular substrate."}, {"title": "Properties of Active Sites, Lock-and-Key Model and Induced Fit Model .txt", "text": "And it's this induced fit model that actually describes correctly the way that the binding actually takes place between the active side of the enzyme and the substrate."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "In our discussion on the epinephrine signal transduction pathway, we mentioned that this pathway uses a special type of receptor we call the seven transmembrane helix receptor or simply the seven TM receptor."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And because these receptors actually use Gproteins, we also sometimes call them g coupled protein receptors."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, it turns out that the epinephrine reference signaling pathway is not the only pathway inside our body that uses these g coupled protein receptors, these seven TM receptors."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Another important pathway that uses these seven TM receptors is the phosphoride signal transduction pathway or simply the phosphorusotide cascade."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, before we actually take a look at the details of this particular signal transduction pathway, what's an example of a g coupled protein receptor inside our body that uses this pathway?"}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Well, one common example is angiotensin two receptors."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So this is a g coupled protein receptor that actually uses this pathway to regulate the blood pressure inside the cardiovascular system of our body."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So we have a primary messenger, a peptide hormone known as angiotensin that binds until angiotensin two receptor and that initiates this phosphonositide signaling pathway."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So now let's actually move on to this pathway."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And let's begin by examining the structure of this g coupled protein receptor before that primary messenger actually binds onto its site."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So we have the membrane, we have the inside the cell, the outside of the cell."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "On the outside the cell, we have this cavity that basically binds the primary messenger."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "On the posing side, the intracellular side, we have a trimmer structure that is bound onto that seven TM structure."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And this trimer consists of three different types of domains."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "We have the gamma domain shown in blue."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "We have the beta domain shown in brown."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And then we have this alpha Q domain which is a g protein."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so that's why we call this the g alpha Q protein."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, before the binding takes place, we see that this g protein contains the GDP guanosine diphosphate bound to it."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And what that means is the affinity of the g alpha Q protein for these two domains is very high."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so it will exist in this trimeric form and it would be bound to that seven transmembrane helix structure shown in green."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "But when the binding process takes place so let's imagine this is the angiotensin two receptor."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "In that case, the primary messenger is angiotensin, the peptide hormone."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "When that peptide hormone binds onto this site here, that creates a conformational change in the structure of the green piece and then that induces a change in this orange piece."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so when that conformational change in the g alpha Q protein takes place, that's that essentially constricts this side where the GDP is found, it squeezes it out to the GDP leaves, but at the same time, it creates a pocket or region that has a high affinity for GTP guanosine triphosphate."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so a guanosine triphosphate found in a cytoplasmic side basically swimming around."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when it gets close to the cavity, as a result of that electromagnetic attraction, it will be pulled into this cavity and that will basically induce a change in the structure."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And once the GTP binds the affinity of this structure here."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So this G alpha Q protein decreases in affinity and does not want to bind to these two domains."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so it detaches from these two structures and also from this seven transmembrane region."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so these two structures, the dimers that consist of the beta and the gala, essentially moves away and remains bound to that fossil lipid bilayer membrane."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And that's because one of these structures actually contains a covalently attached lipid that is attached into the membrane."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so the G beta gamma protein remains bound to this membrane."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "But this G alphaq that now contains the GTP goes on and binds onto a special membrane bound enzyme known as phospholipac."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And this is shown in green."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when the Glfaq protein binds until the fossil lipase C, it stimulates its activity."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And what the phospholipac does is it binds or it cleaves a specific lipid that is found in the membrane known as pip two, where Pip two stands for phosphatididyl inostatol 45 by phosphate."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So the first P means phosphor."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Phosphatidal, the I means inositol the P two means we have two phosphates at the four and fifth position."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So this is Pip two, and this is what Pip two actually looks like."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when the Galpha Q protein activates the phospholipase C, as the Pip two moves across this side, right, because the Pip two can diffuse across the membrane as a result of this large hydrophobic region, as it moves across the phospholipac, cleaves this structure into two molecules."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So essentially breaks this bond here."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when this bond actually breaks, we see that there are two molecules form."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "One molecule is this hydrophobic tail or two hydrophobic tails."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And this means this will not be able to dissolve in a cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so this entire tail here, shown here, will remain dissolved in that hydrophobic membrane, while the other component, this entire region here, because it will contain one, two, three phosphate groups, it will contain many negative charges, it will be polar, and it will be able to dissolve in the cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so this component basically detaches and remains in the cytoplasm, and the other component remains dissolved in that membrane."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, the part that is dissolved in the membrane is known as Dag, which stands for diasoglycerol, while the IP stands for inostato one, four, five, triphosphate, and it remains dissolved in that cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, the IP three and the Dag are actually two types of secondary messenger molecules."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So what fossil lipasec does is it cleaves this molecule, the pivot two, that produces two different secondary messenger molecules."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now let's discuss what the IP three does."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So when the IP three is cleaved, it is readily able to dissolve in that aqueous cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And what it does is it moves on to a special ligand gated calcium ion channel that is found on the membrane of the endoplasmic reticulum."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So this is one calcium channel, a second calcium channel."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And so these IP three molecules, the nosatoll one, four, five triphosphates, go on and bind onto a special location on these ligand gated calcium channels."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when they bind, they cause a conformational change that opens up that internal passageway."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And now what happens is because we have a high calcium concentration in the Er lumen and a low concentration in the cytoplasm, it causes these calcium ions to move down their electrochemical gradient from the lumen into the cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And these calcium ions do two different things."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Number one, the calcium ions find a ubiquitous protein molecule we call calmodulant."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And we'll discuss the specifics of what calmodulen does and what it looks like in a future lecture."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "But basically the calmodulen looks like this."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "It looks like a hand and it has a side, a pocket that binds that calcium."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And once it binds the calcium, it forms the calcium calmodulent complex."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And this complex can go on and stimulate the activity of different types of protein kinases."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And remember, protein kinases phosphorylate and activate target enzymes and proteins."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, the other thing that the calcium mines can do is they can go on and bind onto a specific type of kinase found on a membrane, on the intracellular side of the cell membrane known as protein kinase C. When the calcium binds onto protein kinase C, it basically creates a pocket that allows the dag."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So remember, when the fossil lipase binds or when the fossil lipase cleaves the Pip two, we not only form the IP three secondary messenger, we also form the dag secondary messenger."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And now that calcium is bound to the protein kinasea, that allows the dag to go on and bind to protein kinase C. And once this takes place, it activates protein kinase C. And protein kinase is a specific type of kinase which means itphosphorylates target enzymes and protein."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So protein kinase C, for instance, can initiate things like smooth muscle contraction, it can also initiate the breakdown of glycogen into glucose molecules and many, many different types of processes."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So ultimately this structure as well as this structure go on to basically initiate many different types of cell processes that ultimately create that physiological effect."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And in the instance, in the case of angiotensin two receptor, that final physiological effect is the increase or the decrease in the blood pressure in the cardiovascular system."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So this is what the phosphorotide signaling pathway actually does."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So once again, let's quickly review this pathway."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So the first step is the binding of the primary messenger to the active side, not the active site, the location on that protein."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And when that takes place, it initiates the removal of the GDP from this G protein and this GTP replaces it."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And once that takes place, this structure is basically dissociated, it goes on and binds onto the phospholipac, which stimulates this enzyme to cleave the Pip two."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "And once the pip two is cleaved into two structures, the Dag and the IP three, these are the secondary messenger molecules."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "IP three goes on and binds onto this calcium channel, opens the calcium channel up and allows the movement of these calcium ions from the lumen of the Er into the cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Then the calcium can either go on and bind to calmodulen, which forms a complex that can initiate many different types of processes, or it goes on and binds to protein kinase C. And in this case, with the help of Dag."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "It initiates protein kinase C, which goes on and basically carries out different types of cell processes and activates other enzymes that initiate cellular processes."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Now, one last thing I want to mention is the following one actually allows the cell to establish an electrochemical gradient in which we have many calcium ions in the Er lumen and very few calcium ions in the cytoplasm."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "Well, it's the activity of a protein, a membrane pump we call calcium ATP, which we actually spoke about in the previous lecture."}, {"title": "Phosphoinositide Signal Pathway.txt", "text": "So it's the activity of the calcium ATPase pump that uses ATP molecules to generate this electrochemical gradient that allows these ion channels to actually take these calcium ions and move them down their electrochemical gradient into the cytoplasm of that Er."}, {"title": "Summary of DNA Replication.txt", "text": "Now that we discussed the process of DNA replication, let's summarize our results."}, {"title": "Summary of DNA Replication.txt", "text": "So DNA replication is the process by which our cell copies its original DNA to produce two identical copies of that DNA and one of the copies can be passed down to the offspring and the other copy can remain in that original cell."}, {"title": "Summary of DNA Replication.txt", "text": "Now DNA replication is known as a semiconservative process and this basically means that each one of the DNA copies that is produced contains one original strand and one synthesized strand."}, {"title": "Summary of DNA Replication.txt", "text": "And to see what we mean by that concept, let's take a look at the following diagram."}, {"title": "Summary of DNA Replication.txt", "text": "So this diagram basically summarizes the net result of DNA replication."}, {"title": "Summary of DNA Replication.txt", "text": "So let's suppose we begin with the following double helix."}, {"title": "Summary of DNA Replication.txt", "text": "Now if the upper strand of DNA runs from the three to the five direction, then the bottom strand runs from the five to three direction because these two strands are known to be antiparallel, they run parallel bond in opposite directions and these two individual single strands are held together by hydrogen bonds between the bases."}, {"title": "Summary of DNA Replication.txt", "text": "Now following DNA replication we basically form two identical copies as shown."}, {"title": "Summary of DNA Replication.txt", "text": "Now notice that these black single strands of DNA are the original strands of DNA and they are commonly known as parent strands or template strands while the blue ones are the newly synthesized strands and they are known as the door strand."}, {"title": "Summary of DNA Replication.txt", "text": "So the process of DNA replication is semiconservative because each one of these copies contains one of the single strands that came from the original double stranded DNA and the other one shown in blue is the newly synthesized strand."}, {"title": "Summary of DNA Replication.txt", "text": "Now how exactly do we initiate the process of DNA replication?"}, {"title": "Summary of DNA Replication.txt", "text": "Well, basically a special type of enzyme, a special type of protein known as DNA helicase moves very quickly along the double stranded DNA molecule and it moves until it reaches a point known as the origin of replication."}, {"title": "Summary of DNA Replication.txt", "text": "So at the origin of replication the DNA helicase binds to that double stranded DNA molecule via electric forces."}, {"title": "Summary of DNA Replication.txt", "text": "Now in eukaryotic cells, eukaryotic cells contain DNA that have multiple origin of replications."}, {"title": "Summary of DNA Replication.txt", "text": "And that means we have DNA replication taking place in multiple positions on that double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "However, in prokaryotic cells, prokaryotic cells contain DNA that usually only contain a single origin of replication."}, {"title": "Summary of DNA Replication.txt", "text": "And that implies that DNA replication only takes place at one location and at one position on that prokaryotic DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "Now what exactly takes place once the DNA helicase enzyme actually binds to the origin of replication?"}, {"title": "Summary of DNA Replication.txt", "text": "Well, let's take a look at the following diagram that describes what is taking place."}, {"title": "Summary of DNA Replication.txt", "text": "So this is our helicase molecules."}, {"title": "Summary of DNA Replication.txt", "text": "So let's suppose the helicase enzyme moves along our DNA molecule very quickly until it reaches the origin of replication which is shown here."}, {"title": "Summary of DNA Replication.txt", "text": "Now notice that each one of these pair of bases are held together by hydrogen bonds."}, {"title": "Summary of DNA Replication.txt", "text": "Now when our helicase binds to the origin of replication it begins to move more slowly."}, {"title": "Summary of DNA Replication.txt", "text": "And as it moves, let's suppose it moves from right to left along the double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "It begins to unzip or unwind that double stranded DNA."}, {"title": "Summary of DNA Replication.txt", "text": "And the way that it does it is by breaking these hydrogen bonds between our base pairs."}, {"title": "Summary of DNA Replication.txt", "text": "And so now we have these single strands that are exposed."}, {"title": "Summary of DNA Replication.txt", "text": "So as our bound helicase moves along the double stranded DNA molecule, it unwinds it even further."}, {"title": "Summary of DNA Replication.txt", "text": "Now, the point at which our helicase is actually found at and the point where our unwinding is taking place is known as the fork of replication."}, {"title": "Summary of DNA Replication.txt", "text": "So where the location where the helicase actually binds to is known as the origin."}, {"title": "Summary of DNA Replication.txt", "text": "But as it moves, this location is known as the fork of replication."}, {"title": "Summary of DNA Replication.txt", "text": "So the direction of the movement of the fork of replication is the same as the direction of the movement of our helicase enzyme."}, {"title": "Summary of DNA Replication.txt", "text": "So as the helicase moves this way, the fork of replication also moves along with it."}, {"title": "Summary of DNA Replication.txt", "text": "Now, as our doublestranded DNA molecule unwinds, it causes the DNA to super coil."}, {"title": "Summary of DNA Replication.txt", "text": "And these super coils are known as positive super coils."}, {"title": "Summary of DNA Replication.txt", "text": "And these positive super coils basically increase the stress, increase the energy of our double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "And this makes it very difficult for the helicase to actually continually unwind that double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "And so what happens is another enzyme known as DNA gyrase, which is a topo isomerase, basically creates negative super coils."}, {"title": "Summary of DNA Replication.txt", "text": "It binds to our double stranded DNA and it induces negative super coils which removes the stress that are caused by the process of unwinding."}, {"title": "Summary of DNA Replication.txt", "text": "So basically, DNA gyrase indirectly assists the process of DNA replication by removing the positive super coils that are formed by the process of unwinding."}, {"title": "Summary of DNA Replication.txt", "text": "So in this diagram we have the DNA gyrase."}, {"title": "Summary of DNA Replication.txt", "text": "So the DNA gyrase binds to our double strand DNA molecule and it creates the negative super coils which decrease the number of positive super coils in our double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "Now, the problem with separating our two single strand of DNA is the following once we separate our two single strands of DNA, they want to naturally and spontaneously reform those hydrogen bonds because by reforming the hydrogen bonds that stabilizes the double stranded DNA molecules."}, {"title": "Summary of DNA Replication.txt", "text": "So we see that to keep the two single strands apart during DNA replication, another type of enzyme known as the single stranded binding protein has to bind to these individual exposed regions of the single strands of DNA."}, {"title": "Summary of DNA Replication.txt", "text": "So these single stranded binding proteins, also known as SSB proteins, are shown in purple on this molecule."}, {"title": "Summary of DNA Replication.txt", "text": "And when they bind, they basically keep these two single strands of DNA from reassociating with one another, from reforming the hydrogen bonds."}, {"title": "Summary of DNA Replication.txt", "text": "Now, once we initiate the process of DNA replication, how exactly do we actually synthesize those new data strands?"}, {"title": "Summary of DNA Replication.txt", "text": "So basically we use a protein known as DNA polymerase."}, {"title": "Summary of DNA Replication.txt", "text": "What DNA polymerase does is it takes the free nucleotides that are found in the environment and it attaches these nucleotides by using phosphodia ester bonds."}, {"title": "Summary of DNA Replication.txt", "text": "So basically it catalyzes."}, {"title": "Summary of DNA Replication.txt", "text": "DNA polymerase catalyzes the formation of phosphol diester bonds."}, {"title": "Summary of DNA Replication.txt", "text": "But before DNA polymerase actually begins the process of synthesis another protein enzyme known as primates, which is an RNA polymerase has to actually create something called the RNA primer."}, {"title": "Summary of DNA Replication.txt", "text": "So the enzyme primase forms the RNA primer which is basically a specific sequence of nucleotides that signals for DNA polymerase to bind and begin the process of synthesis."}, {"title": "Summary of DNA Replication.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Summary of DNA Replication.txt", "text": "So basically, once we initiate the process of DNA replication, once our helicase bind to the origin and creates the fork of replication, once our SSB proteins bind to these exposed regions on the single stranded DNA molecule, and once the gyrase molecule binds to our double stranded DNA molecule."}, {"title": "Summary of DNA Replication.txt", "text": "What happens is the primate molecule creates the RNA primers which are shown on this diagram as these slightly purple regions."}, {"title": "Summary of DNA Replication.txt", "text": "Now once we form the primers DNA polymerase then bides to those primers and it begins the process of synthesis."}, {"title": "Summary of DNA Replication.txt", "text": "So it basically takes these blue nucleotides that are found in the environment and it connects these nucleotides by using the phosphodia ester linkages, the phosphodia ester bonds."}, {"title": "Summary of DNA Replication.txt", "text": "Now let's take a look at the following bottom parent DNA molecule that runs in the three to five direction."}, {"title": "Summary of DNA Replication.txt", "text": "Now our DNA polymerase can only read the parent strand from the three to the five direction and this means that it can only synthesize the new strand in the five to three direction."}, {"title": "Summary of DNA Replication.txt", "text": "So for this bottom strand that basically means that when the primates creates the RNA primer the DNA polymerase can basically synthesize our new daughter strand in the same direction as the movement of the fork as the movement of the DNA helicase molecule."}, {"title": "Summary of DNA Replication.txt", "text": "So if this DNA molecule, the DNA helicase molecule moves in the forward direction that means that this DNA polymerase also moves in the forward direction because it creates this new strand from the five to the three direction."}, {"title": "Summary of DNA Replication.txt", "text": "However, let's take a look at this upper strand here."}, {"title": "Summary of DNA Replication.txt", "text": "So for the case of this upper parent strand if our DNA polymerase reads it this way in the same forward direction then it reads our strand in the five to three direction."}, {"title": "Summary of DNA Replication.txt", "text": "But remember our DNA polymerase can only read the parent strand in the three to five direction."}, {"title": "Summary of DNA Replication.txt", "text": "So that means the DNA polymerase has to move in the opposite in the backward direction."}, {"title": "Summary of DNA Replication.txt", "text": "So what actually happens the way we synthesize this strand, which is known as the Lagging strand is in the following manner."}, {"title": "Summary of DNA Replication.txt", "text": "Our primase actually lays down many of these RNA primers."}, {"title": "Summary of DNA Replication.txt", "text": "So we have one two RNA primers as shown and our DNA polymerase binds to each one of these primers and it creates our blue strands which are the dota strands in the opposite direction with respect to the movement of this DNA polymerase and this DNA helicase molecule."}, {"title": "Summary of DNA Replication.txt", "text": "So the DNA polymerase is still synthesizing in the five to three fashion, but in this case, it must move in the opposite direction with respect to this DNA polymerase."}, {"title": "Summary of DNA Replication.txt", "text": "So we see that this trend that is synthesized in a continuous fashion, piece by piece, is known as the leading strand."}, {"title": "Summary of DNA Replication.txt", "text": "But this trend is known as the lagging strand because each one of these fragments is synthesized piece or is synthesized one at a time."}, {"title": "Summary of DNA Replication.txt", "text": "First we synthesize this fragment, then we synthesize this fragment, then we have to synthesize this fragment, and so forth."}, {"title": "Summary of DNA Replication.txt", "text": "And each one of these fragments is known as the Okasagi fragments, after the scientist who basically discovered this process."}, {"title": "Summary of DNA Replication.txt", "text": "Now, once all of these Okasaki fragments are actually synthesized, our polymerase removes our RNA primers and replaces with our nucleotides."}, {"title": "Summary of DNA Replication.txt", "text": "And an enzyme known as DNA ligase basically connects these Okasagi fragments together and that completes the synthesis or the replication of our lagging strand."}, {"title": "Summary of DNA Replication.txt", "text": "And once this process is over, we basically produce two identical copies of the original DNA and each one of these two identical copies each contains the original pan strand as well as the newly synthesized strand."}, {"title": "Summary of DNA Replication.txt", "text": "And this is known as a semiconservative process."}, {"title": "Summary of DNA Replication.txt", "text": "Now, notice in this diagram that on this parent strand, the DNA polymerase moved in the forward direction, but this DNA polymerase moved in the reverse backward direction."}, {"title": "Summary of DNA Replication.txt", "text": "So we see that the process of DNA replication is said to be bidirectionalal because it takes place along two opposite directions."}, {"title": "Summary of DNA Replication.txt", "text": "It takes place along this direction and it takes place along this direction."}, {"title": "Summary of DNA Replication.txt", "text": "So this concludes our summary of DNA replication."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Our liver cells and skeleton muscle cells are responsible for glycogen breakdown."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what that basically means is they have to be able to regulate the process of the breakdown of glycogen."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, how exactly do these two different types of cells regulate glycogen breakdown?"}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Well, one point of regulation is the enzyme glycogen phosphorlase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And remember, as we discussed us in the previous lecture, this is the enzyme that is responsible for actually catalyzing step one of glycogen breakdown."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So glycogen phosphorylase basically cleaves the alpha one four glycocitic bond and releases a glucose one phosphate from the glycogen polymer molecule."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, because skeleton muscle cells and liver cells have slightly different functions in terms of what they actually do with the glucose, once they release the glucose from glycogen, they also regulate glycogen phosphorylase in slightly different ways."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So in this lecture, I'd like to focus on how the skeleton muscle cells actually regulate glycogen phosphorylase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "In the next lecture, we're going to focus on liver cells and discuss how they regulate glycogen breakdown via the regulation of glycogen phosphorase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, glycogen for sporlase is actually a dimer molecule."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "It consists of two polypeptide subunits and it is an allosteric enzyme."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "What that means is there exists certain types of molecules inside our cells that can actually either inhibit or activate activity of glycogen phosphorase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, within skeleton muscle cells, phosphorase exist in two interconvertible forms."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "We have phosphorase A and we have phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, each one of these phosphoralase enzymes in turn exist in two different states."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "We have the T state, known as the ten state and we have the r state, also known as the relaxed state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, what's the difference between the T state and the r state?"}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Well, in the T state, as a result of the confirmation of the dimer structure, these active sites of the enzyme are partially blocked."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what that means is the activity of the enzyme when it's in the T state will be low."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "In contrast, in the r state, as a result of the loose confirmation of the dimer structure, the active sites are actually open."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what that means is the r state is the fully active form of this enzyme."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "In the r state the activity will be high, while in the T state the activity will be low."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, what's the difference between phosphorase A and phosphorase B?"}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Well, phosphorlase A, the equilibrium of phosphorase A exists predominantly on the r side, while the equilibrium for the phosphorase B molecule exists predominantly in the T state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So what that means is at equilibrium we're going to have much more of the R state than the T state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "On the other hand, for this particular case at equilibrium we're going to have much more of the inactive T state than the active R state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, how do we go from phosphorase B to phosphorlase A?"}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Well, we have an enzyme known as phosphorase kinase, which we'll discuss in just a moment."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what it does is it basically phosphorylates specific serine amino acids on this glycogen phosphorylase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So remember this is a dimer, we have two polypeptide chains, so one polypeptide chain and a second polypeptide chain."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And the 14th amino acid position is a serene amino acid."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So this one has a serine 14 and this one also has a seren 14."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And phosphorase kinase can use two ATP molecules to actually attach the phosphoryl groups on the two seren 14 molecules to basically form phosphorase A."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And that's what we mean by an interconvertible form."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "We can go from phosphorase B to phosphorylase A bidactivity of phosphorase kinase, but this requires ATP molecules."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now let's discuss when phosphorase B predominates and when phosphorase A actually predominates in our body."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So let's discuss low energy charge conditions."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Remember that energy charge, loosely speaking is simply the ratio of ATP to A and P inside our cells."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so if we have low energy charge values within our skeleton muscle cells, we have a low ATP concentration relative to A and P. And what that means is our cells want to produce more ATP molecules and so they want to break down glycogen to glucose to use the glucose via glycolysis to form ATP."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so what happens is when the cell contains a low level of ATP compared to amp, the ANP adenosine monophosphate will actually act as an allosteric activator of phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "It will bind to an allosteric site on phosphorase B in the T state because the T state is the state that predominates for phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what it does is it basically shifts the equilibrium towards the r state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "It opens up the activity and that causes, it increases the activity of this phosphorase B."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so what that will do is it will stimulate the phosphorlase B to actually go on and break down the glycogen into glucose molecules to form more ATP."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now in addition, sudden or strenuous activities such as for instance sprinting will basically stimulate the release of specific hormones, for instance epinephrine."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what these hormones basically do is they stimulate the enzyme phosphorase kinase."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And remember, phosphorase kinase uses ATP to transform the phosphoralase B which exists predominantly in the inactive T state, into phosphorlase A which exists predominantly in the r state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what that does is it helps us produce more ATP molecules by breaking down glycogen into glucose and using the glucose in glycolysis to form those ATP."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So when our cells are basically exercising that means we have a low energy charge value."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "We want to produce more ATP because we have a low ATP relative to Amp concentration."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "The high Amp shifts the equilibrium of his fourlase B to the r state making it more active."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And on top of that, we have the hormones that stimulate this enzyme to transform phosphorase B into phosphorase A which automatically exists predominantly in the r state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so we're going to break down glycogen much more readily into glucose to actually form ATP via glycolysis."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "Now, conversely, we can also have a high energy charge value."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And what that means is we essentially have high ATP concentration relative to amp."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so under these conditions, our cells don't need to and don't want to produce ATP."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And the ATP will actually act as an allosteric inhibitor."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "It will compete with A and P, and it will bind to the R state of S four lase b and shift the equilibrium back to the T state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "In addition, when we have high ATP concentrations, that also implies we're going to have high glucose six phosphate concentrations."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And so the glucose six phosphate will also act as an allosteric inhibitor to phosphorase B, and it will help shift the equilibrium of phosphorase B toward the T state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So for the resting tissue, which basically means that normal physiological conditions, when we have a high energy charge, we have lots of ATP and lots of glucose six phosphate."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And together they're going to act as Alastairic inhibitors, basically shift the equilibrium of a sporlase b from the R state back to the T state."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "And under these conditions, glycogen breakdown inside the skeleton muscle tissue will basically not take place because we won't need to produce the ATP."}, {"title": "Regulating Glycogen Breakdown in Muscle .txt", "text": "So in the next lecture, we're going to focus on how the hepatocides, the liver cells of our body, actually regulate glycogen breakdown by controlling this allosteric enzyme, glycogen phosphorlase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "The citric acid cycle consists of eight individual steps."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so far we discussed the first four steps of the citric acid cycle."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now let's move on to discuss the remaining four steps."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So in this lecture, we're going to focus on steps five, six, seven and eight of the citric acid cycle."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So remember that in step four we synthesize a molecule known as succinct coenzyme a."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And this is the same molecule that is used as a reaction reactin in step number five."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now in this reaction, this is actually the only step of the citric acid cycle in which we generate a high energy purine nucleuside triphosphate molecule."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "We generate a GTP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So what we ultimately want to do in this process is we want to attach a phosphoryl group onto the GDP, the guanitine diphosphate, to form the guanosine triphosphate GTP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "The problem with carrying out this step is it requires an input of energy."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So the process by which we attach the pi onto the GDP to form the GTP is an endergonic process."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so we actually have to undergo some other process that is exergonic to basically couple this endergonic process."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now remember one important fact about succincto enzyme A, and generally speaking, in the citric acid cycle, whenever we see a thyl ester bond between the carbon and the sulfur of the coenzyme a molecule, that bond showed in red is a very unstable high end energy bond."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In fact, when we cleave this bond, that will release a certain amount of free energy."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And that free energy that is released when we cleave this bond is basically used to drive the attachment of this molecule onto the GDP to form the GTP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In the process we also release that coenzyme A and form this four carbon succinate molecule that will go on to react in step six of the citric acid cycle."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And this reaction is catalyzed by succinct coenzyme asynthetase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, once we form the GTP molecule, the GTP is generally used for two purposes."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "They can either be used by g proteins for instance, we saw that in signal transduction pathways we have g proteins and the g proteins utilize the GTP molecule and so we can use it for that specific purpose or the GTP can actually be transformed into ATP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "How?"}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Well, by the action of an enzyme known as nucleotide diphosphokinase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "This enzyme actually catalyzes the transfer of a phosphoryl group from the GTP onto an ADP to form the ATP and this GDP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So in this process we utilize the GTP form in step five of the citric acid cycle to generate ATP molecules that can be used by a variety of processes inside our body."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So once again, we see that the unstable and high in energy thio esther bond in sucaved to release the coenzyme A and also release free energy."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And that free energy is then used to power the endergonic process of attaching of a sporal group onto the GDP to form the GTP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And this is catalyzed by succinct coenzyme asynthetase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, before we move on to the next several steps, let's actually discuss what the reaction mechanism is of this process."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So what actually takes place in the active side of this enzyme?"}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So let's focus on the following five diagrams to basically answer that question."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In diagram one, we basically have the inorganic orthophosphate that goes into the active side along with the succinl coenzyme a."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So we have the succinct coenzyme a, we have the orthophosphate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And notice the GDP is not found in this location."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In fact, the GDP is found nearby, but not in the same location."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And we'll see what happens in the final two steps that allows us to actually bring that orthophosphate to that GDP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So in the first step, what happens is the inorganic orthophosphate actually acts as a nucleophile."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "It attacks the carbon of this carbonyl, breaking this unstable bond, and that releases that coenzyme a, and it forms an intermediate molecule known as succinal phosphate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So in step one, we displace the coenzyme a, we release the coenzyme a from the active side, and so we produce this product in step one."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Once we form the succinct phosphate within the active side of this enzyme, we have a specific catalytic histazine residue that basically catalyzes the next step."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so the two electrons of the nitrogen of this catalytic histazine residue basically acts as a nucleophile attacking the p atom."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And that breaks the sigma bond."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so that detaches this entire four carbon component."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And now the carbon basically gains the oxygen, and we form this succinate molecule here."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, once we undergo step two, we form the succinate and the coenzyme a."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So coenzyme a is formed in step one, while the succinate is formed in step two."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And once we form this intermediate, this is known as phosphorhistidine."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And notice we cannot stop here."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "For one thing, we still haven't formed the GTTP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Another thing, though, is we have to regenerate that original catalytic residue because remember, enzymes are always regenerated after the reaction."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "We cannot actually use up our enzymes."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so in step three, what happens?"}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "This phosphorhistidine basically swings over to another site within our enzyme, and that site contains a GDP."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And now in step four, the GTP receives the orthophosphate from this histidine residue to basically form that GTP and also regenerate that original catalytic histidine residue that is found in the active side of the enzyme."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So we see that in this process."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In step one, we form the coenzyme a."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In step two, we form the succinate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In steps three and four, we form the GTP molecule."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So let's move on to step six, seven, eight, the final three steps of the citric acid cycle."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So these are our three steps."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now remember that the citric acid cycle begin with an oxyloacetate intermediate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And because the citric acid cycle is literally a cycle, so if we begin with an oxyloacetate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "What that means is we have to end up with that same oxyloacetate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so what this process involves is in these three steps six, seven, eight, we transform the four carbon succinate into the four carbon oxyloacetate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so the only difference between these two molecules is on this region, we have a methylene group, a ch two component."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "But on this region of the oxyloacetate, we have a carbonyl component."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so we see that what happens in this three step process is we basically transform the methylene group on the Succinate into the oxyloacetate that contains a carbonyl group."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In the process, we also extract we extract high energy electrons by the carrier NAD plus as well as Fads."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Remember, Fad is flavin adenucleotide that is able to obtain two H atoms, while the NAD plus is a carrier nicotine amide adenine nucleotide that is able to obtain Hydride ions."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So a single Hydride ion that contains two electrons on that H ion."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So that's the difference between these two molecules."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In step six, we use Fad."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In step eight, we use NAD plus."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now let's focus on step six."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In step six, we have the Succinate dehydrogenates enzyme that catalyzes this step."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so what happens is these two H atoms, and each one of these H atoms contains one electron each, are abstracted from the succinate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Those two electrons left over form a double bond, a pi bond."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so he formed the fumerate that contains the double bond between these two carbons."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And these two H atoms then bind onto the carrier Flaving adenine dinucleotide to form the Fadh two."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, one important fact that you have to know about Succinate dehydrogenase is, unlike the enzymes that we discussed so far, this enzyme, Succinate dehydrogenase, is actually part of the inner mitochondrial matrix."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In fact, it's an iron sulfur protein that is also part of the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So what actually happens is when the Sad well, first of all, the Sad is covalently attached onto the Succinate dehydrogenase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "But once this reaction takes place, once this oxidation reaction takes place and we reduce the Fad into the Fadh Two, that Fadh two that is formed remains attached, covalently onto the subsidy dehydrogenates."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And once we form this, what it does is it donates those two electrons onto a special iron sulfur component of the enzyme, and those two electrons then move on along the other proteins of the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And that generates a proton gradient that allows us to form ATP molecules."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And we'll focus on that much more in a future electrode."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So ultimately, we oxidize the succinate into the fumerate, and we reduce the Fad into Fadh Two."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So, once again, step six is an oxidation reduction reaction that oxidizes the Succinate into the fumer rate while abstracting those H atoms."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So the ions along with the pair of electrons to form that Fad H two."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, Succinate dehydrogenate, the enzyme that catalyzes step six, is balance of the inner mitochondrial membrane."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And it is an iron sulfur protein."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "That means it contains these iron sulfur groups that can basically abstract those electrons."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, the Fad is actually covalently bound to that particular enzyme."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And when the Fad gains those two H atoms, it becomes the Fad two and it continues to be attached onto the enzyme."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And then it can basically pass those electrons onto the iron sulfur component of the enzyme, which passes along the remaining proteins of the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So this step is very important because it's essentially the link between the citric acid cycle and that oxidative phosphorylation process that takes place on the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Oh, and one other thing that I'd like to mention about the formation of the GTP, just like in Glycolysis, where we had substrate level phosphorylation, this is also an example of substrate level phosphorylation, where a substrate molecule is used by enzyme to generate a high energy GTP molecule."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And that's in contrast to oxidative phosphorylation that takes place on the proteins of the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So let's finish off with step seven and step eight."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So we have an oxidation reduction reaction in step six."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And step seven produces or step seven is a hydration reaction."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So the fumerate is transformed into a malade via a hydration reaction."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So a water basically attacks, or more specifically, a hydroxide of the water attacks this carbon from this side."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And the H ion basically attaches on this side."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And we form the L isomer of malate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And the enzyme that catalyzes step seven is fumrase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So Fumarase catalyze the hydration of fumarate into malate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Note that the water tax only at a specific site from this side and not anywhere else."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so we only form the L isomer of the malate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So this exists in the L isomeric form."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And in the final step of the citric acid cycle, we actually want to regenerate the oxyloacetate."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so the malade is oxidized into oxyloacetate by the activity of malade dehydrogenase."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In the process, we abstract a Hydride ion, so an H ion and two electrons."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so here we use the NAD plus to form the NADH, and the NADH then can be used by the electron transport chain."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "Now, one thing I want to mention briefly about this step eight is it's actually a very undergone step."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "It actually requires energy."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "And so what happens is several processes that take place in the citric acid cycle and on the transport chain are actually used to power to couple this particular process."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "For instance, step one of the citric acid cycle that takes place as soon as we produce oxylacetate is actually used to drive this particular reaction forward."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "In addition, the NADH molecules, which are oxidized along the proteins of the electron transport chain, those react reactions are also used to actually drive this particular reaction forward."}, {"title": "Steps 5-8 of Citric Acid Cycle .txt", "text": "So these are the four remaining steps of the citric acid cycle."}, {"title": "Prions and Protein misfiling .txt", "text": "The process by which a polypeptide folds into its final threedimensional structure is very complex and very intricate."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, what happens if that polypeptide that initially begins with the correct primary sequence?"}, {"title": "Prions and Protein misfiling .txt", "text": "What happens if it folds incorrectly?"}, {"title": "Prions and Protein misfiling .txt", "text": "So normally if it folds incorrectly that means the final threedimensional structure of that polypeptide will not be correct."}, {"title": "Prions and Protein misfiling .txt", "text": "And because it's the three dimensional structure of the polypeptide that determines what the function of that polypeptide is the function of that final misfolded protein will not be the same."}, {"title": "Prions and Protein misfiling .txt", "text": "And usually these types of misfolded proteins are biologically inactive."}, {"title": "Prions and Protein misfiling .txt", "text": "And what that means is our cells will either denature and break down these proteins or refold them into the correct structure."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, in some very rare cases these misfolded proteins can actually form these biological molecules we call prions."}, {"title": "Prions and Protein misfiling .txt", "text": "And prions are very, very dangerous molecules as we'll see in just a moment."}, {"title": "Prions and Protein misfiling .txt", "text": "Prions are these infectious agents that can actually cause a variety of different types of diseases not only in humans but also in other animals."}, {"title": "Prions and Protein misfiling .txt", "text": "For example, mad cow disease in cattle and screeping sheep is caused by these prion molecules."}, {"title": "Prions and Protein misfiling .txt", "text": "In fact, in humans a disease known as crytesval yaka disease which is a deadly disease."}, {"title": "Prions and Protein misfiling .txt", "text": "It's called by prion molecules."}, {"title": "Prions and Protein misfiling .txt", "text": "So what exactly is a prion and what are some properties of prions?"}, {"title": "Prions and Protein misfiling .txt", "text": "Well, prions are these aggregate, these collection of proteins which normally exist in our body but which have misfolded."}, {"title": "Prions and Protein misfiling .txt", "text": "And because they misfolded, they form these insoluble aggregates."}, {"title": "Prions and Protein misfiling .txt", "text": "And so what that means is because they are insoluble there is no way our cells and the body can actually break them down and denature them by the same method as it normally does."}, {"title": "Prions and Protein misfiling .txt", "text": "And because our cells cannot break them down eventually the aggregate proteins will somehow cause the death of the cell killing off the cells of our body and eventually that individual."}, {"title": "Prions and Protein misfiling .txt", "text": "So to gain some insight into how prions actually function let's take a look at the following molecule."}, {"title": "Prions and Protein misfiling .txt", "text": "The following protein that normally exists in the brain cells of our body, in our neurons, in the brain."}, {"title": "Prions and Protein misfiling .txt", "text": "So PRP, as shown in the following diagram is a normal protein that is found in the brain."}, {"title": "Prions and Protein misfiling .txt", "text": "And under certain conditions, for example, if some type of mutation takes place this protein can actually miss fold into this protein known as PrPSc."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, what's the major difference between this protein here and this protein here?"}, {"title": "Prions and Protein misfiling .txt", "text": "Well, one major difference is the fact that this protein consists predominantly of alpha helixes but in this case it consists predominantly it has a very high content of beta pleated sheets."}, {"title": "Prions and Protein misfiling .txt", "text": "So when this misfolding process takes place instead of forming all these alpha helixes we form these betappleted sheets."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, what's the big deal about betappleted sheets?"}, {"title": "Prions and Protein misfiling .txt", "text": "Well, because we have a high content of beta pleated sheets these molecules will have a high potential will have a high propensity of binding to other molecules that also contain beta pleated sheets."}, {"title": "Prions and Protein misfiling .txt", "text": "Why is that?"}, {"title": "Prions and Protein misfiling .txt", "text": "Well, recall that the structure of the beta pleated sheet consists of these linear polymers of amino acid."}, {"title": "Prions and Protein misfiling .txt", "text": "So we have one linear polymer of amino acid, a second linear polymer stacked on top of one another, a third one stacked on top, stacked on top of that and so forth."}, {"title": "Prions and Protein misfiling .txt", "text": "So these beta pleated sheets consist of these linear polymers stacked on top of one another."}, {"title": "Prions and Protein misfiling .txt", "text": "And because they're stacked on top and they're linear, they're parallel with respect to each other, they will have a great potential of bonding to other beta pleated sheets via non covalent bonds."}, {"title": "Prions and Protein misfiling .txt", "text": "So recall that beta pleated sheets have a high propensity, high potential for forming bonds with other beta pleated sheets."}, {"title": "Prions and Protein misfiling .txt", "text": "Therefore, the beta pleated sheets of one protein can interact with the beta sheets of another protein and that can form these aggregate molecules."}, {"title": "Prions and Protein misfiling .txt", "text": "So, if this protein that normally appears in the brain cells of our body transforms misfolds into this protein, it can basically form aggregates with other proteins and that will eventually form even larger fibers, as we'll see in just a moment."}, {"title": "Prions and Protein misfiling .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Prions and Protein misfiling .txt", "text": "Let's suppose some type of mutation took place or some type of event happened that eventually led to the formation of these molecules."}, {"title": "Prions and Protein misfiling .txt", "text": "So we have, let's say, three of these misfolded proteins."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, because they consist predominantly of these blue betapeted sheets, they are drawn in blue."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, because of the presence of these beta pleated sheets, they will bond with each other as a result of those beta beta pleated sheets being attracted to one another via non covalent bonds."}, {"title": "Prions and Protein misfiling .txt", "text": "And so, eventually we form this multi unit and aggregate of three PrPSc molecules."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, let's suppose we have these red molecules in close proximity that are normal."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, somehow by mechanism that we are still unsure of these infected molecules, these misfolded proteins can somehow transform these normal proteins into these abnormal proteins."}, {"title": "Prions and Protein misfiling .txt", "text": "And so these will bind to our multiunit aggregate, transforming these into the blue ones."}, {"title": "Prions and Protein misfiling .txt", "text": "And eventually we form this fiber like a protein we call an amyloid fiber."}, {"title": "Prions and Protein misfiling .txt", "text": "So these are known as amyloid fibers."}, {"title": "Prions and Protein misfiling .txt", "text": "Now, eventually they form even larger aggregates."}, {"title": "Prions and Protein misfiling .txt", "text": "And eventually these aggregates, because they cannot be broken down by the cells of our body by the same exact methods will basically affect the efficiency and the efficiency and the different types of functions that take place in our cells."}, {"title": "Prions and Protein misfiling .txt", "text": "And the cells in this case are the brain cells, the nerve cells found inside our brain."}, {"title": "Prions and Protein misfiling .txt", "text": "So eventually that will kill off many nerve cells in our brain."}, {"title": "Prions and Protein misfiling .txt", "text": "In fact, if we examine the brain of an individual that has Kryitzfeld Yakub disease we'll see that the brain will resemble a sponge in the sense that it will contain many holes because those holes are a result of the fact that many nerve cells have died because these aggregates have killed off those cells."}, {"title": "Prions and Protein misfiling .txt", "text": "So in the case of CJD."}, {"title": "Prions and Protein misfiling .txt", "text": "These proteins end up killing off many of the nerve cells, which eventually degenerates the mental capability and the brain function of that particular individual."}, {"title": "Prions and Protein misfiling .txt", "text": "And patients with these conditions develop a sponge like brain that basically resembles a sponge in the sense that it contains many holes."}, {"title": "Prions and Protein misfiling .txt", "text": "And those holes come from the fact that these aggregate molecules kill off the different types of cells, different types of nerve cells inside our brain."}, {"title": "Prions and Protein misfiling .txt", "text": "So we see that usually the misfolding of a protein doesn't actually do much because our body is capable of denaturing and breaking down that misfolded protein or folding it correctly into that correct shape."}, {"title": "Prions and Protein misfiling .txt", "text": "But sometimes we get something called a Pryon, and these are very, very dangerous infectious agents."}, {"title": "Prions and Protein misfiling .txt", "text": "So up until recently, we thought that only bacterial cells and viruses are capable of infecting our bodies and the bodies of other animals."}, {"title": "Prions and Protein misfiling .txt", "text": "But now we know that these aggregate of misfolded proteins, those prions, can also act as infectious agents."}, {"title": "Prions and Protein misfiling .txt", "text": "They can easily be passed down from one individual to another and even from one organism to another."}, {"title": "Prions and Protein misfiling .txt", "text": "As we saw."}, {"title": "Prions and Protein misfiling .txt", "text": "The case was with those people, those individuals that ate beef that came from cows that had mad cow disease."}, {"title": "Prions and Protein misfiling .txt", "text": "So basically, those prions were passed down to those individuals via the beef because the beef contain those pryons in the cells."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "In this."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And the next lecture, our focus will be on what it means for genes to be linked and what it means for genes to be not linked with respect to one another."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's begin by supposing."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We have the following two organisms, these two plants."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have a female plant and we have a male plant."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, this is the genotype of the female plant."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have heterozygous for two different traits."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We have the color trade, which is given by the letter G. And we have the high trait, which is given by the letter T. So we have uppercase G is the gene that codes the dominant green color."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And we have the lowercase G that codes for the recessive yellow color."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Likewise, we have uppercase T, which codes for the dominant tall trait, and lowercase T, which codes for the recessive short gene or the recessive shore trait."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have the phenotype of the female individual."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We have a tall plant and a green plant."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "In the case of the male, we have a homozygous recessive for both of these genes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have lowercase G, lower case G, lower case C, lowercase C. So we have a yellow short plant."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So in this lecture, we're only going to focus on non linked genes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So genes that are not linked with respect to one another."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we're only going to focus on Part A."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "In the next lecture, we're going to focus on part B."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So in Part A, if the color gene and the hygiene are said to be not linked with respect to one another."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So if we know that these two genes, the color gene and the hygiene, are not linked, what would be the ratio or the distribution of the offspring that are formed when these two different individuals actually made?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "For example, if we made these individuals 1000 times, what will be the distribution of the offspring in terms of the phenotype or the genotype?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So to answer this question, let's actually differentiate between linked genes and not link genes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So what exactly do we mean by these two genes not being linked?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Well, remember that our genes are actually found on chromosomes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's suppose this is our chromosome that contains our hygiene."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we know that let's suppose we're dealing with this individual here, that these two genes here, uppercase, uppercase G and lowercase G will be found on a single pair of homologous chromosomes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And what that means is we're going to have chromosome number one and homologous chromosome number two."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And this will be our pair of homologous chromosomes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, one of these chromosomes will carry the uppercase G. So let's suppose this is the uppercase G. And so this is shown in green."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now the other G will be found on that homologous chromosome."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's say this will be that homologous chromosome and so it's given in orange."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have lowercase G and we have upper case G. Now, this is one homologous chromosome."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Of course, it can have many other genes as well."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have many genes along this chromosome and many homologous genes along this chromosome as well."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "But because in part A, we are told that the color gene that is given by the G letter and the hygiene that is given by the T letter are not linked."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "What that means is these two gene types are not found on the same chromosome."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we're not going to find the uppercase T along this chromosome, and we're not going to find the lowercase T along this chromosome."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "What we're going to find is another homologous pair of chromosomes that will contain that uppercase T and that lowercase T. So let's suppose that this chromosome will contain that upper case T. So this upper case T, once again, we're only focusing on this individual right here."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we're going to have the blue color for uppercase T, and we're going to have the purple color for lowercase T. Okay, so this is homologous chromosome pair number one, homologous chromosome pair number two."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And these genes are not linked because if they were linked, as we'll see in the next lecture, these would be found on the same exact chromosome because they are not linked."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "What that means is this upper case G and lowercase T is found on opposite on different chromosomes in the same way that this lowercase G and lowercase T are also found on different chromosomes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have chromosome number one, chromosome number two."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now the next question is what would be the ratio of the offspring that are produced in this particular case?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Well, to answer this question, we have determined what the game needs, what the sex cells are, what their genotypes are in the case of this individual, and then in the case of this individual."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we're not going to go through all the different stages of meiosis."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We're simply going to focus on certain stages."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's suppose where in metaphase one of meiosis and in metaphase, what we have is the homologous, the replicated homologous chromosome pairs basically line up along the aquarium."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's suppose we're looking at metaphase."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We have metaphase one of meiosis."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so what happens is each one of these chromosomes will be replicated during the f phase."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And when we're going to get to the metaphase, those tetromer pairs will line up along the equator."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So this will be replicated."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so what we form is the following two sister identical cystic, sister chromatids."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "This one will replicate as well."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We're going to form two identical cystochromatids, and each one of these will also replicate it, but they will be found somewhere below or somewhere above that equatorial line."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's suppose it will be found below."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we're going to have right over here."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So they will be placed right over here."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, so this one here is replicated."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we're going to have a green gene here and that same identical green gene here."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have basically uppercase g, uppercase g. And then we're going to have that lowercase g, lowercase g that are also identical."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And then we're going to have an uppercase T here, uppercase T. And we're going to have a lowercase T, a lowercase T. So all I'm doing right now is basically determining what the distribution is in metaphase one of meiosis when this individual here forms gametes, because before they actually mate, they form gametes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "The sex cells that must combine to form that individual."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, we know by the law of independent assortment we can either have this arrangement or these can be switched."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, if we have this arrangement right here during metaphase, one of meiosis these will be pulled apart and so we're going to form two haploid cells one of the cell will have these here and the other cell will have these two pairs here and then in meiosis too, these will separate and these will separate."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so at the end, what we're going to form is basically two types of cells."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we're going to form a cell that contains the upper case g. So we're going to simplify by simply drawing the uppercase g. And we're going to have uppercase T and we're going to have lowercase G and lowercase T. So this should be lowercase T, lowercase T and lowercase g. Now, this is in the case that we have the following arrangement along our equatorial line of the cell."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "But by the law of independent assortment, it is equally likely that these two will switch and the lowercase T will be on this side."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And what that means is when segregation takes place, the cell over here will receive this one and this one and so in that case, if that takes place, we're going to form uppercase G, lowercase T on that side."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So uppercase G, lowercase T and on this side, if we simply switch this we'll get lowercase G, uppercase T so we have lowercase G and uppercase T so that is the color blue, okay?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And to basically show you what I mean by that so basically 50% of the cells will be arranged like so and the other 50% of the cells will be arranged like this."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So this will basically not change but these here will switch and so we're going to get something that looks like this."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So this will be lowercase T, lowercase T this one will be uppercase T, uppercase T and all I'm doing right now is I'm switching these two chromosomes, these two stay the same so we have GG and then we have our lowercase G, lower case G, okay?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so if this will be the arrangement of the cells, then we form this gamete and this gamete, these two types of gametes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, the thing about this arrangement is that each one of these are equally likely."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have a one four chance that this will occur, a one four chance that this will occur, one four chance that this will occur, and one fourth chance that this will occur."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have a one to one to one to one ratio that each one of these will basically form."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And what that implies is that in this particular case, because we have a 25% chance of each one of these gametes forming."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So let's say because this is our female individual, these will be x cells."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So they're going to look like this, okay?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "There's a 25% chance that each one of these will form."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And we carry out the same exact procedure with this."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Except in this particular case, because we have both lowercase GS and lowercase T's."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "The only type of cell that is produced by this male individual is a gamete that will have lowercase G, lower case T that should be purple."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So this is the only type of gamete that will be produced by this male individual."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we're always going to have 100% of this being produced."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "But here we have a one to one to one to one ratio of these being produced."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So 25% of this, 25% of this, 25% of this, 25% of that."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we see that if this is the cell that is produced, then this Xcel will basically combine with the sperm cell and we produce a genotype that is uppercase G, lower case G, uppercase T, lowercase T. So if these two combined, let's suppose that is case number one."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We produce uppercase G, lower case g, then we produce uppercase T, lowercase T. And so this is the case of heterozygous, a heterozygous individual, okay?"}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now because this is 25% likely, we see that this so one likelihood multiplied by zero point 25 likelihood."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "That means this will be produced at a 25% likelihood."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So 25% of our offspring will be this right over here."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we can say 25%."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So if we produce 1000 individuals, 250 will be the following genotype."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now we can follow this same exact procedure and basically determine what the other phenotype, the other genotypes are."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So now if we don't produce this, we produce this, then this will combine with this to basically produce all recessive genes."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have lowercase g, lower case g, and we have upper lowercase T, lowercase T, and also 25% likelihood."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Now, if this reacts with this, then we have uppercase g, lowercase g, so we have uppercase g, lowercase g, and then we have both lowercase T's."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have lowercase t's."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We need purple for that."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So lowercase t. Lowercase t because lowercase t's."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "Or we can combine wait, this should be lowercase T, or we can combine this one with this one."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "We produce lowercase genes and then uppercase g. So we have lowercase g, lower case g, lower case T, and an uppercase T. So the dominant always comes first."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we have uppercase T, lowercase T, and once again because the likelihood of this taking place is one."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "One multiplied by two up by zero point 25 is basically 00:25."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we have 25% chance of each one of these actually taking place."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "And so we see at the end, if we produce 1000 offspring the way that we tell that these two genes are not linked is by noticing that we have 250 of each one of these offspring being produced."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So we're going to have 250 of these offspring being produced, 250 of these being produced, 250 of these being produced and 250 of these being produced."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "This is assuming that these basically make 1000 times."}, {"title": "Non-linked Genes and Offspring Distribution.txt", "text": "So if we get a distribution, a ratio of offspring that has the five."}, {"title": "Extraembryonic Membranes .txt", "text": "During embryological development."}, {"title": "Extraembryonic Membranes .txt", "text": "When the embryo is developing into that adult organism, there are four extra embryonic membranes that are formed and these four membranes are eventually discarded by that individual following birth."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, these four extra embryonic membranes include the Coryon, the amnion, the lantoids, as well as the Umbilical vesicle, and an animal such as reptiles and birds."}, {"title": "Extraembryonic Membranes .txt", "text": "The Umbilical vesicle is actually called a yolksag because it contains a nutritious substance made of liver proteins known as yolk."}, {"title": "Extraembryonic Membranes .txt", "text": "So in this lecture, we're going to focus primarily on the embryonic development of the human embryo."}, {"title": "Extraembryonic Membranes .txt", "text": "And to see what we mean by these four extra embryonic membranes."}, {"title": "Extraembryonic Membranes .txt", "text": "Let's take a look at the following diagram."}, {"title": "Extraembryonic Membranes .txt", "text": "So this diagram describes the developing fetus as well as the four extra embryonic membranes as they sit inside the endometrium of the uterus of that female individual, the mother."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, the actual developing embryo is this structure here."}, {"title": "Extraembryonic Membranes .txt", "text": "And notice that the coroner is the extra embryonic membrane, is this structure that encloses not only the embryo but also the other three extra embryonic membranes."}, {"title": "Extraembryonic Membranes .txt", "text": "So the Coryon consists of cells that come from the trophy blast as well as the mesoderm germ layer."}, {"title": "Extraembryonic Membranes .txt", "text": "And the Coronon functions in two important ways."}, {"title": "Extraembryonic Membranes .txt", "text": "Firstly, it creates a special fluid we call the coryonic fluid that is located inside the coreonic cavity."}, {"title": "Extraembryonic Membranes .txt", "text": "This space shown here."}, {"title": "Extraembryonic Membranes .txt", "text": "And what that fluid does is it absorbs some of that shock and the force that is experienced as a result of the outside environment."}, {"title": "Extraembryonic Membranes .txt", "text": "And what that does is it protects that developing embryo from any sort of damage."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, the second function of the Corianne is to create these Corianic extensions."}, {"title": "Extraembryonic Membranes .txt", "text": "And these Corianic extensions permeate through the endometrium and eventually they connect with the blood vessels of that female individual and the Coriane."}, {"title": "Extraembryonic Membranes .txt", "text": "These Corianic extensions eventually develop into a structure known as the placenta."}, {"title": "Extraembryonic Membranes .txt", "text": "And the placenta plays a role in exchanging the nutrients, the oxygen and the waste products between that developing fetus, developing embryo and that mother."}, {"title": "Extraembryonic Membranes .txt", "text": "So these are the two functions of the Corian."}, {"title": "Extraembryonic Membranes .txt", "text": "Now let's move on to the embryonic membrane, the extra embryonic membrane that actually encloses that fetus itself."}, {"title": "Extraembryonic Membranes .txt", "text": "This is known as the emeon."}, {"title": "Extraembryonic Membranes .txt", "text": "So the Emeon is an extra embryonic membrane that directly surrounds that developing embryo."}, {"title": "Extraembryonic Membranes .txt", "text": "And in this diagram, the Emeon is this blue structure here."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, the Emeon actually consists of two layers."}, {"title": "Extraembryonic Membranes .txt", "text": "The outer layer is the layer that comes from the mesoderm germ layer, but the inner layer comes from the actoderm germ layer."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, the Amneon basically produces the cells of the amnion produce a special type of watery fluid that is released into the amniotic cavity in the space between the amyon itself and that growing embryo."}, {"title": "Extraembryonic Membranes .txt", "text": "And what that fluid does is it also protects that fetus by absorbing some of that shock."}, {"title": "Extraembryonic Membranes .txt", "text": "So it cushions the fetus and prevents any damage from actually happening to the fetus."}, {"title": "Extraembryonic Membranes .txt", "text": "So this function is similar to the function of the Coryon."}, {"title": "Extraembryonic Membranes .txt", "text": "But what the amnion also does is it prevents the embryo from drying out and it enables the embryo some freedom of movement."}, {"title": "Extraembryonic Membranes .txt", "text": "So it allows the embryo to actually move as it grows."}, {"title": "Extraembryonic Membranes .txt", "text": "And that's important in the process of embryological development."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, let's move on to another extra embryonic membrane known as the umbilical vesicle."}, {"title": "Extraembryonic Membranes .txt", "text": "So in humans, the yolk sac is actually called umbilical vesicle because it doesn't actually contain any yolk."}, {"title": "Extraembryonic Membranes .txt", "text": "So what the umbilical vesicle of functions is, in early embryological development, it actually helps produce some of the red blood cells."}, {"title": "Extraembryonic Membranes .txt", "text": "So it produces some of the blood that the fetus actually contains."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, the final extra embryonic membrane is the lantoise."}, {"title": "Extraembryonic Membranes .txt", "text": "So in non humans, this is a very important structure and it grows relatively large because what it does is it serves in waste disposal."}, {"title": "Extraembryonic Membranes .txt", "text": "So in nonhumans, in reptiles and in birds, the lantoid stores nitrogen containing byproducts within that structure and eventually following birth, that alantoise is actually discarded."}, {"title": "Extraembryonic Membranes .txt", "text": "Now, in humans, the lamp toys is a small outgrowth of developing the gestep tract."}, {"title": "Extraembryonic Membranes .txt", "text": "And what it does is it basically helps create the blood vessels that line along that umbilical cord."}, {"title": "Extraembryonic Membranes .txt", "text": "And we'll discuss what the function of the umbilical cord is in the next lecture."}, {"title": "Extraembryonic Membranes .txt", "text": "So these are the four extra embryonic membranes, the corian, the amneon, the umbilical vesicle and the lantoids."}, {"title": "Extraembryonic Membranes .txt", "text": "And these four membranes are eventually discarded following the birth of that individual, in this case, the human being."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Previously, we discussed the absorption of carbohydrates by the cells of the small intestine."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now let's focus on the absorption of proteins, biontericides the cells found in the small intestine."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, let's begin by recalling the pathway by which we actually digest our proteins."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So when we eat the proteins, when the proteins into the oral cavity of our mouth, we begin the process of mechanical digestion."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "That simply means we increase the surface area of the protein by breaking down our food."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, mechanical digestion does not mean chemically breaking our bonds."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Chemical digestion of proteins begins within the stomach."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So within the stomach, we have specialized types of cells known as chief cells, that secrete a protein enzyme known as pepsin."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And pepsin is responsible for cleaving chemical bonds on proteins."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So within our stomach, the protein denatures as a result of the high acidity, and it also begins to break down."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So pepsin breaks down the protein chemically into smaller units we call polypeptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, those polypeptides will eventually reach the small intestine."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And in this small intestine, we know that pancreas produced and secretes pancreatic peptidases that are responsible for breaking down our peptide bonds."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So we have three important peptidases."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "We have trypsin chimotrypsin, and we have carboxy peptidase."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And together, these three proteolytic enzymes are responsible for breaking down our polypeptides into smaller peptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And finally, these small peptides basically reach the border, the cell membrane of antaricides, and on the cell membrane on the apical side, as shown in this diagram."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So this is the apical side of the interocide with, this is our entericide."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And the apickle side simply means it faces the lumen portion of the small intestine."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So basically, on the membrane of the apical side, we have the microvilli, which is also known as the brush water."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And on this membrane, we have many peptidases that are responsible for breaking down the small peptides into amino acids, dipeptides and tripepptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So once again, to summarize, let's go through the following flow chart."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So we begin by ingesting our proteins into the oral cavity."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "They eventually travel down into the stomach."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "The high acidity denatures those proteins, and the pepsi breaks those proteins down into smaller polypeptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, those polypeptides travel into the lumen of our small intestine."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And in the lumen, these three proteolytic enzymes cleave the polypeptides into small peptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And then those small peptides interact with the enzymes, the proteolytic digestive enzymes of the brush border of this microvilli, as shown here, and they break them down into tripeptides, dipeptides and amino acids."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Dipeptide simply means we have a single peptide bond."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So we have two amino acids in the peptide."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And tripeptide means we have three peptide bonds, so we have two peptide bonds, so we have three amino acids within that peptide."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So all proteins are digested by proteolytic enzymes into either amino acid constituents or dipeptides and tripeptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And the interrogate, the cell found in the small intestine is actually capable of absorbing, not only these individual amino acids, but also our dipeptides and tripepptides."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "But the pathway by which our cell absorbs these differs."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So it differs from amino acids and dipeptides and tripeptides, as we'll see in just a moment."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So individual amino acids are absorbed by the intercity using the sodium dependent co transport system."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "This is basically a secondary active transport, and we'll see exactly what we mean by that in just a moment."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Basically, an ATPA pump is used to establish an electrochemical gradient for sodium."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And then as the sodium moves down its electrochemical gradient, it basically brings the amino acid with it."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, for the case of dipeptides and tripeptides, instead of using the sodium dependent system, we use a hydrogen ion dependent cotransporter system and we'll see exactly what that means in just a moment."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So basically, in this system, we have to use a hydrogen sodium exchange system, where we establish a proton gradient, a hydrogen ion electrochemical gradient, and we use that gradient to basically transport the dipeptides and tripepptide."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So, to see exactly what we mean, let's look at the following diagram."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So, let's suppose our digestive enzymes found on the brush border break down the small peptides into tripepptides, dipeptides and amino acids."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Let's begin by focusing on only the amino acids."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So before the amino acids actually travel into the cytoplasm of our cells."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So this is the cytoplasm side, this is the lumen side, so the apical side, and this other side is the basil lateral side."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "It basically is in close proximity to our blood vessels."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So before these amino acids enter our cytoplasm, we have to establish an electrochemical gradient for sodium ions."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So on the basil lateral side, we have this sodium potassium ATPase pump."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And what this pump does is it uses an ATP molecule."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "It breaks down ATP to ATP."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "In the process, it pumps three sodium ions against its electrochemical gradient to the outside of the cell, and it brings two of these potassium ions into the cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So this is the same exact pump that was used to basically transport the glucose molecules into our cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, as this takes place, the concentration of sodium inside the side of plasma decreases."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Eventually, the concentration of sodium outside is greater than inside of the cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "At this point, the sodium on the outside begins to travel into the cell via this cotransporter membrane protein."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "At the same time that the sodium travels, it basically brings those amino acids with it into our cytoplasm."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, what about the tripepptides and dipeptides?"}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So, at the same time that this pump basically brings the sodium on the outside, this basically brings the sodium back inside."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So for every three sodium we bring outside, there's a sodium on the apical side that is brought inside."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And at the same time, this pumps our age to the outside of the cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So this membrane protein is known as the sodium hydrogen exchange protein."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So it exchanges one sodium for one hydrogen."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, the reason for that is because we also want to establish a hydrogen ion gradient, a proton electron gradient, so that we build a higher concentration of h on the outside, on the lumen side than inside the cytoplasm."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And what that allows us to do is it allows this other membrane protein, known as the hydrogen ion dependent cotransporter protein, as these h ions rush into the cell down their electrochemical gradient, that was established as a result of these two protein, protein integral proteins, the tripeptides and the dipeptides, also travel with these h ions."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So it's the sodium that brings the amino acids in, but it's the hydrogen that brings the tripeptite and dipeptides into our cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, the majority of dipeptides and tripeptites in the cell are converted, are broken down into their amino acid constituents."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And then these amino acids, as well as a few dipeptides and tripepptides, basically travel via special protein proteins found in the membrane of the basil lateral side."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So these proteins can either be our proteins that allow passive diffusion or passive transport, or they can also be those proteins that are co transported."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So either way, the end result is these amino acids, dipeptide and tripepptides, are brought out of the cell via the Bossel lateral site and into the blood vessel system found adjacent next to the bossylateral membrane."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And then these amino acids basically travel to the many cells of our body, specifically in us, in the liver cells."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And these cells basically use the amino acids to synthesize protein."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So once again, to review, let's take a look at the following numbers."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So, number one basically describes we take our small peptide and we hydrolyze them at our protein enzymes found on the membrane of the apical side on the brush border."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "So we transform them into tripeptides, dipeptides and amino acid."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, number two and number three basically describes the establishment of our electrochemical gradient."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "In the case for number two, we establish our sodium electrochemical gradient by using ATP to bring three sodium out, three sodiums outside, two potassiums inside, and that create a lower concentration of sodium inside, and that causes the sodium on the outside to travel inside in number three."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And this brings exchanges and h and that flows outside to the lumen side, and that creates a high amount, high concentration of h on the lumen side and that establishes the hydrogen electrochemical gradient."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, in number four, we have a co transport system that uses the movement of sodium into the cell down its electrochemical gradient to bring the amino acids in."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "But in number five, we use the hydrogen to bring our tripepptides and dipeptides into the cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "As these h move down their electrochemical gradient, these tripeptides and dipeptides also move into our cell."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "Now, in number six, we break down the majority of dipeptides and tripeptide into our amino acids, and then the amino acid, as well as a tiny portion of dipeptide and tripeptides, move via these membrane proteins on the basil lateral side, and they exit into our blood vessel and then are carried to the many different cells in our body."}, {"title": "Absorption of Proteins in Small Intestine.txt", "text": "And those cells, once again, use those amino acids to synthesize the proteins that are needed by that cell."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Recombinant DNA technology involves manipulating or modifying preexisting genes to form new genes, novel genes known as recombinant genes that did not exist before."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, once we form the modified gene, once we form the recombinant gene, the next logical step is to clone our gene to make many copies."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And one way by which we can amplify the gene gene of interest is by introducing that novel gene into a cell and allowing the cell to basically replicate that gene many, many times."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, we can't simply take a gene and place it into a cell."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "We first have to find a vector."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And a vector is simply some type of carrier that can actually take that gene and bring it into that cell without the cell destroying that DNA molecule."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And one typical carrier or one typical vector that we use is a bacterial plasma."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, let's remember what a plasma is."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So prokaryotic cells, such as bacterial cells contain plasma."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So some of them contain plasmids."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And we can find as many as 20 plasmids inside a single cell."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, a plasmid is a relatively small, naturally occurring circular DNA that exists inside the cell in addition to that cell's main DNA main genome."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, a plasmid is a circular, double stranded DNA molecule."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And by circular, we simply mean it does not have a beginning and it doesn't have an end."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, the plasmid is able to replicate by itself independently of that main genomes replication process."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And the entire purpose of this plasmid is to basically contain these special genes that gives the cell special abilities."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "For example, these plasmids can contain genes that produce special toxins that protect the cell from other cells and other organisms."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Or the plasma can contain these genes that give the cell resistance to antibiotics."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Or these plasmids can contain special genes that code for special proteins, special enzymes that help the cell break down different types of products, as we'll see in just a moment."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So these plasmids can essentially be engineered in a laboratory and we can insert different types of recombinant DNA molecules into these plasmids."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And then we can take the plasma and place it into the cell."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And when the cell replicates, it will replicate that plasma."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And by that method, we can essentially produce many copies of that DNA of interest, the recombinant DNA molecule."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, in biochemistry, there are two types of plasmids that we commonly use."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So we use PBR three, two, two, and we also use PUC 18."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So let's begin by discussing PBR three, two, two."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, this was one of the first plasmids that was used to basically clone make many copies of the recombinant DNA molecules."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, this is what the plasma actually looks like."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So we have this circular, double stranded DNA molecule."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "The orange section basically describes non coding genes."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But these colored regions, the blue section and the green section, describe a special gene that codes for special protein."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "The blue gene basically codes for protein that gives the cell the ability to resist a special type of antibiotic known as tetracycline."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "While the green section codes for protein that allows the cell to remain resistant to the antibiotic ampicillin."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And so together, these two genes give the cell the ability to resist antibiotics."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, this section is basically the origin of replication."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "This is where replication essentially initiates."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So remember, because circular DNA, unlike linear DNA, do not have a beginning and an end, we have to have the origin of replication position for the DNA polymerase to actually know where to begin the process of replication."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "That's why we have the origin of replication."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So the PBR three, two, two plasmid contains genes that give it resistance to antibiotics."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Ampicillin, the green one and tetracycline, that blue one."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So how exactly can we take that novel gene, the recombinant gene that we create in a lab, and insert it inside that plasma?"}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Well, we have to use restriction enzymes."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Restriction and the nucleases, these are the enzymes that are able to actually cleave our DNA molecule at specific locations."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And by using different restriction enzymes, we can basically place insert that DNA fragment into different sections along our plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So a DNA fragment of interest, the recombinant DNA for example, can be inserted into a plasmid by using restriction enzymes, we can use different restriction enzymes to insert the fragment at different locations along that plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, if we use a restriction enzyme that cuts along a gene and we insert that DNA molecule into a gene in the middle of a gene, that will essentially inactivate that gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that gene will no longer be able to produce the protein that the gene actually encodes."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And this process is known as insertional inactivation."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So by inserting the fragment into a gene, we inactivate that gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And this is called insertional inactivation."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "That means that gene will not produce the corresponding protein."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And to see what we mean and how this is useful, let's take a look at the following diagram."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So let's take this PBR three, two, two plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And as shown on the board, so we have this green gene that codes for that protein that gives the cell resistance to ampicillin."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And we have this blue gene that gives the cell resistance to tetracycline."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, we can use a variety of different types of restriction enzymes and three restriction enzymes that we can use are shown on the board."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So if we use the restriction enzyme ECoR one, then it will cleave at this non coding section."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "If we use the enzyme cell one, it will cleave right in this blue region."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that means if we insert that fragment into this section, it will inactivate that blue gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And likewise, we can also use a third restriction enzyme known as PST one."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And if we use that, it will make a cut right here and insert that fragment into this section, thereby inactivating this green gene that codes for the protein against ampicillin."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So let's suppose this is the DNA fragment that recombinant DNA, that novel DNA that we create in a lab that we want to replicate."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So let's suppose we want to insert it into this plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And let's say we use the PSTI, the PST one restriction enzyme."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So that means this is where we cleave it."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And if we use this same restriction enzyme and this same DNA molecule, we can insert it into this region."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And so we produce the following plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, notice, because the plasma contains this insertion inside the green gene, this green gene is now inactivated."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But because the blue gene does not contain any insertions, it still is able to actually produce that protein."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "That gives the cell the ability to resist the antibiotic tetracycline."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that can be a very useful procedure."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "For example, we can use this as a marker to basically differentiate between those cells that did not take up the plasmid and a cell that did take up the plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So let's suppose we have a bunch of cells in our solution and we essentially introduce this plasmid into our cells."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, some of the cells will take up that plasmid, but some cells will not take up the plasma."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, those cells that did take up this plasmid will now have the ability to resist this tetracycline antibiotic because they'll have the gene for it."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But those bacterial cells that did not take up this plasma will not have that ability to resist a tetracycline."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So if we add the tetracycline antibiotic into that mixture, all the cells that did not successfully uptake this plasmid will essentially die."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But the cells that did take up the plasma will live on."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that's exactly how we'll know that all the cells in our solution that remain alive have that plasma that contains that particular gene that we want to replicate."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And then we can force those cells to divide via binary fission and that will replicate our DNA of interest."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And at the end, we can extract that DNA."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And now we have many, many copies of that DNA fragment."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So this is one out of the many different ways that we can use these different genes as markers."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, let's move on to the second type of plasma that is more commonly used because it is actually more versatile than this plasma here."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So we have PUC 18 plasma."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So another more versatile plasma that we can use as a vector to basically amplify recombinant DNA molecules is the PUC one eight."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And just like this plasma here, this plasma also contains an origin of replication."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that means we have a beginning."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "The DNA polymerase will know exactly where to begin replication."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And just like this one, this one also contains the ampicillin resistance gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So that means we can use this gene as a marker to basically differentiate between those sounds that did not take up the plasma and those cells that did."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now in addition, on top of these two things, this plasmid also contains a beta galactosidase gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And that is a very important gene because what this gene does so remember, a plasmid not only can contain a gene that gives a resistance to antibiotics, but it can also contain a gene that produces special proteins needed to break down different types of molecules in that cell."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And what this gene actually does is it produces a special enzyme that allows that cell to break down a particular type of sugar molecule for energy."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So as an energy source."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now what this gene also does is we can actually use that protein produced by this gene, we can react it with a special type of analog molecule and that will give us the color blue."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So it will cause the solution to turn blue and that can be used as a very good visual marker to basically differentiate between those plasmids that did take up, those cells that did take up the plasma, those cells that did not."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So we see that the plasma also contains an origin of replication, as shown, as well as an antibiotic resistant gene that can be used as a marker in the way that we discussed earlier."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But in addition to this, it also contains the beta galactose today's gene."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "This gene codes for an enzyme that breaks down sugars and can be used to give a distinct blue color when that enzyme reacts with a special analog molecule, as we'll discuss in a future lecture."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "Now, in addition, this plasma has also been modified, engineered in the following way."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "We essentially insert a small section known as a polylinker."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And what a polylinker is, it's this region that we can cut by using restriction enzymes and we can place any type of DNA molecule into the polyinkerer by cutting it with a restriction enzyme."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And so that's a very convenient property because if we have this polylinker, we can essentially insert any type of DNA fragment that we wish to."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And once we insert that fragment, it will essentially inactivate this gene that codes for the beta galacticadase molecule."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And if this gene is inactivated, then what that means is the cells that do uptake this plasmid will not have the ability to turn our solution blue."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And so if the solution in a beaker becomes blue, that means the cells did not uptake that plasmid."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But if the solution does not turn blue, that means the cells successfully uptook that particular plasma because this gene has been inactivated."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And we'll talk more about different examples and different experiments that involved with these different plasmids in a future lecture."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "So basically, the field of recombinant DNA technology allows us to create these recombinant novel genes."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "But if we actually want to amplify or clone these genes, we have to use vectors."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "And one type of vector are bacterial plasmids, as discussed in this lecture."}, {"title": "Plasmids and Recombinant DNA technology .txt", "text": "In the next lecture, we're going to discuss another type of vector known as a bacteriophage."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "In multicellular organisms such as humans individual cells can organize themselves into groups of cells known as tissues that carry out a specific type of function or purpose."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "In an analogous way to humans organizing themselves into groups to carry out a specific type of function."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "For example, a group of people compose a corporation that carries out a specific type of function."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "In the same way, a tissue basically is an organization of cells that carry out a specific type of function."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, in the human body we have four different types of tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So we have four different types of ways in which our cells can organize themselves into these groups known as tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "We have epithelial tissue, muscle tissue, connective tissue as well as nervous tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, let's begin by generalizing each one of our tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Let's begin with the epithelial tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, the epithelial tissue consists of individual cells that basically serve to cover the outside portion of the body as well as the internal cavities such as the stomach, the small and large intestine as well as the kidneys."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, these cells, the epithelial cells of the epithelial tissue are not only involved in protecting our body from outside harmful sources such as bacteria, viruses or UV radiation these cells are also responsible for absorption as well as secretion."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "For example, the epithelial cells found on our skin are responsible for protecting us from UV radiation."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "The epithelial cells found in our stomach, on the lining of our stomach are basically responsible for secreting hydrochloric acid which gives our stomach its high acidity."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And finally, the epithelial cells found in our intestines are responsible for absorbing the nutrients that we ingest into our body."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, let's move on to our muscle tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "The cells in our muscle tissue are basically responsible for generating the movement that our body is capable of making."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "For example, the reason I can bend my arm is a result of the muscle tissue that is found in my arm."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, these cells have great contractile strain and they can also resist very high compressive as well as tensile forces."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And there are three main types of muscle tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "We have cardiac muscle tissue we have smooth as well as skeletal muscle tissue and we'll discuss this in more detail when we'll examine the muscle tissue as well as our skeletal tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now let's move on to the third type of tissue known as our connective tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So the cells of the connective tissue come in many different forms and have different types of function."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So they can basically provide the organism structural support as well as a way for the different cells in the body to interact with one another."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And some examples of connective tissue include bones, blood, tendons, cartilage as well as adipose tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And the final type of tissue in the human body is the nervous tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So the individual cells of the nervous tissue are known as nerve cells or simply neurons."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And these nerve cells are responsible for generating action potential, our electrical signals that basically allow the cells to communicate with one another and will focus more on what an action potential is when we'll discuss the nervous system of the human body."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, these are the four different types of tissues and a tissue is basically individual cells that are organized to carry a specific type to carry out a specific type of function."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now the question is, what exactly is found in between these cells in our tissue?"}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So this is known as the extracellular matrix, and there are three major constituents of the extracellular matrix."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So we have structural proteins, Adhesive proteins and proteoglycan."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So once again, groups of cells that carry out a similar function are called tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And different tissues have different composition of their extracellular matrix."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So the extracellular matrix or ECM, is a collection of all the molecules and fibers that are found outside the cells, that hold the individual cells together to form our tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And there are three major molecules that constitute our ECM or extracellular matrix."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So we have structural proteins, we have Adhesive proteins and proteoglycans."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So structural proteins are basically those proteins that give our extracellular matrix the tissue its tensile as well as compressive strength."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So the most common type of structural protein in the human body is collagen."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "It provides the matrix with strength and it's found in connective tissue such as bone, our cartilage, blood vessels and so forth."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, the next type of molecule that is found inside the extracellular matrix is the Adhesive protein."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And we have many different types of Adhesive proteins."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So these are basically the proteins that combine, that glue our individual cells together to form our tissues."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And some examples include integrates as well as Catherine, and we'll talk more about these types of proteins when we get into biochemistry."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, the final type of major constituent of the extracellular matrix inside tissues is the proteoglycan."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now the proteoglycan itself is a protein that contains a carbohydrate component."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And usually in the extracellular matrix, proteoglycans are attached to molecules known as glycosaminoglycans."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So these are found in connective tissue as well as are responsible for functioning in cell Adhesion."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, what exactly is a glycos aminoglycan?"}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Well, a glycosaminoglycan is basically some type of disaccharide repeating unit that contains an aminosugar derivative."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And one common example of a glycos aminoglycan in the human body is a molecule known as heparin, which basically looks something like this."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So we have a disaccharide component that contains our amino sugar derivative and this is basically repeated many, many times."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And then we connect this to our proteoglycan and that is our proteogly glycos aminoglycan molecule."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Now, what exactly is the purpose of these proteoglycans attached to our glycos aminoglycan?"}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Well, the purpose is to give our tissue pliability, to give our tissue the ability to basically bend."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So it makes our tissue flexible."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And one common example is Carthage."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "For example, Carthage is found in the ears or our nose."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And the reason we're able to bend our ears or nose without actually breaking it."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "The reason that our ears are so flexible is because of the proteoglycans and the glycos aminoglycan sound inside that cartilage tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "Remember, cartilage is a type of connective tissue."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And inside cartilage found inside the human body, we basically have a protein, a structural protein known as collagen that we discussed earlier, as well as a proteoglycan known as agricon."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And together these molecules basically combine to form our extracellular matrix."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And the extracellular matrix in our cartilage basically gives cartilage the ability to be flexible."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "A cartilage is also found between bones and cartilage also basically acts as a shock absorber."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "So when we jump, the reason that our bones don't rub together is a result of the cart carclage found between those bones."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "And proteoglycans and glycosaminoglycans basically serve as our shock absorb."}, {"title": "Tissue Types and Extracellular Matrix .txt", "text": "As they absorb most of that shock."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "This fructose one six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "But abys phosphate will go on and bind onto pyruvate kinase and activate that molecule and that will increase the rate at which we actually produce those ATP molecules that are needed by our cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "So if we look at this process we see that increase in the concentration of ATP or alanine can cause a negative feedback loop and inhibits activity of periodicinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "But if we have low amounts of ATP that means we'll have high amounts of fructose one six bisphosphate which creates a positive feedback loop and stimulates the Peruvian kinase to carry out its process."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "So now let's summarize our results and let's begin by assuming that we're not exercising so our skeletal muscle tissue is at rest and what that means is we'll have plenty of ATP molecules to go around and so the energy charge of the cell will be high, the ratio of ATP to amp will be high."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "So if that is high, then that means ATP, the excess ATP will go on and bind onto that phosphorokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And what that will do is it will inhibit the activity of that enzyme."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And if that enzymes activity is inhibited, it will stop producing the fructose one six bits phosphate and that will increase the concentration of fructose six phosphate."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And this increase bilastritle edge principle will cause the increase in this glucose six phosphate and that creates a negative feedback loop and inhibits the activity of Hexokinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "Now if these two enzymes are inhibited then these two pathways are inhibited and that will basically turn off the process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "On top of that, the ATP will also bind onto pyruvate kinase and inhibit the third process irreversible process of glycolysis."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And so when we have high amounts of ATP all three irreversible processes are inhibited and glycolysis stops producing ATP."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "But on the other hand, if we're exercising very vigorously we're going to have a low energy charge value because of this process."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "We're going to produce many ATP molecules as these ATP molecules are continually used up by the cells."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And so we have a lowering in the energy charge ratio and these amp molecules will go on and bind onto phosphor fructose kinase and that will stimulate the activity of these molecules, it will produce many more of these fructose one six bits phosphate which will create a positive feedback loop with this pyruvate kinase."}, {"title": "Regulation of Glycolysis in Skeletal Muscle Part II .txt", "text": "And so that will essentially cause the production production of many more ATP molecules and that will help meet the need of these ATP molecules by the contracting skeletal muscle tissue."}, {"title": "Propagation of Action Potential.txt", "text": "Now that we know what an action potential is and how the cell generates this action potential, let's discuss how the action potential actually propagates or moves along the axon of our nerve cell."}, {"title": "Propagation of Action Potential.txt", "text": "So let's begin by recalling some basic information about the neuron."}, {"title": "Propagation of Action Potential.txt", "text": "So basically, the neuron contains the soma, also known as the cell body, that contains the nucleus and the organelles."}, {"title": "Propagation of Action Potential.txt", "text": "It contains these projections known as dendrites, that receive the electrical signal from other cells."}, {"title": "Propagation of Action Potential.txt", "text": "And then our dendrite sends those electrical signals through the soma and to the axon hilloc."}, {"title": "Propagation of Action Potential.txt", "text": "Now, that axon hillock receives the stimulus, and if the stimulus is high enough, if it reaches the threshold value, an action potential is generated on the axon hillock."}, {"title": "Propagation of Action Potential.txt", "text": "And then that action potential somehow moves along the axon and all the way to the axon terminal, away from the soma of the neuron."}, {"title": "Propagation of Action Potential.txt", "text": "Now the question is, how exactly does our action potential actually travel along the exxon?"}, {"title": "Propagation of Action Potential.txt", "text": "And why does our action potential only move in this direction, away from our soma?"}, {"title": "Propagation of Action Potential.txt", "text": "So let's begin by zooming in onto our exxon hilloc, as shown in the following diagram."}, {"title": "Propagation of Action Potential.txt", "text": "So this is before any stimulus is actually applied."}, {"title": "Propagation of Action Potential.txt", "text": "So before we apply our stimulus, the inner portion of the cell membrane."}, {"title": "Propagation of Action Potential.txt", "text": "So this is one cell membrane on this side, and this is the other cell membrane on the other side."}, {"title": "Propagation of Action Potential.txt", "text": "And this is our cytoplasm of the exxon hillock."}, {"title": "Propagation of Action Potential.txt", "text": "So before we apply our stimulus, our cell membrane is resting."}, {"title": "Propagation of Action Potential.txt", "text": "And remember, the resting membrane potential means that the inner portion is negatively charged and the outer portion, the extracellular portion of the cell membrane, is positively charged, as shown."}, {"title": "Propagation of Action Potential.txt", "text": "So before any stimulus is applied, the membrane is negatively charged inside the cell and positively charged right outside the cell."}, {"title": "Propagation of Action Potential.txt", "text": "Now, let's suppose our dendrites receive that signal and transmit that signal through the cytosol of the soma and to the exxon hillock."}, {"title": "Propagation of Action Potential.txt", "text": "Now, if the stimulus is high enough, if it is equal to or exceeds the threshold value, then what that basically causes is the opening of the sodium voltage gated channels."}, {"title": "Propagation of Action Potential.txt", "text": "And as soon as our stimulus is applied to a certain region, let's say this region, our channels, the sodium channels on the membrane open up and the sodium travels down its electrochemical gradient and from the outside and into that cell."}, {"title": "Propagation of Action Potential.txt", "text": "So we have an influx of sodium into our cell."}, {"title": "Propagation of Action Potential.txt", "text": "Now, as soon as our sodium ions rush inside the cell, they will reverse the polarity of the cell."}, {"title": "Propagation of Action Potential.txt", "text": "And this is known as the depolarization period."}, {"title": "Propagation of Action Potential.txt", "text": "So that basically means because we have positively charged sodium ions flowing into the cell, that will make the inside of the cell momentarily positive and the outside of the cell will become momentarily negative in the region where the stimulus is applied."}, {"title": "Propagation of Action Potential.txt", "text": "So that is shown in the following diagram, the sodium channels open up and our sodium ions move into the cell, as shown."}, {"title": "Propagation of Action Potential.txt", "text": "And that will cause the inside of the cell membrane to become positively charged and the outside to become negatively charged."}, {"title": "Propagation of Action Potential.txt", "text": "Now, notice, the adjacent region of the cell membrane still contains a negative charge on the inside and the positive charge on the outside."}, {"title": "Propagation of Action Potential.txt", "text": "The question is, how exactly will the adjacent section of the cell membrane be influenced by the influx of the sodium ions into the cell?"}, {"title": "Propagation of Action Potential.txt", "text": "So it turns out that the increase of the positive charge inside the cell where the stimulus actually took place will cause an increase in the positive charge found in the region right next to where the stimulus actually took place."}, {"title": "Propagation of Action Potential.txt", "text": "So what that means is, as we have a build up of sodium ions in this region, that will influence the charge value on the region right next to it."}, {"title": "Propagation of Action Potential.txt", "text": "And so this will begin to become more positively charged."}, {"title": "Propagation of Action Potential.txt", "text": "And remember, as the inside of the cell initially becomes more positively charged, that will begin to stimulate the opening of the sodium ion channels, the sodium voltage gated channels."}, {"title": "Propagation of Action Potential.txt", "text": "So what that basically means is we stimulate the NA channels to open up adjacent to where the stimulus actually took place."}, {"title": "Propagation of Action Potential.txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Propagation of Action Potential.txt", "text": "So, as soon as the sodium channels begin to open up on the adjacent region, the sodium channels where the stimulus actually took place begin to close."}, {"title": "Propagation of Action Potential.txt", "text": "And as they begin to close, that will basically inactivate our sodium channels and that will open up the potassium channels."}, {"title": "Propagation of Action Potential.txt", "text": "And now potassium ions where the stimulus actually took place, the potassium channels will begin to open up and our potassium ions will begin to move down the electrochemical gradient from the inside of the cell to the outside of the cell."}, {"title": "Propagation of Action Potential.txt", "text": "And this is known as our repolarization period."}, {"title": "Propagation of Action Potential.txt", "text": "Now, we're going to once again change the polarity of the cell."}, {"title": "Propagation of Action Potential.txt", "text": "And so the inside will become negatively charged, because we have these positively charged sodium potassium irons leaving."}, {"title": "Propagation of Action Potential.txt", "text": "So that means the inside will become negatively charged, the outside will become positively charged, but at the same exact time, the concentration of charge, of positive charge increases in the adjacent region."}, {"title": "Propagation of Action Potential.txt", "text": "And that causes our sodium voltage gated channels to open up in the adjacent region."}, {"title": "Propagation of Action Potential.txt", "text": "And so we have an influx of sodium ions into the cell around this region."}, {"title": "Propagation of Action Potential.txt", "text": "And in this manner we can see that the action potential moves from this initial position where the stimulus took place, to the next position along the cell membrane of our axon."}, {"title": "Propagation of Action Potential.txt", "text": "So once again, at around the same time as the sodium channels begin to close and the potassium channels begin to open in the stimulus region, in this region here, the sodium channels in the adjacent region will begin to open, causing depolarization to take place here."}, {"title": "Propagation of Action Potential.txt", "text": "So we have depolarization taking place here and repolarization taking place here."}, {"title": "Propagation of Action Potential.txt", "text": "Now in this same effect, so we basically have a domino effect taking place."}, {"title": "Propagation of Action Potential.txt", "text": "And so each adjacent consecutive region will basically be depolarized as our action potential moves along our cell membrane."}, {"title": "Propagation of Action Potential.txt", "text": "Now, the next question that we want to basically answer is why doesn't our action potential move in the opposite direction?"}, {"title": "Propagation of Action Potential.txt", "text": "So we said earlier that as the positive charge increases on this side, this inside negative charge becomes more positive."}, {"title": "Propagation of Action Potential.txt", "text": "And that's exactly why what causes this section to depolarize."}, {"title": "Propagation of Action Potential.txt", "text": "And the same thing is true here."}, {"title": "Propagation of Action Potential.txt", "text": "So as this inside becomes more positive, this inside also begins to become more positive."}, {"title": "Propagation of Action Potential.txt", "text": "And so as this, as these ions begin to close, these sodium ions will begin to open."}, {"title": "Propagation of Action Potential.txt", "text": "And so the actual potential will begin to move in this direction."}, {"title": "Propagation of Action Potential.txt", "text": "But notice in this case, we also have a negative charge to the left of this increasing positive charge."}, {"title": "Propagation of Action Potential.txt", "text": "So in the same way that this negative charge becomes more positive, when we have the influx of sodium, why doesn't this, the one right and back also become more positive?"}, {"title": "Propagation of Action Potential.txt", "text": "And so we also have an actual potential traveling this way."}, {"title": "Propagation of Action Potential.txt", "text": "Why doesn't that actually take place?"}, {"title": "Propagation of Action Potential.txt", "text": "Well, it turns out that this region that is being rep polarized is actually experiencing an absolute refractory period."}, {"title": "Propagation of Action Potential.txt", "text": "And that means that all the sodium gated channels are actually closed, all the sodium voltage gated channels are actually closed and inactivated."}, {"title": "Propagation of Action Potential.txt", "text": "And that means no matter how high the stimulus is, no action potential can be generated in the region right before our action potential."}, {"title": "Propagation of Action Potential.txt", "text": "So once again, you might be wondering why the action potential does not move back towards our cell body."}, {"title": "Propagation of Action Potential.txt", "text": "So we know it moves this way, but why doesn't it move backwards?"}, {"title": "Propagation of Action Potential.txt", "text": "Well, this is because the region of the membrane right before the depolarized section is in its absolute refractory stage."}, {"title": "Propagation of Action Potential.txt", "text": "And that means no matter how large our stimulus actually is, no action potential will take place in that region."}, {"title": "Propagation of Action Potential.txt", "text": "And this is because the sodium channels are inactivated."}, {"title": "Propagation of Action Potential.txt", "text": "There's nothing we can do that will activate those inactivated channels."}, {"title": "Propagation of Action Potential.txt", "text": "So we have to wait until they recover from that inactivation period."}, {"title": "Propagation of Action Potential.txt", "text": "So this is explained in the following diagram."}, {"title": "Propagation of Action Potential.txt", "text": "So, as our action potential moves over this way, the region right and back of that action potential is experiencing a refractory period, absolute refractory."}, {"title": "Propagation of Action Potential.txt", "text": "And that means our sodium channels on the cell membrane here and here are inactivated."}, {"title": "Propagation of Action Potential.txt", "text": "And no matter how high our stimulus is, no action potential can be generated in this section."}, {"title": "Propagation of Action Potential.txt", "text": "And so our action potential does not actually move in a backward direction towards Arasoma and only moves towards our axon terminal."}, {"title": "Propagation of Action Potential.txt", "text": "And this is shown in the following diagram."}, {"title": "Propagation of Action Potential.txt", "text": "So our stimulus is applied to this section."}, {"title": "Propagation of Action Potential.txt", "text": "If it's high enough, we basically have this propagation of the action potential take place and it only moves away from the soma away from the cell body and towards our axon terminal."}, {"title": "Propagation of Action Potential.txt", "text": "So this is the mechanism by which our propagation of the action potential actually takes place."}, {"title": "Propagation of Action Potential.txt", "text": "In the next lecture, we're going to discuss a concept known as myelination."}, {"title": "Propagation of Action Potential.txt", "text": "We're going to discuss what makes our signal propaganda faster on the axon."}, {"title": "Propagation of Action Potential.txt", "text": "And we're going to discuss something called saltatory conduction."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "Max value, the maximum rate of activity of that enzyme as well as the Km value, the mechaelis constant is actually lowered in uncompetitive inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "Now, one major difference between uncompetitive and competitive is the fact that in this particular case, if we increase the substrate concentration, that will not actually affect affect that activity of the enzyme."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So uncompetitive inhibitors cannot be overcome by increasing the concentration of the substrate."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And this is also true in a final type of inhibition known as non competitive inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So we saw that in competitive inhibition, that inhibitor binds onto the active side of that enzyme because of the resemblance in structure."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "We saw that in non competitive, the only time the inhibitor can bind onto that enzyme is when the substrate is actually bound onto the active side of that enzyme, because only then will we create that pocket of space, the allosteric side that the inhibitor can actually bind to."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "Now, we see that in non competitive inhibition, sometimes the enzymes will have that active side as well as that additional pocket, that additional allosteric space, regardless of whether or not that enzyme is actually bound onto that substrate inside the active side."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So some enzymes have a permanent allosteric site that can buy inhibitors."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And these inhibitors are known as non competitive inhibitors because they do not buy into the active side."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And so they do not actually compete for the active site with that substrate."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And so these non competitive inhibitors can bind to the enzyme regardless of whether or not the substrate is actually bound into the active site region."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And this is shown in the following diagram."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So we have the enzyme, this is the active side, this is our allosteric site to which the red inhibitor can actually bind to."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So once we have this enzyme, if we have the substrate in close proximity, and this is far away, the substrate will bind until the active side to basically form this particular enzyme substrate mixture and then the enzyme substrate complex."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "If no inhibitors bound onto that allosteric side, this can basically catalyze the transformation of that substrate, the green molecule, into the product and by the way, forgot to throw a product."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So let's say that that green structure is transformed into this final molecule, which is our product, and this will only take place if no inhibitors actually bound onto that allosteric site."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "Now, instead, we can also have this pathway that is followed."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "If this is in close proximity, it binds onto the allosteric site to form that enzyme inhibitor complex."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "But just because we form the enzyme inhibitor complex, that doesn't mean that the substrate will not be able to bind into the active site."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "In fact, the substrate usually does bind into the active site."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "But the problem is, once we form the enzyme substrate inhibitor, as in this particular case, that prevents that enzyme from actually catalyzing the transformation of that green substrate into this purple product."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And so here, no reaction takes place."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "Now, if the inhibitor departs, then we form this enzyme substrate complex, and only then can it go on to form that particular product."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So unlike in competitive inhibition, and unlike in non competitive inhibition, in non competitive inhibition, what the binding of the inhibitor does is it lowers the turnover number of that enzyme, kcat."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So remember, the kcat value, the turnover number represents the number of substrate molecules that can be transformed into the product molecules over some period of time by a single enzyme."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And what this inhibition does is it decreases that turnover number."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So essentially, the v max is lowered, the turnover number is lowered, but the km value, the Mikhaila's constant value, actually doesn't change in non competitive inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And again, we'll talk about that in much more detail and why that actually takes place in the next lecture."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So again, reversible inhibition, the inhibitor binds onto that enzyme, but it binds relatively weakly."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And what that means is that the dissociation can take place very quickly under the proper conditions."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And this is in contrast to irreversible inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "So in reversible inhibition, we have three types."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "We have competitive inhibition in which that inhibitor binds directly to the active side."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "We have on competitive inhibition, in which the inhibitor binds onto that allosteric side that is formed only when that substrate is bound onto the active side of the enzyme."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And finally, we have noncompetitive inhibition in which that enzyme always contains an allosteric site."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And so what that means is that inhibitor can bind onto that allosteric site of the enzyme regardless of whether or not that substrate is bound onto the active site of the enzyme."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And finally, I guess I'll mention it briefly, we also have a fourth type of inhibition known as mixed inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "And in mixed inhibition, what that inhibitor does is it basically decreases the affinity of that active side for that substrate, and it also decreases the turnover number of that particular enzyme."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "This is known as mixed inhibition."}, {"title": "Irreversibile and Reversible Inhibition Part II .txt", "text": "It's a much more complex type of inhibition than either of these three forms of inhibition."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "In our discussion on skeleton muscle cells and the regulation of glycogen breakdown, we ultimately said that to initiate the process of glycogen breakdown phosphorase B has to be transformed into phosphoralase A."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And that's because it's phosphoralase A that predominates in the RSA, the relaxed state that is fully active."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And once we form phosphorase, this enzyme basically initiates step one of glycogen breakdown."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Now, we also said that the enzyme that catalyzes this step is known as phosphorlase kinase."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So ultimately what phosphorase kinase does is it takes sulfosphoryl groups from two ATP molecules and places them onto Seren residues found on phosphorase B and that creates phosphorase A."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Now, the question that I'd like to address in this lecture is what exactly activates phosphoralase kinase?"}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "What exactly allows this molecule to carry out this process in the first place?"}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So once again, phosphorase kinase is the enzyme that catalyzes the conversion of phosphorase B in the T state into phosphorlase A, which predominates in the R state."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "But what exactly activates this phosphorlase kinase?"}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Well, before we look at that question, let's actually discuss what the structure of phosphorase kinase actually is."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Well, the structure of this kinase actually consists of four different types of subunits, four different types of polypeptide chains."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "We have the alpha, the beta, the gamma and the delta."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And we actually have four of each type."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So this is what the structure looks like."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So we have four beta shown in orange."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "We have these four gamma, the four delta and the four alpha."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Now, only these green structures, the gamma structures actually have catalytic activity and these green structures are the ones that are responsible for catalyzing this particular step."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "But the other three subunits basically have regulatory abilities."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And as we'll discuss in just a moment, it's the beta subunits and the delta subunits which are ultimately responsible for fully activating the phosphorylase kinase."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So during times of rapid and sudden strain use activity, we know that our body begins producing and releasing hormones into our bloodstream."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And what these hormones ultimately do is they allow our body, they allow the cells of our body to actually activate these beta subunits and they activate the beta subunits by attaching phosphoryl groups."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So when we release the hormones that ultimately basically these four beta subunits to form the following structure."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Now, although this structure does contain partial activity, it is not yet fully functional."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And to transform this molecule into a fully functional enzyme that can basically catalyze this particular reaction, what must happen is calcium ions must bind to these red structures."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "These red structures are the delta structures and the delta structures are actually calmodulent proteins."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "Remember that calmodulen is a protein that consents calcium ions."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "It can bind calcium ions."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So in skeletal muscle tissue, when we contract the calcium ions stored in the sarcoplasm reticulum is basically released into the cytoplasm."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And once inside the cytoplasm, the calcium ions can basically bind onto these rep structures and once the calcium ions bind onto the rep structures, that transforms this partially active enzyme into the fully active phosphorlase kinase."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And only now can this structure actually carry out this process with full activity."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "So we see that in order for phosphorylase kinase to actually initiate this process, which in turn initiates glycogen breakdown, this molecule itself must be initiated."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "And it is initiated by two different processes the phosphorylation of these beta subunits as well as the binding of the calcium ions on these red delta structures."}, {"title": "Activation of Phosphorylase Kinase .txt", "text": "The kel modulent subunits."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Lipid molecules are the major constituents of cell membranes."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But the question is why?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "What makes lipids perfect for cell membranes?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Well, remember that lipid molecules are amphipathic."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And what that means is they contain a polar region and a nonpolar region."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And it turns out that it's the amphipathic nature of lipids that gives them the propensity, the ability to actually form, form these cell membranes."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So when we take a lipid molecule and we place it into an aqueous environment where water is a solvent, the polar water molecules will tend to form favorable interactions, hydrogen bonds with the polar region of that lipid."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But the non polar hydrophobic section of that lipid will not want to interact with the water molecules."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so what happens when we place many of these lipids into an aqueous environment to basically stabilize that system, to create a system, a structure that is lower in energy, they will spontaneously rearrange themselves and form these structures."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And we have two types of structures that they can form."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "We can form micelles or we can form the bimolecular sheet, the lipid bilayer, which basically is the cell membrane that is found around the eukaryotic cells of our body."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Now, the type of structure that is formed depends on the type of lipid molecule that we have in the aqueous environment."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And we'll see why in just a moment."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So when certain lipids are placed into water, they will spontaneously rearrange themselves to form structures called MiCell."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So let's suppose we have a single fatty acid and we take that fatty acid and place it into solution."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Now let's suppose this fatty acid is ionized."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So what does that mean?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So we have an ionizable fatty acid which means we have this hydrocarbon backbone shown in red that is not polar, so it's hydrophobic."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And we have this polar section which is basically the carboxylic acid."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And the ionized version of this fatty acid means this carboxylic acid is the protein."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So it contains a full charge."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Now, because this contains a charge, it can interact via hydrogen bonds with these nearby water molecules and these bonds are shown in purple."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Now, these interactions between the polar water and this polar head of the ionized fatty acid, those interactions are good, they are energetically stabilized, they are energetically favorable."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But all these other water molecules that surround this hydrophobic red chain basically cannot interact in the same energetically favorable way because this is non polar and the water molecules are polar."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so ultimately all these water molecules remain trapped and cannot interact any favorable bonds and that is not a stabilizing system."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so what happens is when we have many of these ionized fatty acids in an aqueous environment, they will form these micelles, these globular spherical structures in which the outside of the sphere, we basically have all these heads because their polar align themselves in a way that they point towards the aqueous environment."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And all these rat tails basically aggregate at the interior of that spherical structure."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And what that does is it releases all these water molecules that are initially trapped around that red hydrophobic tail."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "It releases them and now they can interact in a stabilizing way with other water molecules or with these polar blue heads and that is an energetically stabilizing interaction."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So what this essentially does, the reason this takes place spontaneously is because it creates a more stable lower and energy system in which we now have the interactions between these water molecules and these polar heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Those are the hydrogen bonds."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "We also have electric interaction between these adjacent polar heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "These are shown in purple and we also have these green interactions and these are the interactions, the London dispersion forces, the Vanderbilt bonds between the adjacent red tails as shown in this diagram."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And this is a stabilized system."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So lipids such as ionized fatty acids will spontaneously form mice cells in water."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "This occurs because it minimizes the polar non polar interactions that we have here."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "It releases the water molecules and that stabilizes the interactions that now can exist between the water molecules and other water molecules and these heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So it allows the polar heads to interact with water as well as with each other and it also basically hides these hydrophobic regions on the interior and allows them to interact with each other."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And this is what we call the hydrophobic effect."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So in the same way that it's the hydrophobic effect that allows the protein structure to basically form into its three dimensional shape and it's the hydrophobic effect that allows the nucleic acids to basically aggregate and form the double helix of DNA."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "It's the hydrophobic effect that is the driving force of the formation of the MyCell structure as well as of the bimolecular sheet, the lipid bilayer."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So let's move on to the lipid bilayer."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So in this particular case, these lipids actually contain a very thin fatty acid, a very thin hydrocarbon portion."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So in any one fatty acid we only have one of these tails."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so this is not a bulky molecule and because it's not bulky, these tails can easily and snugly fit on the interior space of that myosyl."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But bulkier lipids so, which are larger and contain thicker hydrophobic tails will spontaneously rearrange themselves in an acoustic environment and form not in my cell but a lipid bilayer."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And if we take a cross section of that lipid bilayer this is basically what it looks like."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So the major difference between this structure and this structure is that this structure actually consists of two different layers."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So two phosphol lipid layers, one and two."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And each one of these sides, each one of these layers is known as a leaflet."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So in this double layer we have the polar heads orient themselves towards the aqueous environment while the nonpolar tails aggregate on the inside to form a barrier, the hydrophobic barrier."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So the interior of the cell membrane."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "The lipid bilayer is hydrophobic because it consists predominantly of these tails, while the outside and the inside portion of this bilayer consists of these heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And those are the polar regions."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "They can interact with each other as well as with the water molecules found on the aqueous environment."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So another major difference between this bimolecular sheets and the my cell is inside the MiCell, because we don't have any polar region, there's really no aqueous environment on the inside."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But in this particular case, this entire lipid bilayer extends to form this globular, this circular structure."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And notice we have an aqueous environment on the inside and the outside of that structure because we have these two leaflets and they both contain these polar regions that contract with the water molecules on either side of that membrane."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So we have an aqueous environment on either side of this structure, but an aqueous environment only exists on the outside of this structure."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So what types of lipids actually form the lipid bilayer?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Well, the bulk here lipids, the larger lipids."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So unlike fatty acids, things like glycolipids or phospholipids or cholesterol molecules, these are too large to fit Snugly on the interior structure of the myosoline."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So instead they form these lipid bilayer."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So phospholipids and glycolipids readily form bilayer structures and not my cells."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "This is because the larger non polar tails of these lipids is too large to fit into the limited space of the MiCell."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So what exactly allows these two structures to form spontaneously?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So, as we said a moment ago, it's the hydrophobic effect that is the driving force in the formation of the cell membrane, the lipid bilayer and micelles."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So the interaction of the hydrocarbon tails releases the water molecules from the nonpolar regions and this is energetically stabilizing, energetically favorable."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So in this particular case, the water molecules were trapped around that hydrophobic region."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "But because we formed these structures and these structures, that leads to a maximum interaction between the water molecules and these polar heads, at the same time it locks in these or it hides these hydrophobic regions on the interior portion of the mind cell and the interior portion of the cell membrane, the bilayer membrane."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so we have these stabilizing lung dispersion forces that exist on the interior."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And then we have the polar interactions, we have hydrogen bonds between the water molecules in the aqueous environment and these polar heads, and also the electrostatic interactions between these nearby polar molecules which are lined right next to one another."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So we see that therefore, the tails spontaneously aggregate in the interior of the membrane because this is what creates a stabilizing system."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So it allows those trap water molecules to be released and how these water molecules can form stabilizing hydrogen bonds with these polar heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "In addition, we have the lung dispersion forces that exist between the adjacent tails on the interior portion of the structure."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "We have the electrical and hydrogen bonds that exist between these adjacent heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And we also have these hydrogen bonds between water molecules and these heads."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So it's the hydrophobic effect that plays the role that drives the formation of the cell membrane and these micelles."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So there are three things that we have to remember about cell membranes because of this discussion."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Number one is the cell membrane forms spontaneously and once it forms, it forms a closed compartment."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So this entire cell membrane will basically form a closed compartment in which we'll have an aqueous environment inside that is separate of the aqueous environment that is found on the outside."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Number two, the major difference, or one important difference between my cells and the lipid bilayer is these structures can only form very small structures, but these can become very, very large."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "In fact, our diameter of my cells is usually 20 nm, but the diameter of these can be up to 1 million."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "That is a big, big difference."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "So these lipid bilayers can be very expensive."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And that's exactly why our cells are made up of these or our cells containing these lipid bilayers, because cells can be very, very large in size and this would not be able to form that same cell membrane structure."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And three, these bilayer membranes have the propensity to fix themselves."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Why?"}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Well, let's suppose some type of hole is formed in that bimolecular sheet, in the lipid bilayer."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "Once that hole is formed, we go back to this picture where the water molecules become trapped around that hydrophobic tail and that is not a favorable system."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And so what will happen is that hole that is formed will be spontaneously fixed to basically decrease the energy of that system."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "And that's exactly what we mean by the bilayer membrane has the spontaneous ability, the propensity, to actually fix itself."}, {"title": "Micelles and Lipid Bilayer .txt", "text": "If there is ever some type of hole that is formed inside that cell membrane."}, {"title": "Fatty Acids Part II .txt", "text": "Double bonds affect the melting point of that particular fatty acid."}, {"title": "Fatty Acids Part II .txt", "text": "So again, let's suppose in one beaker, let's say we have the following fatty acid without this double bond."}, {"title": "Fatty Acids Part II .txt", "text": "And in the second beaker, we have a fatty acid that contains this CIS double bond."}, {"title": "Fatty Acids Part II .txt", "text": "What exactly is the difference between one beaker and the a second beaker?"}, {"title": "Fatty Acids Part II .txt", "text": "Well, in the case of no double bonds, so this molecule, minus this double bond, the molecule will essentially be a linear straight chain molecule."}, {"title": "Fatty Acids Part II .txt", "text": "And that means they can stack on top of one another very well."}, {"title": "Fatty Acids Part II .txt", "text": "And by stacking very well, we have a very small distance between the molecules."}, {"title": "Fatty Acids Part II .txt", "text": "And if the distance is smaller, the intermolecular bonds are stronger."}, {"title": "Fatty Acids Part II .txt", "text": "But in the mixture that contains these CIS double bonds, the stacking isn't very well."}, {"title": "Fatty Acids Part II .txt", "text": "So one molecule is positioned this way, the other one is this way."}, {"title": "Fatty Acids Part II .txt", "text": "And so we have much less of the intermolecular interaction taking place in the case where we have those double bonds."}, {"title": "Fatty Acids Part II .txt", "text": "And so, essentially because double bonds create these kinks, these deviations in the geometry of the fatty acid, what that does is it decreases the intermolecular traction between the molecules, the fatty acids, and that decreases the melting point because we have to input less energy to break those intermolecular bonds, because we have less of those bonds and ultimately, because the fatty acids don't attract as well as a result of these double bonds."}, {"title": "Fatty Acids Part II .txt", "text": "Increasing the number of double bonds in the fatty acid not only lowers the melting point, it also increases the fluidity of that fatty acid."}, {"title": "Fatty Acids Part II .txt", "text": "So unsaturated fatty acids have a lower melting point due to weaker intermolecular interactions."}, {"title": "Fatty Acids Part II .txt", "text": "Less energy must be input to actually break those weaker bonds."}, {"title": "Fatty Acids Part II .txt", "text": "And so that means a lower melting point."}, {"title": "Fatty Acids Part II .txt", "text": "Now, the weaker the intermolecular bonds are, the less likely they are actually held together."}, {"title": "Fatty Acids Part II .txt", "text": "And so that makes them much more fluid."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "In our discussion on the primary structure of polypeptides, we said that it's the primary structure, it's that specific sequence of amino acids in that polypeptide that ultimately determines what the final threedimensional confirmation of the polypeptide is."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, the question is, how exactly do we know that?"}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And how did we discover this important fact about proteins in biochemistry?"}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Well, basically in 1950s, an American chemist by the name of Christian Anthony conducted a series of important experiments that demonstrated that all the information that we need to basically form that threedimensional structure of the polypeptide is found is stored in the specific sequence of amino acids within that polypeptide."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And later experiments confirm the fact that the primary structure determines that confirmation of that protein."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, before we actually examine what these experiments were, let's take a look at some important molecules and reagents that he used in his experiment."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So he used two important denaturing agents."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Denaturing agents are these molecules that basically break down the structure of our protein."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So he used urea and betama capto ethanol."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, urea is basically used to break down the non covalent bonds, such as hydrogen bonds and ionic bonds that hold together that secondary structure of the protein as well as parts of the tertiary structure."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And he used bader mercaptoethanol to basically break down the covalent bonds, the disulfide bonds that exist and hold that tertiary structure of the protein together."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So Beter Mcappto ethanol uses an oxidation reduction reaction."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So this itself is oxidized and reduces the disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "It breaks them down."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "It breaks down the cysteine units into the two individual cysteine amino acids, as we'll see in just a moment."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So together, these two agents can be used to denature to break down the tertiary and secondary structure of our protein."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, the next question is, what protein did Christian actually use?"}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Well, Christian used a ribonuclease, which is basically an enzyme of protein that catalyzes the breaking down of RNA molecules in the cells of organisms."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And this particular protein has 124 amino acids in its primary sequence."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And in the tertiary structure, it contains four individual disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So we have one bond between the 26th and the 84th 15 amino acid."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "We have a second bond between the we have a third bond between the 65th and 72nd, and we have the final bond between the 58th and 110th 15 amino acid in our ribonuclease."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And this three dimensional structure, this confirmation basically describes the native confirmation of that ribonucleus."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "The native structure describes the biologically active structure of our enzyme."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, the next question is, what did he actually want to do with these different molecules?"}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Well, the plan was to destroy the tertiary and the secondary structures of the ribonuclease by using these appropriate agents and then to see under which conditions did the native structure of that ribonuclease basically reform."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So now let's take a look at these three experiments."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Let's begin with experiment number one."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "In experiment number one, he took that active ribonuclease enzyme that contains this secondary and tertiary structure and he placed it, he mixed it with an excess amount of Beter Mcaptoethanol and a large amount of urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So eight molar concentration of urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So what happened is the excess Beter mecaptoethanol broke down all those covalent disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So it broke down this bond, this bond, this bond and this bond, and the urea broke down the non covalent interactions that hold parts of the tertiary and the secondary structure together."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So at the end, we basically formed the following denatured enzyme, the enzyme that if not in its active form."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, what he did next was by using a semipermeable membrane, he removed these two agents at the same exact time."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So he isolated this denatured enzyme by removing these two agents at the same time."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And eventually he saw what happened is because this denatured enzyme was in the presence of oxygen, the oxygen in the air was able to basically reform those disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So it oxidized those disulfide bonds, reform those disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And eventually, because the urea was also removed at the same time, the non covalent interactions also reformed."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And we reformed the proper secondary and tertiary structure of that particular enzyme."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So initially, we place this native enzyme with access Beter mechatoethanol and ate molar urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And what happens is our enzyme is denatured."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "But when the denaturing agents were removed via the process of dialysis by using a semipermeable membrane, the enzyme eventually reformed its original tertiary structure."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, what this basically shows is it gives us evidence that it's the primary sequence, it's the primary structure, it's that specific sequence of amino acids that essentially dictates the proper formation of the tertiary structure of that enzyme."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now let's move on to experiment two and see what experiment two was."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "In experiment two, he basically took that beaker that contained our denatured enzyme as well as the excess beta mercapto ethanol and our urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And instead of removing these two agents at the same exact time, he first removed the beta mercapto ethanol."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And then after some time, he removed that urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "What he found was the enzyme that was formed was not in its biologically active state."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "In fact, this enzyme was scrambled."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "It contained the incorrect pairing of dixulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So what we mean by that is this native active biologically active form of the enzyme contains these pairings, these disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So, for example, the first one is between the 26th and the 84th amino acid."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "But here the first bond is formed between the 26th and the."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So that means this will contain the improper linkages between our 15 molecules and that will create an inactive molecule."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now, the question is, why did that actually take place?"}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Well, the answer is simple."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "It's the primary sequence."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "It's that specific sequence of amino acids in that polypeptide that basically dictates the type of non covalent interactions that will exist on that polypeptide."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And it's these non covalent interactions that basically drive the correct formation of our disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So if these non covalent interactions cannot exist in that polypeptide, then that polypeptide has no way of knowing what the proper disulfide bonds are that have to be foreign."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And so what happened in this experiment was because we initially removed the beta macapto ethanol before actually removing our urea, we saw that in our denatured mixture we had the urea."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So the non covalent bonds could not actually form and they could not actually drive the correct formation of those disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And so because we had you read in the mixture improper incorrect disulfide bonds were actually formed."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So when the beta mercapto ethanol was removed, first an inactive enzyme was formed."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And this is because the improper disulfide bonds were formed because those non covalent reactions could not basically dictate the formation of those proper disulfide pairings."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now let's move on to experiment number three."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So in experiment number three, what he saw is if he took this scrambled enzyme and he added a tiny amount of beter mccaptoethanol."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So basically we have a beaker that contains our scrambled enzyme and we don't have any type of agent inside that beaker."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And now we add a trace amount of beta mecapto ethanol."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So what he found was because we had a tiny bit amount of this catalyst, this catalyst essentially catalyzed the breakage of these incorrectly paired disulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And eventually because of thermodynamics, we formed this native enzyme."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "Now what that means is it's the conformation, it's the structure of that native enzyme that is the most stable thermodynamically."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And it's because of this that we have the breaking of these bonds and eventually the formation of this native structure."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So if we take the scrambled enzyme and we add a tiny amount of beter mercapto ethanol, the betama captive ethanol will basically break these incorrectly paradisulfide bonds."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And eventually, because this is the most thermodynamically stable structure, this structure will form."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "And he saw that after about 10 hours, this structure did in fact reform."}, {"title": "Anfinsen\u2019s Experiment of Protein Folding .txt", "text": "So these were the experiments, experiments that were conducted by Christian Anderson in the 1950s that eventually showed that it's the primary structure, it's that specific sequence of amino acids inside that polypeptide that eventually gives us information to form that final threedimensional structure of that polypeptide."}, {"title": "Allergens and Allergic Reactions .txt", "text": "The overall goal of our immune system is to protect the healthy cells of our body from invading pathogens, such as bacterial cells or viruses."}, {"title": "Allergens and Allergic Reactions .txt", "text": "It's to generate and maintain a state of homeostasis."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, as with many things in life, our immune system is not a perfect system."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And sometimes it does make mistakes."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Sometimes the immune immune system incorrectly labels an otherwise non harmful foreign substance that enters our body as being harmful as pathogenic."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And this elicits, it initiates a defensive response called an allergic reaction."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And that causing agent that caused that allergic reaction in the first place is known as an allergen."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, different people are allergic to different things."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So allergens differ from one individual to another."}, {"title": "Allergens and Allergic Reactions .txt", "text": "People are generally allergic to certain foods or drugs or certain things found in our environment."}, {"title": "Allergens and Allergic Reactions .txt", "text": "For example, people can be allergic to pollen found in grass or flowers."}, {"title": "Allergens and Allergic Reactions .txt", "text": "They can be allergic to certain foods such as peanuts, or certain drugs such as penicillin."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, let's discuss the mechanism by which an allergic reaction takes place and let's focus on some of the or one of the most common types of allergic reactions known as hay fever."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Hay fever is not an actual fever in the sense that it doesn't actually increase the core temperature."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Instead, hay fever is simply the name for the allergic reaction that takes place when grass pollen actually enters the air passageways of our lungs."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So one very common allergic reaction is hay fever, which is the way our immune system actually responds to grass pollen."}, {"title": "Allergens and Allergic Reactions .txt", "text": "When the allergic individual inhales pollen, that pollen, which is essentially a microscopic particle, can begin to release antigens that our body sees as pathogenic."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So let's take a look at the following diagram to illustrate how our mechanism is actually carried out."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So, let's suppose this is the air pathogeway, the bronchiol of our lungs."}, {"title": "Allergens and Allergic Reactions .txt", "text": "These are the epithelial cells, as shown, and these are the microscopic pollen particles."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, as the pollen particle moves, it can release these tiny particles, even smaller particles that our body labels as pathogenic."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So these are basically seen as pathogenic antigens by our body."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So these tiny antigens can diffuse across the epithelial cells and into the nearby tissue, where we have different types of wide blood cells."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So bealympicides produce plasma cells and these plasma cells can recognize these antigens and begin to produce the corresponding antibody that binds to this antigen."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And the most common type, the predominant antibody involved in allergic reactions, is immunoglobulin E. So immunoglobulin E is produced by the plasma cells."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, what these immunoglobulin E antibodies do is they move on to the cell membrane of special wide blood cells found in the nearby tissue known as mast cells."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So these mast cells contain these receptors that can bind to the constant region of our antibody, as shown in the diagram."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, once the binding takes place, now, these antigens that were released by the pollen particles can move on and bind onto the variable portion on our antibody as shown in this diagram in section five."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And once this binding takes place these mast cells in the cytoplasm contain these granules, these tiny vesicles that carry special chemicals, special immune chemicals such as histamine."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And once the antigen binds onto the antibody found on the membrane of these mast cells, these mast cells release these vesicles, these granules and in turn release the histamine and other immune chemicals."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, what the histamine and these other chemicals do is they initiate an inflammation response and that dilates the blood vessels that carry blood to this area, to this infected area."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So we say infected because this otherwise non harmful foreign substance was labeled as pathogenic by our immune system."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And so this technically is an infected area to that particular individual because the immune system of that individual treats the pollen antigens as pathogenic."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So more blood flows into our infected area as a result of this vassal dilation process."}, {"title": "Allergens and Allergic Reactions .txt", "text": "The increase in diameter of those blood vessels, that brings more blood as well as more wide blood cells."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, what histamine also does is it increases the permeability of the nearby capillaries to water and that makes those capillaries leaky."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And that's exactly why people that experience hay fever have a red nose as well as a leaky nose because the capillaries become more permeable to water and we have more blood flowing to this area."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And that's exactly why it appears more red than usual because of the effect that histamine has on our body."}, {"title": "Allergens and Allergic Reactions .txt", "text": "So once again, tiny pollen, microscopic pollen particles enter the air passageways of our body our nasal canal, our trachea, the bronchi and the bronchioles."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And they release these tiny allergens we call antigens that flow via these epithelial cells and in two our plasma cells."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And the plasma cells see these antigens as pathogenic and begin producing the corresponding complementary immunoglobulin er antibodies."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, these antibodies then bind onto our mast cells, onto these special receptors."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And now these antigens can go on and bind onto these antibodies at the variable portion."}, {"title": "Allergens and Allergic Reactions .txt", "text": "And when the binding takes place these release histamine and other chemicals that basically dilate the blood vessels and that brings more blood to that area, causing redness."}, {"title": "Allergens and Allergic Reactions .txt", "text": "It also increases the leakiness, the leakiness of our capillaries which can lead to edema the process of swelling."}, {"title": "Allergens and Allergic Reactions .txt", "text": "It can also create what we call a runny nose."}, {"title": "Allergens and Allergic Reactions .txt", "text": "Now, this type of allergic reaction is not that dangerous but sometimes individuals are extremely allergic to certain types of things such as peanuts or penicillin and that can be very lethal if not treated immediately by a medical professional."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Whenever disease causes multiple different types of symptoms, that disease is said to be a syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, virtually all chromosomal abnormalities that arise in humans are syndromes and that's because they cause multiple symptoms, both physical as well as mental symptoms."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, the most common type of chromosomal abnormality in humans is down syndrome syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And this will be the focus of this lecture."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we're going to see that there are two forms of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "The first form, the more common form, is trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And the other form, the less common form, is translocation."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So let's begin by focusing on trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So the majority of the people in the world that have down syndrome have the tricemy 21 form of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, what do we mean by tricemy 21?"}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Well, trisomy means we have an extra copy of a chromosome and 21 refers to chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So remember, the carreotype of any normal individual describes 23 pairs of homologous chromosomes and each pair normally consists of two individual chromosomes."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we have a total of 46 chromosomes in a normal carriotype."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But if we examine the carriotype of an individual that has trisomy 21, let's suppose the individual is a male individual."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "This is what we're going to see."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So notice, every single one of these homologous pairs of chromosomes consists of two individual chromosomes, except chromosome pair 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So in an individual, in a male individual that has trisomy 21, they have an extra additional copy of chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we have not two, but three of these individual chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so that's why this condition is known as trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So this is the carotype that describes the carreotype of A."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So this should be male individual who has down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Notice that she has or he has an extra copy of chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And hence this form of down syndrome is said to be trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So the reason this is a male individual and not a female individual is because this is the X chromosome sex chromosome, and this is the Y sex chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "If this was an X chromosome, then in that case we would have a female individual."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now let's discuss how the age of the female actually affects or actually increases the likelihood of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So remember, in female individuals, all the excels that the female individual will ever have in her lifetime are formed before birth."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So all the excels a female individual will ever have are formed before birth."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And what that means is, as the female individual actually ages, so do her ex cells."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so as that individual ages, her X cells ages."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And as the excel age, the likelihood that nondisjunction will take place in meiosis and form an employed excels increases."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so if the likelihood of nondisjunction increases, that means the likelihood of down syndrome is also higher."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So although the currents of down syndrome in the general population is actually very low, it's about zero point 15%, it increases with the increase in the maternal age in the age of that mother for the reason that we just discussed."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So recall that female individuals produce all their ex cells before birth."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So as the female individual ages, the Xcels also age."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And the greater the age of the X cells, the more likely that those X cells will actually undergo nondisjunction during meiosis."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, to see exactly what we mean by that, let's take a look at the following diagram."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So this is one example of how tricemy 21 can actually take place, can actually occur."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So let's suppose we're dealing with a normal female individual."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So since we're dealing with a normal female individual, that means each one of these pairs of chromosomes will consist of two, and that includes chromosome pair 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And because we're focusing on trisomy 21 in this diagram, I've only drawn this chromosome pair 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we have a normal female individual."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So after interface, we have the precursor excel, basically replicates each one of these two chromosomes."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So remember, we have a normal individual."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we have one of these and one of these."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now we replicated and so we produce the cystochromatid that is identical to this chromatid and we produce this second cystochromatid that is identical to this one."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so we have the pair of cystochromatids as shown in the following diagram."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So this is after interface takes place."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So now let's fast forward to metaphase one of meiosis."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "This is what we're going to basically see."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "We're going to have the tetromers align along the equatorial plate."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Technically, we have all these different chromosomes that also align."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But once again, to save space and time, I've only discussed I've only included chromosome pair 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So normally what happens is we have this mitotic spindle apparatus that forms and these fibers extend from our mitotic spindle apparatus."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And these fibers should attach onto each one of these respective chromosome pairs."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And during anaphase one of meiosis, we have the segregation, the movement of these chromosome pairs to opposite poles."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so after meiosis one takes place, we form these two haploid cells."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, because we're assuming no nondisjunction took place within this stage, we're going to have two normal haploid cells after meiosis one."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, let's suppose because the female's age is, let's say, relatively high, the chance of nondisjunction will increase."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so now let's suppose non disjunction takes place within this cell, but this cell divides normally."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So what happens is, within this particular cell, each of these fibers attaches onto each one of these respective identical cysticromatides."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so following cytokinesis, after metaphase two of meiosis, we formed the following two normal X cells."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Notice that these two X cells are normal because they contain the proper number of chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "They contain one chromosome 21 each."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But what happens in this case?"}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Because the age of this XL is high, the likelihood that nondisjunction takes place is also high."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so what that means is what might happen is this fiber doesn't actually attach onto this chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "This is the chromatid here."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so what happens is this entire pair of cystochromatids, basically segregates, moved to one side and nothing moves to the other side."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so we form these two X cells, XL one and XL two, which are abnormal."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "They have anuploid."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "One of these cells lacks a copy of chromosome 21, but the other cell has not one, but two copies of chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so now if we take a sperm cell, so this is our sperm cell that also has let's suppose we have a normal sperm cell and that means we have a normal amount of chromosome number one."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "We only have one."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "When this sperm cell, normal sperm cell combines with Xcel number two, we're going to form a Zygote that has the following genotype distribution for chromosome 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So instead of having two, as in a normal case, we have three copies."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And this is what we call tricemy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So if a normal sperm cell like the one shown here, that contains a single copy of chromosome 21, combines with Xcel number two that contains an extra copy of chromosome 21, we're going to produce a Zygote, an individual that has trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, notice in this particular case I've discussed nondisjunction taking place during anaphase two of meiosis."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But nondisjunction can also take place during anaphase one of meiosis."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And in both cases we can basically produce a Zygote that contains trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So trisomy 21 is the much more common case of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, the other much less common form of down syndrome is translocation."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, translocation, if you remember from our discussion on chromosomal abnormalities, translocation is the process by which a segment of a chromosome breaks off and moves onto and attaches onto a different non Homologous chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So translocation can also lead to down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But in an individual that has down syndrome due to translocation, that individual actually contains the normal number of chromosomes 46."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But one of those chromosomes is actually abnormal."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So not all down syndrome cases are due to trisomy 21, although the majority are due to trisomy 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "About 4% of the individuals with down syndrome actually still have the normal number of chromosomes 46, but one of them is abnormal as a result of the process we call chromosomal translocation."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So for example, let's suppose we have the following two normal pairs of chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "We have chromosome 14 and so this chromosome pair right here and chromosome pair 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "Now, what do we mean by chromosomal translocation?"}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So what chromosomal translocation means is a segment of one chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So in this case, a segment of chromosome 21 basically detaches and moves on to this non homologous chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So remember, these are non homologous chromosomes with respect to one another."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So we have a breakage of a segment of that DNA take place here and this basically moves on to this chromosome right over here."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And so what we form is this larger abnormal chromosome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And the way that we call it is because we have a fusion of a segment of 21 onto 14, we call this chromosome 1421."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So a segment of DNA on chromosome 21 can basically break off and reattach onto a non homologous chromosome, chromosome 14."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And the fuse chromosome, this abnormal chromosome, is called chromosome 1421."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So when the individual, when the Zygote basically gains this particular chromosome here, that individual, the Zygote, still has 46 of these chromosomes."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "But the 14th one, this one, is abnormal because it contains this duplication, this duplicated portion of the gene."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And that can also lead to the same symptoms of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "So there are two forms of down syndrome."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "The much more common case, the one that is affected by the age of that mother, is tricymi, 21."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "And the less common case is translocation."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "This is the case where we still have 46 chromosomes, the normal number of chromosomes, but one of them, usually chromosome 14, is actually abnormal."}, {"title": "Down syndrome (Trisomy 21 and Translocation).txt", "text": "It contains this extra segment of genetic information that leads to the same exact symptoms that we see in down syndrome individuals."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Aside from all the different types of endocrine glands that we focused on previously, there exist other organs in our body that also have endocrine capabilities."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "That is, many organs in our body have the ability to actually produce hormones and release them into our bloodstream."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So let's discuss these other organs that also have endocrine capabilities."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So we have have kidneys, we have the heart, we have the skin, we have the pineal gland or the pineal body, we have the liver and we have our stomach."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So let's begin by briefly discussing some of the hormones released by our kidneys."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, the two hormones that we're going to discuss is Erythropoietin and also our calcitriol."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, I also briefly discussed a proteolytic enzyme known as Renan."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "But Renan is not actually a hormone and that's exactly why I place the star next to number one."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So a special type of cell, our kidney cell, known as the granular cell or the juxtaglomero cell, is responsible for synthesizing and secreting the proteolytic enzyme Rena."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, Renan is not actually a hormone, it's a proteolytic enzyme."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "But renain is used in this Rena angiotensin aldesterone pathway to actually produce important types of hormones, namely angiotensin II and aldosterone, as well as ADH that basically are responsible for regulating blood pressure as well as the blood volume inside our blood vessels."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So Rena is not a hormone, but it is an important molecule that is used to produce important hormones."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, an actual hormone that is released by the cells in the kidney is Erythropoietin, as well as calcitriol."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, Erythropoietin is released by special type of cell inside the kidney known as the extra Grammylarl Messangel cells."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, these cells release our Erythropoietin, which is basically a glycoprotein hormone."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "It's a hormone that is composed of a peptide that has a glycogen, it has a sugar component attached to that protein."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, this protein, this hormone is released when we have a low concentration of oxygen inside our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And what it does is it stimulates the red bone marrow inside our bone to basically produce and release red blood cells, also known as Erythrocytes."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And that's exactly why this is known as Erythropoietin, because it produces more Erythrocytes."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, if we have more red blood cells inside our bloodstream, that means our oxygen level inside our blood will increase."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So that means urethropoietin basically increases the amount of oxygen that is found inside our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, the second type of hormone released by our kidneys is calcitriol."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And calcitriol is actually a lipid soluble hormone that is an active form of vitamin D. And what it basically does is it stimulates the increase in the calcium and phosphate ion concentration inside our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So this is basically used to control and regulate the amount of calcium found inside our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So it is stimulated, it is released when we have a low concentration of calcium in the blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And what it does is it ultimately increases the amount of calcium inside our blood by two methods."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Firstly, it increases the ability of our cells in the gut and our intestines to basically absorb more calcium from our food and more phosphate ons from our food."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And secondly, it also increases bone resorption, it increases the amount of bone matrix that breaks down and releases our calcium and phosphate ions into our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So the kidneys produce two important hormones, erythropoietin and calcitriol."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And it also produces a proteolytic enzyme, Rename, that is necessary in producing angiotestin one, angiotestin two and aldosterone, as well as stimulates the release of ADH, the antidiaretic hormone, by the posterior pituitary gland."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now let's move on to our second organ, the heart."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So the heart is basically an organ that consists of our cardiac muscle cells, also known as cardiac MIT."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, special types of cardiac MIT located in the atria region of our heart, in the upper chambers of the heart, basically are responsible for releasing an important type of peptide hormone known as the atrial natriuretic peptide or amp."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And what this hormone basically does is it dilates our blood vessels."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So this is a vasodilator, that basically means it increases the thickness of our blood vessels and that decreases our blood pressure."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And what it also does is it decreases the amount of blood volume found inside our blood and that also decreases our blood pressure."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So basically the A and P hormone is the opposite of aldosterone."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So recall that aldosterone actually increases the amount of sodium that we take back into our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "But what amp does, what the atrial natriure retic peptide hormone does is it basically increases the amount of sodium that we secrete into our urine and that decreases the amount of solute inside our blood and that ultimately increases the amount of water that leaves our blood system."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So the atrial natriuretic peptide hormone released by the heart is responsible for controlling the blood pressure, for decreasing our blood pressure inside our body."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So this is released when we have a very high blood pressure inside our blood vessels of the heart and of the body."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now let's move on to another organ, the third organ, the skin."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now the skin doesn't actually produce a hormone directly."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "What it does is it produces a pre hormone, a molecule that eventually is used to form a hormone."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "In fact, we produce this molecule inside the skin known as our cola calciferol, that is eventually used to produce calcitriol."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So basically, inside our skin cells we use UV radiation."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So the energy that comes from UV radiation to basically transform colicalcipheral, or actually to form colicalcipherel."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And then the colicalcipheral, which is basically vitamin D, travels into our liver."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And inside the liver the colicalciphal is transformed into our calcitial."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And then the calcitial that is formed in the liver travels into our kidneys."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And inside the kidneys the calcitiol is transformed into our calcitriole."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And the calcitriol is ultimately used to regulate the calcium concentration inside our blood."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So we see the colicalciphrol is the molecule that is ultimately used to produce our calcitriol by the kidneys."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, let's move on to our opinional body, also known as the pineal gland."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So basically, this is the section, the gland in our brain that is used to produce a hormone known as melatonin."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And melatonin is used to basically regulate our sleep wake cycle in our body."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So there should be an E after the K. Now let's move on to our liver."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So we actually briefly discussed an important type of hormone that is produced by the liver when we mentioned and discussed the renan angiotestin aldosterone pathway."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So basically, the liver is responsible for producing our angiotensin hormone."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Remember, our Xymogen form of this hormone that is produced by the liver is known as angiotensinogen."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And the angiotensinogen is basically used and transformed into the active form by the rena that is produced by the kidneys."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So angiotensin is the peptide hormone produced and released by the liver cells in its inactive Xymogen form called angiotensinogen."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "It helps us regulate the blood volume as well as the blood pressure inside our body."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, another important type of hormone released by our liver is a hormone known as thrombopolitan."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And what this is basically is a glycoprotein."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And this glycoprotein hormone which binds onto the cell membrane of target cells, basically helps us produce platelets that are used in blood clotting."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And we'll discuss the function of this much more in much more detail when we'll discuss the blood clot cascade."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "Now, the final organ that I'd like to briefly discuss is the stomach."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "The stomach actually produces many different hormones and many different enzymes, as does our small intestine."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And we'll discuss this in much more detail when we'll discuss our digestive system."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "In this lecture, I'd like to briefly mention that the stomach releases a peptide hormone known as gastrin."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And gastroin is basically used to stimulate the secretion of hydrochloric acid, known as gastric acid, by the parietal cells of our stomach."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And that basically decreases our PH and increases our acidity inside our stomach."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "And that gets our body ready for the process of digestion breakdown of the macromolecules in our food that we ingest into smaller pieces."}, {"title": "Endocrine Ability of Heart, Kidney, Liver and Skin .txt", "text": "So we can ingest those pieces into our body, into our bloodstream."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Previously, we discussed the Boar effect."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And we said the Boar effect is a phenomenon by which hydrogen ions and carbon dioxide molecules bind onto special allosteric sites on hemoglobin and they decrease hemoglobin's affinity for oxygen."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And what this does physiologically is it allows the hemoglobin to deliver many more oxygen molecules to the exercising tissue cells of our body."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, what I'd like to discuss in Dyslexia is how the carbon dioxide is actually transported inside our cardiovascular system from the tissue to the lungs."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And let's begin by focusing on the following diagram."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So, in this diagram, we have the cells of the exercising tissue."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "We have the endothelium of the blood capillary."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "This is the blood plasma and this is the red blood cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So let's suppose I move my hand back and forth."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So as I'm moving my arm, what's taking place is the muscle cells are producing ATP molecules in a process we call aerobic cellular respiration, which uses up oxygen and produces carbon dioxide and ATP molecules."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, the ATP molecules are used as the energy source."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And the carbon dioxide molecules, because they cannot be used in any useful way, they have to be released by those cells of the exercising tissue."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So we have these non polar carbon dioxide molecules."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And because these carbon dioxide molecules are non polar, they don't have any charge."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "They can easily move across the cell membrane of the cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So the carbon dioxide molecules make their way across the cell membrane into the space and then they make their way across the endothelium and into the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, once they're inside the blood plasma, what happens to the carbon dioxide molecules?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Well, carbon dioxide molecules are non polar."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And what that means is CO2 molecules will not generally dissolve in the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Why is that?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Well, because blood plasma consists predominantly of water molecules, which are polar."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And polar water molecules do not mix very well with nonpolar CO2 molecules."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So only about 5% of the carbon dioxide, a very small portion, will remain dissolved in the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And the remaining 95% of the carbon dioxide will move across the cell membrane of the red blood cell and into the environment found inside the red blood cell into the cytoplasm of the red blood cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, what happens once the CO2 is actually inside the red blood cell?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Well, some of that CO2 will go on and bind directly onto special groups on hemoglobin."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And this is what we discussed in the previous lecture."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "This is what we call the Bore effect."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So part of the part of the Bore effect tells us that CO2 molecules will bind onto special regions on the hemoglobin molecules and that will essentially form salt bridges and that will stabilize the T state structure of the deoxy hemoglobin and that will essentially decrease its affinity for oxygen."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So how many or how much, what percentage of the CO2 molecules will bind to hemoglobin?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Well, about ten to somewhere around 14% of the CO2 molecules will actually bind to hemoglobin."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So for our discussion, let's assume that it's 10%."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So that we're dealing with a single value."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So about 10% of the CO2 molecules, once they're inside the red blood cell, will bind direct to the hemoglobin and will travel to the lungs by being bound to that hemoglobin."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, the remaining percentage, so we have 5% here, 10% here."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So the remaining 85% of the carbon dioxide will combine with water and by the enzymatic activity of the special enzyme we call carbonic anhydrates, the carbonic anhydrates will catalyze the conversion of these two molecules into carbonic acid."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, because carbonic acid is a relatively good acid, it will dissociate into H plus ions and bicarbonate ions."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, the H plus ions will create part of the Bore effect."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And so they will bind on special regions onto hemoglobin, and that will decrease the affinity of hemoglobin for oxygen, allowing hemoglobin to unload even more oxygen molecules to the exercising tissue."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So remember, we have oxygen molecules moving from the red blood cells into this area, then into this area, and eventually that makes their way into the cells of the exercising tissue."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, what about the bicarbonate ions?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Well, bicarbonate ions are simply another form of the carbon dioxide."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "But the major difference between the carbon dioxide and the bicarbonate is the bicarbonate contains a full negative charge."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And that makes this molecule polar."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And what that means is if the molecule moves into the blood plasma, it will have no problem dissolving in the polar blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And so what happens is the bicarbonate ions, about 85% of the initial carbon dioxide that entered this blood plasma exists in the form of the bicarbonate ions."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So a special protein membrane in a cell, in the membrane in the red blood cell transports these bicarbonate ions into the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now, at the same time, this transport protein also pumps these chloride ions into the red blood cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And the reason we have this exchange is because we have to ensure that there is no change in the electrostatic charge between the inside portion of the red blood cell and the outside portion of the red blood cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And this exchange in ions, this effect is known as the chloride shift."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So the chloride shift is simply the process by which this special protein membrane basically balances the charges by pumping this molecule to the outside and this chloride molecule to the inside."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Now let's move on to the lungs."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So once we're inside the lungs, this is basically what we're going to see."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So we have the blood capillary, and now instead of having the exercising tissue, we have the alveolar space of the alveoli found inside the lungs."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So now what happens is basically the opposite of what happens here."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So now we have the reverse reaction taking place."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So we have about 85% of the carbon dioxide molecules existing in the bicarbonate ion form."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And so what happens is these bicarbonate ions will move down their concentration gradient and into the red blood cell."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And at the same time, the chloride shift takes place, but in the opposite direction."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So as we move these bicarbonate ions into the red blood cell, not to have a build up or a change in electric charge, these chloride ions, also containing a negative charge, are basically pumped to the outside into the blood plasma space."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And once we bring these bicarbonate ions into the sound, the hemoglobin basically releases those H plus ions."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And the H plus ions now combined with the bicarbonate to form back this."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So this actually should have this should be H two."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So let's just use the color black and this forms the carbonic acid."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And now the carbonic acid is broken down in the reverse reaction to basically form the water as well as the carbon dioxide."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "But remember, about 10% of the carbon dioxide was also being held by the hemoglobin."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And what happens within the red blood cells in the lungs?"}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "The hemoglobin releases that carbon dioxide."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "The 10% into this bundle here and together the 10% released by hemoglobin, the 85% that was held by bicarbonate, and the 5% that was dissolved in the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "All this carbon dioxide basically leaves the red blood plasma cell and events essentially enters the alveolar space."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And then via the process of exhalation, we essentially expel and release all that carbon dioxide into the outside environment."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And then the plants use this CO2 in a process called photosynthesis to basically produce sugar molecules."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "Then we either eat the plants or we eat the animals that ate the plants."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And the cycle basically repeats itself."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So we conclude that carbon dioxide is carried in our cardiovascular system in three different ways."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "About 5% of the nonpolar carbon dioxide is directly dissolved in the blood plasma and so travels to the lungs directly in the blood plasma."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "About 10% to about 14% in some cases is being held by that hemoglobin."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And that carbon dioxide, when it combines with hemoglobin, it creates the bore effect and that basically decreases the Vinity of hemoglobin for oxygen and the remaining about 85%."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "So the majority of the carbon dioxide in our blood plasma is in the form of bicarbonate ions."}, {"title": "Transport of Carbon Dioxide and Chloride Shift .txt", "text": "And together all these carbon dioxide forms are transported into the lungs where the lungs eventually expel those carbon dioxide molecules of the outside in the process we call exhalation."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Inside any hemoglobin molecule will always find four individual polypeptide chains."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Two of these chains are identical alpha units, and the other two chains are identical beta units."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And what this means is in any given hemoglobin molecule, we'll always find a ratio of one alpha unit to one beta unit."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So one alpha polypeptide always combines with one beta polypeptide unit to form that hemoglobin molecule, in which we have two dimers, two alpha beta dimers."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, interestingly enough, if we examine and studied the human genome molecule, so all the DNA molecules found inside the human cell, we're going to find four genes that code for the alpha unit, but we're only going to find two genes that code for the beta unit."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So for some reason, inside our genome, we have twice as many genes that code for the alpha subunit than the beta subunit."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, why can that be a problem?"}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Well, let's assume that all these genes are expressed and they're expressed at the same exact rate."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, what that implies is at the end, we're going to produce twice as many alpha subunits as beta subunits because we have twice as many alpha genes."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So if we produce, let's say, 1 million alpha units, we're going to produce only 500,000 of the beta subunits."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So twice as less."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, why is that a problem within our red blood cells?"}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Well, because inside any hemoglobin molecule, we have a one to one correspondence, one to one combination between the alpha and beta subunits."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "At the end of our reaction, when all the beta subunits are used up, we're going to have an excess amount of alpha submunes left over inside our blood plasma."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And the problem with that is these alpha subunits can form aggregates because they can bind to one another to form these complexes."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And these complexes will become insoluble."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And what that means is they will precipitate out of the blood plasma, and that can form and that can cause many different types of problems."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So what does our body do to prevent the aggregation and the precipitation of these alpha complexes?"}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Well, inside red blood cells, we have these special proteins known as the alpha hemoglobin stabilizing protein, or simply Ahsp."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And this protein is shown on the board with this brown color."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So this is the alpha hemoglobin stabilizing protein."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, this is a single monomer of the alpha polypeptide chain of the hemoglobin molecule."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So we have these alpha helixes."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "This is the heme group, and this is an oxygen atom."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So the oxygen can either be bound to that heme group or it can be unbound."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "In this particular case, the oxygen is bound to that heme group."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, what the alpha hemoglobin stabilizing protein does is it actually binds onto this alpha polypeptide chain on the same region of that alpha unit as where the beta unit would bind."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And when the alpha hemoglobin stabilizing protein binds onto this alpha unit monomer, it forms a dimer complex that is more stabilized than when it exists in its individual form."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And it is also soluble in the blood plasma."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And by forming this complex, it basically prevents the aggregation and the precipitation of those alpha unit complexes."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And this prevents many, many problems."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So, once again, red blood cells produce a protein called alpha hemoglobin stabilizing protein."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "This protein binds onto the alpha subunomers to form soluble dimers."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And this is precisely what prevents the aggregation of those alpha subunits to form insoluble precipitates that can basically precipitate out of the blood plasma and form and cause many different types of problems."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "Now, as the red blood cells produce the beta subunit, what happens is that beta subbune will basically displace and replace the alpha hemoglobin stabilizing protein."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "It will basically kick off this protein and form the alpha beta dimer."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And that's because if we examine the energy value of the alpha beta dimer and the alpha Ahsp complex, this will have a higher energy and will be slightly less stable than the alpha beta dimer."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And because of this energy difference, that basically drives the equilibrium towards the side where we form that alpha beta dimer."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So this is described in the following diagram."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So initially, we have an access amount of alpha subunits."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And so what happens is to prevent the aggregation of these alpha complexes, our cells use the alpha hemoglobin stabilizing protein to basically form this complex that is stable enough and soluble in the blood plasma."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So the alphahsp complex, and then when we have enough beta subunit, so when the beta subunits are produced by the red blood cells, they can then begin displacing this molecule and forming the alpha beta dimer."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And this dimer is more stable than this dimer."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "That's precisely what drives the equilibrium towards this side, towards this molecule."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And notice that our beta unit binds onto that alpha unit on the same side, on the same face as the Ahsp molecule."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "So to conclude, to prevent aggregation of these alpha subunits inside our blood blood plasma, our body, our red blood cells use this special protein, we call alpha hemoglobin stabilizing protein to form these dimers that are soluble in water in our blood plasma."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And so they can exist without precipitating out of that blood plasma."}, {"title": "Alpha Hemoglobin and Stabilizing Protein .txt", "text": "And this can prevent many different types of medical problems and medical conditions."}, {"title": "Linked Genes.txt", "text": "In our previous discussion, we focused on genes that are not linked."}, {"title": "Linked Genes.txt", "text": "So we basically answered question A."}, {"title": "Linked Genes.txt", "text": "So we saw that if we made these two plants, one having a heterozygous genotype for two traits and the other one having a homozygous recessive genotype for two traits and if the Hype gene is not not linked with respect to the color trade, the color gene."}, {"title": "Linked Genes.txt", "text": "So if we have non linked genes, then we always produce a ratio that is equal to one to one to one to one."}, {"title": "Linked Genes.txt", "text": "So what that means is if we make these two individuals 1000 times 250 of those offspring will have one genotype, 250 will have a second genotype, 250 will have a third genotype and 250 will have a fourth genotype."}, {"title": "Linked Genes.txt", "text": "That's what we mean by a one to one to one to one ratio."}, {"title": "Linked Genes.txt", "text": "Now let's focus on linked genes."}, {"title": "Linked Genes.txt", "text": "So in Part B, if these two traits, so the high trait and the color trait were in fact linked, what will be the ratio in that case?"}, {"title": "Linked Genes.txt", "text": "Would it change or would it actually remain the same?"}, {"title": "Linked Genes.txt", "text": "So let's begin by once again recalling what it means for two genes to actually be linked with respect to one another."}, {"title": "Linked Genes.txt", "text": "So let's focus on this female plant right here in this female diploid organism."}, {"title": "Linked Genes.txt", "text": "We know that every single chromosome comes with a homologous pair."}, {"title": "Linked Genes.txt", "text": "So if this is the chromosome that carries, let's say, the color traits, then it's going to have a homologous chromosome that will carry another gene that will also code for that color trait."}, {"title": "Linked Genes.txt", "text": "So one of these chromosomes will carry the upper case green gene, the other one will carry the lowercase recessive orange G. So let's suppose this is our lowercase recessive orange gene and the other one is the upper case dominant green gene."}, {"title": "Linked Genes.txt", "text": "Now, in Part B, we're assuming that the genes are linked."}, {"title": "Linked Genes.txt", "text": "So we're assuming that the color gene is linked with respect to that hygiene."}, {"title": "Linked Genes.txt", "text": "And what that means is if two genes are said to be linked, then they are found on the same chromosome."}, {"title": "Linked Genes.txt", "text": "And what that means is this chromosome will not only carry the gene for uppercase G, it will also carry the gene for uppercase T. So let's say on the bottom, along the chromosome, we'll have the uppercase T, and on the bottom, along the homologous chromosome, we're going to carry the lowercase T. Remember, only focusing on this individual here, the female individual."}, {"title": "Linked Genes.txt", "text": "So in this particular case, if these two genes, if these two traits are actually linked, then all of these genes will be found along this single homologous pair of chromosomes."}, {"title": "Linked Genes.txt", "text": "So we have homologous chromosome pair and this gene here and this gene here are linked in the same way that this gene and this gene are also linked with respect to one another."}, {"title": "Linked Genes.txt", "text": "Now, before these individuals actually mate, they have to produce gametes, they have to produce excel."}, {"title": "Linked Genes.txt", "text": "So let's discuss what the distribution will be of this particular individual in terms of the offspring, the gametes that are produced."}, {"title": "Linked Genes.txt", "text": "So the gametes are produced in the process of meiosis."}, {"title": "Linked Genes.txt", "text": "So we know what happens in the estates before meiosis actually takes place."}, {"title": "Linked Genes.txt", "text": "This chromosoma is replicated and so is this replicated and we produce basically four individual chromatids."}, {"title": "Linked Genes.txt", "text": "Now, during metaphase one of meiosis, those tetromer chromosomes align along the equatorial plate."}, {"title": "Linked Genes.txt", "text": "So we're basically going to have the following arrangement."}, {"title": "Linked Genes.txt", "text": "So we're going to have this will replicate itself."}, {"title": "Linked Genes.txt", "text": "And so what that means is we're going to have two identical cystic chromatids that each carry identical traits."}, {"title": "Linked Genes.txt", "text": "So we have an uppercase green g in uppercase green g, and then on the bottom we're going to have an uppercase blue t in uppercase blue t and likewise on this chromosome, so this one will replicate itself."}, {"title": "Linked Genes.txt", "text": "And So we're going to have this purple lowercase T and purple lowercase T on the identical cystochromatid and we're going to have the lowercase G lower case G. Now, notice that unlike in Part A, in Part B because the genes are actually linked."}, {"title": "Linked Genes.txt", "text": "Now, when crossing over takes place, the fact that crossing over takes place and we have linked genes, we're going to produce a different distribution of the gamete."}, {"title": "Linked Genes.txt", "text": "So in the case of part A, we saw that there are four possibilities of gametes and each one are equally likely to take place."}, {"title": "Linked Genes.txt", "text": "And so we have a one to one to one to one ratio."}, {"title": "Linked Genes.txt", "text": "Now we're going to have a slightly different case because crossing over takes place at random."}, {"title": "Linked Genes.txt", "text": "So now in metaphase one, before metaphase one actually takes place during ProPhase one of metaphase one."}, {"title": "Linked Genes.txt", "text": "So actually let's change that to ProPhase because we first want to focus on the process of crossing overtaking place."}, {"title": "Linked Genes.txt", "text": "So crossing over takes place as we know, during prophase I of meiosis."}, {"title": "Linked Genes.txt", "text": "So when crossing over takes place, what basically happens is this piece of DNA here switches exchanges with this piece of DNA."}, {"title": "Linked Genes.txt", "text": "And so what we produce are the following four chromosomes."}, {"title": "Linked Genes.txt", "text": "So we have one, we have two, then we have exchange taking place, three, four, so nothing happens here."}, {"title": "Linked Genes.txt", "text": "So this one basically remains the same."}, {"title": "Linked Genes.txt", "text": "So we have uppercase t and this one also remains the same."}, {"title": "Linked Genes.txt", "text": "So we have an uppercase g. Now, no, crossing over takes place along the top portion of this chromosome but along the bottom portion."}, {"title": "Linked Genes.txt", "text": "So we have this one intertwines with this one and we have an exchange taking place."}, {"title": "Linked Genes.txt", "text": "And so this goes on to here."}, {"title": "Linked Genes.txt", "text": "And so we have a lowercase t here."}, {"title": "Linked Genes.txt", "text": "We have an uppercase t here because this one went on to this one."}, {"title": "Linked Genes.txt", "text": "So we have an uppercase t and this one doesn't actually change."}, {"title": "Linked Genes.txt", "text": "And the top portion of this also doesn't change."}, {"title": "Linked Genes.txt", "text": "So we're going to have orange here, an orange here, lowercase g, lower case g, and this one won't change as well, lowercase t and then they will align along our equator."}, {"title": "Linked Genes.txt", "text": "So let's suppose now we're in metaphase one of meiosis."}, {"title": "Linked Genes.txt", "text": "And so what happens is these two separate to opposite poles and we form two haploid cells."}, {"title": "Linked Genes.txt", "text": "And then each one of those two haploid cells basically undergo meiosis two, and we form four individual gametes that are haploid."}, {"title": "Linked Genes.txt", "text": "So there are four possibilities of gametes that we can form."}, {"title": "Linked Genes.txt", "text": "So the four possibilities are, so we can have one chromosome, a second chromosome, a third chromosome, and a fourth chromosome."}, {"title": "Linked Genes.txt", "text": "So when this segregates and separates into its individual cell, we can have uppercase G and we have uppercase T for this particular case, for this chromosome here."}, {"title": "Linked Genes.txt", "text": "So this is one gamete that could be formed."}, {"title": "Linked Genes.txt", "text": "So because we're dealing with the female individual, we're focusing on this one."}, {"title": "Linked Genes.txt", "text": "This will be our Excel number one."}, {"title": "Linked Genes.txt", "text": "We could also have an Excel number two, an Excel number three, and an Excel number four."}, {"title": "Linked Genes.txt", "text": "In this particular case, we have uppercase G and we have a lowercase T. In this case, we have an uppercase."}, {"title": "Linked Genes.txt", "text": "Well, let's actually finish off we have this one here, this one doesn't change."}, {"title": "Linked Genes.txt", "text": "So we have a T, lowercase T, and an uppercase G. This one here is this one here."}, {"title": "Linked Genes.txt", "text": "So we have a lowercase G and an uppercase T. So that one changes with respect to this initial starting point."}, {"title": "Linked Genes.txt", "text": "Okay, so we see that just like in part A, we have these four possibilities taking place, but in part A, we saw that the ratio was one to one to one to one in part b, because crossing over takes place at random, about 10% of our gametes produced from this individual."}, {"title": "Linked Genes.txt", "text": "So about 10% will be lowercase G, uppercase T, about 10% will be uppercase G, lowercase T. And so these two types of gametes are known as the recombinant gametes because they are a result of the process of crossing over."}, {"title": "Linked Genes.txt", "text": "Now, these are the same as the initial parental chromosomes and so they are non recombinant."}, {"title": "Linked Genes.txt", "text": "Now, we have about a 40% chance of these occurring, and about a 40% chance of these occurring."}, {"title": "Linked Genes.txt", "text": "So that means now the ratio of this to this to this to this is not one to one to one to one, but it's 40 1010 40, or we can say 40 40 1010."}, {"title": "Linked Genes.txt", "text": "Now, what about this particular case?"}, {"title": "Linked Genes.txt", "text": "Well, because these are all recessive, we have one type of gammy that occurs for this particular male individual."}, {"title": "Linked Genes.txt", "text": "So we have, because it's the male, we have let's say a sperm cell, these are the egg cells."}, {"title": "Linked Genes.txt", "text": "And so we have one type of chromosome, lowercase G, lowercase T. So we have lowercase G and a lowercase T. When recombination takes place, when crossing over takes place, nothing really changes because they are identical."}, {"title": "Linked Genes.txt", "text": "And so we have lowercase G, lowercase T taking place, occurring 100% of the time."}, {"title": "Linked Genes.txt", "text": "So we have 100% of the time."}, {"title": "Linked Genes.txt", "text": "So a likelihood of one."}, {"title": "Linked Genes.txt", "text": "In this case, we have a 0.4 likelihood 0.1 likelihood 0.1 likelihood and a 0.4 likelihood."}, {"title": "Linked Genes.txt", "text": "And let's just mention that these are the recombinant recombinant gametes, okay?"}, {"title": "Linked Genes.txt", "text": "So now when this combines with this Excel, we form so uppercase g, lower case G, uppercase T, lowercase T. So let's put that here."}, {"title": "Linked Genes.txt", "text": "We have uppercase G, lowercase G that comes from the sperm cell right here."}, {"title": "Linked Genes.txt", "text": "And then uppercase T, lowercase T, so uppercase T, lowercase T. Now the likelihood of this occurring is so one multiply by zero four, that gives us 0.4."}, {"title": "Linked Genes.txt", "text": "So that means let's say out of 1000 of these individual mating processes, about 400 will be we'll have this genotype right here."}, {"title": "Linked Genes.txt", "text": "So the likelihood of this is 0.4."}, {"title": "Linked Genes.txt", "text": "And so that implies that if we mate them 1000 times, about 400 we'll have this phenotype."}, {"title": "Linked Genes.txt", "text": "Now, we can carry out the same exact process if we assume that this mates with this one right here."}, {"title": "Linked Genes.txt", "text": "We have uppercase g, lower case g, lowercase t. Lowercase t. So we have two lowercase t's."}, {"title": "Linked Genes.txt", "text": "We have an uppercase G that came from the Xcel and a lowercase g that came from that sperm cell."}, {"title": "Linked Genes.txt", "text": "This one here, the likelihood is one multiplied by zero one."}, {"title": "Linked Genes.txt", "text": "And so that gives us about 0.1 likelihood."}, {"title": "Linked Genes.txt", "text": "And in the case of 1000 mating processes we have about 100 that are formed with this genotype."}, {"title": "Linked Genes.txt", "text": "We could continue the process with these as well."}, {"title": "Linked Genes.txt", "text": "So if this mates with this, we have lowercase G, lower case G, lower case G, lower case G, and then we have uppercase T, lowercase T, and one a likelihood of one multiplied by likelihood of zero one gives us zero one."}, {"title": "Linked Genes.txt", "text": "And so that implies that about 100 of the offspring produced out of the thousand offspring will have this genotype."}, {"title": "Linked Genes.txt", "text": "And finally we have this mating with this."}, {"title": "Linked Genes.txt", "text": "So we have lowercase G, lower case g, so lowercase G, lower case G, lower case C, lowercase T. And so we form once again if we multiply one by zero four."}, {"title": "Linked Genes.txt", "text": "So we have one multiplied by zero four gives a 0.4 probability."}, {"title": "Linked Genes.txt", "text": "And so that means out of 1000 offspring, 400, about 400, we'll have this genotype here."}, {"title": "Linked Genes.txt", "text": "So we see that in the case of part A, if the two genes are actually unlinked, not linked, then we have a one to one to one to one ratio of these genotypes."}, {"title": "Linked Genes.txt", "text": "But in the case of these genes being linked, the ratio changes, the ratio becomes we have 40 to ten to ten to 40 or 40 to 40 to ten to ten."}, {"title": "Linked Genes.txt", "text": "So that means out of 1000 offspring produced when we made these two individuals 1000 times, because we have the two genes being linked with respect to one another, we're going to have 400 of these individuals appearing, about 400 of these about."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Thus far in our discussion on eukaryotic cells, we discuss single eukaryotic animal and plant cells."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, the question is, in animals we usually have multicellular structures."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So our cells basically combine to form multicellular organisms."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "The question is, how exactly do these eukaryotic animal cells actually connect to one another?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, in this lecture, we're going to focus on this topic."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "We're going to discuss intracellular junctions or intracellular connections, also known as cell junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So in animal cells, there are three major types of connections or attachments."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Basically, there are three major ways by which cells can connect to one another, and these include tide junctions, gap junctions, as well as desmosome."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So let's discuss what each one actually looks like, what it is composed of, and what the function of each type of junction is."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And let's begin by examining the tide junction."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So tide junctions basically form watertight seals or watertight connections between adjacent cells."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And what this basically means is molecules and ions cannot actually get around cells."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "They must actually pass through that cell to get from one side, the lumen side, to the other side, our extracellular fluid side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So basically, this means that in order for things like water to actually get past one side of the cell, the lumen cavity, to the other side of the cell, the extracellular fluid, something actually must pass through the cell membrane on the lumen side and to the cell membrane on the extracellular side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, the apical side is the lumen side of the cell, and this side is the Basil lateral side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "It's the side found on our extracellular side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, type junctions are composed primarily of a network of proteins known as claudine."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So there are different types of claudine proteins."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, what exactly are the functions of the tight junction connection?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So there are two major functions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Notice that each side of the cell, let's say, on the lumen side, contains a certain type of integral proteins or certain types of integral proteins."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And the basilateral side, this side also contains its share of different types of integral proteins, proteins that basically allow the passageway of different types of ions and molecules."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And what the Thai junctions do."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So this is one tie junction, this is the second type of tie junction."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "What these Tie junctions basically do is they do not allow the lateral movement of integral proteins from our apical side, the lumen side of the cell membrane, to the basilateral side, the extracellular side of our cell membrane."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Remember, inside an individual cell, inside the cell membrane, the phospholipids as well as the proteins are in a constant state of lateral motion."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So our proteins can move around the cell."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "But when we have tie junctions, these integral proteins cannot actually go to this side of our cell membrane."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And that's very important in basically controlling endositotic and exocytotic processes."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So our tigunctions blocks the lateral movement of integral proteins from the apical side of the cell membrane."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "To the basil lateral side of that cell membrane."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "This means, or this makes sure that the proper endocytotic and exoptototic processes actually take place on the correct side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So on this side we usually have of the endocytotic process, on this end we usually have the exocytotic process."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "For example, if water actually wants to get in on the lumen side, it has to pass via our passive diffusion and then leave this side via, once again, passive diffusion."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "But if some other large molecule wants to get in, for example, a sugar molecule, it has to actually get in through our integral protein on this side and then get out through another integral protein on the bottom side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So the other function of our Thai junction is to control the movement of molecules and ions such as water and sugar molecules by only allowing a limited quantity to get into the cell on the apical side and out of the cell on the basil lateral side."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "This means that if a molecule, such as a water molecule wants to actually get into the cell, it cannot move around the cell because of these tie junctions and it must actually pass through the membrane via the process of passive diffusion."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, where exactly are these tight junctions found?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Well, these junctions are found in epithelial tissues such as lungs, bladder, intestines, stomach and organs."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So these are the different types of organs that contain epithelial tissue that are basically connected via tight junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now let's move on to the second type of intracellular junction known as our gap junction."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So gap junctions are the connective tunnels that exist between adjacent cells."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So these types of tunnels, these types of channels or gap junctions, allow the movement of different types of molecules and ions up to a certain size, usually up to 1000 deltons."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So they allow molecules and ions up to a certain size to pass from one cell to the other cell."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So these are our examples of our gap junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "For example, if calcium ions want to get from this cell to this cell, they could move via these intracellular connections known as gap junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, what's a particular example of a cell that contains gap junctions?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Well, it's basically a special type of muscle cell known as the cardiac cell, the cells found in our heart."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So gap junctions are found in muscle tissues such as cardiac cells, and there they play an important role in allowing calcium ions to move across our cells, which basically propagates the action potential from one cell to the next cell."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And this ultimately causes the heart to contract and that creates our heartbeat, which pumps our blood through the body."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And we'll talk more about this when we discuss the cardiovascular system and the heart."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "The final connection, the final intracellular junction that we want to discuss are desmosomes."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So what exactly is a desmosome and what is the purpose of the desmosome connection?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Well, they basically attach themselves to intermediate filaments found in the cytoplasm of the cell that are composed of a protein known as carotene."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, they hold so Desmondomes hold two or more adjacent cells tightly together at a localized region."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So on this diagram, for example, this is one Desmond, and this is the other Desmond."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Notice these protrusions are our carotene intermediate filaments that are found in our cytoplasm of the cell, that are part of the cytoskeleton of that cell, and they connect directly to these localized regions known as desmosomes."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, desmosomes themselves do not actually prevent the movement of molecules and ions such as water, but desmosomes are usually found in combination with Thai junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So if we have a tie junction and a desmosome found on the same side, that means the desmosome will basically hold the cell together, while the tide junctions will not allow the movement of molecules and ions across our cells."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Now, where exactly do we find our desmosomes?"}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Well, desmosomes are located in tissue that undergoes a constant state of stretching and experiences a constant state of pressure."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And one example is the skin."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So when I pull my skin, what basically keeps the cells together are our decimosomes, and what allows water not to get inside are basically the tide junctions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "Another location of Desmondomes in is the intestinal tissue, and we'll see why they're important when we discuss the intestinal system."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So, basically, in animal cells, there are three major ways by which our individual cells connect to one another."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "We have our tide junctions, which create a watertight connection and basically seals one side of the cell so that nothing can get past this side and around the cell."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "So things actually have to move across the cell membrane, and it also keeps the integral proteins from moving across to the other side of our cell membranes."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "We have the gap junctions, which basically are the channels or the tunnels through adjacent cells that allow the movement of small molecules and ions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And we also have desmosomes, which basically connect and hold those adjacent cells together via individual localized regions."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "And these regions are known as desmosomes."}, {"title": "Tight Junctions, Gap Junctions, and Desmosomes.txt", "text": "They connect directly to the cytoskeleton of aracel, to the intermediate filaments found in a cytoplasm that are composed of a protein known as keratin."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Irreversible inhibitors are molecules that bind onto active sites of enzymes and inhibit that enzymes functionality, inhibit their activity."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, the thing about these Irreversible inhibitors is they can bind onto the active side either by covalent or noncovalent means."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "But once they bind onto that active side, they will not let go."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And that means they bind very, very, very tightly, very, very strongly."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And even if we remove access inhibitor from that mixture, that will not dissociate that inhibitor, that will not reform that active version of the enzyme."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So, all the different types of inhibitors, irreversible inhibitors that we have in nature and that we can synthesize in a lab, can basically be categorized into three different groups, into three different categories."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "We have group specific inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "We have substrate analogs, also known as affinity labels, and we have suicide inhibitors, also known as mechanism based inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, we can actually use these three different types of Irreversible inhibitors to actually probe and study the residues found inside active sites of enzymes."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And out of these three different types of groups, the most specific type of group is the suicide inhibitor."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And the least specific type of group is the group specific inhibitor."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So let's begin by discussing the group specific inhibitor."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Well, the group specific inhibitor is an example of an Irreversible inhibitor that binds to and reacts with specific side chain groups of amino acids."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "For instance, on the board we have two examples of group specific inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "We have Idoscenemide that reacts with Sistine side chains, and we also have di isopropyl phosphoridate, or simply DIPF that reacts with serine amino acids."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "For instance, if we take an enzyme that contains an active site, and inside that active site, we have a catalytic amino acid, namely the cysteine, well, then this Idocidamide will react with that catalytic amino acid, the cysteine, to form a covalent bond between this carbon here and this sulfur atom here."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And because this is the sulfur atom, part of the side chain of the cysteine, that is used to basically catalyze some specific type of reaction, because we form a covalent bond, as shown in the following diagram, that essentially deactivates and inhibits the activity of that particular enzyme."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so, as a result of this covalent modification, we essentially deactivate that active side of the enzyme."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And notice in this process, we essentially kick off the I dye and we also break off that H atom."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so we form this molecule, as shown here."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "The H has a positive charge, the iodide has a negative charge."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, this is the other example."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And in this particular case, we see that di isopropyl phosphoridate actually reacts with serene amino acids."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "For instance, we know that in the active side of acetylcholinesterase, we have these serine amino acids that catalyze the reactions."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so, if we mix this active side, so an enzyme that contains an active side with a serene, then this diesopropyl."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Phosphorfluoridate will essentially form a covalent bond between this phosphor and this oxygen and that will kick off the f, the fluoride and also that H to form the following Covalent modification."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so these are two examples of group specific irreversible inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now let's move on to the second type of category known as substrate analogs or more or more commonly affinity labels."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So the thing about these affinity labels is the structure of that particular irreversible inhibitor actually resembles the structure of the natural substrate that binds into the active side of that enzyme."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So these irreversible inhibitors are molecules that resemble substrates and this allows them to actually fit into the active side of that enzyme."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And once inside, they essentially react in a covalent manner."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "They modify the residues found inside the active side in a covalent manner and that inhibits that enzyme's activity."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, what's one example of an affinity label?"}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Well, when we'll discuss the process of glycolysis, we'll see that an intermediate molecule in glycolysis is known as dihydroxy acetone phosphate."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And what happens in glycolysis is dihydroxy acetone phosphate is transformed into another isomer by an enzyme we call triosphosphate isomerase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, inside the active side of triosphosphate isomerase, we have this glutamate molecule."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And this glutamate molecule, the amino acid glutamate, essentially is responsible for this catalyzation process from transforming dihydroxy acetone phosphate into another isomer."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, if we add bromoacetal phosphate, this molecule into the mixture, notice how this is almost exactly the same in structure as this original natural substrate."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "The only difference is, instead of this hydroxyl group, we have this bromide."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And because of that, this will act as a substrate analog and affinity label."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And what happens is this carbon here reacts with this oxygen to form a Covalent bond, a Covalent modification, and that kicks off that bromide in the process because we form the Covalent modification that essentially inactivates the active side of that enzyme, the trio's phosphate isomerase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And now this enzyme cannot convert this molecule, the dihydroxy acetone phosphate, into its isomeric form."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And we'll talk much more about that in our discussion on glycolysis."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now let's take a look at the final category, suicide inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So these are the most specific type of irreversible inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And what that means is we can build and we can use these suicide inhibitors to basically bind to specific active sites of specific enzymes."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now suicide inhibitors are also known as mechanism based inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And that's because these suicide inhibitors, they can actually bind onto the active site of that enzyme and begin the normal catalyzation process as if this was a normal substrate molecule."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "However, down the line, somewhere down that pathway of that reaction, what will happen is that suicide inhibitor will produce a reactive intermediate that will modify the active side in some covalent way."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And once that modification takes place, that inhibits that enzyme irreversibly."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so two examples that we commonly use in medicine of suicide inhibitors is penicillin and aspirin."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So remember, in our discussion on Irreversible inhibitors, we said that penicillin is essentially an antibiotic."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And this penicillin molecule binds into the active side of a specific type of enzyme used by bacterial cells to build bacterial cell walls."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And this enzyme is known as transpeptidase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So bacterial cells use trans peptidase to basically build cell walls."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And what penicillin does is it acts as a suicide inhibitor, that is, it binds into the active side of that enzyme, and it begins the catalyzation process."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "But somewhere down that line, it forms an intermediate that essentially blocks and inhibits the activity of that enzyme, the transpeptidase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "Now, aspirin, which has the following structure, is a suicide inhibitor to an enzyme we call cycloxygenase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And what cycloxagenase normally does is it basically catalyzes the formation of a special type of signal molecule that is used in the inflammation process."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so when we actually ingest aspirin, aspirin acts as a suicide inhibitor, and it binds into the active side of that cycloxigenase."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so what that does is it disables the ability to produce that signal molecule."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so the inflammation process cannot take place properly."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And so that relieves pain, it decreases pain, it removes headaches and so forth."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So another type of suicide inhibitor that we commonly use is AZT."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And AZT is a molecule that acts as a suicide inhibitor, and it basically treats HIV."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So these are the three different types of Irreversible inhibitors."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "So we have group specific inhibitors, which are basically these Irreversible inhibitors that bind onto specific groups, specific residues, specific amino acids."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "We have substrate analogs, also known as affinity labels, that essentially resemble that substrate, and so they can fit into the active side of that substrate and modify that particular active side in some covalent way."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "And we also have suicide inhibitors that basically bind into the active side, and they begin the normal process as if they were the normal substrate molecule."}, {"title": "Group Specific Affinity Labels and Suicide Inhibitors .txt", "text": "But somewhere down that reaction pathway, they essentially create a reactive intermediate that modifies the catalytic residue found inside the active site in some covalent way, and that inhibits the activity of that enzyme."}, {"title": "Gibbs Free Energy .txt", "text": "Based on a second law of thermodynamics."}, {"title": "Gibbs Free Energy .txt", "text": "We know that whenever any reaction takes place in nature, whenever any physical or biological process takes place in nature, the entropy of the universe, the change in entropy of the universe must be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "So the entropy of the universe must always increase."}, {"title": "Gibbs Free Energy .txt", "text": "And that's equivalent to saying the total amount of energy in the universe after the reaction must be more spread out than before that reaction actually took place."}, {"title": "Gibbs Free Energy .txt", "text": "Now, we can also describe the second law of thermodynamics by using a mathematical equation."}, {"title": "Gibbs Free Energy .txt", "text": "So we can say that the change in entropy of the system plus the change in entropy of the surroundings is equal to the change in entropy of the universe."}, {"title": "Gibbs Free Energy .txt", "text": "And that must always be greater than zero."}, {"title": "Gibbs Free Energy .txt", "text": "It must always increase."}, {"title": "Gibbs Free Energy .txt", "text": "It must always be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "So we can still have a decrease in the entropy of the system."}, {"title": "Gibbs Free Energy .txt", "text": "So this can still be a negative value as long as the increase in the entropy of the surroundings is greater than the decrease in the entropy of the system."}, {"title": "Gibbs Free Energy .txt", "text": "So as long as this quantity is greater than this quantity, this will always be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "This will always be greater than zero."}, {"title": "Gibbs Free Energy .txt", "text": "Now, what we want to attempt to do in this lecture is to derive an equation by beginning with this equation and by using the definition of entropy, we want to derive an equation known as the Gibbs free energy."}, {"title": "Gibbs Free Energy .txt", "text": "And this equation basically gives us the conditions under which a reaction is spontaneous and under which the reaction is not spontaneous."}, {"title": "Gibbs Free Energy .txt", "text": "So let's call this equation number one, and let's recall what the definition of entropy is for constant temperature."}, {"title": "Gibbs Free Energy .txt", "text": "Now, the reason we're going to assume constant temperature is because all the different types of biological reactions that take place in nature usually take place under constant temperature conditions."}, {"title": "Gibbs Free Energy .txt", "text": "So, for example, reactions that take place inside our body and inside the cells of our body take place at a constant temperature of about 36.8 degrees Celsius."}, {"title": "Gibbs Free Energy .txt", "text": "So let's suppose we're inside our cell, and inside that cell, some type of intracellular process takes place."}, {"title": "Gibbs Free Energy .txt", "text": "So our cell and the process is a system, and everything outside the cell are the surroundings."}, {"title": "Gibbs Free Energy .txt", "text": "So when that process actually takes place, a certain amount of energy is exchanged between that system and the surroundings."}, {"title": "Gibbs Free Energy .txt", "text": "So let's suppose that the energy left ourselves and entered our surroundings."}, {"title": "Gibbs Free Energy .txt", "text": "What exactly does that mean about the entropy of the surroundings?"}, {"title": "Gibbs Free Energy .txt", "text": "Well, because the energy left the system and it dispersed throughout the surroundings, that means the entropy of the surroundings increased in this particular case, and in this case, we can define what the entropy is in terms of the amount of energy that's left the system and the temperature of that particular system."}, {"title": "Gibbs Free Energy .txt", "text": "So the way that we define entropy in physics is the change in entropy of the surroundings, which is a positive value as long as entropy left our system is equal to the quantity of entropy, the quantity of energy that left the system as a result of heat divided by the temperature given to us in Kelvins."}, {"title": "Gibbs Free Energy .txt", "text": "Now, the negative sign simply means when the enthalpy when the heat basically flows out of the cell, when the energy is absorbed by the surroundings, this system loses energy, but the surroundings gains that energy."}, {"title": "Gibbs Free Energy .txt", "text": "And so our delta S of the surroundings will be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "That's why we have this negative value here."}, {"title": "Gibbs Free Energy .txt", "text": "So by using this definition of entropy and by using the second law of thermodynamics, we can basically derive the equation for Gibbs free energy that we can use to basically determine whether or not a reaction is spontaneous."}, {"title": "Gibbs Free Energy .txt", "text": "So let's call this equation one and this equation two."}, {"title": "Gibbs Free Energy .txt", "text": "We can now take equation two and substitute this quantity into this quantity."}, {"title": "Gibbs Free Energy .txt", "text": "So the delta S of the surroundings is equal to negative of the Delta H system divided by the temperature."}, {"title": "Gibbs Free Energy .txt", "text": "So we replace this quantity with the right side of this equation, and we get equation three."}, {"title": "Gibbs Free Energy .txt", "text": "So the change in entropy of our system is minus the change in entropy of the system divided by the temperature, which is the same thing as the change in entropy of our surroundings is equal to the change in entropy of our universe."}, {"title": "Gibbs Free Energy .txt", "text": "Let's call this equation three."}, {"title": "Gibbs Free Energy .txt", "text": "Now, if we take equation three and multiply each term by negative T, we get this equation here."}, {"title": "Gibbs Free Energy .txt", "text": "So this becomes negative T, delta S system."}, {"title": "Gibbs Free Energy .txt", "text": "This becomes positive delta H system."}, {"title": "Gibbs Free Energy .txt", "text": "The T's cancel and negative times a negative gives us a positive, and this quantity becomes negative T multiplied by delta S universe."}, {"title": "Gibbs Free Energy .txt", "text": "So we can rearrange this equation, basically bring this to that side, and we get the following equation."}, {"title": "Gibbs Free Energy .txt", "text": "Let's call this equation four."}, {"title": "Gibbs Free Energy .txt", "text": "So the negative of the temperature in Kelvins multiplied by the change in entropy of the universe is equal to the change in entropy of the system."}, {"title": "Gibbs Free Energy .txt", "text": "So basically, how much energy was exchanged between the system and the surroundings minus the temperature multiplied by the delta S of the system."}, {"title": "Gibbs Free Energy .txt", "text": "So let's call this equation four."}, {"title": "Gibbs Free Energy .txt", "text": "Now, if we take this and we basically represent this term as delta G, then this is the more common equation that you're used to seeing."}, {"title": "Gibbs Free Energy .txt", "text": "So this quantity is actually Gibbs free energy."}, {"title": "Gibbs Free Energy .txt", "text": "So the negative T multiplied by delta S of the universe is called Gibbs free energy."}, {"title": "Gibbs Free Energy .txt", "text": "It has the units of Joules, and it is represented by delta G. So in equation four, if we rewrite this term with delta G, we basically get equation five."}, {"title": "Gibbs Free Energy .txt", "text": "And this is the equation that gives us the Gibbs free energy when a process takes place."}, {"title": "Gibbs Free Energy .txt", "text": "Now, if we look at equation three and we look at equation one, so we know from the second law of thermodynamics that in any real biological process, the change in entropy of the universe must always be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "So after the reaction takes place, the energy must be more dispersed and more spread out than before that reaction actually took place."}, {"title": "Gibbs Free Energy .txt", "text": "And what that means is, for this to actually be true, the right side of the equation, the delta S of the universe, must always be a positive value, right?"}, {"title": "Gibbs Free Energy .txt", "text": "So this is the same thing as saying this."}, {"title": "Gibbs Free Energy .txt", "text": "Now, this quantity, the right side of the equation, is going to be a positive value only if this quantity here, the delta S of the system, is greater than this quantity here."}, {"title": "Gibbs Free Energy .txt", "text": "If this is greater than this, then when we take the difference of these two values, this will be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "So we see that according to the second law of thermodynamics, in any real biological process, the entropy of the universe must always increase as per this equation."}, {"title": "Gibbs Free Energy .txt", "text": "Therefore, from equation three, we see that if this delta s universe is to be positive, then what that means is this quantity."}, {"title": "Gibbs Free Energy .txt", "text": "So the delta S of the system must be greater than this quantity, this term here, because if this is a greater number than this, then the difference will be a positive value."}, {"title": "Gibbs Free Energy .txt", "text": "So let's call this inequality inequality six."}, {"title": "Gibbs Free Energy .txt", "text": "Now, if we take inequality six and we multiply both sides by T, so we simply bring T to the left side, then we get the following equation."}, {"title": "Gibbs Free Energy .txt", "text": "What this equation tells us is for our process to actually increase the entropy of the universe, this inequality must be true."}, {"title": "Gibbs Free Energy .txt", "text": "So T multiplied by delta S of the system should be greater than the delta H of the system."}, {"title": "Gibbs Free Energy .txt", "text": "Now let's take a look at Gibbs free energy, equation five."}, {"title": "Gibbs Free Energy .txt", "text": "So, on the right side of this equation, this term is the same as this term here, and this term is the same as this term here."}, {"title": "Gibbs Free Energy .txt", "text": "So, according to equation five, and according to this inequality, this quantity must be less than this quantity."}, {"title": "Gibbs Free Energy .txt", "text": "And if this quantity is greater than this quantity, if we take their difference, we get unnegative value."}, {"title": "Gibbs Free Energy .txt", "text": "So what that means is a biological reaction that takes place inside our body or inside our cells increases the entropy of the universe only if the gifts free energy is actually a negative value."}, {"title": "Gibbs Free Energy .txt", "text": "And that means when the gifts free energy is a negative value, our reaction under that particular condition, at that particular temperature, is a spontaneous reaction."}, {"title": "Gibbs Free Energy .txt", "text": "So spontaneous reaction that increases entropy of the universe under this particular temperature will always have a gift free energy that is a negative value."}, {"title": "Gibbs Free Energy .txt", "text": "And that's what we mean by a spontaneous reaction."}, {"title": "Gibbs Free Energy .txt", "text": "So a reaction is only spontaneous as that particular temperature."}, {"title": "Gibbs Free Energy .txt", "text": "If the GIBS free energy is negative, if the GIBS free energy is positive at that particular temperature, then that reaction will not be spontaneous."}, {"title": "Gibbs Free Energy .txt", "text": "It will not take place naturally or spontaneously in nature."}, {"title": "Introduction to Amino Acids .txt", "text": "All the different types of proteins found inside our body are built from a collection of 20 different types of amino acids."}, {"title": "Introduction to Amino Acids .txt", "text": "And all of these types of amino acids are known as alpha amino acids."}, {"title": "Introduction to Amino Acids .txt", "text": "So let's begin by discussing what an alpha amino acid is."}, {"title": "Introduction to Amino Acids .txt", "text": "Why do we call an amino acid and alpha amino acid?"}, {"title": "Introduction to Amino Acids .txt", "text": "Well, let's recall some basic organic of chemistry."}, {"title": "Introduction to Amino Acids .txt", "text": "So we know from organic chemistry that if we have a carbonyl group, so a carbon oxygen double bond, and we have another carbon attached to this carbonyl group, like so then this carbon here is known as an alpha carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And for example, if we have a hydrogen atom attached to the alpha carbon, this H atom is known as an alpha hydrogen atom."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, what is an alpha amino acid?"}, {"title": "Introduction to Amino Acids .txt", "text": "Well, an alpha amino acid contains a center carbon, that is an alpha carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And to see what we mean by that, let's take a look at the following diagram, which is basically the general structure of an alpha amino acid."}, {"title": "Introduction to Amino Acids .txt", "text": "And let's compare it to this diagram we've drawn right here."}, {"title": "Introduction to Amino Acids .txt", "text": "So let's suppose that the other group attached to this carbon is an oxygen group."}, {"title": "Introduction to Amino Acids .txt", "text": "So what that means is this entire group here is a carboxylic acid group in which this oxygen has been deprofename."}, {"title": "Introduction to Amino Acids .txt", "text": "So we have a negative charge here."}, {"title": "Introduction to Amino Acids .txt", "text": "So what an alpha amino acid is, if it's basically a molecule that contains a sensor carbon, that is an alpha carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And so it contains this carboxylic acid group that has been deprotonated as shown in the following diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "And not only that, the other group attached to this center alpha carbon is an amino group that has been protonated."}, {"title": "Introduction to Amino Acids .txt", "text": "Now we'll see why this is protonated and why this is deprotonated in just a moment."}, {"title": "Introduction to Amino Acids .txt", "text": "So we have this other amino group, as shown in the diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "So let's draw it in the protonated form with the positive charge."}, {"title": "Introduction to Amino Acids .txt", "text": "And we have one of the other groups is an H atom, as shown here."}, {"title": "Introduction to Amino Acids .txt", "text": "So that's the alpha H atom."}, {"title": "Introduction to Amino Acids .txt", "text": "And the final group is a side chain group we also call the R group."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, the reason we call it an R group is because the R group actually differs from one amino acid to another."}, {"title": "Introduction to Amino Acids .txt", "text": "And we'll discuss exactly what that means in just a moment."}, {"title": "Introduction to Amino Acids .txt", "text": "So this is what an alpha amino acid is."}, {"title": "Introduction to Amino Acids .txt", "text": "It contains the center carbon, that is an alpha carbon, that is, it is attached to this carbon of this carbonyl group, as shown in the following diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, alphamino acids usually contain a Chiral carbon and the only exception is Glycine, because in Glycine, this R group is a simple H atom."}, {"title": "Introduction to Amino Acids .txt", "text": "So let's remember what Chiral groups are."}, {"title": "Introduction to Amino Acids .txt", "text": "A Chiral carbon is a carbon that contains four different groups attached to that carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "So in this particular case, one of these groups is the carboxylic acid."}, {"title": "Introduction to Amino Acids .txt", "text": "The other group is the amino group."}, {"title": "Introduction to Amino Acids .txt", "text": "The third group is the H atom."}, {"title": "Introduction to Amino Acids .txt", "text": "And the final group is the side chain, the R group, that is unique to that particular amino acid."}, {"title": "Introduction to Amino Acids .txt", "text": "So 19 out of the 20 amino acids are Chiral, because this R group is not the same as these other three groups."}, {"title": "Introduction to Amino Acids .txt", "text": "But for Glycine, as we'll see in Lex lecture, this R group is actually an H atom."}, {"title": "Introduction to Amino Acids .txt", "text": "So glycine is not chiral."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, 18 out of the 19 Chiral amino acids, they exist in their S absolute configuration form, and only 15 exists in the R absolute configuration form."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, what do we mean by absolute configuration?"}, {"title": "Introduction to Amino Acids .txt", "text": "Well, let's remember a little bit of organic chemistry."}, {"title": "Introduction to Amino Acids .txt", "text": "So in organic chemistry, in order to determine the absolute configuration, we have to prioritize the different types of atoms attached to this carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "So we have the sensor Chiral carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And we basically give these four groups a value that ranges between one and four."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, one is that group, that atom that contains the highest atomic number."}, {"title": "Introduction to Amino Acids .txt", "text": "So notice that this carbon is attached to a nitrogen."}, {"title": "Introduction to Amino Acids .txt", "text": "It attached to a carbon, to an H atom and to the R group."}, {"title": "Introduction to Amino Acids .txt", "text": "And usually this is given a four, or actually always this is given a four."}, {"title": "Introduction to Amino Acids .txt", "text": "This is always given a one, and usually this is given a two and this is given a three."}, {"title": "Introduction to Amino Acids .txt", "text": "So this is given a one because the nitrogen has a higher atomic number than the carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And this R group, which is usually carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, this is given the highest of four because it has the lowest atomic number."}, {"title": "Introduction to Amino Acids .txt", "text": "And usually this is a carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "This is a carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "And then the next atom is a carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "Here it's an oxygen."}, {"title": "Introduction to Amino Acids .txt", "text": "So this is a two and this is a three."}, {"title": "Introduction to Amino Acids .txt", "text": "And so we have one, two, three and four."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, to determine whether it's the R or the S absolute configuration, we basically have to take this molecule oriented in such a way so that the fourth group, H, points into the board so that we can't actually see it."}, {"title": "Introduction to Amino Acids .txt", "text": "So after we oriented like so we get this age group points into the board, and these three groups will point out as shown in the following diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "So we basically rotate it slightly so that these two are coming out of the board."}, {"title": "Introduction to Amino Acids .txt", "text": "This is coming out of the board, and this group will point into the board."}, {"title": "Introduction to Amino Acids .txt", "text": "And so now we have one, two and three."}, {"title": "Introduction to Amino Acids .txt", "text": "And we basically have to follow this order, one to three."}, {"title": "Introduction to Amino Acids .txt", "text": "And we draw our arrow and notice the arrow points in the counterclockwise direction."}, {"title": "Introduction to Amino Acids .txt", "text": "And that means it's the S. If it pointed in the clockwise direction, that would mean it would be an R ABS configuration."}, {"title": "Introduction to Amino Acids .txt", "text": "So the majority of the L isomers in our body have the S ABS configuration, as shown in the following diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, earlier I said that this is a protein version of the amino group."}, {"title": "Introduction to Amino Acids .txt", "text": "And this is the deprotonated version of the carboxylic acid group."}, {"title": "Introduction to Amino Acids .txt", "text": "Why?"}, {"title": "Introduction to Amino Acids .txt", "text": "Well, it turns out that the PH of the solution in which that amino acid is in determines whether or not these are proteinative or deprovinated."}, {"title": "Introduction to Amino Acids .txt", "text": "And it turns out that at a neutral PH of around seven, our amino acids exist predominantly in their dipolar form."}, {"title": "Introduction to Amino Acids .txt", "text": "And the dipolar form is also known as the Zvitorion form."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, what do we mean by the Zvitorion form?"}, {"title": "Introduction to Amino Acids .txt", "text": "So, in the Zvitor ion form, this amino group is protonated."}, {"title": "Introduction to Amino Acids .txt", "text": "It has a full positive charge."}, {"title": "Introduction to Amino Acids .txt", "text": "And this carboxylic acid group is deprofenated."}, {"title": "Introduction to Amino Acids .txt", "text": "It has a full negative charge."}, {"title": "Introduction to Amino Acids .txt", "text": "And so we have a dipolar species."}, {"title": "Introduction to Amino Acids .txt", "text": "Dipolar simply means we have two dipole moments."}, {"title": "Introduction to Amino Acids .txt", "text": "So we can basically redraw this diagram in the following way."}, {"title": "Introduction to Amino Acids .txt", "text": "Where this carbon is this center carbon."}, {"title": "Introduction to Amino Acids .txt", "text": "This orange group is this H atom."}, {"title": "Introduction to Amino Acids .txt", "text": "This green group is the R atom."}, {"title": "Introduction to Amino Acids .txt", "text": "This carboxylic acid group contains a negative charge."}, {"title": "Introduction to Amino Acids .txt", "text": "This amino group contains a positive charge."}, {"title": "Introduction to Amino Acids .txt", "text": "And so, because we have these two separate and opposite charges, this is the dipolar form of the amino acid, the Zvitarion form."}, {"title": "Introduction to Amino Acids .txt", "text": "And because the majority of the cells and the solutions inside our body have a PH of around four, the majority of the amino acids exist in this Zvitor ion form."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, the next question is what exactly happens to our amino acid, to the Zvitor ion, if we decrease the PH, make it more acidic, or increase the PH, make it more basic?"}, {"title": "Introduction to Amino Acids .txt", "text": "Well, it turns out, in various acidic solutions, if the PH of our solution is, let's say, one, then because we have so many H ions in our solution, this here will be protonated."}, {"title": "Introduction to Amino Acids .txt", "text": "And so our amino acid will exist in the following form."}, {"title": "Introduction to Amino Acids .txt", "text": "It will have an overall charge of positive one."}, {"title": "Introduction to Amino Acids .txt", "text": "This is called the positively charged amino acid species."}, {"title": "Introduction to Amino Acids .txt", "text": "So at a PH, at a very acidic PH of around one, this amino acid, and in general, amino acids, exist in their positively charged species form."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, as we begin to increase our PH, we decrease the concentration of the H plus ions inside our solution."}, {"title": "Introduction to Amino Acids .txt", "text": "And at around two, this H found on the carboxylic acid group begins to dissociate."}, {"title": "Introduction to Amino Acids .txt", "text": "It deprotonates."}, {"title": "Introduction to Amino Acids .txt", "text": "It loses that H atom, and so it gains that full negative charge."}, {"title": "Introduction to Amino Acids .txt", "text": "So we see that if we continue going higher, at a PH of around four, five, six and seven, our amino acid exists in its Zitter ion form."}, {"title": "Introduction to Amino Acids .txt", "text": "That means we have a positive charge here."}, {"title": "Introduction to Amino Acids .txt", "text": "We have a negative charge here."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, as we continue driving the PH up, as we continue decreasing the amount of H plus ions in our solution, eventually we get to the point where we have so little H plus ions in solution that this H found on a nitrogen is going to deprotonate."}, {"title": "Introduction to Amino Acids .txt", "text": "It will dissociate as to increase the amount of H plus ions in solution."}, {"title": "Introduction to Amino Acids .txt", "text": "And at around a PH of nine, that is exactly where that begins to happen."}, {"title": "Introduction to Amino Acids .txt", "text": "So at a PH of nine."}, {"title": "Introduction to Amino Acids .txt", "text": "This is deproyated."}, {"title": "Introduction to Amino Acids .txt", "text": "And notice that now this has a neutral charge."}, {"title": "Introduction to Amino Acids .txt", "text": "This has a negative charge."}, {"title": "Introduction to Amino Acids .txt", "text": "And so what?"}, {"title": "Introduction to Amino Acids .txt", "text": "That means this entire amino acid will be negatively charged as a result of this fact."}, {"title": "Introduction to Amino Acids .txt", "text": "And so this is a positively charged amino acid, and that is found in a very low PH, in a PH of around one."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, in the middle, we have this zvitarion form."}, {"title": "Introduction to Amino Acids .txt", "text": "And at this end, when we are above a PH of nine, when it's very basic, we have a negatively charged species, as shown in the following diagram."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, the final thing that I'd like to mention about amino acids is so amino acids essentially are the same on this group, on this group, and on this group."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, where we can differentiate one amino acid from another is by the R group, by that side chain."}, {"title": "Introduction to Amino Acids .txt", "text": "So we have different types of side chains."}, {"title": "Introduction to Amino Acids .txt", "text": "And these different types of side chains basically determine the type of amino acid that we are discussing."}, {"title": "Introduction to Amino Acids .txt", "text": "Now, these side chains can basically differ based on their size, based on their shade, based on their structure."}, {"title": "Introduction to Amino Acids .txt", "text": "They can differ based on the amount of charge found on that side chain, based on the polarity, based on the hydrophobic character, as well as on their ability to create hydrogen bonds."}, {"title": "Introduction to Amino Acids .txt", "text": "And so these differences, these different properties of these side chain groups, basically determine the properties and the chemical reactivities of our amino acids."}, {"title": "Introduction to Amino Acids .txt", "text": "And in the next several lectures, we're going to focus on these different types of amino acids."}, {"title": "Introduction to Amino Acids .txt", "text": "And there are different types of side chains that are found on those amino acids."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now that we discuss the many details of our immune system let's actually connect the dots."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Let's describe how the innate immune system interacts with the adaptive immune system and how they work together to actually carry out the function of protecting and defending our healthy cells of the body from different types of pathogenic infections."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And let's begin by imagining the following scenario."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Let's suppose we have the surface of our skin as shown in the diagram."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Then we have the skin tissue and below that we have our blood vessel that carries our blood plasma from this side to this side of our diagram."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now let's imagine that we have some type of cut that is formed on the surface of our skin as shown in this diagram."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And let's imagine that in close proximity to our cut we have some type of pathogen."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now the pathogen could be some type of parasite."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "It could be some type of viral agent."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "It could be some type of bacterial cell or it could be a simple allergen."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "In."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Either way once our pathogen makes its way into our skin tissue our immune system will elicit some type of defensive response."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So let's suppose our pathogen invades our skin tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "What will happen next?"}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Well the first thing that will happen is a cell called a mass cell and a cell called a derivative cell will react to the antigens that are produced by that pathogen."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So the pathogen will begin producing an antigen."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And let's assume the antigen is some type of pathogenic peptide."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So that is shown by these red dots."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So let's begin with the mass cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So mass cells on their surface contain these receptors and these receptors can bind antigens nonspecifically."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And what that basically means is it doesn't matter what type of antigen is found in close proximity these mass cells will bind any antigen and once they bind that antigen they know that there is some type of pathogen in close proximity."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And so what they begin to do is they remain within the tissue and they begin releasing chemicals."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So what types of chemicals?"}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Well they release histamines and histamines when they move into our blood they dilate the blood vessel and that increases the flow of blood to this infected area."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And that in turn as we'll see in just a moment brings more of the white blood cells that basically help protect this area."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now the other chemical that they release is heparin and heparin is basically an anticoagulant."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And what that means is it decreases the blood clotting capability of our blood and that makes the blood more leaky and also increases the flow of blood to this area."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "On top of that these chemicals also make the capillaries more leaky and that means more blood can actually get into the tissue and that means more of these white blood cells can end up in the tissue that is infected by this pathogen."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these chemicals essentially initiate the process of inflammation that takes place in the innate immune system."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now these also release cytokines and the cytokines essentially call upon other cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "For example macrophages, neutrophils and other cells as we'll discuss in just a moment."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now let's move on to this other cell found within a tissue known as aridandritic cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now dendritic cells are also capable of taking these antigens but they engulf those antigens into that cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Inside the cell they can digest or break down those antigens into smaller antigens and they take a small portion of the antigen known as an epitope and they place it on a special membrane known as the major historicompatibility complex that is found on that membrane."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So once these antigens showed in red are on the membrane protein."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "What the dendritic cell does isn't actually exit."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "It leaves the tissue, enters our blood system and it moves to the lymph nodes of our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And this is the cell that calls upon our adaptive immune system as we'll see in just a moment."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "This cell is also capable of binding any antigen nonspecifically."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "But it takes that antigen and it brings it to the adaptive immune system and we'll see exactly what the interaction is in just a moment."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So it's the dendritic cell that connects the innate immune system to our adaptive immune system of our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now let's move on to the cells that are found in the blood that are called upon by these chemicals released into our blood in the first place by the mast cell and by other cells of our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So let's begin with a group of cells known as granulocytes."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And these granulocytes are called granulocytes because they have granules."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They have tiny vesicles that contain chemicals within the cytoplasm."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So we have neutrophils, we have basophils and we have eosinophils."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And all these cells are found within the blood and they respond to these chemicals released into the blood and then they move into the skin tissue where our infection is taking place."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now let's begin with neutrophils."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Neutrophils are phagocytic cells and what that means is when they move into our skin tissue they begin to engulf these pathogens."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these pathogens once again could be bacterial cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They can be some type of viral agent in which case these viruses will infect our cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And what these neutrophils can do is actually engulf those cells that have been infected by our virus."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, what about basophils?"}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Well, basophilus and eosinophilus are found in high concentration if the invading pathogen is some type of allergen or some type of parasite."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these respond to infections due to parasite or allergic reactions."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They move from the blood and into our tissue and also release histamine."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And heparin just like the mast cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And that once again dilates our blood vessel, makes our capillaries more leaky so that there is a higher flow of fluid into our tissue and it also decreases the ability of our blood to actually clot itself and that increases the flow of our blood as a result."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these eosinophils also are found in high concentration when we have some type of allergic reaction if this pathogen is an allergen or if it is some type of parasite."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, another type of innate immune cell is the natural killer cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, these natural killer cells as shown the following diagram basically have a special receptor on that cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And these receptors can bind onto either infected cells that have been infected with some type of viral agent or they can abide onto cancer cells and destroy those cancer cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these natural killer cells circulate inside our blood and they respond to these cytokines released by the math cell and other cells and they move into that infected area from the blood into the tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these natural killer cells circulates in the blood and moves into effective tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They bind onto cancer cells or infected cells and once they bind they release powerful digestive enzymes that drill holes in that infected cell or cancer cell and that lysis our cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, once the cell lyses we have these macrophages that are also called upon by these cytokines released into our blood as a result of that mast cell and other cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, these macrophages are the largest type of phagocytic cell in our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They basically move from the blood into our tissue and they begin engulfing anything that is harmful or pathogenic to the healthy cells of our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And that includes the ly cell that was lies by the natural killer cell or any infected cell or any pathogen found inside our tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So macrophages are large phagocytic cells that engulf pathogens infected cells cancer cells and any debris that is found within a tissue that might be harmful to the cells of that tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these move from the blood and into our tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So these seven cells we just described are the major seven cells that are nonspecific and which are part of the innate immune system."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Two of these cells are usually found within our skin tissue."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "We have the mast cell and the dendritic cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "But it's the dendritic cell that moves into our blood and carries the antigens into the adaptive immune system of our body the white blood cells found in our lymph nodes and in our lymph system."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So let's move on to our adaptive immune system."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So we have two types of cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "We have B lymphocytes or B cells and we have T lymphocytes or T cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So once our dendritic cell brings those antigens to these cells this is what begins to take place."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "If our antigen presenting cell this dendritic cell interacts with B lymphocytes those B lymphocytes with the help of another cell known as a helper T cell will differentiate into plasma cells or memory B cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And it's the plasma cells that will begin to produce antibodies specific to these antigens that are brought to these B lymphocytes by our dendritic cell and other cells such as our macrophage."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So basically, our plasma cells produce these antibodies that are released into our blood system and then these antibodies can bind to these specific antigens."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And once they bind onto the antigens they label them for destruction by cells like macrophages, neutrophils and other cells of our body."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, memory cells are those cells of our body that remain with us for the duration of our lifetime."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And they keep a copy of this antigen in case reinfection ever takes place."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And if reinfection does take place, they elicit a secondary immune response that is much quicker and more efficient than a primary immune response."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, what about the T lymphocytes?"}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So this dendritic cell can also interact with T lymphocytes."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "There are four different types of T lymphocytes."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "We have helper T cells, cytotoxic T cells, depressor T cells and memory T cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So helper T cells are a very important type of lymphocyte because they assist many other cells with a differentiation process."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Helper T cells help B lymphocytes differentiating the plasma cells and memory B cells and they also help tillyphasize themselves differentiate into cytotoxic T cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So helper T cells assist with B and T cell differentiation and these also release their own cytokines and interlocutines different chemicals that essentially call upon cells like macrophages to that specific area."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, cytotoxic T cells are like natural T cells because these basically attack infected cells, cells that have been infected by a viral agent or they can also attack cancer cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "But there is an important difference."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Cytotoxic T cells are specific and what that means is they will only bind to a specific antigen while natural killer cells are nonspecific."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "It doesn't matter what type of antigen is found on the, on that pathogenic cell, this will bind to it."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "But this only binds to a specific cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "And that's because this dendritic cell brought a specific type of antigen to this cytotoxic T cell."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So it will only react to this specific antigen that was brought to it."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Now, finally, we also have suppressor T cells and memory T cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Memory T cells are like memory B cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They essentially help us with reinfection."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They keep a copy of our antibody while suppressor T cells help us regulate the different types of white blood cells in our body and they use a negative feedback mechanism to tone down or turn down our immune response."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "So we see that the innate immune system does in fact interact with adaptive immune system even though this is the first one to actually react to our infection."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "We have special cells like our derivinic cells and macrophages that basically are antigen presenting cells."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "They present antigens on the surface of their membrane and they move to our adaptive system, to our lymph nodes and they basically cause the differentiation of B lymphocytes and T lymphocytes."}, {"title": "Innate and Adaptive Immune Systems .txt", "text": "Which then you use a specific mechanism to attack specific antigens and specific pathogens found in our body."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now that we discussed what the structure of the skeletal muscle is and what a sarcomere is, let's discuss how the muscle contraction actually takes place within our skeletal muscle."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And let's begin with the generation of an action potential."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So, before we actually contract our skeletal muscle, the brain has to initiate, has to create that electrical signal in the form of an action potential."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So it creates the action potential and it sends the action potential down to our somatic nervous system."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And the somatic nervous system contains motor neurons."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And these motor neurons connect to our skeletal muscles."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So basically, these motor neurons pick up the electrical signals that are produced by our brain and they carry these electrical signals in the form of an action potential down their axon and onto the axon terminal that connects to the cell membrane of our muscle cell."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is our muscle cell, also known as a muscle fiber, also known as the myocyte."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And the muscle cell is wrapped around with a special membrane known as our sarcolema."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, the sarcolema consists of these imaginations, these tunnels that basically go deep into the cell, and these are known as T tubules or transverse tubules."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "They are shown in the diagram with these white dots."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is the axon of the motor neuron that is carrying our action potential."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And essentially the action potential travels along the axon until it gets to our axon terminal."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is one axon terminal, a second axon terminal, a third axon terminal."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, if we zoom in on this axon terminal, we basically get the following diagram."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "This is the axon terminal of this end region of the motor neuron, and this is the membrane that is shown in red."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So basically, once the action potential arrives onto the axon terminal, the axon terminal will release synaptic vesicles that carry a special type of neurotransmitter known as acetylcholine."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So once acetylcholine is released into this synaptic cleft, these acetylcholines are shown by these black dots."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "They basically bind to the membrane proteins on our sarcolema and that will depolarize our sarcoma."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, once the sarcolema depolarizes, that action potential that is created on the sarcolema will travel into the cell via these deep imaginations known as our T tubule."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So what these tubules basically do is they allow the action potential to very quickly and evenly spread throughout the entire muscle cell."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So once our action potential travels into the cell, it will basically cause the activation of these channels found on the membrane of the sarcoplasmic reticulum."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So remember, the sarcoplasmic reticulum is basically the specialized type of endoplasmic reticulum found inside our muscle cell."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So if we take a cross section of our muscle cell, the green region is basically our sarcoplasmic reticulum."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is our sarcoplasm reticulum."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Once it accepts that action potential, once the action potential travels to our sarcolema, it will basically open up these special channels on the membrane that will basically allow calcium ions to flow into our cytoplasm."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Remember, the cytoplasm of our muscle cell is also known as our sarcoplasm."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So inside our sarcoplasm reticulum, we have a high concentration of calcium."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "On the outside, in the cytosol, we have a low concentration."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So these calcium ions will travel down their electrochemical gradient end into our cytosol."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, inside the muscle cell, we have many, many of these myofibrils."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And what these myofibrils are, are basically our sarcomeres connected end to end."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So we have many of these myofibrils."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And if we examine one of these myofibrils and we zoom in on the myofibril, we basically get the following diagram."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So, we have many of these sarcomeres connected end to end to form our myofibility."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, once the calcium is released into our surroundings, into the cytoplasm of the cell, they will go on."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "The calcium ions will go on and bind to a special region on the thin filament, as we'll see in just a moment."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, by the way, this junction between the axon terminal and the membrane of our muscle cell is known as the neuromuscular junction, and it's also sometimes known as the motor and plate."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So if you ever hear the expression motor and plate, that simply is referring to the synapse between our end of the motor neuron and our sarcoplasm of our muscle cell."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "This is also known as the neuromuscular junction."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So now that we know how the signal actually arrives onto our muscle cell and what it causes, let's see what the calcium actually does and how it interacts with the thin and thick filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is our sarcomere."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "The sarcomir consists of these thin filaments that are composed of globular proteins known as actin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And we also have the thick filaments, shown in purple, that are composed of our protein known as myosin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So let's discuss how they actually interact."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So let's label this step as step number one."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So, basically, the release of our calcium into the cytoplasm, into the cytosol of the cell, that is step number one."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, what about step number two?"}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Step number two is the binding of that calcium to a special protein found on our actin filament, on the thin filament known as troponin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So we have this protein that is shown by these three globular pink regions."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "This is troponin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "A tropomycin basically is this other blue protein that extends all the way around our actin filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And our troponin is actually bound to our tropomycin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So as soon as calcium binds to our troponin, the troponin basically changes its shape."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "It experiences a conformational change."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And as it changes its shape, it causes our trophymycin to also change its shape and shift."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And as our trophymycin, shown in blue, actually shifts, it exposes special binding sites on the actin filament known as our myosin binding site."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is basically where our myosin heads found on the thick filament, actually bind to our thin filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this green region, which was blocked on this diagram is exposed as soon as our calcium binds onto our troponin."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is our calcium, it binds onto our troponin, it changes its shape, which in turn changes the shape of our tropomycin and that exposes our myosin binding side."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is step number two."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, as soon as our binding side is exposed, right before the binding between the thick and the thin filament actually takes place, our myosin head has to basically hydrolyze an ATP molecule."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So the myosin heads contain ATP molecules or an ATP molecule."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So one ATP per hour myosin head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now before they can actually bind to the mycin binding side that was just exposed as a result of the binding, the calcium, the ATP must be hydrolyzed into ADP and a phosphate group."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So basically this ATP that is found on the myosin ahead of our thick filament, so this is a thick filament, this is our myosin head, which is basically our myosin heads."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "On this thick filament shown here, it is hydrolyzed and the ADP and the P that are produced remain on that myosin head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this is step three."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, once we hydrolyze the ATP into ADP and the phosphate and once the calcium binds onto our troponin exposing that binding site, now the binding can actually take place."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So now the myosin head is oriented correctly."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So what also happens when we have our hydrolysis is in this diagram, the myosin head is oriented at a 45 degree angle with respect to our thick filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "But when we have hydrolysis taking place, when we produce the ADP and the P, this myosin head orients itself approximately at a 90 degree angle with respect to our thick filament as shown in this diagram."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And now the orientation is just right for this mice and head to actually bind to our binding side as shown in this diagram."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And this binding, let's label this as step number four."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, what takes place once they actually bind?"}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So once the thick filament and our thin filament actually bind to each other as a result of our myosin head, step number five takes place."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "In step number five, the phosphate group and the ADP group are basically released from our myosin head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And as this is released, that causes the change in orientation of the mycin head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "The myosin head once again goes from a 90 degree angle to about a 45 degree angle."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And as that takes place, that moves our thin filaments towards each other."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So if this is one portion of the thin filament, this is a second portion of the thin filament of the sarcomere, they basically are pulled towards each other."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So these z lines, the z line number one and the z line number two basically are pulled towards each other."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And so we have this motion taking place."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "This entire thin filament basically is pulled this way as our ADP and P basically detach from the myosin head and the myosin head is oriented once again at the 45 degree angle."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So once it binds, once the myosin head binds onto the binding side, it must expel the ADP and the phosphate molecules in order to actually move the myosin head oriented at an angle of 45 degrees with respect to our thick filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And that essentially pulls the thin filament as shown in this diagram."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So this thin filament basically is pulled this way so that these two z lines are basically pulled inward."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Now, this process of actually pulling on our thin filament by the movement of our mice and head is known as the power stroke."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And the power stroke must take place when our phosphate is basically expelled from that myosin head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So once that power stroke actually takes place, we have to detach that myosin head from our thin filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And the way that we do that is we basically bind an ATP molecule onto our mic and head."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So in the last step, we basically take an ATP molecule and we bind it onto our myosin head and that releases our thin filament from our thick filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "At the same time, the calcium that is bound to our troponin is basically released and that means our tropomycin closes that binding site."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So now our myosin head can no longer bind to our actin filament."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So when ATP binds to our mycin head, it causes it to detach."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "Calcium also detaches, thereby blocking those myosin in binding sites."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "And this concludes our contraction of the muscle and this process basically repeats itself."}, {"title": "Contraction of Skeletal Muscle .txt", "text": "So essentially when I'm moving my skeletal muscle back and forth, this process is taken over and over and over."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Gluconeogenesis is the process by which certain types of cells of our body have the ability to actually synthesize glucose molecules by using noncarbohydrate precursor molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So these precursor molecules include pyruvate molecules, lactate molecules, glycerol molecules, and amino acids."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So these are the major types of nonsugar precursors that we use inside our body to synthesize glucose via glucaneogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, only specific types of cells in our body are actually able to undergo gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So these include liver cells and to a small extent, kidney cells, because it's the liver and the kidneys that are responsible for actually regulating and maintaining the proper glucose level in our blood."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So liver cells, hepatitis and kidney cells are able to actually undergo the process of gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And cells like cardiac muscle cells, skeleton muscle cells and brain cells cannot actually undergo gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "These cells depend on liver cells and kidney cells ability to actually create these glucose molecules, dump these glucose molecules into the blood plasma, and then the blood plasma brings these glucose molecules to the cells, like the cardiac cells, muscle cells and brain cells of our body."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, let's briefly discuss where we actually obtained these non sugar precursor molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So we know where pyruvate comes from."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "That comes from the breakdown of glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So when we don't have enough glucose in our body, we can actually take that pyruvate and essentially reverse the steps of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, that's not exactly true, and we'll talk more about that in just a moment, but basically, gluconeogenesis is actually the process by which we take the pyruvate and turn it back into glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, what about lactate?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Well, we know if we're exercising vigorously, our skeleton muscles will begin to produce ATP to actually contract our skeletal muscle."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And when that happens, eventually we're going to run out of oxygen."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So when the rate of glycolysis is much higher than the rate of oxidative asphylation that takes place in the mitochondria of our cells, in that case, we're going to begin the process of lactic acid fermentation."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so these skeleton muscle cells produce lactic acid, which dissociates into H plus ions and lactate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And that's where we obtain the lactate from."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, eventually, that lactate enters our blood plasma and makes its way into our liver cells."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And the liver cells transform that lactate into pyruvate by the action of an enzyme we call lactate dehydrogenase."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And once that transformation takes place, only then can pyruvate actually begin the process of gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So lactate itself doesn't actually enter gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "It must first be transformed into pyruvate before it can actually begin the process of gluconeogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, what about glycerol molecules?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Where do we get glycerol molecules?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Well, glycerol molecules are components of fats."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "More specifically, they're components of triglyceride."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So that's the major type of fat molecule that exists in adipose tissue."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so when we actually need glucose in our body, when we can get the glucose from food, our fat cells, the adipose tissue cells, basically begin breaking down these triglycerides to form fatty acids and glycerol molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, fatty acids cannot actually be used to form glucose molecules, and we'll discuss why in a future lecture."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "But the glycerol molecules can be used to form the glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so the glycerol basically makes its way into the blood plasma and travels to our liver cells."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And once inside these hepatitis, they undergo a two step process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "The first step is catalyzed by glycerol kinase, and we use an ATP molecule."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so we transform glycerol into glycerol phosphate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And in the second step, that is catalyzed by glycerol phosphate dehydrogenase, we basically use an NAD plus molecule to oxidize the glycerol phosphate into DHAP."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So dihydroxy acetone phosphate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And it's this molecule that enters the process of gluconeogenesis and begins the conversion of this molecule into glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So we see that Pyruvate enters gluconeogenesis as Pyruvate, lactate enters gluconeogenesis as Pyruvate, and glycerol enters gluconeogenesis as DHAP."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Dihydroxy acetone phosphate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, what about the final type of precursor molecule?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Amino acids."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So what do we get amino acids from?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Well, typically we get amino acids from food products."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So if we ingest protein, we break down the protein, and that's where we get those amino acids."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "But under starvation conditions, we can actually obtain the amino acids by breaking down our own proteins found in a skeletal muscle tissue."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And in that case, we actually deteriorate the skeletal muscle by breaking down the protein."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "But we can use those amino acids that we obtained by the breakdown to basically form glucose molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, certain amino acids are transformed into pyruvate, and so they enter gluconeogenesis as pyruvate molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Some of them can actually form DHAP molecules, and so they interguineogenesis as DHAP molecules and eventually produce the glucose that our cells actually need for energy for ATP creation."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, we still really haven't answered a very important but very simple question."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Why do our cells, why does our body actually need glucose?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Mugenesis why can't we depend solely on the food for our sugar source?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Well, that's because we can actually store a limited amount of sugar inside our body."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So to be more specific, in our fluid, so places like our blood plasma and the fluid found in the cell, so cytoplasm and fluid found in our tissue, in these areas, we can store a maximum of about 20 grams of glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, in our glycogen stores, we can basically store about 190 grams of usable sugar, sugar that can be readily used and can be readily accessible by those cells."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so together, 20 grams in the body fluid and 190 grams in glycogen, we essentially store about 210 grams of sugar."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, on a daily basis, an individual that, let's say, is not an athlete needs about 160 grams to actually survive."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And 75% of that is actually used by the brain cell."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So about 120 grams of the 160 grams is used by the brain."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "The rest is used by other areas of our body."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, of course, if you're an athlete, for example, if you're a swimmer and you swim, let's say a double practice, and that that adds up to, let's say, ten k, then obviously you need many more grams of sugar."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So those individuals need about 500, 600 grams of sugar."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so what we see is if gluconeogenesis did not actually take place inside our body, the individual would only be able to actually survive for a little longer than a day, because once the preserves of these sugars actually runs out, our cells have no way of creating new sugar molecules from these non sugar components."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And in that case, we essentially die."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So after a little over a day, we would run out of our glucose supply and our cells would not be able to actually continue functioning."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And if we don't ingest the food, we would essentially die."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So that's why glucoinogenesis is so crucial, so important, because it gives our body the ability to actually produce these sugar molecules needed by our cells to form ATP from non sugar molecules such as proteins."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So, amino acids, fats, the glycerol molecules, as well as the lactate and pyruvate molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So now let's take a look at gluco neogenesis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So I said earlier that gluconeogenesis is essentially the process by which we transform the pyruvate molecules into glucose."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And remember that glycolysis transforms glucose into Pyruvate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So at first it might seem like gluconeogenesis is simply the reverse of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, that's not actually true, and gluconeogenesis is not simply the reverse of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Why?"}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Well, because glycolysis is a very exergonic process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So remember in our discussion of glycolysis, we said that when 1 mol of glucose is broken down inside our body under physiological conditions, that releases about 96.2 kilojoules per mole of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so the breakdown of glycolysis as it is an extremely exercise process, it takes place spontaneously and irreversibly."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So what that means is if gluconeogenesis was simply the reverse of this process, then every time 1 mol of Pyruvate is transformed into 1 mol of glucose, that would require an input of 96.2 kilojoules of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so what that means is gluconeogenesis would be a very, very inefficient and expensive process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And so gluconeogenesis, for that reason, cannot be simply the reverse of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So once again, gluconeogenesis is essentially the conversion of Pyruvate into glucose, which is the opposite of what happens in the process of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "However, gluconeogenesis does not simply follow the reverse steps of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And this is because glycolysis is a very extragonic process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "It releases an amount that is equal to 96.2 kilojoules per mole of free energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So we know that in glycolysis, the overall step involves so we have glucose, two AGP, two Pi, so orthophosphates two NAD."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Plus we have ten steps that take place that essentially make this process an irreversible process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And we form two Pyruvate molecules, two ATP molecules, two NADH molecules, two H plus and two water molecules."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, we know that glycolysis takes place in ten steps and actually seven of these steps are not very exergonic."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In fact, in some cases the individual steps actually require an input of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And seven of these steps are actually at equilibrium or very close to being at equilibrium."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And what that means is when a reaction e is at equilibrium, the gift free energy is equal to zero or very close to zero."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "But three of these steps, step one, step three and step ten are very exergonic steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In fact, these are the three steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So step one, step three and step ten, that essentially make up the majority of the free energy that is released in the process of glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So remember, in step one we take glucose, use up an ATP molecule neproduct of Hexokinase."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "We transform that into glucose six phosphate and this releases 33.5 kilojoules of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Step three, which is the committed step that's catalyzed by phosphorinase."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In this step we transform fructose six phosphate into fructose 116 bisphosphate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And this is also an exergonic process that releases 22.2 kilojoules per kilojoules per mole of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And the final stop and the final step is also an exergonic process."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "This is catalyzed by Pyruvate kinase."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So we have Pep, which stands for phosphateenopyruvate."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In the presence of these two, we basically transform that into Pyruvate and ATP and this releases 16.7 kilojoules of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Now, if we sum these values up, so 33.5 plus 22.2 basically gives us 55.7 and then 55.7 plus 16.7 gives us 72.4."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So basically these three steps alone release 72.4 kilojoules of energy every time a single glucose molecule is broken down."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And that makes up the predominant amount of this total 96.2 kilojoules per mile."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So what that basically means is for gluco neogenesis to actually take place effectively, it must somehow be able to bypass these three steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In fact, that's exactly what happens as we'll see in a future lecture."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "Gluconeogenesis and glycolysis actually have seven steps in common, but three steps are not in common and it's these three steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And that's because glucaneogenesis, if it simply reversed these steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So for instance, if we look at step ten, if gluconeogenesis went from Pyruvate to Pet, by using this specific reaction pathway, it would need to use 16.7 kilojoules per mole of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And to prevent this from happening, to make this reaction, this step, an exergonic step, it uses a completely different pathway to transform Pyruvate into that phospholenyl Pyruvate molecule."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So once again in glycolysis, the three irreversible steps release the majority of the free energy in glycolysis."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And that means that for gluconeogenesis to be an effective process, to be a spontaneous process, it must actually somehow bypass these three extremely exergonic steps."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And that's exactly what happens."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "And essentially these three steps are the steps that are used to bypass these three steps here."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "So let's begin with step number ten."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In step number ten, if Gluconeogenesis simply follows the reverse of step ten and Glycolysis, we basically transform Pyruvate into pep."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "In the process, we'd use ATP P to form ADP and H, and this would require 16.7 kilojoules per mole of energy."}, {"title": "Introduction to Gluconeogenesis .txt", "text": "But what happens in Gluconeogenesis is a completely different reaction pathway is actually."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Glycocitic bonds are the bonds that exist between the individual monosaccharides in any given polysaccharide."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And of course, we can also have glycocitic bonds between sugars and proteins or between sugar and lipids."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, anytime we have a glycocity bond formed inside our body, that reaction is catalyzed by specific type of enzyme."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And the enzymes that catalyze the formation of glycocitic bonds are known as glycostal transferases."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, let's take a look at the reaction that is actually catalyzed by this type of enzyme."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So what exactly does the reaction actually look like?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So let's suppose we have a sugar and the sugar is basically shown in red."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And what we want to do is we want to attach another sugar, let's say a glucose molecule, onto that red sugar."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So this is the purple glucose that we want to attach onto that sugar molecule."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, before the glycosyl transferase can actually catalyze this reaction, what we have to do is we have to activate this incoming glucose molecule."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we have to activate it, we have to make it more reactive."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And the way that we make it more reactive is we add a nucleotide component onto this glucose."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, how exactly does that make it more reactive?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Well, by adding the nucleotide, we add these negative charges."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And anytime we add negative charges onto a system, we make that system more reactive."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Its energy increases and that makes it more reactive."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And so we basically activate the sugar by adding that nucleotide component."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And now we have an activated glucose nucleotide."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And now we can use the glycosal transferase to basically catalyze the formation of the glycocitic bond between this carbon of the incoming glucose and a carbon on that sugar molecule."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, in this particular case, because this is glucose, this molecule is known as urine and diphosphate glucose."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, once we form that bond, this is the bond that is formed, showed in green, that's the glycocitic bond."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And of course, instead of having the sugar here, we can also have a protein or we can have a lipid."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In either case, we form a glycocitic bond as a result of the action of glycostal transferases."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So glycosyl transferases use an activated sugar, usually a sugar nucleotide, such as in this case, Eurogene diphosphate glucose, to basically catalyze the formation of that glycosytic bond."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now, just like any other group of enzymes, glycosylatransphrases are highly specific molecules."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "They basically catalyze specific sugar reactions."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "They use specific sugars to form glycocitic bond."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So what exactly does that mean?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Well, to demonstrate what that means, let's take a look at the Abo blood type that exists inside our body."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So let's remember a bit of biology."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So any individual either has blood type O, blood type A, blood type B, or blood type AB."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So what exactly differentiates one blood type from another blood type?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So essentially, on the membranes of our red blood cells, there are specific antigens, more specifically specific glycoproteins that are expressed and it's the type of glycoprotein on the cell membrane of the red blood cell that determines your blood type group."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So let's take a look at the following three diagrams."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So this is the cell membrane of our red blood cells."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now in an individual who has the O type, they have the O antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "An individual who has the A type blood, they have the A antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In the individual who has the BType, they have the B antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And in the individual who has the AB, they have both A and B antigens."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now this is the protein component of the glycoprotein, the antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And notice the protein component is exactly the same in each one of these cases."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In fact, we also have these carbohydrates attached onto the protein component and that's what makes them glycoproteins."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And notice that all these three antigens have a common sequence in common."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So this sequence is also found here as well as here."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So what exactly is the sequence?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Well, these blue triangles are galactose sugars."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "This circle here is the anacetal glucose amine and this square here is the Foucaults."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we have this oligosaccharide sequence known as the oligosaccharide sequence that exists on the O antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And we also find that on the A antigen and the B antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So what exactly is the difference between these three antigens?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Well, it's basically the absence or presence of an additional sugar molecule."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In the case of the O antigen, this is all we have."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In the case of the A antigen we have an additional sugar that is linked via the alpha 13 linkage between the Galactose and this and acetyl galactose amine."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In the case of the B antigen we have this galactose linked via the alpha one three linkage to another galactose."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And that's what differentiates these three types of antigens."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we see that the antigens in the ABL system are all glycosylated glycoproteins."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And what that means is not only do we have the protein on the antigen, we also have this oligosaccharide as shown in this diagram."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now it turns out that the terminal sugar residues on the antigen determines the type of blood group as we discussed just a moment ago."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So if we have this type of linkage and this type of additional sugar, that's the A."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "If we have this one, that's the B."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "If we have neither, then it's the O."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we see that all three antigens have the oligosaccharide sequence in common."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Now what ultimately determines if an individual has one of these three types of antigens or if they have both of these antigens?"}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Well, basically it's the genetic information in the DNA."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "If the individual contains a gene that codes for a specific glycosal transferase that is able to actually form this bond, then they're going to have the A antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "If they have that specific gene that expresses the glycosal transferase that creates this bond, then they're going to have the B antigen."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "If they have both genes that basically create both of these glycosyl transferases that form both of these linkages then they're going to have both of these antigens and so they're going to have the blood group AB."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "On the other hand, if the gene is absent from that individual and the individual cannot synthesize either one of these Glycosyl transferases that can actually form these two types of linkages, then they're not going to be able to form the linkages and so they're going to have this molecule here, this glycoprotein."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "In that case they're the O blood type."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we see that a specific Glycoly transfer rates must be present in order to add an extra sugar to the galactose of the olymagride sequence."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "Oligosaccharide sequence, this for sugar sequence shown here."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So a type A Glycosyl transferase is needed to add to an acetyl galactose while a type B Glycosyl transferase is needed to add the galactose to that oligosaccharide."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "And blood type O individuals basically have genes that cannot express either one of these type A or type B Glycosal transferase in which case they cannot form these bonds and so they end up having this glycoprotein on the red blood cell membrane."}, {"title": "Glycosyltransferases and ABO Blood Groups .txt", "text": "So we see that glycosyl transferases are highly specific molecules and instead our body we have these specific Lycosal transferases that can catalyze the formation of specific bonds between specific types of sugar molecules."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "Agents basically reach the alveoli of our lungs."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And what these oxidizing agents can actually do is they can actually change or mutate the structure of alpha one antitrypsin."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "Now, if we examine the structure of alpha one antitrypsin, we're going to find a very important residue, namely methionine 358."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And it's the methionine 358, this side chain of methionine 358, that is responsible for actually interacting with the active side of elastics."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "Now, if these oxidizing agents, as a result of smoking, basically interact with this side chain group, they essentially will oxidize it to form the following product."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And this sulfonated product isn't able to actually interact with the active side of the elastase very well."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And so we see what smoking does is as a result of the presence of these oxidizing agents, it changes or mutates the structure of the alpha one antitrypsone."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "So that isn't able to bind to the active side of elastase very well."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And what that means is we'll have a higher concentration of elastase inside our lungs."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And a higher concentration of active elastase means that's going to destroy the tissue found in the alveoli of the lungs."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And by destroying the tissue that changes the elasticity of those alveoli and that will make it much more difficult to breathe, we're going to have to breathe harder to exchange the same volume of air."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "So we see that smoking brings oxidizing agents into the alveoli of the lungs."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "These agents can interact with the methionine 358 of alpha one antitrupsin and oxidize it."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And this will decrease the ability of the inhibitor to bind into the active site of the last days, because it's this methionine 358 that is responsible for actually interacting with that active side of elastase."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "Therefore, smoking leads to a higher concentration of active elastase in the alveoli of the lungs."}, {"title": "Inhibition of Digestive Enzymes .txt", "text": "And this can basically destroy the tissue in the lungs and that can increase, increase the likelihood of the person who smokes will develop the medical condition we call pulmonary emphysema or destructive lung disease."}, {"title": "Alcaptonuria .txt", "text": "Alkeptineuria is an autosom recessive disease in which there is a defect in one of the enzymes involved in the metabolic pathways of phenylalanine and tyrosine."}, {"title": "Alcaptonuria .txt", "text": "So normally within our liver, the cells break down phenolalanine into tyrosine, or they use fetal alanine to form tyrosine via this pathway."}, {"title": "Alcaptonuria .txt", "text": "So the enzyme that catalyze this step is phenyl Allenine hydroxylase."}, {"title": "Alcaptonuria .txt", "text": "It uses a cofactor tetrahydrobiopterin to basically form tyrosine."}, {"title": "Alcaptonuria .txt", "text": "And once we form tyrosine, it then reacts bidactivity of tyrosine immune transferase to form dehydroxy phenyl pyruvate this intermediate as then transform into homogeneousate bidactivity of the enzyme phydroxy phenomenon diruvate dioxygenase."}, {"title": "Alcaptonuria .txt", "text": "And then this molecule continues via these series of steps to ultimately form acetylacetate and fumarate."}, {"title": "Alcaptonuria .txt", "text": "Now, in our liver, this molecule can be used to form ketone bodies, while fumarrate can be used to form glucose."}, {"title": "Alcaptonuria .txt", "text": "And both ketone bodies and glucose molecules can be used by the cells of our body to generate high energy molecules."}, {"title": "Alcaptonuria .txt", "text": "Now, in a person who has al captainuria, they basically have genes that are defective."}, {"title": "Alcaptonuria .txt", "text": "So the genes that code for this enzyme humagentosate wants to dioxygenase, essentially code for a defective enzyme."}, {"title": "Alcaptonuria .txt", "text": "And so this enzyme's activity isn't high or the enzyme doesn't have any activity at all."}, {"title": "Alcaptonuria .txt", "text": "And so the homogeneous aid cannot be transformed into four male acetoacetate, and this will ultimately not be transformed into these two molecules."}, {"title": "Alcaptonuria .txt", "text": "And so because of that, we're going to see that homogenesate will accumulate in our cells, in our tissues, in our blood."}, {"title": "Alcaptonuria .txt", "text": "Ultimately, the kidneys will be able to excrete this via the urine."}, {"title": "Alcaptonuria .txt", "text": "And when the homogeneousate will be found in the urine and exposed to air, it will begin to polymerize."}, {"title": "Alcaptonuria .txt", "text": "And that polymer product will basically cause a color change of the urine."}, {"title": "Alcaptonuria .txt", "text": "So the urine will turn black."}, {"title": "Alcaptonuria .txt", "text": "And that's one clinical manifestation of individuals who have al captive nuria."}, {"title": "Alcaptonuria .txt", "text": "Now, luckily, this condition is relatively benign, and most individuals with this condition don't actually get diagnosed until later on in their lives."}, {"title": "Alcaptonuria .txt", "text": "So ultimately, what this can cause is problems with our joints, problems with our bone."}, {"title": "Alcaptonuria .txt", "text": "It can cause kidney stones."}, {"title": "Alcaptonuria .txt", "text": "It can also create problems with our heart valves."}, {"title": "Alcaptonuria .txt", "text": "So to summarize, al capia is an autosomal recessive disease in which we have a defective enzyme, namely homogeneous aid."}, {"title": "Alcaptonuria .txt", "text": "Once you dioxygenase and this enzyme is found in the pathway, in the metabolic pathway of phenylalanine and tyrosine."}, {"title": "Alcaptonuria .txt", "text": "So we essentially can break down these two amino acids into homogenesisate, but then homogenesisate will not be able to be broken down into these two intermediate needs here."}, {"title": "Alcaptonuria .txt", "text": "And so what that means is we're going to accumulate this molecule within our body that will begin to appear in our urine, causing a color change of the urine to black."}, {"title": "Alcaptonuria .txt", "text": "And ultimately, over time, that accumulation within our tissues can lead to heart valve problems, joint problems, as well as kidney stones."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, let's compare and contrast the primary and a secondary response of our immune system to some particular pathogen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So let's begin by defining and discussing what a primary response is."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So the first time that our body is ever invaded by some particular pathogen that carries its own antigen, our body, our immune system, responds in a certain way."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And this response we call the primary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So let's suppose our pathogen makes its way into our tissues and releases its pathogenic antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, at this particular moment in time, we have never actually seen our immune system has never actually seen this particular antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And what that means is we're going to have no corresponding antibodies in our body, in our blood, that can actually bind to that particular antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So at least in the beginning, our concentration of antibody that is specific for that antigen will be zero."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, right away when we're infected, the innate immune system kicks in and we can have the process of inflammation take place that essentially prevents that infection from spreading to other parts of our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But our adaptive immune system will actually take time to take into effect."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so we're going to have to wait a certain amount of time for our adaptive immune system to mobilize itself and to actually create the appropriate lymphocytes that are needed to create those antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So our adaptive immune system will need to create the appropriate plasma cells that can produce the antibodies that are specific to that infecting antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, once we have all those plasma cells, once we have all those active lymphocytes, then our antibodies will begin to be produced and those antibodies will be released into our blood."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so the concentration of the antibodies in our blood will begin to increase sharply."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So if we plot the concentration of antibodies that are produced versus time, we basically get the following diagram."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So the Y axis is the concentration of our antibodies, our immunoglobulins, and the X axis is the time given to us in weeks."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So at week zero, we essentially have that pathogen invading our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Infection takes place."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, it's the first time that we are ever infected by that particular pathogenic antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And that means, at least initially, during the latent period, we're going to have a zero concentration of antibody in our blood because we're not going to have those antibodies that can bind specifically to that infecting antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "However, over time, when the adaptive immune system actually is mobilized, it will have those plasma cells that will be able to produce those antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And at that moment in time, we have the logarithmic phase taken to effect."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And what the logarithmic phase describes is these plasma cells producing and releasing the antibodies into our blood."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so we see a sharp increase in our concentration of immunoglobulins."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But eventually, we have this leveling off process taking place, and then we have the decline phase."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And the decline phase takes place because our body is actually winning."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Our antibodies are binding to the antigens and they are labeling them for destruction."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so our immune system is able to destroy the infecting pathogens along with their antigens."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so that's why eventually, over time we see a drop in our concentration of immunoglobulbulins until it drops to very low undetectable levels as shown in the following diagram."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so this process ultimately takes place about four weeks as shown in this particular case for this particular invading pathogen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, the primary immunoglobulin that is used for this particular primary response and in general, the major type of antibody that is used for all primary responses is immunoglobulin M. So remember, we have five different classes of antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "We have five different types of antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And one of these antibodies is immunoglobulin M. And it's immunoglobulin M that is produced predominantly in the primary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, immunoglobulin M forms a pentamer and what that means is five individual antibodies orient in the following format to basically create this pentamer structure and they are held together by disulfide bonds."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So this is our primary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, what about a secondary response?"}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So let's suppose as soon as the primary response is over, our pathogen reinfects our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So the same type of pathogen with the same exact antigens reinfects our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, the type of response that our immune system will essentially elicit is called not a primary, but a secondary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "It's secondary because it's the second time our pathogen makes its way into our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, the response will be different."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "The question is why?"}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Well, because during the primary response not only was the adaptive immune system producing plasma cells but it was also producing memory cells."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And recall that memory cells are those white blood cells that actually store a copy of that antibody for that specific antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And the reason the memory b cells store that antibody is in case reinfection actually ever reoccurs actually ever takes place again."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So what happens when the body is reinfected by the same type of pathogen?"}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "In this case, the immune system will elicit a secondary response and it will be different than the primary response because of the presence of these memory B cells and memory T cells."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So let's redraw this diagram as shown."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So we have first infection taking place and then we have the end of our primary phase, our primary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And right when our primary response is over, we have the second reinfect, the second infection taking place."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So we are reinfected by that same exact pathogen that contains that same exact antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, because we have those memory B cells in our blood circulating our blood, our lymph and our tissue, we have that specific antibody that can actually bind and destroy that antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so what that means is the latent period will be much shorter because our adaptive immune system already consists of those memory B cells and memory T cells that contain that specific antibody."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so the latent period will be much shorter."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "On top of that, the concentration of the peak, the highest amount, the highest concentration of immunoglobulins that we produce will be much greater than in the primary case as a result of the presence of those memory cells."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And also notice what happens in this phase."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "In this case, we have a very sharp decline in the concentration and it drops to very low undetectable level."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But in this particular case, it doesn't drop to low value, it remains relatively high."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And that essentially ensures that all that pathogenic antigen is completely destroyed by the antibodies in our blood."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, in the case of the primary response, the major immunoglobulin was immunoglobulin M. But in the case of our secondary response, the major immunoglobulin is immunoglobulin G. So once again, following the first infection, the immune system will produce memory cells that will carry that copy of the antibody that is specific to that particular antigen."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And when the antigen reinfects our body the second time we're already going to have that antigen, that antibody circulating inside our blood."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And so that will create a much quicker, a much more rapid response with a shorter latent period because of those memory B cells."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "In addition, the amount of antibodies that is formed will be much greater."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And actually we're going to need a much lower concentration of antigen to elicit a secondary response than to elicit a primary response."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "That's another difference between the primary and the secondary responses."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So let's conclude by comparing and contrasting these two different types of responses."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So for the primary response we have a relatively long latent period."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But for the secondary response we have a relatively short latent period."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So that means our secondary response is much quicker to take into effect as a result of those antibodies already being present inside our blood."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, for the case of the primary, we form a relatively low concentration, peak concentration of antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But here we form a much larger peak concentration of antibodies."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "So peak simply means the highest value of these particular hills."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, notice that during our decline phase we dropped to very low undetectable value in the primary case."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But in the secondary case we dropped to a higher value."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And because we have a higher value of antibodies during our decline phase, the secondary immune response will be much more efficient in actually binding the antibodies onto our antigens and destroying those antigens."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "And finally, we see that in the primary response we use immunoglobulin M. But in the second response we use immunoglobulin gene."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "Now, the final difference is to initiate a primary response we need a relatively high amount of antigen in our body."}, {"title": "Primary vs. Secondary Immune Response .txt", "text": "But to elicit the secondary immune response we actually need a much lower concentration of antigen inside our blood."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, let's focus on active immunity and passive immunity and let's discuss a concept known as immunization."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, let's begin by discussing how the natural process of infection takes place and what our body does to fight off that infection."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So let's suppose we have a cut in our skin and the pathogen makes their way into our body."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "What happens is infection begins."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And as soon as infection begins, the innate immunity of our immune system kicks in and it begins the process of inflammation."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, what inflammation does is it ultimately aims to block off that infection to localize that infection to a specific location in our body and that prevents that infection, the pathogen, from actually spreading to other parts of our body."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, at the same time that inflammation is taking place the adaptive immunity of our immune system begins to mobilize."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "It begins to activate itself."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what happens is special wide blood cells of the adaptive immunity begin to form."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we have plasma cells and we have memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Plasma cells are those white blood cells that produce antibodies specific to that invading antigen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And these antibodies are released into our blood, our lymph, and our tissue."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And when the antibodies bind onto that antigen, they label that antigen for destruction by other wide blood cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And so that calls upon macrophages, natural killer cells, cytotoxic, T cells and many other different types of white blood cells to that area and that destroys that pathogen along with its antigen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, this is basically how our immune system defends and protects our body from these invading pathogens."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, following our infection, our body develops something called active immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what that means is our body develops these memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And these memory cells contain a copy of the antibody that is specific to that antigen that infected our body in the first place."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what that is useful for."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "If we are ever reinfected by that same pathogen that contains that same antigen, we have these memory b cells that can now initiate a very quick and a very rapid response."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And we actually won't feel the same exact effect that we felt the first time when we were infected by that pathogen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So the process of active immunity is a process in which our body develops immunity, these memory cells to the pathogen by being directly exposed to our antigens."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "For example, people who are exposed to chickenpox gain active immunity and will be very unlikely to ever feel that same effect they felt the first time when they were exposed."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, there are two processes by which we can gain active immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "What we just discussed a moment ago is a natural process."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So active immunity can be achieved either naturally through some type of exposure to that pathogen, for example, an infection, which is what we discussed earlier or we can actually induce active immunity artificially via process known as immunization."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And immunization involves injecting something called vaccines into our body so what exactly is a vaccine?"}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So, a vaccine is essentially this little test tube that contains some sort of pathogen inside that test tube."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, the pathogen has been altered in some way or form."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "It has been inoculated."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what that means is we change that pathogen in the laboratory and we change it in such a way to ensure that it does not damage the body as severely as it would normally when we are infected by that pathogen in a natural way."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, in both of these cases, in the natural case and in the artificial case we obtain the same exact result."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "We essentially either inject or somehow obtain these antigens."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Our immune system begins to develop antibodies as well as memory cells that contain a copy of that antibody in case we are ever reinfected."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And that's how we develop something called active immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So vaccines are normally developed in laboratories by many different methods that we're not going to focus on in this lecture."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Typically, the pathogen is inoculated which means that it is changed in some way or form as to ensure that not too much damage is actually taken by the body so that we don't feel the same exact bad effect that we would normally feel in the natural process of infection."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And in many cases, receiving a vaccine essentially creates no effects whatsoever no effects that we can actually visibly see or physically feel."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, to further prevent us from actually experiencing any form of discomfort during vaccination what medical researchers do is they essentially kill off that pathogen altogether and they only take a very small portion of an antigen of that pathogen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So they essentially cut that pathogen and use only the epitote, the antigenic determinant of that antigen because it's that part of the antigen that ultimately binds to the antibodies of our body."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And in this way, the body can still produce antibodies following vaccination and at the same time, it will create a very, very little effect that will actually hurt the body."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, everything we discussed so far is active immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And active immunity involves developing our memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And we said we can gain active immunity either artificially or either via natural means when infection actually takes place."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, let's discuss something called passive immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Passive immunity basically means we do not develop any memory B cells or memory T cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And that's because we actually inject antibodies directly into our blood, into our lymph or into our tissue."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And by injecting the antibodies we're not exposing the immune system to our antigens and so we're not giving our immune system the adaptive immunity of our immune system the chance to actually develop those antibodies themselves."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So another form of immunity is called passive immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "In passive immunity, antibodies are developed in the laboratory that are specific to some particular pathogen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And these antibodies, when they're injected into our body they begin to circulate in our blood system, in our lymph system and in our tissue."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And if we are exposed to that pathogen that carries that antigen that is complementary to the antibody that was injected into our body in the first place, those antibodies will bind onto those antigens."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "The artificial antibodies will bind onto the antigens and that will initiate a response in which it will label those antigens as well as the pathogen for destruction by our white blood cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, one very important point about passive immunity, once again, is it does not develop memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And so this means that eventually these antibodies will be degraded inside our body and they will cease to exist."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And at that point we will lose our immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And that's exactly why this is called passive immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "It only persists for several months following injection of those antibodies while active immunity usually persists for the duration of our lifetime."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we saw that active immunity can be acquired naturally or artificially."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And so far we discussed the artificial process by which we gained passive immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we actually synthesize those antibodies in a lab."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, it turns out that we also have a natural way to obtain passive immunity and this takes place in a woman when a woman is pregnant with a child."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So passive immunity can also be developed naturally."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Pregnant women give their developing fetus passive immunity by producing specific antibodies known as immunoglobulin g. And immunoglobulins g are small enough to actually pass across the placental membrane and into the blood found inside our fetus."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what that gives the fetus is passive immunity to any type of antigen or pathogen that might infect that fetus."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And this is important because as the fetus is developing his or her immune system is also developing."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So it's important that during this process of development our fetus has an ability to fight off an infection that infects that mother."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, another way we pass down or we create passive immunity naturally is via the process of breastfeeding."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So the milk that is found in women during the process of breastfeeding contains yet another type of immunoglobulin antibody known as immunoglobulin A."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And once our child gains the immunoglobulin A via the milk via the process of breastfeeding, that boosts their immune system because the child's immune system is still developing following childbirth."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So this is basically a diagram of flow chart that describes everything we just discussed."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "It summarizes our results, our discussion."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we have our immune system that is split into two categories."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So the innate immune system that begins to act immediately after infection it involves cells like macrophages, neutrophils and so forth."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And then we have our adaptive immunity that develops over some period of time because it has to synthesize the plasma cells, the memory cells, as well as other cells such as helper T cells and cytotoxic T cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, adaptive immunity can be split into two."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "We have artificial and we have natural and each one of these can be split into active and passive."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So basically, during the process of vaccination, during the process of immunization, when we take a vaccine and we inject it into that organism, into that individual, we inject an inoculated form of that pathogen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And what that does is it gives us active immunity by not having to have to experience the same exact detrimental effect that we would naturally experience if we are infected in a natural way."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, in this process, we gain memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "If we examine the natural process, we have to get the actual infection from that pathogen."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "We have to be infected by that pathogen to gain the same exact response to basically form those same memory cells that contain the antibody."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So both of these two are two methods of gaining active immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "One is via an artificial so immunization via a vaccine and the other one is a natural via the process of infection."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, what about the temporary process of passive immunity which basically injects in one way or form antibodies into our body and those antibodies can bind onto the pathogenic antigens, labeling them for destruction."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we also have artificial and natural."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, artificial includes actually taking those antibodies, injecting those antibodies into our body and allowing those antibodies to circulate our system."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "Now, the problem with this is it doesn't produce any memory cells."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And so after several months, we essentially lose any immunity that we initially had as a result of that passive immunity."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "And we also have the natural process of passive immunity as we discussed just a moment ago."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So antibodies transferred via the placenta when the woman is essentially pregnant or during the process of breastfeeding when the milk is transferred to that child along with those immunoglobulin, specifically immunoglobulin A."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "So we conclude that immunization is a very useful process of actually giving our body active immunity, the ability to fight off infections if we are ever actually infected with some particular viral or bacterial agent."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "For example, we have vaccinations for things like polio, botulism, tetanus."}, {"title": "Immunization, Active Immunity and Passive Immunity.txt", "text": "We also have vaccination for the whooping cough as well as many, many other lethal pathogenic infections and pathogenic agents."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "Can bind onto that enzyme regardless of whether or not the inhibitor is actually bound, and it binds with the same exact affinity."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "And that means the km value will not change."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "And if km doesn't change, then one divided by km certainly will not change."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "And so that's exactly why the x intercept is the same in this particular case."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "Now, why does the slope actually increase?"}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "Well, the slope is km divided by VMAX."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "If the km value doesn't change but the v max decreases, this ratio will increase."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "And if the slope increases, that means we're going to have a steeper curve, as we see in this particular case."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "So again, if we compare the no inhibitor and the inhibitor, we compare the two curves and we see this result, then that means we have a noncompetitive inhibitor present inside our mixture."}, {"title": "Lineweaver Burke Plot and REversible Inhibition Part II .txt", "text": "And so this is another very useful and very important application of how we can use the double reciprocal plot, also known as the line weaverburg curve, to basically differentiate between the three types of reversible inhibitors."}, {"title": "Mechanism of Transketolase .txt", "text": "The pentosphosphate pathway consists of two phases."}, {"title": "Mechanism of Transketolase .txt", "text": "We have the oxidative and the nonoxidative phase."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, previously, we focused on the nonoxidative phase and we saw that in the nonoxidative phase, we have two important enzymes that helped catalyze that particular reaction, that particular phase."}, {"title": "Mechanism of Transketolase .txt", "text": "And these two enzymes were transaldelase and transketelase."}, {"title": "Mechanism of Transketolase .txt", "text": "So in this lecture, I'd like to focus on the reaction mechanism of transheatalase."}, {"title": "Mechanism of Transketolase .txt", "text": "So transketilase is the enzyme that catalyze the transfer of the two carbon component from one sugar molecule onto another sugar molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "The question is, how does that reaction actually take place?"}, {"title": "Mechanism of Transketolase .txt", "text": "Well, that reaction occurs as a result of the presence of an important Cofactor molecule, a prosthetic group known as Thiamine Pyrophosphate or TPP."}, {"title": "Mechanism of Transketolase .txt", "text": "And what Thiamine Pyrophosphate actually does is it helps carry out this particular reaction."}, {"title": "Mechanism of Transketolase .txt", "text": "It acts as a nucleophile, as we'll see in just a moment."}, {"title": "Mechanism of Transketolase .txt", "text": "So let's begin with this diagram here."}, {"title": "Mechanism of Transketolase .txt", "text": "So this is the Thymine pyrophosphate, and it is actually attached onto the enzyme."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, what happens in step one is this transforms from a poor nuclear file to a good nuclear file."}, {"title": "Mechanism of Transketolase .txt", "text": "And what happens is we have an ionization reaction taking place in which this hydrogen ion basically departs and it leaves a full negative charge on this carbon."}, {"title": "Mechanism of Transketolase .txt", "text": "So we form a carbonate intermediate molecule, the Thiamine Pyrophosphate carbonate."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, as a result of the presence of the two electrons on this carbon atom, this becomes a good nuclear file."}, {"title": "Mechanism of Transketolase .txt", "text": "And that and now it acts as a strong nuclear file and attacks this electrophile."}, {"title": "Mechanism of Transketolase .txt", "text": "So this is one of the substrate molecules that we discussed in the previous lecture."}, {"title": "Mechanism of Transketolase .txt", "text": "So it's the ketosubstrate."}, {"title": "Mechanism of Transketolase .txt", "text": "In this particular case, we're using Zelulose phyphostate."}, {"title": "Mechanism of Transketolase .txt", "text": "So this carbon of the carbon equal groups acts as a lectrophile."}, {"title": "Mechanism of Transketolase .txt", "text": "This acts as a nucleophile."}, {"title": "Mechanism of Transketolase .txt", "text": "And essentially, we form a bond between this carbon of this Thizol ring."}, {"title": "Mechanism of Transketolase .txt", "text": "By the way, this is the thisol ring of the Thiamine Pyrophosphate."}, {"title": "Mechanism of Transketolase .txt", "text": "And so we form a bond between this carbon and this carbon at the same exact time."}, {"title": "Mechanism of Transketolase .txt", "text": "This H ion that basically left is now picked up by this oxygen."}, {"title": "Mechanism of Transketolase .txt", "text": "So as this bond is being formed, the Pi bond is being broken and a Sigma bond is being formed between this oxygen and this H atom."}, {"title": "Mechanism of Transketolase .txt", "text": "And we form a tetrahedral intermediate molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, this tetrahedral intermediate molecule is not very stable."}, {"title": "Mechanism of Transketolase .txt", "text": "And so what will happen is a rearrangement will take place."}, {"title": "Mechanism of Transketolase .txt", "text": "And in this rearrangement, the molecule that is basically kicked off is the first product of this reaction."}, {"title": "Mechanism of Transketolase .txt", "text": "In this particular case, because we used Zelulose phyphosphate, the product molecule is glyceroldehyde three phosphate."}, {"title": "Mechanism of Transketolase .txt", "text": "So this is the aldos product that we form in this reaction."}, {"title": "Mechanism of Transketolase .txt", "text": "So what happens is this Sigma bond is broken as a result of a Pi bond that is formed between this oxygen and this carbon."}, {"title": "Mechanism of Transketolase .txt", "text": "And so when this Sigma bond is broken, this H ion basically departs."}, {"title": "Mechanism of Transketolase .txt", "text": "We form this Pi bond and that breaks the sigma bond."}, {"title": "Mechanism of Transketolase .txt", "text": "But as the sigma bond is broken, a pi bond is being formed between this carbon and this carbon."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, as the pi bond is being broken, this pi bond breaks, and the two electrons in the pi bond end up on the nitrogen."}, {"title": "Mechanism of Transketolase .txt", "text": "And so the nitrogen in this Thiozol ring of the Thiamine pyrophosphate basically acts as an electron acceptor."}, {"title": "Mechanism of Transketolase .txt", "text": "It accepts those electrons, and it bears those two electrons in this intermediate molecule we call the activated glycoaldehyde."}, {"title": "Mechanism of Transketolase .txt", "text": "So we have the pi bond and the sigma bond between the carbon that came from this cellulose phyphosphate and this carbon here."}, {"title": "Mechanism of Transketolase .txt", "text": "Notice we kick off our one, two, three carbon molecule, the glyceroaldehyde three phosphate, and the remaining two carbon atoms remain on this activated glyceroaldehyde."}, {"title": "Mechanism of Transketolase .txt", "text": "Now, in the next step, we have the other substrate molecule basically coming in."}, {"title": "Mechanism of Transketolase .txt", "text": "So in this particular case, we're going to use ribose phyphosphate."}, {"title": "Mechanism of Transketolase .txt", "text": "So we have an Aldosubstrate molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "Remember, we have two substrate molecules and two product molecules that are formed."}, {"title": "Mechanism of Transketolase .txt", "text": "So this is one of the substrate molecules."}, {"title": "Mechanism of Transketolase .txt", "text": "This is the second substrate molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "And this pi bond here acts as a nucleophile, attacks the carbon, this electrophile, and that basically forms a sigma bond between this carbon here and this carbon here."}, {"title": "Mechanism of Transketolase .txt", "text": "And so this is basically what we have."}, {"title": "Mechanism of Transketolase .txt", "text": "Again, we have a tetrahedral intermediate."}, {"title": "Mechanism of Transketolase .txt", "text": "And so this tetrahedral intermediate is not very stable."}, {"title": "Mechanism of Transketolase .txt", "text": "And again, a rearrangement will take place so that we create more stable molecules."}, {"title": "Mechanism of Transketolase .txt", "text": "And so this sigma bond between this H atom and this oxygen is broken."}, {"title": "Mechanism of Transketolase .txt", "text": "At the same time, we form the pi bond between the oxygen and the carbon, and that breaks the sigma bond, and those two electrons once more end up on that carbon."}, {"title": "Mechanism of Transketolase .txt", "text": "So we form this Thiamine Pyrophosphate in the carbon anion form, and we also form that seven carbon second product molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "In this case, because we used the Xyulose phyphosphate and the ribose phyphosphate."}, {"title": "Mechanism of Transketolase .txt", "text": "This product is the cetohptylos seven phosphate molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "It's the ketos product."}, {"title": "Mechanism of Transketolase .txt", "text": "So in the final step, we want to reform this initial Thiamine Pyrophosphate in the protonated form."}, {"title": "Mechanism of Transketolase .txt", "text": "And so the H atom that was kicked off is basically picked up by this carbon atom to reform that protonated Thiamine pyrophosphate molecule."}, {"title": "Mechanism of Transketolase .txt", "text": "So we see that in this six step process, what ultimately happens is the transketulase uses that prosthetic group, the thymine pyrophosphate, to help transfer a two carbon group from the Xylose phyphosphate, the keto substrate, molecule two, that Aldo substrate, that ribose phyphosphate."}, {"title": "Mechanism of Transketolase .txt", "text": "In the process, we form two product molecules."}, {"title": "Mechanism of Transketolase .txt", "text": "We form the glycero aldehyde three phosphate, the Aldos product, and we form the seven carbon sugar molecules, cetohptulose seven phosphate, that keto's product."}, {"title": "Mechanism of Transketolase .txt", "text": "So we ultimately transfer that two carbon component from this section onto this section here to form these two product molecules."}, {"title": "Mechanism of Transketolase .txt", "text": "So this it's how this is the reaction mechanism of transketulase."}, {"title": "Mechanism of Transketolase .txt", "text": "And in the next lecture, we're going to discuss the reaction mechanism of the other enzyme used by the nonoxidative phase of the pentose phosphate pathway known as transaldalase."}, {"title": "Gamma Delta T-cells .txt", "text": "In our discussion on T lymphocytes we mentioned that there are two different types of T lymphocytes and we can categorize these two different types of T lymphocytes based on the type of membrane receptor that they actually have."}, {"title": "Gamma Delta T-cells .txt", "text": "So one type of T cell is the AlphaBeta T cell."}, {"title": "Gamma Delta T-cells .txt", "text": "And we call this an alphabeted T cell because it contains a T cell T cell receptor that has an alpha subunit and a beta subunit."}, {"title": "Gamma Delta T-cells .txt", "text": "Now, in our discussion on AlphaBeta T cells we said that AlphaBeta T cells can only bind to either the MHC class one or the MHC class two complex found on some antigen presenting cell of our immune system."}, {"title": "Gamma Delta T-cells .txt", "text": "So recall that antigen presenting cells are cells such as macrophages, dendritic cells and belymphocytes that engulf antigens and then present those antigens to the T lymphocytes by using their major histocompatibility protein complexes found on the membrane."}, {"title": "Gamma Delta T-cells .txt", "text": "And we have these two different classes of these major histocompatibility complexes."}, {"title": "Gamma Delta T-cells .txt", "text": "The class one are responsible for differentiating between infected cells and healthy cells."}, {"title": "Gamma Delta T-cells .txt", "text": "And class two is used for communicating between different types of white blood cells."}, {"title": "Gamma Delta T-cells .txt", "text": "So AlphaBeta T cells can only interact with these antigen presenting cells."}, {"title": "Gamma Delta T-cells .txt", "text": "Now, what about the other category of T cells known as the gamma delta T cells?"}, {"title": "Gamma Delta T-cells .txt", "text": "So the gamma delta T cells contain T cell receptors that are slightly different."}, {"title": "Gamma Delta T-cells .txt", "text": "Instead of having an alpha and a basic polypeptide submune we have a gamma and a delta polypeptide subune as shown in the following diagram."}, {"title": "Gamma Delta T-cells .txt", "text": "So the purple is our gamma and the blue is our delta."}, {"title": "Gamma Delta T-cells .txt", "text": "Now, we have a variable portion on our T cell receptor, the protein."}, {"title": "Gamma Delta T-cells .txt", "text": "And this basically varies from one cell to a different cell."}, {"title": "Gamma Delta T-cells .txt", "text": "And that's because this is the portion of the T cell receptor that contains that specific sequence of amino acids that can bind to some particular antigen."}, {"title": "Gamma Delta T-cells .txt", "text": "So it contains the antigen binding site."}, {"title": "Gamma Delta T-cells .txt", "text": "The constant region of our T cell receptor on the gamma delta T cell basically does not change too much when we go from one cell to a different cell."}, {"title": "Gamma Delta T-cells .txt", "text": "And this is the portion of our T cell receptor that actually binds onto the cell membrane of the gamma delta T cell."}, {"title": "Gamma Delta T-cells .txt", "text": "So we know that alpha beta T cells only bind to those antigens found on either the class one and class two major histocompatibility complex on these antigen presenting cells."}, {"title": "Gamma Delta T-cells .txt", "text": "But what about the gamma delta T cells?"}, {"title": "Gamma Delta T-cells .txt", "text": "What types of antigens can these gamma delta receptors actually bind to?"}, {"title": "Gamma Delta T-cells .txt", "text": "Well, it turns out that the gamma delta T cells don't actually need the MHC class one or MHC class two complexes to actually bind to our antigens."}, {"title": "Gamma Delta T-cells .txt", "text": "In fact, these gamma delta T cells can bind to fully intact antigens that have not yet been degraded by other wide blood cells."}, {"title": "Gamma Delta T-cells .txt", "text": "For example, the macrophages and the other antigen presenting cells."}, {"title": "Gamma Delta T-cells .txt", "text": "Recall that these antigen presenting cells degrade."}, {"title": "Gamma Delta T-cells .txt", "text": "They break down the antigens and only display a small portion of that antigen on that MHC complex."}, {"title": "Gamma Delta T-cells .txt", "text": "But these gamma delta T cells don't have to rely on that single portion of the antigen."}, {"title": "Gamma Delta T-cells .txt", "text": "They can actually fully bind to a fully intact antigen in the same way that free floating antibodies bind onto fully intact antigens."}, {"title": "Gamma Delta T-cells .txt", "text": "So gamma delta T cells can bind to any antigen that is not bound to the MHC class one and MHC class two molecules found on other white blood cells."}, {"title": "Gamma Delta T-cells .txt", "text": "And what that implies is they do not depend on antigen presenting cells to actually carry out some type of immune defense response."}, {"title": "Gamma Delta T-cells .txt", "text": "So we see that gamma delta T cells bind to antigens that alphabeted T cells cannot actually bind to."}, {"title": "Gamma Delta T-cells .txt", "text": "And what that means is our gamma delta T cells do not contain the CD four and CD eight glycoproteins that are needed to actually bind onto the major histocompatibility complex, class one or class two."}, {"title": "Gamma Delta T-cells .txt", "text": "Now, let's move on to the location where we normally find our gamma delta T cells."}, {"title": "Gamma Delta T-cells .txt", "text": "And then let's briefly discuss what the function of these gamma delta T cells is."}, {"title": "Gamma Delta T-cells .txt", "text": "So, in the same way that our AlphaBeta T cells are produced in the bone marrow and mature in the thymus, the gamma delta T cells are also produced in our bone marrow and differentiate in our thymus."}, {"title": "Gamma Delta T-cells .txt", "text": "But these gamma delta T cells actually end up in the tissue of our body that interfaces with the outside environment."}, {"title": "Gamma Delta T-cells .txt", "text": "And that implies that these gamma delta T cells are found in the epithelial cells, in the epithelial tissue of our body, for example, in our skin, in our lungs, in our intestines, as well as other regions of our body."}, {"title": "Gamma Delta T-cells .txt", "text": "Now, what about the function?"}, {"title": "Gamma Delta T-cells .txt", "text": "Well, because we don't know too much about these gamma delta T cells, we don't actually know what the exact function of these cells are."}, {"title": "Gamma Delta T-cells .txt", "text": "But we have a pretty good idea."}, {"title": "Gamma Delta T-cells .txt", "text": "Well, since these T cells do not actually bind onto the MHC class one or the MHC class two regions of these antigen presenting cells such as macrophages dendritic cells and B lymphocytes, that implies that gamma delta T cells do not actually depend on these antigen presenting cells to carry out their immune defensive response."}, {"title": "Gamma Delta T-cells .txt", "text": "So, although their function and mechanism of action is still not very well understood, they are believed to be part of the first line of defense and team to react faster at a quicker rate than our AlphaBeta T cells do."}, {"title": "Gamma Delta T-cells .txt", "text": "In fact, these gamma delta T cells are believed to be involved with immuno surveillance."}, {"title": "Gamma Delta T-cells .txt", "text": "And what that means is basically swimming around the epithelial tissue of our body and making sure that everything is working correctly and no pathogen is found inside those regions of the body."}, {"title": "Gamma Delta T-cells .txt", "text": "So we see that the antigens to which these gamma delta T cells actually bind to are not only found on the actual pathogen, for example, our bacterial cell, but they are also found on infected cells of our body."}, {"title": "Gamma Delta T-cells .txt", "text": "For example, if we have some type of epithelial cell that is infected, for example, this cell, what the infected cell does is it displays an antigen on the membrane of that cell."}, {"title": "Gamma Delta T-cells .txt", "text": "And our gamma delta T cell can use the gamma delta T cell receptor to bind onto that antigen."}, {"title": "Gamma Delta T-cells .txt", "text": "And once bound, it basically begins to release special chemicals we call cytokines."}, {"title": "Gamma Delta T-cells .txt", "text": "And what these cytokines are believed to do is they carry out the following several functions."}, {"title": "Gamma Delta T-cells .txt", "text": "First of all, they begin the process of repairing these cells."}, {"title": "Gamma Delta T-cells .txt", "text": "They continue the process of immunosurveillance."}, {"title": "Gamma Delta T-cells .txt", "text": "As we discussed previously, they seem to indirectly affect the cytolysis of local antigenic presenting cells."}, {"title": "Gamma Delta T-cells .txt", "text": "So why would we want to lyce, for example, a macrophage?"}, {"title": "Gamma Delta T-cells .txt", "text": "Well, if a macrophage eats too many of these pathogens it will essentially stop functioning correctly."}, {"title": "Gamma Delta T-cells .txt", "text": "And at that point we essentially want to lyse that particular cell."}, {"title": "Gamma Delta T-cells .txt", "text": "Now these cytokines and these gamma delta T cells are also believed to regulate the influx of white blood cells to that specific area."}, {"title": "Gamma Delta T-cells .txt", "text": "So if this epithelial cell is infected, we want to bring more white blood cells to this area."}, {"title": "Gamma Delta T-cells .txt", "text": "And that's exactly what the gamma delta T cell is believed to do."}, {"title": "Gamma Delta T-cells .txt", "text": "Once it binds onto that antigen portion of the membrane it initiates a response that essentially calls upon more white blood cells to this area so that the white blood cells can actually carry out an effective defensive response."}, {"title": "Introduction to Nervous System .txt", "text": "The human nervous system can be divided into two divisions."}, {"title": "Introduction to Nervous System .txt", "text": "We have the central nervous system or the CNS and the peripheral nervous system or the PNS."}, {"title": "Introduction to Nervous System .txt", "text": "Now, the central nervous system consists of the brain and the spinal cord."}, {"title": "Introduction to Nervous System .txt", "text": "And the only type of neurons found in the central nervous system are internal neurons."}, {"title": "Introduction to Nervous System .txt", "text": "Now, on the other hand, the peripheral nervous system consists of everything else, of everything outside of the brain and the spinal cord and it does not contain any interneurons."}, {"title": "Introduction to Nervous System .txt", "text": "The only type of neurons this system contains are motor neurons and sensory neurons."}, {"title": "Introduction to Nervous System .txt", "text": "And we'll see what those are in just a moment."}, {"title": "Introduction to Nervous System .txt", "text": "Now, we can subdivide the peripheral nervous system into the somatic nervous system and the autonomic nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "Now, within the autonomic nervous system we have special type of motor and sensory neurons known as pre ganglionic neurons and post ganglionic neurons."}, {"title": "Introduction to Nervous System .txt", "text": "Now, the autonomic system can be divided into the sympathetic and the parasympathetic system."}, {"title": "Introduction to Nervous System .txt", "text": "Now, in the next several lectures we're going to basically discuss the details and the functionality of each one of these systems individually."}, {"title": "Introduction to Nervous System .txt", "text": "In this lecture, we're going to focus on a terminology that we're going to need to know that we're going to come across in our discussion on the human nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So let's discuss and define what a motor neuron is what a sensory neuron is, what an inter neuron is."}, {"title": "Introduction to Nervous System .txt", "text": "Let's define what the nucleus and the ganglia is with respect to our nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "Let's discuss pre ganglionic and post ganglionic neurons and then let's focus on a simple reflex arc."}, {"title": "Introduction to Nervous System .txt", "text": "So let's begin with defining what a motor neuron is."}, {"title": "Introduction to Nervous System .txt", "text": "A motor neuron is basically a neuron that begins within the central nervous system and then extends into the peripheral nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "And it basically carries an electric signal to some type of target cell."}, {"title": "Introduction to Nervous System .txt", "text": "Usually the target could be an organ."}, {"title": "Introduction to Nervous System .txt", "text": "It could be a gland, it could be a muscle and so forth."}, {"title": "Introduction to Nervous System .txt", "text": "And because that target is usually known as an effector so the organ that our motor neuron is trying to send that signal to is known as our effector."}, {"title": "Introduction to Nervous System .txt", "text": "And that's exactly why sometimes the motor neurons are also known as efferent neurons."}, {"title": "Introduction to Nervous System .txt", "text": "So basically, these two terms are synonymous."}, {"title": "Introduction to Nervous System .txt", "text": "They are used interchangeably."}, {"title": "Introduction to Nervous System .txt", "text": "So we said that motor neurons basically exit our nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "Now, when they exit the spinal cord, motor neurons exit from the front side of the spinal cord and the front side is also known as the ventral side."}, {"title": "Introduction to Nervous System .txt", "text": "So if this is the cross sectional area of the spinal cord then this is the front side, it's the ventral side and this is where the motor neuron will leave."}, {"title": "Introduction to Nervous System .txt", "text": "So let's move on to the sensory neuron."}, {"title": "Introduction to Nervous System .txt", "text": "So what exactly is a sensory neuron?"}, {"title": "Introduction to Nervous System .txt", "text": "A sensory neuron is basically the neuron that begins at some receptor."}, {"title": "Introduction to Nervous System .txt", "text": "It receives a signal from the environment and then it sends that signal into the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So sensory neurons are neurons that receive electrical signals from receptors and carry those to other neurons or to the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "Now, sensory neurons are also known as aphary neurons."}, {"title": "Introduction to Nervous System .txt", "text": "So notice that we have an E here and we have an A here."}, {"title": "Introduction to Nervous System .txt", "text": "So a ferric neuron basically means it carries it away from that receptor."}, {"title": "Introduction to Nervous System .txt", "text": "So these types of neurons enter our spinal cord from the back side and that means from the dorsal side."}, {"title": "Introduction to Nervous System .txt", "text": "So dorsal means from the back of our spinal cord."}, {"title": "Introduction to Nervous System .txt", "text": "Now, what about interneurons?"}, {"title": "Introduction to Nervous System .txt", "text": "Well, intraneurons are basically simply those neurons that connect other neurons to one another."}, {"title": "Introduction to Nervous System .txt", "text": "For example, we can have an inter neuron that connects a sensory to a motor neuron as we'll see in just a moment in our example of the simple reflex arc."}, {"title": "Introduction to Nervous System .txt", "text": "Now let's define what a nucleus is with respect to the nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So the nucleus here doesn't actually refer to the individual nucleus inside the cell body of our neuronuron."}, {"title": "Introduction to Nervous System .txt", "text": "So the nucleus refers to a collection of many neurons of many cell bodies found within the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "On the other hand, if we are examining a collection or a group of cell bodies a group of neurons inside the peripheral nervous system this is known as a ganglia."}, {"title": "Introduction to Nervous System .txt", "text": "So ganglia are those cells inside our peripheral nervous system and nucleus refers to our groups of neurons inside the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "Now, what about the pre ganglionic neuron and the post ganglionic neurons?"}, {"title": "Introduction to Nervous System .txt", "text": "So these are the two types of neurons that exist within the autonomic nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So in the autonomic division of the peripheral nervous system the neurons that begin at the central nervous system the brain or the spinal cord and extend into the ganglia of our peripheral nervous system remember, the ganglia are simply the groups of cell bodies found inside the peripheral nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "These types of cells are known as pre ganglionic neurons."}, {"title": "Introduction to Nervous System .txt", "text": "So pre ganglionic neurons begin in the central nervous system and extend into the peripheral nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So this is basically a type of motor neuron."}, {"title": "Introduction to Nervous System .txt", "text": "Now, what about post ganglionic neurons?"}, {"title": "Introduction to Nervous System .txt", "text": "Well, post ganglionic neurons are simply those neurons that synapses that connect to our pre ganglionic neuron."}, {"title": "Introduction to Nervous System .txt", "text": "So the pre ganglionic neuron begins at the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "It extends into the peripheral nervous system and then it connects with the post ganglionic neuron."}, {"title": "Introduction to Nervous System .txt", "text": "And the post ganglionic neuron then carries that electric signal to some type of target organ or target cell known as our effector or effector organ."}, {"title": "Introduction to Nervous System .txt", "text": "So the post ganglionic neurons are the cells that synapse or connect with the pre ganglionic neurons coming from the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "And this takes place within the autonomic division of the peripheral nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So post ganglylionic cells carry those electric signals and extend to the effect their organ, whatever it might be."}, {"title": "Introduction to Nervous System .txt", "text": "It could be a muscle, it could be some type of organ, it could be a tissue and so forth."}, {"title": "Introduction to Nervous System .txt", "text": "So let's take a look at the following simple reflex arc."}, {"title": "Introduction to Nervous System .txt", "text": "And let's follow our electric signal as it begins on one part of the body and ascends somewhere else."}, {"title": "Introduction to Nervous System .txt", "text": "So let's suppose we take our finger and we pinch or we take a prick and we prick our finger and let's see what happens."}, {"title": "Introduction to Nervous System .txt", "text": "So on our finger, let's say we apply pressure."}, {"title": "Introduction to Nervous System .txt", "text": "We have specific types of receptors, pressure receptors that basically take that pressure and create and transform that pressure into an electrical signal."}, {"title": "Introduction to Nervous System .txt", "text": "And that electrical signal is picked up by the sensory neuron."}, {"title": "Introduction to Nervous System .txt", "text": "Remember, the sensory neuron is our neuron known as the African neuron that picks up the signal that comes from the environment by that receptor and sends it into the central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So this is our spinal cord."}, {"title": "Introduction to Nervous System .txt", "text": "Now, the spinal cord has a backside, the dolphin side."}, {"title": "Introduction to Nervous System .txt", "text": "It has a front side, the ventral side."}, {"title": "Introduction to Nervous System .txt", "text": "And remember, sensory neurons basically pick up that signal and enter our spinal cord from the backside so from the Doral society."}, {"title": "Introduction to Nervous System .txt", "text": "So the electric signal is carried through the axon and eventually ends up in this region."}, {"title": "Introduction to Nervous System .txt", "text": "So this inner region is our grain matter."}, {"title": "Introduction to Nervous System .txt", "text": "This outer region, shown here, is our white matter."}, {"title": "Introduction to Nervous System .txt", "text": "So the neurons here are myelinated."}, {"title": "Introduction to Nervous System .txt", "text": "The neurons inside the gray matter are not myelinated."}, {"title": "Introduction to Nervous System .txt", "text": "So we have our axon terminal."}, {"title": "Introduction to Nervous System .txt", "text": "It's found right here."}, {"title": "Introduction to Nervous System .txt", "text": "Now, this section here is an interneuron."}, {"title": "Introduction to Nervous System .txt", "text": "Remember, inside our central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "And the central nervous system is basically the spinal cord and the brain."}, {"title": "Introduction to Nervous System .txt", "text": "So inside the spinal cord, we only have individual interneurons."}, {"title": "Introduction to Nervous System .txt", "text": "And so we have this interneuron that connects our sensory to our motor neuron."}, {"title": "Introduction to Nervous System .txt", "text": "So once the electric signal is transmitted into the interneuron, it travels and eventually it synapses with the motor neuron."}, {"title": "Introduction to Nervous System .txt", "text": "Now, the motor neuron once again begins in a central nervous system."}, {"title": "Introduction to Nervous System .txt", "text": "So it begins in a spinal cord and it leaves the spinal cord from the front side, from the ventral side."}, {"title": "Introduction to Nervous System .txt", "text": "And that's exactly why it leaves from the ventral side in this diagram and travels and it carries that electric signal back to some effector organ."}, {"title": "Introduction to Nervous System .txt", "text": "So this is where the signal arrives and this is where the signal is received by that receptor."}, {"title": "Introduction to Nervous System .txt", "text": "So we have sensory neuron, we have the interneuron and we have this motor neuron."}, {"title": "Introduction to Nervous System .txt", "text": "So this is a simple reflex arc."}, {"title": "Introduction to Nervous System .txt", "text": "So in the next several lectures, we're going to discuss the individual functionality of each one of these systems in detail."}, {"title": "Protein Sequencing Example .txt", "text": "So previously we discussed protein sequencing."}, {"title": "Protein Sequencing Example .txt", "text": "So we said that if we want to sequence the amino acids in our protein, the first step is to break down that protein into smaller fragments."}, {"title": "Protein Sequencing Example .txt", "text": "Once we break it down to smaller fragments by using proteolytic enzymes, we can then isolate the fragments and take the individual small fragment and use admin degradation on that fragment fragment to basically determine what that sequence in that smaller fragment is."}, {"title": "Protein Sequencing Example .txt", "text": "Now, to actually order the different fragments together to find the correct order of the fragments, we have to use two or more different proteolytic enzymes to produce different sets of fragments."}, {"title": "Protein Sequencing Example .txt", "text": "And then we can use the overlapping regions of those fragments in the two different sets to basically determine what that sequence is."}, {"title": "Protein Sequencing Example .txt", "text": "Now, to see another example of what we mean, let's take a look at the following example."}, {"title": "Protein Sequencing Example .txt", "text": "So, suppose you purify protein, and that protein consists of seven amino acids."}, {"title": "Protein Sequencing Example .txt", "text": "Now, your goal is to basically find what the exact sequence of amino acids is in that given protein."}, {"title": "Protein Sequencing Example .txt", "text": "And what you do is you expose the protein to two different proteolytic agents, thereby producing two sets of different fragments."}, {"title": "Protein Sequencing Example .txt", "text": "So in experiment number one, you take your seven amino polypeptide, you expose it to trypsin."}, {"title": "Protein Sequencing Example .txt", "text": "And what trypsin does is it essentially cleaves at the carboxyl end of lysine and arginine."}, {"title": "Protein Sequencing Example .txt", "text": "And what you obtain is these three fragments."}, {"title": "Protein Sequencing Example .txt", "text": "Then you isolate these fragments and you conduct admin degradation on each one of these fragments and you find out that the first fragment is glycine tryptophan, arginine."}, {"title": "Protein Sequencing Example .txt", "text": "The second fragment is tyrosine, lysine, and the third fragment is aspartate and serene."}, {"title": "Protein Sequencing Example .txt", "text": "Now you take that same polypeptide and now you expose it to a different proteolytic enzyme, in this case, Chimetrypsin."}, {"title": "Protein Sequencing Example .txt", "text": "Now, Chimotrypsin cleaves our peptide at the carboxyl end of the bulky and aromatic amino acids."}, {"title": "Protein Sequencing Example .txt", "text": "For example, tyrosine, phenylalanine and tryptophan, as well as methionine and leucine."}, {"title": "Protein Sequencing Example .txt", "text": "Now you get three fragments as well."}, {"title": "Protein Sequencing Example .txt", "text": "And once again, you isolate the three fragments and you sequence the amino acids in those three fragments by using the ethnic degradation process."}, {"title": "Protein Sequencing Example .txt", "text": "And you find that fragment number one is lysine, aspartate, serene."}, {"title": "Protein Sequencing Example .txt", "text": "Fragment number two is glycine tryptophan, and fragment number three is arginine and tyrosine."}, {"title": "Protein Sequencing Example .txt", "text": "So now that you have these six different fragments, so you have two sets of fragments, you want to use the overlapping regions of the fragments to basically sequence these fragments in the correct order with respect to one another."}, {"title": "Protein Sequencing Example .txt", "text": "So let's begin on this fragment here."}, {"title": "Protein Sequencing Example .txt", "text": "So we have glycine, tryptophan, arginine."}, {"title": "Protein Sequencing Example .txt", "text": "We have tyrosine, lysine and aspartate and Cerin."}, {"title": "Protein Sequencing Example .txt", "text": "So we only have a single glycine amino acid in the entire sequence."}, {"title": "Protein Sequencing Example .txt", "text": "Now, if we look at the second experiment, where does our glycine appear?"}, {"title": "Protein Sequencing Example .txt", "text": "So the glycine appears in the second fragment appear."}, {"title": "Protein Sequencing Example .txt", "text": "So this glycine is the same glycine here because we're dealing with the same exact peptide."}, {"title": "Protein Sequencing Example .txt", "text": "Now, in this case, we have glycine tryptophan, arginine."}, {"title": "Protein Sequencing Example .txt", "text": "In this case, we only have glycine and tryptophan."}, {"title": "Protein Sequencing Example .txt", "text": "So from the sequence, this arginine is missing."}, {"title": "Protein Sequencing Example .txt", "text": "Now, where does the arginine appear in these other two fragments?"}, {"title": "Protein Sequencing Example .txt", "text": "So this is arginine, which is the same arginine as we have here."}, {"title": "Protein Sequencing Example .txt", "text": "Now, in this case, nothing is attached onto this arginine."}, {"title": "Protein Sequencing Example .txt", "text": "But in this case, we have tyrosine attached to this arginine."}, {"title": "Protein Sequencing Example .txt", "text": "So we know that the glycine tryptophan and then we have arginine."}, {"title": "Protein Sequencing Example .txt", "text": "So this must be attached here."}, {"title": "Protein Sequencing Example .txt", "text": "And because the tyrosine is attached to our arginine, we have glycine tryptophan, arginine, tyrosine."}, {"title": "Protein Sequencing Example .txt", "text": "Now, the next question is what do we put at the tyrosine?"}, {"title": "Protein Sequencing Example .txt", "text": "Well, let's go back to this diagram here, to this experiment number one."}, {"title": "Protein Sequencing Example .txt", "text": "So we have tyrosine appearing essentially right over here."}, {"title": "Protein Sequencing Example .txt", "text": "And tyrosine, based on experiment one, is attached to lysine."}, {"title": "Protein Sequencing Example .txt", "text": "And the only time that lysine appears in this section is right over here."}, {"title": "Protein Sequencing Example .txt", "text": "So we conclude that we have glycine tryptophan, then arginine entire scene and then lysine aspartate serene."}, {"title": "Protein Sequencing Example .txt", "text": "So once again, to see how all that works, let's take a look at the following section."}, {"title": "Protein Sequencing Example .txt", "text": "So it's actually right our result out."}, {"title": "Protein Sequencing Example .txt", "text": "So let's begin with this fragment here."}, {"title": "Protein Sequencing Example .txt", "text": "Let's begin with this one."}, {"title": "Protein Sequencing Example .txt", "text": "So we have glycine and tryptophan."}, {"title": "Protein Sequencing Example .txt", "text": "We have glycine and then we have tryptophan."}, {"title": "Protein Sequencing Example .txt", "text": "Now, to find out what comes next, we have to go to this experiment one."}, {"title": "Protein Sequencing Example .txt", "text": "So we have glycine tryptophan, and the only time we have glycine tryptophan here is in this fragment one glycine tryptophan."}, {"title": "Protein Sequencing Example .txt", "text": "Now, this third amino acid basically tells us which fragment must be connected to this one."}, {"title": "Protein Sequencing Example .txt", "text": "So we have arginine appears in this fragment and nowhere else."}, {"title": "Protein Sequencing Example .txt", "text": "And so that means the next fragment connected to this one is this fragment here."}, {"title": "Protein Sequencing Example .txt", "text": "So let's place arginine and tyrosine, the third fragment here."}, {"title": "Protein Sequencing Example .txt", "text": "And then we have arginine, tyrosine."}, {"title": "Protein Sequencing Example .txt", "text": "So we have arginine, and the only place where tyrosine appears is here."}, {"title": "Protein Sequencing Example .txt", "text": "So we have tyrosine should go here."}, {"title": "Protein Sequencing Example .txt", "text": "We have tyrosine lysine, and the only time we have tyrosine and lysine, or the only time we have lysine in this case is infragmate number one."}, {"title": "Protein Sequencing Example .txt", "text": "So we have lysine, then we have Aspartate and we have Cereine."}, {"title": "Protein Sequencing Example .txt", "text": "Now let's place these underneath this row."}, {"title": "Protein Sequencing Example .txt", "text": "So we essentially have our glycine tryptophan arginine, which basically appears here."}, {"title": "Protein Sequencing Example .txt", "text": "So we have glycine, we have tryptophan, and then we have arginine."}, {"title": "Protein Sequencing Example .txt", "text": "Then we have these two fragments."}, {"title": "Protein Sequencing Example .txt", "text": "So we have tyrosine lysine, and we have tyrosine lysine."}, {"title": "Protein Sequencing Example .txt", "text": "So let's put that here."}, {"title": "Protein Sequencing Example .txt", "text": "We have Tyrosine lysine, and the final fragment is Aspartate Serene, which are these two amino acids here."}, {"title": "Protein Sequencing Example .txt", "text": "So aspartate and serene."}, {"title": "Protein Sequencing Example .txt", "text": "Okay, so we can piece together these overlapping sections."}, {"title": "Protein Sequencing Example .txt", "text": "So let's use, let's say, the color green to basically describe the overlapping section."}, {"title": "Protein Sequencing Example .txt", "text": "So we have what do we have here?"}, {"title": "Protein Sequencing Example .txt", "text": "We have Arginine, which is right over here and we have tryptophan, which is right over here."}, {"title": "Protein Sequencing Example .txt", "text": "And so there should be a bond right over here."}, {"title": "Protein Sequencing Example .txt", "text": "And likewise, we have arginine antiracine right and Arginine, tyrosine."}, {"title": "Protein Sequencing Example .txt", "text": "So there should be a bond over here."}, {"title": "Protein Sequencing Example .txt", "text": "If we look on this side, we have Lysine Aspartate, and this is Lysine Aspartate."}, {"title": "Protein Sequencing Example .txt", "text": "So there should be a bond here, and tyrosine Lysine tells us that Tyrosine, Lysine, there should be a bond here."}, {"title": "Protein Sequencing Example .txt", "text": "So we can piece all this together to basically write down what the final amino acid sequence is, where is in my pocket."}, {"title": "Protein Sequencing Example .txt", "text": "Okay, so if we write down the final sequence, we get Glycine tryptophan, then we have a bond here because of these overlapping regions."}, {"title": "Protein Sequencing Example .txt", "text": "So we have Arginine, then we have Tyrosine, and then based on these overlapping regions here, we have Tyrosine and Lysine are connected, and so then we have Aspartate and Serene."}, {"title": "Protein Sequencing Example .txt", "text": "So we have 123-4567, which is our initial seven amino acid polypeptide chain."}, {"title": "Protein Sequencing Example .txt", "text": "So this is basically how you sequence the proteins, how you use these different types of proteolytic agents to produce different sets of fragments."}, {"title": "Protein Sequencing Example .txt", "text": "And then once you know the actual sequence of these fragments by using admin deradation, you can then basically piece the information together by using these overlapping regions of these different fragments."}, {"title": "Protein Sequencing Example .txt", "text": "And that's how you sequence proteins."}, {"title": "ABO Blood Types .txt", "text": "Now that we discussed how our immune system actually works, let's discuss the types of blood groups or blood types found in humans."}, {"title": "ABO Blood Types .txt", "text": "And then let's briefly discuss the process of blood transfusion."}, {"title": "ABO Blood Types .txt", "text": "Now, humans contain four different types of blood groups."}, {"title": "ABO Blood Types .txt", "text": "So we have blood type A, blood type B, blood type AB, or blood type."}, {"title": "ABO Blood Types .txt", "text": "First question is what exactly determines the difference between these different blood types?"}, {"title": "ABO Blood Types .txt", "text": "And more specifically, what determines the blood type of any given individual?"}, {"title": "ABO Blood Types .txt", "text": "Because any given individual can only have one of these four different types of blood groups."}, {"title": "ABO Blood Types .txt", "text": "Now, it turns out that on chromosome nine of our Carreotype, we basically have the allele the gene that codes for a special protein membrane that is found on red blood cells."}, {"title": "ABO Blood Types .txt", "text": "So each human inside our DNA, we have a gene that codes for this protein."}, {"title": "ABO Blood Types .txt", "text": "Now, before the protein is actually attached onto the membrane of red blood cells, it is modified in the Golgi apparatus and a carbohydrate attachment is made onto that protein to form a glycoprotein."}, {"title": "ABO Blood Types .txt", "text": "And this glycoprotein then is transferred onto the membrane of red blood cells."}, {"title": "ABO Blood Types .txt", "text": "And it's the terminal sugar on that glycoprotein that determines the type of blood group or blood type that our individual actually has."}, {"title": "ABO Blood Types .txt", "text": "So basically, let's take a look at the following diagram to see exactly what we mean."}, {"title": "ABO Blood Types .txt", "text": "So, we have the phospholipid bilayer of the red blood cell."}, {"title": "ABO Blood Types .txt", "text": "This is our cytoplasm portion, and this is the extracellular matrix."}, {"title": "ABO Blood Types .txt", "text": "So this is the protein component of the glycoprotein."}, {"title": "ABO Blood Types .txt", "text": "And these purple extensions are the sugar components."}, {"title": "ABO Blood Types .txt", "text": "And it's the terminal sugar of that glycoprotein that determines the type of blood type or blood group that our individual has."}, {"title": "ABO Blood Types .txt", "text": "Now, these glycoproteins are also sometimes known as self antigens or simply antigens, as we'll see in just a moment."}, {"title": "ABO Blood Types .txt", "text": "And we'll see why that's the case."}, {"title": "ABO Blood Types .txt", "text": "It has to do with our immune system."}, {"title": "ABO Blood Types .txt", "text": "Now, there are two different types of glycoprotein."}, {"title": "ABO Blood Types .txt", "text": "So there are two different types of antigens."}, {"title": "ABO Blood Types .txt", "text": "One of them we call antigen A or glycoprotein A, and the other one we call antigen B or glycoprotein B."}, {"title": "ABO Blood Types .txt", "text": "And it's the presence or absence of these glycoproteins that determines and differentiates these blood groups from one another."}, {"title": "ABO Blood Types .txt", "text": "For example, blood type A means our red blood cells contain antigen A and not antigen B."}, {"title": "ABO Blood Types .txt", "text": "Blood type B means our red blood cell membrane contains antigen B, but not antigen A."}, {"title": "ABO Blood Types .txt", "text": "Blood type A b means our red blood cells contain both antigen A and antigen B."}, {"title": "ABO Blood Types .txt", "text": "And finally, blood type O means we have neither antigen A or antigen B on the red blood cell of the membrane of our red blood cell."}, {"title": "ABO Blood Types .txt", "text": "Now, the next question is what exactly is the big deal?"}, {"title": "ABO Blood Types .txt", "text": "And what's the relationship between these groups and our immune system?"}, {"title": "ABO Blood Types .txt", "text": "Well, let's begin with blood type A."}, {"title": "ABO Blood Types .txt", "text": "So, in an individual that has blood type A, what that means is on chromosome nine of that individual, they have a gene that codes for antigen A."}, {"title": "ABO Blood Types .txt", "text": "And that means all the red blood cells will contain this particular glycoprotein antigen A."}, {"title": "ABO Blood Types .txt", "text": "Now the immune system, because these are self antigens, that means the immune system will not produce any antibodies against the antigen A glycoprotein."}, {"title": "ABO Blood Types .txt", "text": "But because the red blood cells of blood type A individual do not have antigen B proteins, what that means our immune system will begin producing antibodies against that particular antigen B."}, {"title": "ABO Blood Types .txt", "text": "And so if that individual with blood type A ever receives blood type B, for example, the red blood cells of the blood type B individual will be destroyed as a result of the presence of those antibodies against antigen B."}, {"title": "ABO Blood Types .txt", "text": "And we'll see exactly what that means in just a moment."}, {"title": "ABO Blood Types .txt", "text": "So this is our red blood cell of a person that has blood type A."}, {"title": "ABO Blood Types .txt", "text": "So blood type A individual contains red blood cells that contain a membrane protein we call antigen A."}, {"title": "ABO Blood Types .txt", "text": "And so that individual will not produce antigen, antigen A antibodies."}, {"title": "ABO Blood Types .txt", "text": "They will only produce antigen B antibodies because they do not have any antigen B proteins on the membrane."}, {"title": "ABO Blood Types .txt", "text": "On the other hand, let's focus on the blood type B."}, {"title": "ABO Blood Types .txt", "text": "So if an individual has blood type B, that means they have a gene that codes for antigen B."}, {"title": "ABO Blood Types .txt", "text": "And all the red blood cells will contain membrane bound antigen B glycoproteins as shown in green."}, {"title": "ABO Blood Types .txt", "text": "And so this will be the self antigen."}, {"title": "ABO Blood Types .txt", "text": "And what that means is our immune system will not produce any antibodies against this antigen B, but now will produce antibodies against antigen A because it doesn't have any antigen A on that protein."}, {"title": "ABO Blood Types .txt", "text": "So this is blood type A and this is blood type B."}, {"title": "ABO Blood Types .txt", "text": "Blood type A contains antigen A and antibodies against antigen B, while blood type B contains our membrane bound antigen B and so contains antibodies against antigen A."}, {"title": "ABO Blood Types .txt", "text": "Now the next question is how exactly do we pass down these blood groups from one individual to our offspring?"}, {"title": "ABO Blood Types .txt", "text": "So basically, each parent has the ability to donate a gene for that particular blood group that they actually have."}, {"title": "ABO Blood Types .txt", "text": "So let's suppose this is the male parent chromosome, this is the female parent chromosome and this is chromosome nine for each case because this is the alley, the gene section that codes for a particular type of blood group."}, {"title": "ABO Blood Types .txt", "text": "So this is the blood type alley."}, {"title": "ABO Blood Types .txt", "text": "Now as we mentioned earlier, the Abo blood group locus is located on the chromosome number nine."}, {"title": "ABO Blood Types .txt", "text": "And each allele is passed down from each one of the two parents."}, {"title": "ABO Blood Types .txt", "text": "Now as it turns out, the blood type is a codominant train, a codominant trait."}, {"title": "ABO Blood Types .txt", "text": "And what that basically means is if one parent gives an antigen A gene while the other parent gives an antigen B gene, they will both be expressed on that red blood cells membrane."}, {"title": "ABO Blood Types .txt", "text": "And what that means is if this is A and this is B, when they combine they will form the AB blood type group."}, {"title": "ABO Blood Types .txt", "text": "And what that means is the red blood cells will have both of these antigens attached onto the membrane of the red blood cell."}, {"title": "ABO Blood Types .txt", "text": "And this is what we call blood type AB."}, {"title": "ABO Blood Types .txt", "text": "And because in this individual the red blood cell membrane contains both of these antigen types, our immune system will not produce antibodies against both of these types."}, {"title": "ABO Blood Types .txt", "text": "And that's because the immune system will see antigen A and antigen B as self antigens."}, {"title": "ABO Blood Types .txt", "text": "So these individuals with blood type AB do not have antibodies for either antigen A or antigen B."}, {"title": "ABO Blood Types .txt", "text": "Now it is also possible that our individual doesn't have this gene on chromosome nine."}, {"title": "ABO Blood Types .txt", "text": "And that means if it doesn't have that gene it cannot actually express and produce any one of these antigens."}, {"title": "ABO Blood Types .txt", "text": "And in such a case if the male parent doesn't have that gene and the female parent doesn't have that gene and they essentially made, they will produce an offspring, an individual in which we basically have neither antigen A nor antigen B on the membrane of that red blood cell."}, {"title": "ABO Blood Types .txt", "text": "And in that case our immune system will produce both antibodies against antigen A and against antigen B."}, {"title": "ABO Blood Types .txt", "text": "And this is what we call a blood type O."}, {"title": "ABO Blood Types .txt", "text": "So such an individual lacks both antigens and their red blood cells on their red blood cells."}, {"title": "ABO Blood Types .txt", "text": "And so the immune system produces antibodies against antigen A as well as against antigen B."}, {"title": "ABO Blood Types .txt", "text": "So now that we discuss the four different types of blood types, blood groups, let's discuss the process of blood transfusion."}, {"title": "ABO Blood Types .txt", "text": "So it is actually possible to transfer blood from one individual to a different individual."}, {"title": "ABO Blood Types .txt", "text": "However, one must keep in mind that certain blood types cannot be mixed and that's because if they are mixed they will agglutinate."}, {"title": "ABO Blood Types .txt", "text": "And what that means is antibodies will combine with their complementary antigens and they will basically clump together and the blood will be rejected during that transfusion process."}, {"title": "ABO Blood Types .txt", "text": "So this is because people carry antibodies for antigens they don't have."}, {"title": "ABO Blood Types .txt", "text": "And so mixing red blood cells that have particular antigens with complementary antibodies will cause them to stick together causing the process of Agglutination."}, {"title": "ABO Blood Types .txt", "text": "So to see exactly what we mean, let's take a look at the following table which basically describes which blood types we can mix and which blood types we cannot mix."}, {"title": "ABO Blood Types .txt", "text": "So on this table, this row, the red row basically describes the blood of that individual that we are donating."}, {"title": "ABO Blood Types .txt", "text": "While this column, the blue column basically describes the blood of that individual that is receiving that donating blood."}, {"title": "ABO Blood Types .txt", "text": "So this is our receiver, it's the recipient and this is the person that is donating that blood."}, {"title": "ABO Blood Types .txt", "text": "Now yes means that by mixing these two blood types we basically do not have Agglutination taking place."}, {"title": "ABO Blood Types .txt", "text": "And so mixing is allowed."}, {"title": "ABO Blood Types .txt", "text": "But no means that we cannot mix these two blood types because Agglutination will take place, an antibody will bind to an antigen, clumping will take place."}, {"title": "ABO Blood Types .txt", "text": "And so our blood will be rejected."}, {"title": "ABO Blood Types .txt", "text": "So let's begin with A."}, {"title": "ABO Blood Types .txt", "text": "Let's suppose our individual that is receiving that blood has blood type A."}, {"title": "ABO Blood Types .txt", "text": "And what that means is it contains antigen A on the red blood cells and it produces antibodies against antigen B."}, {"title": "ABO Blood Types .txt", "text": "And so what that means is if a person, if the donating person has the same blood type A, then that means that person also has these red blood cells with the same type of antigen A."}, {"title": "ABO Blood Types .txt", "text": "And so when we mix these two bloods, they will readily mix and no Agglutination actually takes place."}, {"title": "ABO Blood Types .txt", "text": "Now what about if we mix if we donate blood from blood type B?"}, {"title": "ABO Blood Types .txt", "text": "Well, blood type B contains antigen B and forms antibodies against antigen A."}, {"title": "ABO Blood Types .txt", "text": "And by mixing our B and A, we basically have the process of Agglutination taking place."}, {"title": "ABO Blood Types .txt", "text": "The antibodies, antibodies against antigen B in the receiver will attack the red blood cells that basically come from this donating person that has blood type B."}, {"title": "ABO Blood Types .txt", "text": "Now."}, {"title": "ABO Blood Types .txt", "text": "What about AB?"}, {"title": "ABO Blood Types .txt", "text": "Well, AB is the same exact case on AB red blood cells."}, {"title": "ABO Blood Types .txt", "text": "We have both antigen A and antigen B."}, {"title": "ABO Blood Types .txt", "text": "And since this produces antigen B's, antibody B, the antibody B will bind onto a B red blood cells, destroying those red blood cells, forming this Agglutination process."}, {"title": "ABO Blood Types .txt", "text": "And so this and this is not allowed."}, {"title": "ABO Blood Types .txt", "text": "But if we take an O individual and we donate blood from the O individual to an A because the O individual doesn't have either antigen A or antigen B, what that means is the antibody against antigen B that this individual blood type A has will not be able to bind to the red blood cells of type O person."}, {"title": "ABO Blood Types .txt", "text": "And so this process of mixing will take place."}, {"title": "ABO Blood Types .txt", "text": "Now, notice one important point about blood type O."}, {"title": "ABO Blood Types .txt", "text": "If we examine this entire column, we have, yes, all the way down."}, {"title": "ABO Blood Types .txt", "text": "And what that means is this is the universal donor."}, {"title": "ABO Blood Types .txt", "text": "A person with blood type O can donate to any individual."}, {"title": "ABO Blood Types .txt", "text": "And that's because their red blood cells have neither antigen A nor antigen B."}, {"title": "ABO Blood Types .txt", "text": "And any antibody against A or B will not be able to bind to these red blood cells."}, {"title": "ABO Blood Types .txt", "text": "And so we can easily donate type O blood to either one of these four red blood types."}, {"title": "ABO Blood Types .txt", "text": "On the other hand, this O cannot actually receive any blood unless it's type O."}, {"title": "ABO Blood Types .txt", "text": "And that's because if, let's say our person has type O red blood cells, that means they produce both antibodies against antigen A and antigen B."}, {"title": "ABO Blood Types .txt", "text": "And by donating a B or AB to this person with blood type O, that means the blood type O person will have antibodies that will kill off all these different red blood cells, AB and AB."}, {"title": "ABO Blood Types .txt", "text": "And only this one, the blood type O donator, will not have the red blood cells with either of these antigens."}, {"title": "ABO Blood Types .txt", "text": "And so the antibodies will not affect that person."}, {"title": "ABO Blood Types .txt", "text": "So you can examine this table in more detail to basically convince yourself that this transfusion system actually works."}, {"title": "ABO Blood Types .txt", "text": "Now, the final thing I'd like to briefly talk about is the type of genotypes that form the different types of blood types."}, {"title": "ABO Blood Types .txt", "text": "So let's take a look at this table here."}, {"title": "ABO Blood Types .txt", "text": "So this column describes our blood types so AB and O."}, {"title": "ABO Blood Types .txt", "text": "And this describes the potential genotype that we must have to basically form these types of blood types."}, {"title": "ABO Blood Types .txt", "text": "So let's begin with blood type a."}, {"title": "ABO Blood Types .txt", "text": "So if our male parent has the A blood and if the female has the a blood, they will mix."}, {"title": "ABO Blood Types .txt", "text": "They will produce blood type A."}, {"title": "ABO Blood Types .txt", "text": "Now, if the male has, let's say, the blood type a, and the female lacks either one of those trace, either one of those codes, what that means is we'll have IA and lowercase IO."}, {"title": "ABO Blood Types .txt", "text": "And what that means is we'll still form form blood type a because the offspring will have the gene from the male parent that will create that protein antigen A."}, {"title": "ABO Blood Types .txt", "text": "Now, the same thing is true for blood type B, IB."}, {"title": "ABO Blood Types .txt", "text": "And IB forms blood type."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Insulin is a peptide hormone that is produced by specialized cells known as beta cells, found in the eyelids of Langerhons of Arabankreas."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, insulin is basically released when we have a high concentration of glucose inside our blood plasma."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And what insulin basically does is it decreases the concentration of glucose inside the blood plasma back to a normal value of about 100 milligrams per deciliter."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So that is the normal concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So what insulin does is it ultimately maintains and regulates a healthy concentration of glucose inside our blood plasma."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, what exactly is the mechanism by which our insulin actually controls our glucose?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Well, basically, under normal conditions, what the insulin does is because it's a peptide hormone, that means it binds onto the membrane of target cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So the receptor proteins for insulin are found on the plasma membrane of target cells, such as liver cells or muscle cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And once our insulin actually binds onto the membrane, it makes the membrane more permeable to glucose."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that means glucose can now travel from the blood plasma and into the cytoplasm of the cell."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And once inside the cell, the cell uses our glucose to basically store glucose in the form of glycogen."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So inside the cell, the glucose is transformed into glycogen, which is a polymer of glucose."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And by this mechanism, our insulin basically controls and decreases the amount of glucose found inside the blood plasma because more glucose travels into the cell."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And so the concentration of glucose inside the plasma, inside the blood decreases."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, in this lecture, we're going to focus on two important abnormalities with respect to glucose and insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So we're going to discuss hypoglycemia as well as hyperglycemia."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So let's begin by defining what hypoglycemia is."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So hypoglycemia is basically the abnormal concentration."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So abnormally low concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So hypo simply means a low amount of and glycemia refers to our glucose."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So hypoglycemia means a low concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, what exactly causes a low concentration of glucose inside our blood?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Well, one reason might be because of the overstimulation of the beta cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So if the beta cells of the pancreas are over stimulated, that means they will produce too much insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And if we have too much insulin inside our bloodstream, that means too much of the glucose will be transported into our cell, and that will lower the concentration of glucose below the normal."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And the concentration of glucose inside the blood that is characteristic of hypoglycemia is 70 milligrams per deciliter or below."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, another reason might be because we fast, we don't eat for a very long period of time."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So if we don't eat for a long time, the cells of our body will use up the majority of the glucose in our blood to produce ATP, to use it for energy, and that can lower the concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that will ultimately lead to hypoglycemia."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, hypoglycemia can be very dangerous because our brain, for example, uses glucose as the main energy source."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So if we don't have enough glucose inside our blood, that can basically damage our brain cells, because the brain cannot use glucose if there is no glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So let's move on to the second type of abnormality known as hyperglycemia."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So hyperglycemia is the opposite of hypoglycemia in the sense that hyper means we have a very high concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, how exactly does this actually come about?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "How do we obtain a high concentration of glucose inside our blood?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Well, let's imagine that our beta cells, for one reason or another, aren't able to produce enough insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that means we have a low amount of insulin inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And so if we don't have enough insulin, not too many of those glucose molecules will be transported into the cells from our blood plasma and that will basically create a hyperglycemia condition."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So the condition of a high concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, another reason might be because our insulin is unable to actually bind to the protein receptor."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And if the interaction between the insulin and the receptor isn't good, that means our glucose molecules cannot move into our cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And so that will basically create a high concentration of glucose inside our blood plasma."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So once again, hyperglycemia is an abnormally high concentration of glucose in our body, in our blood system."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "This can result due to the inability of the beta cells of the pancreas to actually produce an ample amount of insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Or it can also be due to the inability of the insulin to actually bind to the protein receptor on the target cell membrane."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "In fact, people that have a consistently high concentration of glucose inside their blood system, people that consistently experience this condition of hyperglycemia, are said to have diabetes mellitus."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So basically, diabetes comes in two forms, and this depends on the abnormality of the insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So we have type one diabetes and type two diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Type one diabetes is the less common diabetes, while type two is the much more common diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So in people with type one diabetes, what happens is their beta cells are destroyed for one reason or another."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And because the beta cells are destroyed, they lose the ability to produce insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So they produce very little or no insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that means that the glucose levels inside our blood will remain high, because if we have no insulin, none of the glucose are actually transported into our cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, these individuals must inject regular doses of medical insulin, insulin that is produced in the lab."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And what that basically does is it helps our body maintain a healthy and normal concentration of our glucose."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, of course, the person has to be careful and not inject too much insulin, because if too much insulin is injected, then that can lead to hypoglycemia."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, type one diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So people with type one diabetes basically depend on insulin that is manufactured in the lab."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that's exactly why type one diabetes is also known as insulin dependent diabetes, because these individuals depend on regular doses of insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, why would our beta cells actually be destroyed?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Well, one reason is because of an autoimmune disease."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So basically, in some individuals, and this is genetic in some individuals, our own immune cells, immune system cells, actually destroy our beta cells."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And this can lead to type one diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now let's move on to the more common diabetes, the type two diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So in people with type two diabetes, their insulin receptors on the target cell membrane have lost their ability to actually bind correctly and associate correctly with the insulin."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And this means that even though we have enough beta cells to actually produce enough insulin, and even though we have enough insulin inside our blood plasma, our insulin cannot actually properly bind the receptors."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And this basically means we cannot actually decrease the concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "We can actually transport the glucose back into our cells to convert them into glycogen."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So this means we'll have a high concentration of glucose inside our blood."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So this is the more common type of diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "It is a result of both genetics as well as environmental factors."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And by environmental factors, I basically mean the type of diet that you follow."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So if you're obese, so if you're overweight, or if you follow a diet that is very high in sugar, you have the chance of basically developing type two diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "This can lead to type two diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that's exactly why this form of diabetes is much more common than type one diabetes."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now let's move on to our kidneys."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So the question is, how exactly does diabetes, how exactly does hyperglycemia, the abnormally high concentration of glucose inside the blood, affect our kidneys?"}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Well, under normal conditions, when we have normal concentration of glucose inside the blood, what the kidney does is it basically absorbs all that glucose that is found inside our filtrate."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And that means none of the glucose will actually end up in our urine under normal conditions."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "However, in a person that has diabetes, in a person that has hyperglycemia, because we have such a high concentration of glucose inside our blood, the kidneys cannot actually absorb all that glucose."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And what happens is the glucose concentration in the filtered increases and the glucose concentration in the urine also increases."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So we'll find urine."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "We'll find glucose in our urine."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "Now, on top of that, what also happens is because we have such a high amount of glucose inside our filtrate, inside our urine, that means we have a high concentration of Solutes inside our urine, and that will increase the zmodic pressure in our filtrate in our urine."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And so less of that water will be absorbed by our bodies, and more of that water will be secreted in our urine."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "And this is known as polyurea."}, {"title": "Hypoglycemia and Hyperglycemia .txt", "text": "So polyurer is the condition by which these individuals with hyperglycemia secrete excess amounts, excess volumes of urine as a result of the presence of glucose, the extra solute in our filtrate, in our urine."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "If we examine the active side of chymatrypsin, we're going to discover a collection of three different residues, three different amino acids that add together, that work together to promote and catalyze the cleavage of peptide bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And this collection of three amino acids is known as the catalytic triad."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So it's the catalytic triad inside the active side of climaterepsin that is essentially catalyzes the cleavage of peptide bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, this catalytic triad consists of three different amino acids."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "One of these amino acids is Serene."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So serene."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "195 the second amino acid is histidine 57."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And the third amino acid is aspartate 102."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So let's begin by discussing the role that each one of these amino acids actually plays in promoting the hydrolysis of peptide bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Well, let's begin with serine 195."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "We know that Kyotrypsin is an example of a Serene protease."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so what that means is it's ultimately the serine residue inside the active side."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "It's this residue here that acts as a nucleophile and will attack the carbon of the carbonyl that peptide bond nucleophilically."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And we'll see exactly how that works out in just a moment."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, the problem with Serene in this form shown here, is the side chain of Serene is in its alcohol form."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And we know from organic chemistry that alcohols aren't very good nuclear files."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So the problem here is this alcohol is not a strong nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And in the form we have it now, it will not be good enough nuclear file to attack that peptide bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so what must happen is the histidine and the aspartate must work together to transform this serine into a strong nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So what we essentially want to do is transform the alcohol into its conjugate base, valcoxide."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Because remember, alcoxide molecules, alcoxide ions have a much better ability to actually act as nucleophiles because they have a better electron density around that oxygen atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So what happens is the negatively charged side chain of aspartate basically interacts with this partially positive hydrogen atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So if we examine so where is the color red."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So let's take red and blue."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So if we examine the charge value on this hydrogen, because the nitrogen is more electronegative than the hydrogen, what that means is this H atom will bear a partial positive charge."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so these two side chains will basically interact."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "As shown in this diagram, we have electromagnetic interaction between the oxygen and the H. And what this does is it basically positions this entire side chain of histidine, 157, in the correct orientation so that the next interaction can take place."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, what exactly is the next interaction?"}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Well, this nitrogen contains two electrons, a lone pair of electrons."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "On top of that, we can also say that the nitrogen has a partial positive charge, a partial negative charge, because nitrogen is more electronegative than the nearby carbons."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so we can say there is this partial negative charge that exists on this nitrogen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so it will interact with the H atom because this H atom of this alcohol of the Serine contains a partial positive charge because this oxygen contains a partial negative charge because of its high electronegativity value."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so Aspartate 102 basically interacts with Histazine 57 to move it and position it into the correct orientation so that the lone pair of electrons on the nitrogen can now interact and pull away this H atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, once the H atom is pulled away, that transforms that alcohol group into an alcoxide group."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And because the alkoxide is a much stronger nuclear file, this will now interact with the carbon of the carbonyl and essentially break that peptide bond as we'll see in just a moment."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So we see that the theory in 195 in its alcohol form is simply not a strong enough nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And to transform it into a better nuclear file, a nearby HistoGene 57 pulls away the hydrogen ion to form an alcoxide and to actually position the histidine so that these two residues can interact very well."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "This Aspartate uses its full positive charge to basically position and move this histidine side chain in the correct orientation."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And together this catalytic triad, as we'll see in just a moment, actually promotes the cleavage of the peptide bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So let's actually discuss what the reaction mechanism is."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So what are the details of the reaction mechanism that takes place inside the active side of climate?"}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Trypsin."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So let's begin in the following stage."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So we have the Aspartate 102 that positions this Histosine 57 so that these electrons can interact with the H atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so they begin to pull away the H atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And as the H atom is being pulled away, this is being transformed into nicoxide."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And the coxide is a strong enough nucleopoly."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "It contains a high enough electron density around the oxygen as to actually attack nucleophilically this carbon of this peptide bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so once the carbon is attacked, that displaces the pi bond and places those two electrons that were initially in the pi bond onto this oxygen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So the serine alcohol acts as a nucleotide and attacks the carbon of the carbonyl."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And what we ultimately form after step one is we form a tetrahedral intermediate."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So in this particular case, if we examine this bond here, we see that we have SP two hybridization."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And what that means is this is going to be a planar molecule and that gives this molecule stability."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "But as soon as this attack takes place, we form a tetrahedral intermediate."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And on top of that we're going to have a negative charge on this oxygen and this tetrahedral intermediate."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Because of that negative charge, and because this molecule is no longer planar, it's not going to be a stable."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So in step one, we formed a relatively unstable tetrahedral intermediate."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So we call it a tetrahedral because here we have one, two, three sigma bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And here the carbon has 1234 sigma bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, because of the instability of this intermediate, a special pocket, a special region on the Chimotryptin enzyme known as the oxyanion hole or oxyanine pocket, basically interacts with the negative charge on this oxygen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So inside the pocket we have these nitrogen atoms that contain H atoms."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And these partially positive H atoms can interact with the fully negative oxygen atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so what the oxygenine nine hole does is it stabilizes this tetrahedral intermediate."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, because of the instability of the tetrahedral intermediate, it's not going to exist for a very long time."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And what that means is it's going to very quickly collapse."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And when it collapses, what happens is the lone pair of electrons on the oxygen forms a pi bond with this carbon and that breaks off this relatively weak nitrogen bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so when this bond breaks off, the electrons on those bond on that bond basically move on and grab this H atom because by grabbing the H atom away from this histidine, this loses that positive charge and becomes more stable."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And that can be seen in this diagram here."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So after step two, after this tetrahedral intermediate collapses, that essentially oscillates this serine residue."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So this acyl group is now attached onto this oxygen and this amide has been formed."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And the amide takes away this H atom from the nitrogen found on this side chain of histidine 57."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so now we have this slight interaction between the nitrogen and the hydrogen and we still have the interaction between the oxygen and this hydrogen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So this oscillates the therine and forms an amide molecule that deprotonates the histidine nitrogen shown here."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And once we form this amide product, in the next step, the amide basically moves away."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And when the amide moves away, we basically make room in the active side for a water molecule to actually enter because remember, it's the water molecule that will ultimately also act as a nuclear phile to basically help hydrolyze that peptide bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So in the next step, once the amide product departs, we have the water molecule that comes into place."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so this water molecule, it basically positions itself into the same position that we had this amide in this step."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And once it positions into this location, the lone pair of electrons on the nitrogen of this side chain of the histidine basically interact with this age and they deprotonate that water molecule."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "Now, this is a very important step because just like serine contains the alcohol and the alcohol is not a strong enough nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So what happens is the H atom is removed to create alcoxide and transform into a good nucleophile."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "In this case, water is also not a strong enough nucleophile to actually attack the carbon of this double bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so what must take place is again, we see that the histidine actually takes away the H from this oxygen and that transforms the water into a hydroxyl."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And the hydroxide is a good enough nucleophile."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So remember from organic chemistry that hydroxide molecules contain a full negative charge on the oxygen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so that makes it a strong nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so this nitrogen takes away the H atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And these two electrons that were in the sigma bond now nucleophilically attack the carbon and this displays the pi bond in the same way that we displace the pi bond here."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And in the same way that we form this tetrahedral intermediate, we also form a tetrahedral intermediate in step five."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And once again, to stabilize that relatively unstable and negatively charged tetrahedral intermediate, we have this oxyanion hole that contains the partially positive charge H atoms that can stabilize this full negative charge."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so, because it's so unstable, it doesn't exist for a very long time."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And what happens is, again, the two electrons on the oxygen basically form a pi bond between the carbon and this oxygen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And now what happens is this bond here showed in green that we basically formed in this step is now broken."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And when this bond breaks, the two electrons that exist in that Sigma bond now basically move on to this H atom and take away that H atom."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And again, the reason we want to take away that H atom is because we want to remove this positive charge that exists on the ring of this Histidine 57 side chain."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so, in the next step, we basically reform that alcohol group found on the serine, we remove that H atom that was on the nitrogen."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So we reform the Histidine 57 side chain and we also form this final product, the carboxylic acid."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so now this is one of the products, this is the other product."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And together we see that the end result is the cleavage of that peptide bond."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So this bond between the nitrogen and the carbon was essentially cleaved in this step as described here."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so in the final step, this carboxylic acid product basically departs."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "It leaves the active side."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And once it leaves the active side, it basically prepares the active side for another cycle of hydrolysis."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So this is the reaction mechanism that actually takes place inside the active side of Chimotryptin."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And so the important point about this mechanism is inside the active side we have this catalytic triad, this collection of amino acids which basically work together to create a strong nuclear file."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And by creating a strong nuclear file, they essentially allowed the hydrolysis, the catalysis of the hydrolysis of peptide bonds."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "And notice that we create a strong nuclear file, not only in this case where we transform the alcohol into an alcoxide, but we also transform the water molecule, a poor nuclear file, into a hydroxide, into a much better nuclear file in step four."}, {"title": "Reaction Mechanism of Chymotrypsin.txt", "text": "So we see that in the reaction action mechanism, this catalytic triad basically acts twice to transform a poor nuclear file into a strong enough nuclear file to actually nucleophilically attack that peptide bond and ultimately break that peptide bond."}, {"title": "Mitochondria .txt", "text": "So let's continue our discussion on the different types of organelles found inside eukaryotic cells."}, {"title": "Mitochondria .txt", "text": "And let's focus on the endoplasmic reticulum and the Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "Now, right outside the nucleus of most eukaryotic cells, and we say most because some eukaryotic cells, such as red blood cells, do not contain the endoplasmic reticulum nor or do they contain the Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "Now, right outside the nucleus of most ekirotic cells is a network of membraneous faults known as the endoplasmic reticulum, or simply the Er."}, {"title": "Mitochondria .txt", "text": "Now, the membrane of the endoplasmic reticulum is a bilayer."}, {"title": "Mitochondria .txt", "text": "It's a phospholipid bilayer that separates the cytosol portion of our cell with the inside space of our Er."}, {"title": "Mitochondria .txt", "text": "Now, the space the fluid inside our endoplasmic reticulum is known as the Er lumen, or this is thermal space."}, {"title": "Mitochondria .txt", "text": "Now, the Er can basically be subdivided into two regions."}, {"title": "Mitochondria .txt", "text": "We have the smooth Er and we have the rough Er."}, {"title": "Mitochondria .txt", "text": "And let's begin by discussing what the rough Er is and what the functions of the rough Er are."}, {"title": "Mitochondria .txt", "text": "So the membraneous folds found closest to the nucleus of our cell contain ribosomes embedded on the cytosol side of our endoplasmic reticular membrane."}, {"title": "Mitochondria .txt", "text": "These ribosomes function to synthesize proteins that are ultimately either embedded into the cell membrane."}, {"title": "Mitochondria .txt", "text": "These proteins are known as integral proteins, or they are destined to leave our cell altogether."}, {"title": "Mitochondria .txt", "text": "Now, the membrane of the rough Er is actually physically connected to the membrane of the nucleus known as the nuclear membrane or the nuclear envelope."}, {"title": "Mitochondria .txt", "text": "And for this reason, we see that the perinuclear space, the space between the double layer of our nuclear envelope and the Er lumen, is actually physically connected as well."}, {"title": "Mitochondria .txt", "text": "And that makes sense, because inside our nucleus, in a region known as the nucleolus, we basically synthesize the ribosomal RNA subunits that are needed to create the ribosomes that end up in the rough endoplasmic reticulum."}, {"title": "Mitochondria .txt", "text": "Now, once the proteins in the rough endoplasmic reticulum are synthesized on the cytosol side, we basically take those synthesized proteins, we place them into the Er lumen, and then they travel through the rough Er lumen and eventually into the smooth Er lumen."}, {"title": "Mitochondria .txt", "text": "So now let's discuss the smooth endoplasmic reticulum."}, {"title": "Mitochondria .txt", "text": "Now, by the way, if this is our diagram of the eukaryotic cell, we have the nucleus, we have our rough endoplasmic reticulum that contains these folds."}, {"title": "Mitochondria .txt", "text": "We have slightly smoother, more tubular folds on the smoothie R, and this is our Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "So let's discuss the smoothie R, which is this section here."}, {"title": "Mitochondria .txt", "text": "Now, the smoothie R contains folds that are slightly more tubular than the folds on the rough Er."}, {"title": "Mitochondria .txt", "text": "And this can be seen from this picture here."}, {"title": "Mitochondria .txt", "text": "Now, unlike the rough Er, the smooth Er does not contain ribosomes embedded in the membrane."}, {"title": "Mitochondria .txt", "text": "And that's exactly why we call it the smooth Er."}, {"title": "Mitochondria .txt", "text": "Now, since it doesn't contain any ribosomes inside our membrane, that means the smooth Er is not directly involved in synthesizing our proteins."}, {"title": "Mitochondria .txt", "text": "However, it does contain some very important enzymes that are basically involved in creating glucose."}, {"title": "Mitochondria .txt", "text": "And this enzyme that I'm talking about is known as glucose six phosphatase."}, {"title": "Mitochondria .txt", "text": "So glucose six phosphatase is an enzyme that is important in the generation of glucose."}, {"title": "Mitochondria .txt", "text": "But perhaps the most important or one of the most important functions of the smooth endoplasmic reticulum is the synthesis of different types of lipids."}, {"title": "Mitochondria .txt", "text": "And this includes fatty acids."}, {"title": "Mitochondria .txt", "text": "It includes phospholipids."}, {"title": "Mitochondria .txt", "text": "It also includes cholesterol."}, {"title": "Mitochondria .txt", "text": "In fact, cholesterol can be transformed into the different types of steroids inside the smooth endoplasmic reticulum."}, {"title": "Mitochondria .txt", "text": "And finally, our smooth endoplasmic reticulum can also detoxify drugs."}, {"title": "Mitochondria .txt", "text": "It can undergo different types of oxidation reactions in which it detoxifies toxin and drugs such as, for example, alcohol."}, {"title": "Mitochondria .txt", "text": "So one might imagine that the cells in our liver contain very large smooth Er, and that's because in the liver, one of the main roles of our liver is to basically detoxify the different drugs and toxins that we ingest into our body."}, {"title": "Mitochondria .txt", "text": "Now, finally, let's move on to our Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "So what exactly is the Golgi apparatus?"}, {"title": "Mitochondria .txt", "text": "Where is it down?"}, {"title": "Mitochondria .txt", "text": "And what are some of its functions?"}, {"title": "Mitochondria .txt", "text": "So, the Golgi apparatus is a series of flattenmbraneous sacs known as cystiny."}, {"title": "Mitochondria .txt", "text": "So if this is a smoothie r, the Golgi apparatus is relatively close to our smoothie r. And notice it's also pretty large, so we can see it clearly under a microscope."}, {"title": "Mitochondria .txt", "text": "Now, once the proteins are synthesized on the cytosalt side of our rough Er, they are injected, they are forced into our Er lumen, and they travel through the Er lumen into our smoothie r. And from the smoothie r, they are basically ejected into the cytosol by using some type of secretory vesicle."}, {"title": "Mitochondria .txt", "text": "So secretory vesicles carry our proteins from our ruffy r and the smoothie r into the Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "And all the proteins basically collect inside our Golgi apparatus."}, {"title": "Mitochondria .txt", "text": "And what the Golgi apparatus does is it basically organizes, it modifies, and it ships out all those proteins into the different parts of the cell, as well as the cell membrane and outside the cell."}, {"title": "Mitochondria .txt", "text": "So basically, one thing that I forgot to mention about the ruff Er is the proteins synthesized in the ribosomes of the ruff Er are the proteins that eventually either end up in our cell membrane or they end up leaving the cell entirely."}, {"title": "Mitochondria .txt", "text": "And that means inside our ribosome, inside our ruff Er, when we synthesize the proteins, we also add a special type of signal known as the signal sequence, or the peptide sequence onto the protein."}, {"title": "Mitochondria .txt", "text": "And that sequence basically signifies the fact that the protein's destination is either in the cell membrane or it's outside the cell."}, {"title": "Mitochondria .txt", "text": "And when the protein ends up in our Golgi apparatus, that sequence is modified."}, {"title": "Mitochondria .txt", "text": "So, basically, we can modify proteins in the Golgi apparatus either by adding carbohydrates on it or modifying in some other type of way."}, {"title": "Mitochondria .txt", "text": "For example, we phosphorylate our proteins."}, {"title": "Mitochondria .txt", "text": "Now, inside the Golgi apparatus, we also form several types of polysaccharides."}, {"title": "Mitochondria .txt", "text": "So our Golgi apparatus contains many important enzymes that are involved in forming different types of polysaccharides of sugars."}, {"title": "Mitochondria .txt", "text": "And one other important function of the Golgi apparatus is to basically create lysosomes."}, {"title": "Mitochondria .txt", "text": "So what happens is certain proteins that end up staying in our cytosol will basically leave the Golgi apparatus in a vesicle, in a secretory vesicle, and that secretary vesicle becomes a lysosome."}, {"title": "Mitochondria .txt", "text": "Now, inside that lysosome, we contain the different types of modified proteins that are able to hydrolyze different types of products when they fuse with our lysosome."}, {"title": "Mitochondria .txt", "text": "So we see that the Golgi apparatus is the organelle where we basically organize, modify, and ship all the proteins throughout the cell, throughout the membrane and outside the cell."}, {"title": "Mitochondria .txt", "text": "It's the place where we form lymphosomes."}, {"title": "Mitochondria .txt", "text": "It's also a place where we form polysaccharides."}, {"title": "Mitochondria .txt", "text": "We modify our proteins in many different ways."}, {"title": "Mitochondria .txt", "text": "Now, the rough endoplasmic reticulum primarily functions to create our proteins that end up being placed either into the cell membrane or leave the cell entirely."}, {"title": "Mitochondria .txt", "text": "And our smooth Er has several important functions."}, {"title": "Mitochondria .txt", "text": "It basically acts to deepen detoxify drugs and toxin."}, {"title": "Mitochondria .txt", "text": "It acts to create or synthesize lipids, such as fatty acids, phospholipids, and cholesterol, as well as create different types of steroids."}, {"title": "Mitochondria .txt", "text": "And it also acts to basically create a source of glucose by using glucose Sticks phosphatase, our enzyme that creates glucose."}, {"title": "Prokaryotes .txt", "text": "The single most important difference between a prokaryote and a eukaryote is that a prokaryote does not have a nucleus."}, {"title": "Prokaryotes .txt", "text": "It does not have a membrane bound organelle that contains the genetic information that DNA, like the eukaryotic organism does."}, {"title": "Prokaryotes .txt", "text": "In fact, all prokaryotes lack any membrane bound organelle."}, {"title": "Prokaryotes .txt", "text": "And this includes organelles such as the mitochondria, the Golgi apparatus, the endoplasmic reticulum, and so forth."}, {"title": "Prokaryotes .txt", "text": "All these membrane banned organelles that are found in eukaryotes are not found in prokaryotes."}, {"title": "Prokaryotes .txt", "text": "So what exactly is the structure of a prokaryotic organism?"}, {"title": "Prokaryotes .txt", "text": "So, in this lecture, we're going to briefly discuss the general structure of the prokaryotic organism."}, {"title": "Prokaryotes .txt", "text": "We're going to examine some of the shapes of our prokaryotes, and then we'll briefly discuss the major differences between prokaryotes and eukaryotes."}, {"title": "Prokaryotes .txt", "text": "So, let's begin with the structure."}, {"title": "Prokaryotes .txt", "text": "Now, all prokaryotic organisms are enclosed in a cell wall."}, {"title": "Prokaryotes .txt", "text": "And the cell wall basically protects our cell, the organism, from the outside environment."}, {"title": "Prokaryotes .txt", "text": "We also have something called a cell membrane, which is basically responsible in cell transport."}, {"title": "Prokaryotes .txt", "text": "Now, within our prokaryotic cell, we have a region that contains our DNA, our genetic information, and this region is called the nucleoid, or the nucleoid region."}, {"title": "Prokaryotes .txt", "text": "Now, the nucleoid region is not the nucleus."}, {"title": "Prokaryotes .txt", "text": "The nucleoid region does not have a membrane like our nucleus does inside the eukaryotic cell."}, {"title": "Prokaryotes .txt", "text": "So usually inside a prokaryotic cell, we basically have a single double stranded circular DNA that is shown in brown."}, {"title": "Prokaryotes .txt", "text": "It basically contains our genes that code for the proteins that exist and function within our prokaryotic cell."}, {"title": "Prokaryotes .txt", "text": "Now, notice within this region, we not only have this large DNA, we also have a small DNA."}, {"title": "Prokaryotes .txt", "text": "And the small DNA is known as the plasma."}, {"title": "Prokaryotes .txt", "text": "And the plasma usually contains several types of important genes."}, {"title": "Prokaryotes .txt", "text": "And these genes are usually responsible for giving the prokaryotic organism resistance to drugs."}, {"title": "Prokaryotes .txt", "text": "Now, our plasmids replicate independently of our large DNA."}, {"title": "Prokaryotes .txt", "text": "In fact, our plasmids can replicate and then can pass down to other prokaryotic organisms."}, {"title": "Prokaryotes .txt", "text": "And other prokaryotic organisms that do not have resistant can gain resistance via this process."}, {"title": "Prokaryotes .txt", "text": "So basically, we have small hair like appendages labeled by five."}, {"title": "Prokaryotes .txt", "text": "So these appendages, which are known as Pyli and the Pyli, are responsible for connecting for bridging two or more organisms together to basically transfer that replicated plasmid structure."}, {"title": "Prokaryotes .txt", "text": "Now, prokaryotic organisms also contain structures called ribosomes, just like eukaryotes do."}, {"title": "Prokaryotes .txt", "text": "But the types of ribosomes, the structure itself is different in the two types of organisms, as we'll see in just a moment."}, {"title": "Prokaryotes .txt", "text": "The ribosomes is basically the location where we synthesize our proteins."}, {"title": "Prokaryotes .txt", "text": "Now, finally, we also have a structure known as the flagella or the flagella."}, {"title": "Prokaryotes .txt", "text": "And the flagella is basically the structure that allows our organism to move."}, {"title": "Prokaryotes .txt", "text": "Now, we're going to discuss this in a future lecture."}, {"title": "Prokaryotes .txt", "text": "But the flagella is different than the flagella that is found in eukaryotes."}, {"title": "Prokaryotes .txt", "text": "So the type of protein that our flagella is composed of inside prokaryotes is different than in eukaryotes."}, {"title": "Prokaryotes .txt", "text": "Now, prokaryotic organisms include two types of domains."}, {"title": "Prokaryotes .txt", "text": "We have bacteria and we also have archae."}, {"title": "Prokaryotes .txt", "text": "So basically, archae are single celled organisms that include those organisms that are capable of living in very harsh and hostile environments, such as very high temperatures, very high or very low PH, very high acidity, very salty, and so forth."}, {"title": "Prokaryotes .txt", "text": "So those organisms that can live in very hostile environments usually fall into domain known as rkey."}, {"title": "Prokaryotes .txt", "text": "And these are the organisms we call prokaryotes."}, {"title": "Prokaryotes .txt", "text": "So we have bacteria and we have these."}, {"title": "Prokaryotes .txt", "text": "Now, what exactly are the different types of shapes of our prokaryotic organism?"}, {"title": "Prokaryotes .txt", "text": "So there are three major shapes that prokaryotic organisms can basically have."}, {"title": "Prokaryotes .txt", "text": "So they can either be round, which is basically our Coxy."}, {"title": "Prokaryotes .txt", "text": "So coccy means we have a round shape."}, {"title": "Prokaryotes .txt", "text": "We can have our basili, which is basically this rod like shape, which is this organism we drew in this diagram here."}, {"title": "Prokaryotes .txt", "text": "And we can also have a spiral like shape, a helical shape, as shown, and this is known as the SPIROLA."}, {"title": "Prokaryotes .txt", "text": "So the spirilla, our bacilli and our Coxy."}, {"title": "Prokaryotes .txt", "text": "These are the different types of shapes that our prokaryotic organisms can take."}, {"title": "Prokaryotes .txt", "text": "Now, what exactly are the sum of the differences that we should know between prokaryotic organisms and our eukaryotic organisms?"}, {"title": "Prokaryotes .txt", "text": "So, as we discussed earlier, prokaryotes have two domains."}, {"title": "Prokaryotes .txt", "text": "We have bacteria and archae."}, {"title": "Prokaryotes .txt", "text": "Eukaryotes are animals, plants, protests and fungi."}, {"title": "Prokaryotes .txt", "text": "Now, prokaryotes do not have a nucleus."}, {"title": "Prokaryotes .txt", "text": "In fact, they do not have any membrane bound organelle whatsoever."}, {"title": "Prokaryotes .txt", "text": "However, eukaryotes do have a nucleus, and they do contain membrane bound organelles, such as the mitochondria or the endoplasmic reticulum."}, {"title": "Prokaryotes .txt", "text": "Now, prokaryotes are mostly unicellular, but some multicellular prokaryotes do in fact exist, while eukaryotes come in both types, we have unicellular and multicellular eukaryotes, as we'll see in a future lecture."}, {"title": "Prokaryotes .txt", "text": "Now, all prokaryotes have cell walls, but not all eukaryotes have cell walls."}, {"title": "Prokaryotes .txt", "text": "For example, plants do have cell walls, but we humans do not have any cell walls."}, {"title": "Prokaryotes .txt", "text": "Animals do not have cell walls around our cell."}, {"title": "Prokaryotes .txt", "text": "Now, what are the different types of ribosomes that exist between prokaryotes and eukaryotes?"}, {"title": "Prokaryotes .txt", "text": "So, earlier I mentioned that although prokaryotic organisms do in fact have ribosomes that synthesize proteins, the type of units that the ribosomes consist of are different in prokaryotic organisms and eukaryotic organisms."}, {"title": "Prokaryotes .txt", "text": "So within prokaryotes, we have the subunits, while in the eukaryotic organisms, we have the subunits that compose our ribosomes."}, {"title": "Prokaryotes .txt", "text": "And finally, our plasmids are very common within prokaryotic organisms."}, {"title": "Prokaryotes .txt", "text": "But although plasmids do exist within eukaryotic organisms, they are actually very rare."}, {"title": "Prokaryotes .txt", "text": "So these are some of the differences, the major differences that exist within our prokaryotes and eukaryotes."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So suppose we have a prokaryotic gene and we want to basically obtain many copies of the proteins that are encoded by that specific prokaryotic gene."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Well, recombinant DNA technology allows us to basically carry out this process."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And what it tells us, Yale, is all we have to do is take that prokaryotic gene, place it into the appropriate vector, then introduce that vector into a bacterial cell."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And the bacterial cell will essentially use its ribosomes, its cell machinery to synthesize the proteins that are encoded by that particular gene."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And then we can extract and collect and study those proteins from that bacterial cell."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, what's one application of this method?"}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Well, instead of using prokaryotic genes, we can also use eukaryotic genes."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And this is especially important in a field of medicine where in medicine we're able to use this procedure to basically synthesize any protein, any enzyme that we want to."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And that's exactly what allows patients with, let's say, diabetes to essentially survive for a very long time because they now have a way to obtain these proteins which are synthesized in the lab via this procedure."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, the major problem with this procedure or the initial problem that we had to solve when we were first developing this process was the following."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Remember, eukaryotic mRNA molecules and prokaryotic mRNA molecules aren't the same in eukaryotic cells."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "The initial eukaryotic mRNA molecule that is synthesized contains introns and exons."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so before that mRNA molecule is used, those introns have to be removed and the exons have to be spliced together."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And the prokaryotic cell simply doesn't have the cell machinery to actually carry out that process because prokaryotic mRNA always only contains the exons, never the introns."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So the complication with using eukaryotic DNA in prokaryotic cells is that these prokaryotic cells, bacterial cells, do not have the proper cell machinery to modify the pre mRNA produced from eukaryotic genes."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "For instance, eukaryotic mRNA contains exxons that must be spliced out and that prokaryotic cell cannot carry out the splicing process."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So how can we solve this problem?"}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "How did we solve the problem?"}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Well, we solved this problem by essentially using an enzyme found in retroviruses known as reverse transcriptase."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And what this enzyme does is it basically reverse transcribes."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "It forms a complementary DNA molecule from an mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So basically the way that we solve the problem is we take the eukaryotic cell that produces the proteins that we essentially want to extract and we extract the fully modified mRNA molecule that contains the polyatail, the five prime cap, and only the exxons, not the introns."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so this is that molecule shown on the board."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And now we expose it to reverse transcriptase which will basically form a DNA molecule that is complementary to this mRNA."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And we call this a complementary DNA molecule or simply CDA."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And then we form the second strand of that DNA molecule to form a double helix and we introduce this into an appropriate vector."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So either a plasmid or a lambda phage."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And now we take that and bring it into our bacterial cell."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And notice when the bacterial cell reads this gene, the gene shown in red, it will produce the mRNA molecule that is already fully modified that only contains those exons and not the introns."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so now, because it doesn't have to worry about removing the introns and slicing together the exons and it doesn't have to worry about the polyatail or the five prime cap, it can easily synthesize that protein that we wanted to basically produce."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And in this method we can produce any type of protein, an enzyme found inside our body."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And that's why it is a very, very important procedure in the field of medicine."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now the question is how exactly one of the steps involved in producing the complementary double stranded DNA molecule that is complementary to this modified mature mRNA."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Well, let's take a look at the following seven steps that basically describes how we can produce this double stranded complementary DNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So we basically take our eukaryotic cell and we extract that modified mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so this blue molecule is that modified mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "It contains the five prime cap and the polyatail on the three prime N and it only contains the exons, it does not contain the introns."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, before we can actually add reverse transcriptase into the mixture, we have to create a DNA primer and we have to attach that DNA primer onto the three prime end of that mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, because all mRNA molecules in eukaryotic cells are modified with a polyatail, what that means is it's pretty easy to produce that DNA primer that is complementary to the polyatail."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Because all we have to do is create a polyceetail."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Because we know if we have the A's on this side, they will base pair with the T's on the other side."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So we basically create a DNA primer complementary to the three end of the modified mRNA molecule and recall that all eukaryotic mRNA have a polyatail on the three prime ends."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So we simply create a DNA primer with the polyt sequence and now we mix the primer with our mRNA molecule in a solution at the right temperature and the kneeling process will take place and the DNA primer will hybridize with this polyatail on the three prime end of that mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now in the next step, in step two we want to add that reverse transcriptase."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "That reverse transcriptase will bind onto that primer and in the presence of, of the four types of deoxy nucleus cytrifosphates, it will begin to synthesize that complementary strain, the DNA strand that is complementary to that mRNA."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so Ian diagram two, the red strand is that complementary DNA molecule while the blue strand is that mRNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "So in step two we basically have this hybrid complex form where one strand is the DNA and the other strand is the RNA."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so in the next step, in step three, we want to reassociate or we want to dissociate."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "We want to break apart these two molecules because ultimately we only want the red molecule and not the blue molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, recall in our discussion of nucleic acids we said that DNA molecules are more stable than RNA molecules."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "In fact, if we increase the PH, if we make our solution very basic DNA molecules will remain intact but RNA molecules will be destroyed, will be hydrolyzed."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so if we take the DNA RNA complex and we increase the PH so we create a basic solution."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "The RNA will be hydrolyzed while the DNA will remain intact."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so after step three, we essentially isolate that individual strand of complementary DNA shown in red."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now the next step is to basically form that other strand, the complementary strand to this cDNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And before we actually add the DNA polymerase so that it can synthesize the complementary strand, we have to once again create a primer."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "The problem is we don't know what this sequence here is."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so what we do is we use a special enzyme that adds a specific sequence of nucleotides onto the three prime end that we know."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so we add an enzyme called terminal transferase."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And this catalyzes the addition of specific types of nucleotides."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so let's suppose we want to add a bunch of deoxyguanosine triphosphates so Dgtps."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so after step four, we essentially add a polygtail to the three prime of this complementary DNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And now we know exactly what the sequence on the three prime end here is."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so just like in diagram one, where we knew exactly what the sequence was and so we knew what type of sequence to build on that DNA primer."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now we also know what sequence that DNA primer should have."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "If this is a polygtail, we have to build a polyceetail."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so in step five, we build a polyceed DNA primer."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "We add it into our mixture and at the right temperature, these two will anneal."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "They will hybridize."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now, one important point that I did not mention in this part is this last t here contains an open hydroxyl group."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And that open hydroxyl group is needed to actually synthesize the phosphodiasta bonds."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so now that we have this hydroxyl group, that transcriptase in this case can begin to synthesize those nucleotides and for the same exact reason."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Now that we have the hydroxyl group on this side attached to this C, now if we add the DNA polymerase in step six, it can begin the synthesis and elongation and the replication of this complementary DNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And after step six, we have the double stranded C DNA molecule that we spoke about in this step."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And this cDNA molecule, double stranded cDNA molecule can now be modified by attaching Cohesive ends, sticky ends to both sides of that DNA molecule."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And once we attach the sticky ends, we can place it into the appropriate vector, either a plasmid, or we can stick it into a lambda phage."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And then we can expose the lambda phage to bacterial cells."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "Those bacterial cells will take up those double stranded cDNA molecules, and they can use them to basically transcribe."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "The modified mRNA molecule that has the polyatail, contains the five prime end and also contains only the exons, not the introns."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And in this manner, our bacterial cell can synthesize any protein that we desire."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so once the proteins are synthesized, we can extract those proteins by protein purification methods."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And we now have a bunch of proteins that we can use for many different types of applications."}, {"title": "Synthesizing cDNA with Reverse Transcriptase .txt", "text": "And so that's exactly why this is a very important method, because it can be used in the field of medicine to basically save people's lives."}, {"title": "Malate Aspartate Shuttle .txt", "text": "The skeleton muscle cells of our body use a process we call glycerol three phosphate shuttle to actually move the NADH molecules produced in the glycolytic pathway from the cytoplasm and into the electron transport chain of the inner membrane of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, other cells of our body, such as cardiac muscle cells and liver cells, use a slightly different shuttle process."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so in this lecture, I'd like to focus on a shuttle known as the malade aspartate shuttle."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And the shuttle is used by cardiac muscle cells and liver cells to actually move the NADH molecules produced in the glycolytic pathway into the matrix of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So let's begin by examining the following diagram."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So, in this diagram, we have the inner membrane of the mitochondria and we have the matrix side of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So this is essentially the cytoplasmic side."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, in step one, we basically want to transform the NADH molecule that is produced in a glycolytic pathway into NAD plus."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And in this process, we ultimately extract those two high energy electrons and we place them onto oxyloacetate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "In the process, we actually reduce oxyloacetate into malate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, the reason that we actually want to transform the oxyloacetate into malate is because, firstly, the oxyloacetate cannot actually move across the mitochondrial membrane."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And secondly, we want to take those electrons from the NADH produced in a glycolytic pathway and transport them onto a molecule that can in fact move across the mitochondrial membrane, the outer and the inner mitochondrial membrane."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So once we actually form the malate, the malate now contains the high energy electrons that were stored on the NADH."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And the malate can now move across a special antiported transport system found on the inner membrane of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And as the malate moves into the matrix of the mitochondria, an alpha ketoglutrate is exchanged for that malate and it moves into the intermembrane space and then the cytoplasm of that particular cell."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in step one, the NADH that is produced in glycolysis is used to reduce oxyloacetate into malate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And what this does is it allows that cell to regenerate the NAD plus that is needed by glycolysis to actually continue glycolysis."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And it also transfers the pair of electrons from the NADH onto that oxyloacetate to form the malate, so that once the malate moves into this matrix of the mitochondria, we can actually oxidize that malate back into oxyloacetate and reduce an NAD plus found in the matrix into NADH."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And that NADH can be used by the electron transport chain, as we'll see in just a moment."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in step two, once we form the malate in the cytoplasm of our cell, the malate then moves into the intermembrane space via the outer membrane of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And then that malate enters the matrix of the mitochondria via a special antiporter transport protein in exchange for an alpha key to gluterate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And in step three, we actually take the high energy electrons on the malate that initially came from NADH, and we place them onto that NAD plus coenzyme to actually form the NADH."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in a way, we actually see that the NADH is transported into the matrix of the mitochondria, and we also form we reform the oxalo acetate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, once the oxyloacetate oh, and by the way, the enzyme that catalyzes this step, the conversion of malade into oxalo acetate, is known as the mitochondrial malade dehydrogenase."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And this is the same enzyme that is used by the citric acid cycle."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, once we form the oxalo acetate, the problem with the oxyloacetate is it can simply pass across the inner membrane of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We have to transform the oxalo acetate first into aspartate before it can actually move across this special antiporter protein system."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so the process by which we transform the oxyloacetate into aspartate is known as transamination."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We essentially take an amino group from another molecule, namely the glutamate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We place it onto oxyloacetate, and that's how we form the aspartate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in step four, shown here, the oxyloacetate cannot move across the inner mitochondrial membrane."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so a transamination reaction converts it into aspartate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, in step five, once we form the aspartate, the aspartate can now flow out of the inner membrane of the mitochondria via an exchange transport system, an antiported system, in exchange for glutamates."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So the aspartate flows out and the glutamate actually flows in."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, what happens to that glutamate?"}, {"title": "Malate Aspartate Shuttle .txt", "text": "What is glutamate actually used for?"}, {"title": "Malate Aspartate Shuttle .txt", "text": "Well, glutamate is actually used in the transamination reaction that we mentioned in step four, that glutamate has an amino group, and that amino group is essentially taken off from that glutamate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "It is placed onto axylopetate, and that's how we form the aspartate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And the remaining portion that is left over once we essentially deaminate that glutamate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "That is what we call alpha ketoglutrate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And the alpha ketoglutrate is used to actually help transport the malate in this antiporter extrane transport system."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in step six, shown here, the glutamate transfers an amino group onto axalo acetate, and that forms aspartate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And the remaining portion of that glutamate is known as alpha key to glutarate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, in the final step, step seven, we have the aspartate that is actually transported back into the cytoplasm of our cell."}, {"title": "Malate Aspartate Shuttle .txt", "text": "The aspartate undergoes a reaction to form the oxalo acetate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "In this process, we basically take the aspartate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We deaminate that aspartate, we remove the amino group, and that forms the oxyloacetate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And that amino group is actually placed onto the alpha key to glutarate that enter the cytoplasm via this antiportic system, and that transforms the alpha key to glutarate into glutamate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And this essentially completes the cycle, and the cycle can repeat itself."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in the final step, step seven, the aspartate in the cytoplasm is deaminated."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We remove the amino group, and we place it onto this alpha key to glutarate to form that glutamate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "In the process, when we deaminate the aspartate, we form that oxalo acetate."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And now, since we reform this molecule, the cycle can basically begin all over again."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So we see that the net result in the malate aspartate shuttle process is we actually move that NADH molecule into the matrix of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So we take those high energy electrons, we extract them from the NADH that is produced in glycolysis, we place them into a molecule that is then transported into the matrix, and then we use those same high energy electrons to actually form the NADH molecule."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in this shuttle process, the NADH is regenerated in the matrix of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So we saw that in the previous discussion when we discussed the glycerol three phosphate shuttle, we saw that a net result of 1.5 ATP molecules were produced from a single NADH that was NADH that was generated in the process of glycolysis."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now the question is, what is the net quantity of ATP molecules produced by this NADH molecule that is transported into the matrix of the mitochondria via the malade aspartate shuttle process?"}, {"title": "Malate Aspartate Shuttle .txt", "text": "So once the NADH is actually formed within the matrix of the mitochondria, it goes on to complex one of the electron transport chain."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And this is in contrast to the previous shuttle system that we discussed, the glycerol phosphate shuttle system, in which the NADH actually ends up the electrons on the NADH end up being transferred onto complex three."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So here the NADH is basically we take the NADH that we form in the matrix and we essentially oxidize it into NAD plus."}, {"title": "Malate Aspartate Shuttle .txt", "text": "In this process, as electrons move along the groups within complex one, a net result of four ATP molecules are actually transported into the matrix into the intermembrane space of the mitochondria."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Now, those electrons eventually end up on quinone."}, {"title": "Malate Aspartate Shuttle .txt", "text": "The quinone becomes the Ubiquinone, the Ubiquinone becomes the Ubiquinol, and the Ubiquinol travels onto complex three."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And those electrons then move on to the groups found within complex three."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And those electrons ultimately end up on cytochrome C. And as these electrons move, we see that a net result of four no two H plus ions actually flow from the matrix into the intermembrane space."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so far, we have four and two, that's six."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And as the electrons are transferred from the cytochrome C on to complex four, we see that a net result of four ATP, four H plus ions are transferred into the intermembrane space."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so a total of four two and four."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So ten H plus ions actually are transferred into the intermembrane space."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And so now these ten ions travel through complex five ATP synthase."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And because four protons are needed to pass along the ATP synthase to actually generate a single ATP molecule, we see that if we do a little bit of math."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So we have ten H plus ions."}, {"title": "Malate Aspartate Shuttle .txt", "text": "We divide that by four H plus ions needed to generate a single ATP molecule."}, {"title": "Malate Aspartate Shuttle .txt", "text": "That gives us 2.5 ATP molecules are generated every time this NADH is transported into the matrix via the Malade aspartate shuttle system."}, {"title": "Malate Aspartate Shuttle .txt", "text": "So in the Malade aspartate shuttle system the NADH is regenerated in the matrix of the mitochondria, therefore in liver, so this should be therefore."}, {"title": "Malate Aspartate Shuttle .txt", "text": "Therefore in liver and heart cells the NADH produced in glycolysis generates a net result of 2.5 ATP molecules."}, {"title": "Malate Aspartate Shuttle .txt", "text": "And this is in contrast to the NADH that is produced in glycolysis in cells such as skeletal muscle cells that use the glycerol three phosphate shuttle system instead of the Malate aspartate shuttle system."}, {"title": "Dihybrid Cross .txt", "text": "So far in our discussion, we only considered monohybrid crosses."}, {"title": "Dihybrid Cross .txt", "text": "And what a monohybrid cross involves is it involves the study of a single trait."}, {"title": "Dihybrid Cross .txt", "text": "Now, we're going to discuss something called dihybrid crosses."}, {"title": "Dihybrid Cross .txt", "text": "So what exactly is a dihybrid cross?"}, {"title": "Dihybrid Cross .txt", "text": "Well, the diprefix simply means two."}, {"title": "Dihybrid Cross .txt", "text": "And what dihybrid crosses involve is they involve the study, study of two different types of traits."}, {"title": "Dihybrid Cross .txt", "text": "Now, to demonstrate what we mean by dihybrid cross, let's suppose we have the following scenario."}, {"title": "Dihybrid Cross .txt", "text": "Let's suppose we have P plans, and our goal is to study two different types of traits within that P plan."}, {"title": "Dihybrid Cross .txt", "text": "So we want to study the height of that pea plan as well as the seed color of that pea plan."}, {"title": "Dihybrid Cross .txt", "text": "So our two traits are height and seed color."}, {"title": "Dihybrid Cross .txt", "text": "Now, we have two possibilities for height."}, {"title": "Dihybrid Cross .txt", "text": "We have tall height and we have short height."}, {"title": "Dihybrid Cross .txt", "text": "And likewise, we have two possibilities for the seat color, we have yellow and we have green seat colors."}, {"title": "Dihybrid Cross .txt", "text": "Now, tall is dominant over short, and likewise green is dominant over yellow."}, {"title": "Dihybrid Cross .txt", "text": "So with that in mind, let's suppose we have the following situation."}, {"title": "Dihybrid Cross .txt", "text": "Let's say we have a parent number one."}, {"title": "Dihybrid Cross .txt", "text": "So plant number one and parrot number two, plant number two."}, {"title": "Dihybrid Cross .txt", "text": "Now, parent number one is said to be homozygous dominant for both the high trait and the color trait."}, {"title": "Dihybrid Cross .txt", "text": "And so what that means is we're dealing with a purely green and a purely tall plant."}, {"title": "Dihybrid Cross .txt", "text": "And if we examine the chromosomes, remember, in any diploid organism, such as the p plant, every single chromosome has a homologous chromosome that carries a gene that codes for that same trait."}, {"title": "Dihybrid Cross .txt", "text": "And so we have two of these pairs of homologous chromosome, pair number one and pair number two."}, {"title": "Dihybrid Cross .txt", "text": "Now, this pair of homologous chromosomes basically carry the two genes, the two alleles that code for the color."}, {"title": "Dihybrid Cross .txt", "text": "And in this particular case, because we're dealing with the dominant color, we have uppercase G, uppercase G that designates the color green."}, {"title": "Dihybrid Cross .txt", "text": "Likewise, if we examine the second pair of homologous chromosomes, we have allele number one and we have allele number two."}, {"title": "Dihybrid Cross .txt", "text": "And each one of these alleles basically is a segment of DNA that codes for protein, that expresses our hydrate."}, {"title": "Dihybrid Cross .txt", "text": "And in this particular case, because we're dealing with a homozygous dominant tall plant, we have uppercase T, uppercase T, where T stands for tall and G stands for green."}, {"title": "Dihybrid Cross .txt", "text": "Now, what about parent number two?"}, {"title": "Dihybrid Cross .txt", "text": "Let's suppose we have a second P plant, but this p plant is homozygous recessive for both of those traits."}, {"title": "Dihybrid Cross .txt", "text": "So that means we have a purely yellow and a purely short plant."}, {"title": "Dihybrid Cross .txt", "text": "So if we examine these two homologous chromosome pairs, this one basically carries the allele."}, {"title": "Dihybrid Cross .txt", "text": "So we have allele number one and allele number two."}, {"title": "Dihybrid Cross .txt", "text": "And both of these genes, both of these alleles basically code for protein that expresses the yellow trait."}, {"title": "Dihybrid Cross .txt", "text": "And so we have lowercase G, lowercase G, where this basically means yellow."}, {"title": "Dihybrid Cross .txt", "text": "Now, what about this one?"}, {"title": "Dihybrid Cross .txt", "text": "Well, here we have a similar type of gene."}, {"title": "Dihybrid Cross .txt", "text": "But in this particular case, because we have a short plant, that means we have lowercase t, lowercase t. So uppercase t creates tall, lowercase t creates short, uppercase g creates green, lowercase g creates yellow."}, {"title": "Dihybrid Cross .txt", "text": "So the next question is what exactly will happen?"}, {"title": "Dihybrid Cross .txt", "text": "What type of offspring will we produce if we actually cross these two parents?"}, {"title": "Dihybrid Cross .txt", "text": "If we cross these two individual p plants, well, before they actually cross, each one of these must produce gametes."}, {"title": "Dihybrid Cross .txt", "text": "So to produce gametes, meiosis actually takes place."}, {"title": "Dihybrid Cross .txt", "text": "So when meiosis takes place within this plant, we produce the following gametes."}, {"title": "Dihybrid Cross .txt", "text": "So let's suppose this is the gamete of parent number one."}, {"title": "Dihybrid Cross .txt", "text": "Likewise, meiosis takes place here, and we produce the gamete of parent number two."}, {"title": "Dihybrid Cross .txt", "text": "And to actually produce the zygote and eventually produce the individual, these two must actually combine infuse to form the zygote."}, {"title": "Dihybrid Cross .txt", "text": "And eventually we form that f one generation offspring."}, {"title": "Dihybrid Cross .txt", "text": "Now, in this particular case, the only type of gamete that we can produce is uppercase G and uppercase T. And in this particular case, the only type of gamete we can produce is lowercase G, lowercase T. So this basically is the arrangement of the chromosomes in the first gamete."}, {"title": "Dihybrid Cross .txt", "text": "And this is the arrangement of chromosomes in the second gamete."}, {"title": "Dihybrid Cross .txt", "text": "And when they combine, they only form one type of individual upper case g, lower case g, uppercase t, lowercase t. And to see how that actually takes place, we can basically use our opponent square."}, {"title": "Dihybrid Cross .txt", "text": "So on the pundit square, these are the two gammy types for parent number one."}, {"title": "Dihybrid Cross .txt", "text": "And notice they're exactly the same."}, {"title": "Dihybrid Cross .txt", "text": "And these are the gammy types for parent number two."}, {"title": "Dihybrid Cross .txt", "text": "Once again, they're exactly the same."}, {"title": "Dihybrid Cross .txt", "text": "So meiosis produces these two gammates, and then basically they combine."}, {"title": "Dihybrid Cross .txt", "text": "Now, when we combine these two gametes, the g is paired with the g, and the t is paired with the t. So we produce uppercase g, lower case g, uppercase t, lowercase t, and each one of these cases produces the same exact type of zygote, the same type of offspring."}, {"title": "Dihybrid Cross .txt", "text": "And that's exactly why this will be the f one generation, the genotype of the f one generation."}, {"title": "Dihybrid Cross .txt", "text": "Now, because uppercase g, the green color is dominant over the yellow color, and because the tall, the uppercase t, is dominant over the short lowercase t, that means the f one generation will always be green and tall, but it will be heterozygous for both of those traits."}, {"title": "Dihybrid Cross .txt", "text": "Now, let's suppose we now want to take the f one generation offspring, and we want to cross it with itself."}, {"title": "Dihybrid Cross .txt", "text": "What exactly will be the product?"}, {"title": "Dihybrid Cross .txt", "text": "What will be the f two generation offspring?"}, {"title": "Dihybrid Cross .txt", "text": "So basically, just like meiosis took place here to form the gametes, before we have the process of fertilization take place, we have to form the gametes for the f one generation."}, {"title": "Dihybrid Cross .txt", "text": "Now, the question is, what are the possible potential possibilities for our gametes in this particular case."}, {"title": "Dihybrid Cross .txt", "text": "So this is basically the cell of the f one generation offspring."}, {"title": "Dihybrid Cross .txt", "text": "So we have these chromosomes."}, {"title": "Dihybrid Cross .txt", "text": "Now this is one homologous pair, this is a second homologous pair."}, {"title": "Dihybrid Cross .txt", "text": "Within this homologous pair we have an uppercase g and a lowercase g. Within this homologous pair we have uppercase T and we have a lowercase t. Now when myosis actually takes place and at the end we form different types of gametes, there are only four possibilities for the gametes."}, {"title": "Dihybrid Cross .txt", "text": "What are these possibilities?"}, {"title": "Dihybrid Cross .txt", "text": "Well, basically the upper case g can combine with the uppercase T to form gamete number one, or uppercase g can combine with lowercase T to form gamete number two."}, {"title": "Dihybrid Cross .txt", "text": "Or we can have lowercase g combined with uppercase T to form gamete number three."}, {"title": "Dihybrid Cross .txt", "text": "And finally lowercase g combined with lowercase T to form gamete number four."}, {"title": "Dihybrid Cross .txt", "text": "So we see that if we take two of these different f one generation offspring and we cross them together, there are four possibilities for the gametes."}, {"title": "Dihybrid Cross .txt", "text": "And so together we'll have 16 possibilities for the offspring."}, {"title": "Dihybrid Cross .txt", "text": "And to see why that is, so let's take a look at the following dihybrid cross, Punnett square so let's begin."}, {"title": "Dihybrid Cross .txt", "text": "Let's suppose that this column represents the column that describes the four possibilities for the gamuts of parent number one."}, {"title": "Dihybrid Cross .txt", "text": "So in this square, what do we place?"}, {"title": "Dihybrid Cross .txt", "text": "Well, let's begin with this one right here."}, {"title": "Dihybrid Cross .txt", "text": "So we have a green g and a green t. So we have a green g and we have a blue or uppercase t. So this is gamete number one."}, {"title": "Dihybrid Cross .txt", "text": "Now what about gamete number two?"}, {"title": "Dihybrid Cross .txt", "text": "Well, it's this one here."}, {"title": "Dihybrid Cross .txt", "text": "So we have a g, uppercase g and we have a lowercase t. What about gamete number three?"}, {"title": "Dihybrid Cross .txt", "text": "Well, we have lowercase g, should have an orange."}, {"title": "Dihybrid Cross .txt", "text": "So we have lowercase g and we have a lowercase g here as well."}, {"title": "Dihybrid Cross .txt", "text": "We have uppercase t here and we have a lowercase t here."}, {"title": "Dihybrid Cross .txt", "text": "So we have our purple t. Now, because we're crossing the same identical types of f one generation offspring, these four gamuts will be exactly the same."}, {"title": "Dihybrid Cross .txt", "text": "So we have a green here, a green here, then we have a blue here and we have a blue here, we have a purple here, a purple here, and we have an orange here and an orange here."}, {"title": "Dihybrid Cross .txt", "text": "So these are the four possibilities for the gametes from parent number two."}, {"title": "Dihybrid Cross .txt", "text": "And these are the four possibilities for the gametes for parent number one."}, {"title": "Dihybrid Cross .txt", "text": "And so essentially we're going to get 16 different possibilities for the offspring."}, {"title": "Dihybrid Cross .txt", "text": "So let's actually carry out the pond and square crossing."}, {"title": "Dihybrid Cross .txt", "text": "So we have, remember, the g's pair together and the t's also pair together."}, {"title": "Dihybrid Cross .txt", "text": "So this multiplied by this gives us uppercase g, uppercase g. So uppercase g, uppercase g and uppercase t, uppercase T. Now what about this one?"}, {"title": "Dihybrid Cross .txt", "text": "We get uppercase g, uppercase g, we get uppercase T, lowercase T, because this gammy, when they fuse, gives the lowercase T chromosome."}, {"title": "Dihybrid Cross .txt", "text": "Now in this case, we now have uppercase g, lower case g, we have uppercase T, lowercase T, so we have uppercase T, where actually we have two uppercase T's, okay, and now we have an uppercase g, a lowercase G, and we have an uppercase T, a lowercase T to actually change the orange."}, {"title": "Dihybrid Cross .txt", "text": "We are done with the first row, let's move on to the second row."}, {"title": "Dihybrid Cross .txt", "text": "We have this gamut, can also combine with this gamut."}, {"title": "Dihybrid Cross .txt", "text": "In that particular case, we form uppercase g, uppercase G, and we form uppercase T, lowercase T, so we have the purple T, this square here, we have this combining with this."}, {"title": "Dihybrid Cross .txt", "text": "So we have uppercase g, uppercase g, lower case T, lowercase T. Now let's move on to the square."}, {"title": "Dihybrid Cross .txt", "text": "We have this gammy can also combine with this gammy."}, {"title": "Dihybrid Cross .txt", "text": "So we have uppercase g, lower case G, and we can have uppercase T, so uppercase T always comes first and lowercase T comes second."}, {"title": "Dihybrid Cross .txt", "text": "Now in this square we have uppercase g, lower case g, so we have uppercase g, lower case G, and then we have lowercase T, lowercase T, so lowercase T, lowercase T. Now the next possibility is this and this."}, {"title": "Dihybrid Cross .txt", "text": "So uppercase, the letter dominant one always comes first."}, {"title": "Dihybrid Cross .txt", "text": "So we have green g and we have an orange g, and then we have two uppercase blue T's."}, {"title": "Dihybrid Cross .txt", "text": "Okay, here we have uppercase g, lower case g, so let's put the lowercase g second, the uppercase g first."}, {"title": "Dihybrid Cross .txt", "text": "Then we have the uppercase T, and then we have the lowercase T, and let's continue onward."}, {"title": "Dihybrid Cross .txt", "text": "We have lowercase g, lowercase g, we have uppercase T, we have uppercase T here."}, {"title": "Dihybrid Cross .txt", "text": "We have lowercase g, lower case g, so lowercase g, lower case G, uppercase T, upper case T, and we have lowercase T coming from this gamete here."}, {"title": "Dihybrid Cross .txt", "text": "And in the final row, we basically have uppercase g, lowercase g, so many markers."}, {"title": "Dihybrid Cross .txt", "text": "And then we have uppercase T, lowercase T, there you go."}, {"title": "Dihybrid Cross .txt", "text": "Now we have uppercase g, lowercase g, so we have uppercase g, lowercase G that comes from this gamete, and we have two lowercase recessive T's for the short trait here."}, {"title": "Dihybrid Cross .txt", "text": "We have lowercase g, lower case g, we have uppercase T and lowercase T, and finally we have the possibility of everything being recessive."}, {"title": "Dihybrid Cross .txt", "text": "So we have lowercase g, lower case g, and we have lowercase T, lowercase T. So these are the 16 different possibilities of the genotype for the offspring when these two mate with themselves."}, {"title": "Dihybrid Cross .txt", "text": "So we have one of these mates with itself."}, {"title": "Dihybrid Cross .txt", "text": "So each one of these produces four types of gametes."}, {"title": "Dihybrid Cross .txt", "text": "And so we have four gametes here, four gametes here from the two different parents, and when they mate, when they fuse to form the Zygote, these are the 16 possibilities for the genotype of our Zygote."}, {"title": "Dihybrid Cross .txt", "text": "Now, the next question is what are the four types of phenotypes of these individuals produced here?"}, {"title": "Dihybrid Cross .txt", "text": "So, we can either have green and tall we can either have green and short, we can have yellow and tall, or we can have yellow and short."}, {"title": "Dihybrid Cross .txt", "text": "So let's actually tally up and determine the probabilities or the distribution probability of the F two offspring."}, {"title": "Dihybrid Cross .txt", "text": "So all these squares describe the offspring, the F two generation offspring."}, {"title": "Dihybrid Cross .txt", "text": "So basically, let's begin with this one."}, {"title": "Dihybrid Cross .txt", "text": "So we have uppercase G, uppercase G, uppercase T, uppercase T. And that means this will have a green and a tall offspring."}, {"title": "Dihybrid Cross .txt", "text": "So this will be the phenotype of that."}, {"title": "Dihybrid Cross .txt", "text": "So we put a tally."}, {"title": "Dihybrid Cross .txt", "text": "Let's mark down one here."}, {"title": "Dihybrid Cross .txt", "text": "We have uppercase G, uppercase G. That means it will be green, uppercase T, lowercase T, death that will be tall because uppercase C is dominant over lowercase T. So another tally for that here."}, {"title": "Dihybrid Cross .txt", "text": "Once again, green and tall."}, {"title": "Dihybrid Cross .txt", "text": "Another one, green and tall."}, {"title": "Dihybrid Cross .txt", "text": "Another one, green and tall."}, {"title": "Dihybrid Cross .txt", "text": "So we have five."}, {"title": "Dihybrid Cross .txt", "text": "Now we have green."}, {"title": "Mechanism of Transaldolase .txt", "text": "The nonoxidative phase of the pentose phosphate pathway involves two important enzymes, transketilase and transaldelase."}, {"title": "Mechanism of Transaldolase .txt", "text": "In the previous lecture, we focused on the reaction mechanism of transquitolase."}, {"title": "Mechanism of Transaldolase .txt", "text": "In this lecture, we're going to discuss the reaction mechanism of transaldelase."}, {"title": "Mechanism of Transaldolase .txt", "text": "Now, unlike transketilase, which basically catalyzed the movement of a two carbon component to carbon group, we see that transaldelase actually catalyze the transfer of a three carbon molecule known as dihydroxy acetone."}, {"title": "Mechanism of Transaldolase .txt", "text": "And unlike transketulates that uses a Cofactor molecule known as thiamine pyrophosphate, we'll see in this lecture that transaldelase does not actually use that Cofactor thiamine pyrophosphate."}, {"title": "Mechanism of Transaldolase .txt", "text": "Instead, what it does is it forms a shift base between the catalytic lysine residue in the active side of the enzyme and the incoming keto substrate molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "So to see exactly what we mean, let's actually take a look at the details of the reaction mechanism."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is the portion of the lysine residue found in the active site of the enzyme, and this is the incoming substrate molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "So remember, we have two substrate molecules."}, {"title": "Mechanism of Transaldolase .txt", "text": "This is one of them in this step, and this is the second one in this step."}, {"title": "Mechanism of Transaldolase .txt", "text": "So we have the keto substrate molecule, and in this particular case, the keto substrate that we're going to look at is the CETO heptulose seven phosphate."}, {"title": "Mechanism of Transaldolase .txt", "text": "So in the first step, we basically have the formation of that shift base."}, {"title": "Mechanism of Transaldolase .txt", "text": "And once these two react, we basically form this molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "In the process, we actually kick off a water molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "So these two H ions and this oxygen basically combine to form a water molecule, and we form a double bond between this nitrogen and this carbon here."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is carbon one, carbon two, carbon 3456 and seven."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so we form a bond between the nitrogen and carbon number two on this incoming ketone substrate molecules."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is what we call a shift base."}, {"title": "Mechanism of Transaldolase .txt", "text": "And a shift base is ultimately a connection between the enzyme molecule and this substrate."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is an enzyme substrate intermediate molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "Now, in the next step, we basically have a proponation taking place."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this nitrogen, which contains two electrons, basically grabs an H plus ion, and that forms a sigma bond between the nitrogen and the H ion."}, {"title": "Mechanism of Transaldolase .txt", "text": "In the process, we also generate a full positive charge on this nitrogen."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so what happens in the next step is to essentially remove that full positive charge from the nitrogen."}, {"title": "Mechanism of Transaldolase .txt", "text": "We have a rearrangement taking place in which this entire component is actually kicked off."}, {"title": "Mechanism of Transaldolase .txt", "text": "So what happens is so if this is carbon 123-4567, we have this sigma bond between the H and the oxygen basically breaks."}, {"title": "Mechanism of Transaldolase .txt", "text": "That kicks off this H plus ion, and that forms a pi bond between this oxygen and this carbon."}, {"title": "Mechanism of Transaldolase .txt", "text": "In the process, we break the sigma bond between carbon three and carbon four."}, {"title": "Mechanism of Transaldolase .txt", "text": "And that sigma bond is used to form a pi bond between carbon two and carbon three."}, {"title": "Mechanism of Transaldolase .txt", "text": "And then that actually breaks this pi bond."}, {"title": "Mechanism of Transaldolase .txt", "text": "And those two electrons in the Pi bond end up on this nitrogen, and we form this stable molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "In the process, we also kick off and we generate the four carbon molecule, the aldos product, in this case, the rethros four phosphate."}, {"title": "Mechanism of Transaldolase .txt", "text": "So we have carbon one, carbon two, carbon three, carbon four that we basically find here."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so the pipeline that is formed between the oxygen here and the carbon here is basically this pipeline here."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is actually one of the two products that will be formed in this particular transaldolase reaction."}, {"title": "Mechanism of Transaldolase .txt", "text": "Now, this molecule is stable, and it's stable until the second substrate molecule actually enters the reaction."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so we have the second substrate molecule and aldosutran, in this case, we're going to use Glycerial, glyceroaldehyde three phosphate, the same molecule that we use when we discussed the non oxidative phase of the pentose phosphate pathway."}, {"title": "Mechanism of Transaldolase .txt", "text": "So what happens is this same H plus ion that was basically kicked off is now used in this particular reaction."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so what we see happen is these two electrons on the nitrogen basically form a pipeline between this nitrogen, this carbon, and that breaks this pipeline here."}, {"title": "Mechanism of Transaldolase .txt", "text": "And that Pi bond acts as a nucleophile."}, {"title": "Mechanism of Transaldolase .txt", "text": "It basically attacks the carbon, forms a sigma bond between this carbon here and this carbon here."}, {"title": "Mechanism of Transaldolase .txt", "text": "And what that also does is breaks this Pi bond."}, {"title": "Mechanism of Transaldolase .txt", "text": "And the Pi bond is used to pick up this hion."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so once this addition reaction takes place, we form the following intermediate."}, {"title": "Mechanism of Transaldolase .txt", "text": "Now, when going from this molecule to this molecule, we had a protonation and now we have a deep protnation."}, {"title": "Mechanism of Transaldolase .txt", "text": "So we essentially kick off the H plus ion, and those two electrons in the sigma bond that is broken end up on this nitrogen."}, {"title": "Mechanism of Transaldolase .txt", "text": "And in the final step, we basically have a hydrolysis reaction take place."}, {"title": "Mechanism of Transaldolase .txt", "text": "And in the end, we produce the final product, the fructose six phosphate, which is our keto product molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "So we have product one, the urethrase four phosphate, that's the aldos."}, {"title": "Mechanism of Transaldolase .txt", "text": "And then we have product two, the fructose six phosphate, that's the ketos products."}, {"title": "Mechanism of Transaldolase .txt", "text": "So these are the two products that are formed."}, {"title": "Mechanism of Transaldolase .txt", "text": "These are the two reactants that are actually used."}, {"title": "Mechanism of Transaldolase .txt", "text": "And notice that unlike the transketulates, the trans aldalase differs in two ways."}, {"title": "Mechanism of Transaldolase .txt", "text": "Number one is it transfers a three carbon component, not the two carbon component."}, {"title": "Mechanism of Transaldolase .txt", "text": "So it transfers the dihydroxy acetone."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this structure here has one, two, three carbons and two hydroxyl groups one and two."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so that's why we call this structure a dihydroxy acetone, and it ultimately came from the first product molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "And this dihydroxy acetone is transferred onto the second product, the second substrate molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "So this is substrate number one and substrate number two."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so we have the transfer of this thy hydroxy acetone from one of the substrates to the other substrate."}, {"title": "Mechanism of Transaldolase .txt", "text": "And so we formed these two product molecules."}, {"title": "Mechanism of Transaldolase .txt", "text": "And unlike in the transketulase case, which used the Thiamine Pyrophosphate Cofactor molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "In this particular case, we don't use that Cofactor molecule."}, {"title": "Mechanism of Transaldolase .txt", "text": "Instead, we create that shift based molecule that we discuss in this particular step."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Inside our lungs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "We have specialized structures called alveolar sacs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And these alveolar sacs contain many tiny balloonlike structures called alveoli."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And within the alveoli is where gas exchange actually takes place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Oxygen is exchanged for carbon dioxide."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now before we actually discuss how the process of gas exchange range takes place within each individual alveoli, let's discuss what the structure of the alveolar sac is and what the individual alveolis actually looks like."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now recalling our discussion on the respiratory system, we said that when we inhale, when we breathe in air, the air enters via the nose, travels through the nasal cavity and then enters our pharynx and then connects with our larynx, the voice box, which then connects with the trachea, our windpipe."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now the trachea ultimately bifurcates, it divides into two bronchi."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And each one of these bronchies subdivides into very tiny bronchioles that permeate through our lungs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And of each bronchio at the end of this very tiny air passageway are the alveolar sacs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this is shown by this diagram."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So structure number two is the bronchio that is shown in brown."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "It basically extends all the way into this space, number seven."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And space number seven is the alveolar sac space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this entire orange section is our alveolar sack."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That is described by number six."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now if we notice along our bronchio we also have these regions shown by red."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So this portion, this portion, this portion, and that is our smooth muscle that extends around our bronchiol and it is capable of contracting and dilating that bronchiole as needed."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now notice we have many of these individual tiny balloon like structures shown by number one and those are our alveoli."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That is where gas exchange actually takes place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So essentially this space, number seven, the alveolar sax space, connects directly to the space within each one of these alveoli and that is known as the alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So if we examine each one of these alveoli, we basically get the following diagram."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And the space inside each one of these tiny alveoli looks something like this."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That's the alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "It's not the same as the alveolar sack space, but they are connected to one another."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And so the concentration of gas molecules inside the alveolar sack space number seven and the alveolar space number eight is exactly the same."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now before we actually take a look at the structure of the actual alveolis, let's discuss what this blue section is and what the red section is."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So this blue section is our blood vessel, the pulmonary artery, that actually brings deoxygenated blood from the heart to our lungs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "While the red blood vessel is our blood vessel called the pulmonary vein."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That brings oxygenated blood from each individual alveolis and to the heart of our body, specifically to the left atrium of our body."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So remember, the pulmonary artery carries the oxygenated blood away from the heart and to the lungs while the pulmonary vein carries oxygenated blood away from the lungs and to our heart."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we see that this entire section, number six is the alveolar sac that contains many of these specialized balloons shaped structures we call alveoli."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And within these alveoli is where gas exchange actually takes place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we exchange oxygen for carbon dioxide."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So remember, oxygen is a very important molecule that is used by our individual cells in the process of cellular respiration to actually produce ATP, the energy molecules used by the cell."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And carbon dioxide is a waste product of cellular metabolism."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And so we have to actually excrete it to the outside of our body."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this is what happens inside our lungs, specifically inside each alveoli."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So now let's actually zoom in on one of these alveoli."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this is what a single alveolis actually looks like."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we have this connecting point, this region here that connects number eight, the alveolar space, to number seven, the alveolar sack space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And because we have this direct connection, the concentration of our air molecules inside eight is the same as inside seven, which is the same as actually no, it's not the same."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So in seven and eight we have the same exact concentration of gas molecules."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now notice that around the entire alveolis we basically have the system of blood vessels."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So this blood vessel is our pulmonary arteriol."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That brings deoxygenated blood and it loops around the entire alveolis until it gets to this section."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this is our capillary."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "It's the pulmonary capillary."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So number seven is the pulmonary capillary and number five is our pulmonary arterio."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now, within the capillary we have exchange taking place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Oxygen goes into the capillary and our carbon dioxide leaves the capillaries and goes into region number eight."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And then our oxygenated blood travels via this blood vessel, number six, which is our pulmonary Venuel."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "It's a very small type of pulmonary vein."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now let's take a look at the actual membrane within which we have this diffusion of oxygen and carbon dioxide taking place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So notice we have two important types of cells within the alveolis."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "We have the cell labeled as number four."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That is our alveolar cell type number two."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And what this cell does is it produces and releases the pulmonary surfactant that is necessary to prevent the alveolis from actually collapsing when we exhale and to decrease the surface tension and therefore the pressure that is needed to actually inflate our alveolis."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now the cells shown by these green cells, number one."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So if we zoom in on this small cross section, we get this blown up image."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And so number one is our epithelial cells of the alveolus."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "These are the cells that line the wall of the alveolis."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And the wall is shown by number two."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "That's the orange section."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this consists of an extracellular matrix we call the basement membrane."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now the basement membrane actually connects the epithelial cells of the alveolis to the endothelial cells of our blood vessels."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So these cells shown in blue are the endothelial cells."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So these cells are the endothelial cells of our pulmonary arterial, and these cells are the endothelial cells of our pulmonary Venuel."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Okay, so now that we know what the structure of our alveolus actually looks like, let's discuss how gas exchange actually takes place and why."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Oxygen is taken up by the capillaries, but carbon dioxide is released by the capillaries."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So how does gas exchange actually take place within each individual alveolis?"}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Within our alveolar sac?"}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So recall that the rich ventricle of the heart pumps deoxygenated blood into the pulmonary trunk, which extends into the pulmonary arteries."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And these arteries bring deoxynated blood into the lungs."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now, eventually, the pulmonary arteries divide into smaller arteries, and they ultimately divide into these pulmonary arterioles that is shown by number five."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And these pulmonary arterioles essentially circle around the alveoli until they connect with the pulmonary capillary."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "This section shown by number seven."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So let's zoom in on this region that contains this capillary section here."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we basically get the following diagram."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we have the pulmonary arterio, we have the pulmonary capillary, and we have the pulmonary venue."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So our deoxygenated blood essentially travels along the pulmonary terio until it gets to our capillary, which is this section right here."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now, deoxygenated blood has a relatively high concentration of carbon dioxide and a relatively low concentration of oxygen compared to the concentrations of these molecules, gas molecules, inside the alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So this region here is region number eight, the alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now, within the alveolar space, we have a partial pressure of oxygen equaling to 105 mercury, while the partial pressure due to our carbon dioxide molecules, that is 40 mercury, now, inside the lumen of our pulmonary arterial, these are the concentrations, these are the partial pressures of these same gas molecules."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Notice the oxygen is 40 mercury, which is less than inside the alveolar space, while the carbon dioxide has a higher concentration, 45 mercury, inside the lumen of the arterial compared to our alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we have a difference in pressure."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And whenever we have a difference in pressure, we know we have a pressure gradient."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And these gas molecules will begin to move down their gradient from a high pressure to a low pressure."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So as soon as the blood enters the capillary, we have this relatively thin wall that consists of the endothelium of the blood vessel, the capillary, the basement membrane, as well as the epithelium of our alveolus."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this entire layer allows our diffusion of these gas molecules."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this layer that consists of these three different things is known as the respiratory membrane inside the capillary that allows diffusion to take place."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And so carbon dioxide will diffuse down its pressure gradient from a high pressure to a low pressure."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And oxygen will also diffuse down its gradient, but it will move from the outside to the inside of the capillary, also down its gradient from a value of 105 to a value of 45 mercury."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So this is exactly why our exchange takes place in the first place because there is a pressure gradient that exists between the space of the alveolis and the lumen of our capillary where the blood actually flows."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Now, by the time the blood actually ends up within our lumen of the pulmonary Venuel, the concentration of carbon dioxide and oxygen will be the same inside the lumen as inside our alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And that's exactly why the diffusion of these two gas molecules essentially stops."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And then our pulmonary Venuel connects with larger pulmonary arteries and that carry the oxygenated blood into the left atrium of our heart."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So, once again, the deoxygenated blood brought by the pulmonary arteriol contains a relatively low partial pressure for oxygen and a relatively high partial pressure for carbon dioxide compared to the space inside our alveolus."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "Therefore, due to this pressure difference, due to the existence of this pressure gradient, oxygen will diffuse into the capillary and carbon dioxide will diffuse out of the capillary, down their pressure gradient."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And this diffusion will continue until our partial pressure, the partial concentration or the partial pressure for oxygen is the same on the inside of the blood vessel as our inside space, the space inside our alveolar."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "And the same thing is true for the carbon dioxide."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "The diffusion of carbon dioxide will continue until the partial pressure inside our lumen of our blood vessel is the same as our alveolar space."}, {"title": "Alveolar Structure and Gas Exchange .txt", "text": "So we see that inside each individual alveolis, the reason that gas exchange takes place is because of the existence of a pressure gradient, a difference in concentration between these two types of gas molecules found in the lumen and inside the alveolar space."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "In diploid organisms, there's a two N number of chromosomes in every single somatic cell."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So, for example, in humans, every single somatic cell has 46 individual chromosomes, or 23 pairs of homologous chromosomes under normal conditions."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, a carreotype is basically a pictorial description of all the chromosomes found within that particular organism within that particular individual."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, in humans, every normal human carotype will show 23 pairs of homologous chromosomes or 46 individual chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, what exactly does a carreotype in a human actually look like?"}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Let's take a look at the following picture that describes the human chariottype under normal conditions."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we have chromosome pair number one, chromosome pair number two, chromosome pair number three, all the way to chromosome pair number 22."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And all of these chromosome pairs, one through 22, are known as autosomal homologous chromosome pairs."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "The final chromosome pair, the 23rd one, is called the sex homologous chromosome pair."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, in males, in normal males, we have one X sex chromosome and one Y sex chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And in normal females, we have one X and the other one is also an X."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So notice that because each one of these pairs consist of two individual chromosomes, that means on the normal conditions, we have two multiplied by 23 or 46 individual chromosomes within the human carotype."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So in every single somatic cell of our body under normal conditions, these are the chromosomes that we're going to find in the nucleus of those somatic cells."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So now that we know what a caraotype actually looks like in a normal, healthy human individual, let's now discuss chromosomal abnormalities."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So one of the common type of chromosomal abnormalities is anneuploids."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So in some individuals, within the somatic cells of some individuals, we can either have an extra copy of a chromosome or we can have one less chromosome than we normally have."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we can either have 47 chromosomes or 45 chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And in either case, these conditions are known as annuploid."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So, once again, as we saw just a moment ago when we discussed the human cargotype, we saw that every single one of these chromosomes came with a pair."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And this is known as dimic conditions."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so each one of these pairs describes a dilmic condition, because we have only two per pair."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Sometimes, however, we can either have a trisomic individual or we can have a monosomic individual."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And what that means is one of these pairs actually has an extra copy of a chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So three in this particular case, or we can have one less."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we can have a monosomic condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So that is what we mean by anuploid."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Anuploid is a type of chromosomal abnormality in which we either have an estro copy of one of the chromosomes or we have one less than we should normally have."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, the next question is why exactly does an employee actually take place?"}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "How does it arise?"}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Well, there are two types of cell cycle processes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "We have mitosis and we have meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And both of these processes can actually lead to anuploid."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And the specific process that leads to anubloid is known as nondisjunction."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So the most common reason for anuploid is nondisjunction of chromosomes that takes place during anaphase of mitosis or during anaphase of meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So let's begin by focusing on nondisjunction taking place in mitosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, normally, what happens in mitosis if, once again, we look at this caraotype."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So mitosis is the process by which a somatic cell in our body chooses to divide."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And that somatic cell produces two identical daughter cells that have the same exact genetic information."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So what happens during mitosis, during interface, what happens is every single one of these chromosomes is replicated."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So this chromosome is replicated, this chromosome is replicated, this one is replicated, this one is replicated, and so forth."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And let's say if this one is replicated, what we produce is a pair of identical cystochromatids."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Remember, cystochromatids are two chromosomes that are exactly the same."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "They have the same exact genetic information."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, in this particular picture, instead of drawing out all these 46 pairs of cystic chromatids, we're only going to look at two to basically save space."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So this is our chromosome, this is our somatic cell."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And inside of somatic cell, let's say we have chromosome one and chromosome two, and we replicate them."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So these are the identical cystochromatis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So these two are identical and these two are identical."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, normally, what happens under normal conditions is these mitotic spindle upper analysis form."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "They extend these fibers, and these fibers attach themselves onto these sections on each one of these cystochromatids."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so during metaphase of mitosis, we have these extensions and these connections that form."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And normally, these two will move to that side, these other cystochromatids will move to the other side."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And in humans, we have 46 chromosomes moving this way, 46 chromosomes moving the other way."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so during anaphase, we should have in this particular picture, we should see two chromosomes moving this way and two chromosomes moving the other way."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "But if nondisjunction takes place, what that means is one of these fibers actually fails to form a proper connection with one of the cystochromatids."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so let's say that this connection formed, this connection formed, and this connection formed."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "This connection did not actually form."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so now what happens during anaphase when these fibers begin to pull these cystochromatids apart?"}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "These are pulled apart correctly, so these begin moving to opposite poles, but this one doesn't move apart correctly."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "In fact, this pair of identical cystochromatids moves to the other side, to one side, and this one fails to move to this side."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so at the end, when we produce our two daughter cells, these will no longer be identical because they will not carry the same amount of genetic information."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "In this particular case, we're going to have a daughter cell, a somatic cell that has one extra chromosome than it should have."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we have a trisomic condition, and this one will lack that particular chromosome, and so it will have a monosomic condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, one important point must be made about mitosis if mitosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So let's suppose I'm a normal individual."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And what that means is inside every somatic cell of my body, I have 23 pairs of 46 individual chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, if inside one of my somatic cells mitosis takes place and nondisjunction takes place, then what that means is I will only have this anaploid condition within these two daughter cells that are formed as a result of the non disjunction in mitosis, all the other somatic cells of my body will still be normal."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And that's exactly why nondisjunction taking place in mitosis is not as dangerous as nondisjunction taking place in meiosis, because in meiosis, as we'll see in just a moment, what ends up happening is all the somatic cells of that individual will have an abnormal number of chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "They will have anuploid."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "While in this case, all of these somatic cells produced via this nondisjunction mitosis will have that anuploid condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So although this still can be dangerous because it can lead to abnormal cells, it can form cancer cells as long as those abnormal cells are actually destroyed either by our immune system or by the process of programmed cell death."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "If that happens, it is not as dangerous as in the case of meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So let's move on to nondisjunction taking place in meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, because meiosis actually consist of meiosis one and meiosis two, that means there are two different places, two different times where nondisjunction can actually take place."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So let's begin by assuming that nondisjunction only takes place during meiosis one."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So, once again, we're dealing with only well, if we take a look at our normal human carotype, technically speaking, we should be showing all these individual chromosomes within the cell."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "But to save time, I'm only going to focus on the 23rd chromosome pair, our sex chromosome pair."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we're not going to consider the autosomal chromosomes in this particular case."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So before meiosis actually takes place and before this male individual can produce sperm cells, those chromosomes must replicate themselves during the process of interface."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so the x chromosome is replicated to produce this identical x chromosome, and the y chromosome is also replicated to produce this identical cystochromatid."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So normally, what should happen during normal conditions is during metaphase one of meiosis, these pairs basically line up at the equator of our cells."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So in humans, we're going to have 23 pairs of these chromosomes line up at the middle."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And then during anaphase, if these connections are formed correctly, these 23 pairs of chromosomes are basically moved to opposite poles."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, if nondisjunction takes place, what that means is, once again, we fail to form this fiber attachment."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so instead of this attaching here and this attaching here, let's say what happens is this attaches here and also attaches there."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so now what happens is we have nondisjunction takes place and both of these pairs of chromosomes basically move to one side of the pole."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so when we have when we produce those two cells, one of the cells will lack the sex chromosome and the other one will have an extra pair of sex chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So this is where nondisjunction took place in meiosis one, in anaphase one of meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, let's suppose we have metaphase two take place, and metaphase two takes place normally."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So all these chromosome pairs line up at the equator as shown, and these fibers form correctly."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And we have the separation of these chromosomes to that side and these chromosomes to the other side."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And so in this particular case, we formed these two identical sperm cells."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And in this particular case, we formed these two sperm cells that don't have those sex chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So all of these sperm cells are abnormal because in this case, in case one and two, we have one more than we should remember."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Each sperm cell should have only one sex chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "In this case, we have two."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "In this case, we have none."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So what will happen next?"}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Well, remember, the entire purpose of forming the sperm cells by the male individual was to basically take the sperm cell and combine it with an Xcel."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So let's suppose we take either one of these two sperm cells, our anuplooid sperm cell and we combine it with a female normal X cell."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Remember, X cells always or normal X cells always have one X chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, if these two gametes actually combine, we're going to form a Zygote that has the unequality condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And what that means is we're going to have two of these X chromosomes, one of these Y chromosomes."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And what happens is we know under normal conditions we should have one X, one Y or one X, one X."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "But because of this rearrangement, we're going to have an extra copy of that X chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And because we have an extra copy, instead of having 46 chromosomes, we're going to have 47 chromosomes in this Zygote."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And when the Zygote divides to form the many different cells of that individual, every single somatic cell of that individual will have this unemployed condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "And that's why nondisjunction in meiosis is much more dangerous than nondisjunction in mitosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Because if it takes place in meiosis, every somatic cell of the body will end up having this unemployed condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "But in mitosis, it's only those two daughter cells that are formed by that process that will have that condition."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So as long as our immune system can protect our body from those abnormal cells, we should have no problem."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So if a normal X cell combines with either sperm cell one or sperm cell two, the Zygote will have an extra X chromosome copy."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So we'll have XY."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, if the normal Xcel combines with either sperm cell three or four, we're going to have Zygote in which we're going to lack the Y chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "We're going to have only one X chromosome, and this condition is known as XO, where O means we don't have that second sex chromosome."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "This is non disjunction taking place in meiosis, one more specifically in anaphase one of meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "Now, we can also have nondisjunction taking place in meiosis two more specifically in anaphase two of meiosis."}, {"title": "Aneuploidy and Nondisjunction .txt", "text": "So."}, {"title": "Enzyme Activity.txt", "text": "Enzymes are proteins that act as biological catalysts in living organisms."}, {"title": "Enzyme Activity.txt", "text": "And this basically means our enzymes speed up the many different biological processes and reactions that take place within our organism."}, {"title": "Enzyme Activity.txt", "text": "Now, enzymes are very sensitive and that basically means that the functionality and the rate of activity of enzymes does not only differ depend on non protein molecules such as Cofactors."}, {"title": "Enzyme Activity.txt", "text": "The functionality and activity of enzymes also depends on the actual environment surrounding that protein molecule."}, {"title": "Enzyme Activity.txt", "text": "Now, three major factors influence the enzymes activity and functionality and these are temperature, the acidity level, so the PH level, as well as the concentration of the substrate."}, {"title": "Enzyme Activity.txt", "text": "So let's examine each one of these factors and see how they influence our proteins, our enzymes functionality."}, {"title": "Enzyme Activity.txt", "text": "So let's begin with temperature."}, {"title": "Enzyme Activity.txt", "text": "Now, increasing the temperature of the surroundings in which our protein enzyme is actually found in generally initially increases the rate or the activity of our enzyme."}, {"title": "Enzyme Activity.txt", "text": "And this is primarily because by increasing the temperature we give the substrate more energy so that it has more energy to basically overcome that activation barrier."}, {"title": "Enzyme Activity.txt", "text": "Now, the problem with increasing the temperature high or increasing the temperature continually is our proteins have tertiary structure."}, {"title": "Enzyme Activity.txt", "text": "And remember that at a high enough temperature, the proteins tertiary structure can break down."}, {"title": "Enzyme Activity.txt", "text": "And at this point we say the protein is denatured and it no longer functions because the tertiary structure is basically the structure that determines the functionality of that protein."}, {"title": "Enzyme Activity.txt", "text": "And because enzymes are proteins, we see that eventually the rate of activity of enzymes reaches a certain point at which it has a maximum activity rate."}, {"title": "Enzyme Activity.txt", "text": "And increasing the temperature past this point will denature or break down the tertiary structure of that enzyme and lower that enzyme's activity sharply."}, {"title": "Enzyme Activity.txt", "text": "Now, one example is the human body."}, {"title": "Enzyme Activity.txt", "text": "The human body has a core temperature of about 37 degrees Celsius."}, {"title": "Enzyme Activity.txt", "text": "And this is because most of the proteins, the majority of the proteins are enzymes in the human body, function optimally at this temperature of 37 degrees Celsius."}, {"title": "Enzyme Activity.txt", "text": "So increasing the temperature will increase the rate until we go up to this optimal temperature."}, {"title": "Enzyme Activity.txt", "text": "And by increasing it further, we see that our activity of that enzyme, which is the Y axis, will jar, will drop sharply."}, {"title": "Enzyme Activity.txt", "text": "Now, this is basically exactly why it's dangerous to have a fever."}, {"title": "Enzyme Activity.txt", "text": "Because when our body temperature increases, we can basically damage our proteins, our enzymes found in the body."}, {"title": "Enzyme Activity.txt", "text": "Now ironically, this is also a mechanism by which our body kills off bacterial cells."}, {"title": "Enzyme Activity.txt", "text": "So when we're sick, the mechanism by which our body kills off the bacterial cells is by increasing the temperature of our body."}, {"title": "Enzyme Activity.txt", "text": "This basically causes the proteins in the bacterial cells to basically denature and that decreases the activity and functionality of our enzymes found in bacterial cells."}, {"title": "Enzyme Activity.txt", "text": "Now, let's move on to our acidity level."}, {"title": "Enzyme Activity.txt", "text": "So how exactly does the PH or the concentration of hydrogen ions affects our functionality and activity of proteins of our enzyme?"}, {"title": "Enzyme Activity.txt", "text": "So the concentration of hydrogen ions, the PH, can also affect the activity of enzymes."}, {"title": "Enzyme Activity.txt", "text": "For instance, the human body actually spends a lot of its energy in making sure that the PH of the blood as well as other systems, other fluids within our body, remains at a specific level."}, {"title": "Enzyme Activity.txt", "text": "And at times it can basically change the PH of certain fluid areas within our body to basically activate or deactivate certain enzymes."}, {"title": "Enzyme Activity.txt", "text": "So for instance, the human body spends a good amount of energy to keep the fluid environment at a specific PH in order to ensure that different enzymes basically function effectively and properly."}, {"title": "Enzyme Activity.txt", "text": "Now, the enzymes in our blood, for example, require a PH of about 7.4."}, {"title": "Enzyme Activity.txt", "text": "And if the PH fluctuates even a small amount the enzymes will basically lose their functionality and this can be a very deadly scenario."}, {"title": "Enzyme Activity.txt", "text": "Now, another case is Aristomic and small intestine."}, {"title": "Enzyme Activity.txt", "text": "So Aristomic, unlike the blood, actually functions or Aristomic contains a relative acidic environment."}, {"title": "Enzyme Activity.txt", "text": "And this is because a lot of our protein enzymes, for example Pepsin found in the stomach function at a low PH."}, {"title": "Enzyme Activity.txt", "text": "For example, Pepsi functions optimally at a PH of about two."}, {"title": "Enzyme Activity.txt", "text": "Now, if we examine and study the small intestine which basically contains the enzymes that are involved in breaking down the macromolecules into their constituent parts which are then ingested into our blood."}, {"title": "Enzyme Activity.txt", "text": "So basically, enzymes in the small intestine function optimally at a slightly basic PH of about 8.0."}, {"title": "Enzyme Activity.txt", "text": "Now, if the PH changes in either direction the activity of our enzyme will basically decrease symmetrically as shown in the following diagram."}, {"title": "Enzyme Activity.txt", "text": "Notice in this case we have a sharp drop but in this case we have the same exact slope on both sides."}, {"title": "Enzyme Activity.txt", "text": "So basically, if this y axis is the rate of activity of the enzyme and the x axis is our PH and a PH of about 8.0 the enzymes in our small intestines, such as Chimetrypsin and Tryptin basically function optimally at this PH of 8.0."}, {"title": "Enzyme Activity.txt", "text": "But if we decrease or increase our PH the activity of those enzymes will drop as shown by these decreasing slopes."}, {"title": "Enzyme Activity.txt", "text": "Now, the final factor that we want to discuss is the concentration of the substrate."}, {"title": "Enzyme Activity.txt", "text": "So let's suppose that we begin with a relatively small quantity of substrate as well as some fixed amount of our enzyme."}, {"title": "Enzyme Activity.txt", "text": "And this basically means that initially most of our active sites on our enzymes are actually empty."}, {"title": "Enzyme Activity.txt", "text": "Now, as we begin to increase the amount of substrate as we begin to increase the concentration of our substrate more and more of the active sites will be occupied, will be filled and that will increase the overall rate of our reaction."}, {"title": "Enzyme Activity.txt", "text": "Eventually, however, we will reach a point at which all the active sites on all our enzymes are filled."}, {"title": "Enzyme Activity.txt", "text": "At that point, our reaction, our enzyme activity, has reached a maximum rate and this is known as the maximum velocity or VMAX."}, {"title": "Enzyme Activity.txt", "text": "And the enzyme at this point is said to be saturated."}, {"title": "Enzyme Activity.txt", "text": "And by increasing the concentration of substrate at this point we are basically not affecting the rate of our activity of the enzyme because all those active sites of all the enzymes are actually filled up or occupied."}, {"title": "Enzyme Activity.txt", "text": "Now, let's take a look at the following diagram briefly."}, {"title": "Enzyme Activity.txt", "text": "So our y axis is the velocity, which is basically another way of saying the rate or activity of that enzyme."}, {"title": "Enzyme Activity.txt", "text": "Now the x axis represents the concentration of substrate."}, {"title": "Enzyme Activity.txt", "text": "So notice as we go to the right, along the x axis, we increase the concentration."}, {"title": "Enzyme Activity.txt", "text": "And as we go up along the y axis, we increase the velocity or the rate of activity of that enzyme."}, {"title": "Enzyme Activity.txt", "text": "Now, this slope, shown in purple basically describes the relationship between the concentration of substrate as well as the velocity or rate of activity of our enzyme."}, {"title": "Enzyme Activity.txt", "text": "So notice initially we have a relatively linear relationship between the concentration and the velocity."}, {"title": "Enzyme Activity.txt", "text": "So initially, as we increase the concentration, our rate or velocity also increases pretty much linearly."}, {"title": "Enzyme Activity.txt", "text": "Now eventually we reach this point here and this point basically represents something known as Km."}, {"title": "Enzyme Activity.txt", "text": "And Km is basically a constant known as the Michaelis constant."}, {"title": "Enzyme Activity.txt", "text": "Now, the mechaelis constant basically represents the concentration of the substrate that basically makes sure that exactly half of the active sites are completely filled for that particular enzyme."}, {"title": "Enzyme Activity.txt", "text": "And at this point, our velocity is given by v one half."}, {"title": "Enzyme Activity.txt", "text": "So v one half corresponds to the velocity or the rate of activity of the enzyme when exactly half of the active sites of all the enzymes are basically occupied by our substrate."}, {"title": "Enzyme Activity.txt", "text": "So the point at which exactly half of the enzyme active sites are being used up or are being occupied is given by a constant given by Km known as the Mikhailis constant."}, {"title": "Enzyme Activity.txt", "text": "At this point, the velocity is given by v one half."}, {"title": "Enzyme Activity.txt", "text": "Now, we're going to discuss this in much more detail when we get into biochemistry, but at this point I simply want to mention the filing for an idea about this Maca Lis constant."}, {"title": "Enzyme Activity.txt", "text": "So the Michael is constant."}, {"title": "Enzyme Activity.txt", "text": "Km does not actually depend on the concentration."}, {"title": "Enzyme Activity.txt", "text": "What it depends on is the type of enzyme that we are dealing with."}, {"title": "Enzyme Activity.txt", "text": "So the MACA's constant basically gives us information about the affinity or the traction of the enzyme to our substrate."}, {"title": "Enzyme Activity.txt", "text": "So a very low Km value for any given enzyme means that the enzyme has a very high affinity for the substrate."}, {"title": "Enzyme Activity.txt", "text": "Because a low Km means a small amount, a small quantity of concentration of substrate basically is required to fill up exactly half of our enzyme actives."}, {"title": "Enzyme Activity.txt", "text": "And conversely, a high Km value, a high mecalus constant for a given enzyme means that we need a lot of substrate to actually fill exactly half of those active sites of our enzyme."}, {"title": "Enzyme Activity.txt", "text": "So basically, these are the three factors that play a role in effecting the activity and the functionality of the enzyme."}, {"title": "Enzyme Activity.txt", "text": "We have temperature, we have the PH level as well as the concentration of our substrate."}, {"title": "Lambda Phages as Vectors .txt", "text": "Previously, we discussed how we can use bacterial plasmids as vectors, as carriers are recombinant DNA molecules."}, {"title": "Lambda Phages as Vectors .txt", "text": "So we can form a recombinant DNA molecule in a lab."}, {"title": "Lambda Phages as Vectors .txt", "text": "We can then place it into a plasma and take that plasmid and place it into a bacterial cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "And that bacterial cell will divide."}, {"title": "Lambda Phages as Vectors .txt", "text": "And as it divides, it will replicate that plasmid."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so we can produce use many identical copies of that recombinant DNA molecule of interest."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, we can use plasma's vectors or we can also use another type of vector, another type of carrier known as a lambda phage."}, {"title": "Lambda Phages as Vectors .txt", "text": "And a lambda phage is a special type of bacteria phage that infects E. Coli cells."}, {"title": "Lambda Phages as Vectors .txt", "text": "So it has two types of cycles."}, {"title": "Lambda Phages as Vectors .txt", "text": "It has the lytic life cycle and it has the lysogenic life cycle."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, in the lytic cycle, this is the dangerous cycle that ultimately kills that cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "In the lytic cycle, that bacteriophage essentially hijacks the machinery of that cell, the ribosomes and so forth."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so it produces many of these viral protein molecules and viral DNA molecules."}, {"title": "Lambda Phages as Vectors .txt", "text": "And what it does is it assembles, it packages these viral molecules into these viral particles."}, {"title": "Lambda Phages as Vectors .txt", "text": "It produces many viral agents inside the cell, so it can produce as many as 100 viral particles inside that cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "And when the cell can hold all those viral agents any longer, it essentially bursts open, releasing all those newly synthesized virins to the outside environment."}, {"title": "Lambda Phages as Vectors .txt", "text": "And then those viral agents can move on onto other bacterial cells and infect other cells."}, {"title": "Lambda Phages as Vectors .txt", "text": "So this is the very dangerous and very activelytic cycle."}, {"title": "Lambda Phages as Vectors .txt", "text": "But that bacteriophage."}, {"title": "Lambda Phages as Vectors .txt", "text": "If the environmental conditions are just right, it can take a much more relaxed approach, a much more inactive approach, in which it essentially takes that viral DNA molecule and incorporates it into the genome of that whole cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so when that genome is replicated, when the cell, for example, divides, that viral DNA will also be replicated along with that host genome."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, of course, eventually, if some type of environmental factor exists, for example, some type of stressful situation, that DNA molecule, the viral DNA molecule inside that cell, can essentially be used to once again undergo the lytic cycle, in which the cell will begin producing the viral particles and eventually will lice."}, {"title": "Lambda Phages as Vectors .txt", "text": "So let's take a look at the following diagram, which basically summarizes these two different cycles."}, {"title": "Lambda Phages as Vectors .txt", "text": "So we have the lambda phage that contains that viral DNA molecule."}, {"title": "Lambda Phages as Vectors .txt", "text": "It attaches onto the cell membrane by using these receptors, and then it injects that DNA molecule into the cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, if the environmental conditions are correct, the cell will basically or the virus will basically undergo the lysogenic cycle in which the DNA will simply be incorporated into the cell's genome."}, {"title": "Lambda Phages as Vectors .txt", "text": "And then the cell can basically live on for generations."}, {"title": "Lambda Phages as Vectors .txt", "text": "And as it divides, this viral DNA molecule along with the genome will be replicated and will be given to that offspring cell."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, on the other hand, it can also take a lytic approach."}, {"title": "Lambda Phages as Vectors .txt", "text": "And in the lytic pathway, what happens is this cell basically turns into a factory that produces many of these viruses."}, {"title": "Lambda Phages as Vectors .txt", "text": "And eventually, when the cell cannot hold all those viruses inside that cell, it will break open, it will lice, releasing all those virus to the outside."}, {"title": "Lambda Phages as Vectors .txt", "text": "And these viruses can then go on and affect other bacterial cells."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, how exactly can we use the lambda phages as vectors?"}, {"title": "Lambda Phages as Vectors .txt", "text": "Well, it turns out that we can actually replace this DNA molecule with the DNA molecule of choice."}, {"title": "Lambda Phages as Vectors .txt", "text": "As long as the size of the DNA molecule that we're essentially putting in is about the same as the size of this DNA molecule found in the lambda phage."}, {"title": "Lambda Phages as Vectors .txt", "text": "So what that means is the lambda phage virus does not need its own DNA to actually survive."}, {"title": "Lambda Phages as Vectors .txt", "text": "We can put in any DNA as long as the size it's pretty much the same as the size of that initial lambda DNA."}, {"title": "Lambda Phages as Vectors .txt", "text": "So to see how we can actually do that, let's take a look at the following diagram."}, {"title": "Lambda Phages as Vectors .txt", "text": "So, in diagram one, we extract this blue DNA, the lambda DNA molecule, as shown in the following diagram."}, {"title": "Lambda Phages as Vectors .txt", "text": "So first we need to cut the lambda phage with a restriction enzyme."}, {"title": "Lambda Phages as Vectors .txt", "text": "So we choose some type of restriction enzyme."}, {"title": "Lambda Phages as Vectors .txt", "text": "And because we're talking about E. Coli cell, let's suppose we're going to use a restriction enzyme found in E. Coli cells known as ECoR one."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, ECoR one will essentially cut our DNA of the alpha phase at two locations somewhere here and here."}, {"title": "Lambda Phages as Vectors .txt", "text": "And we produce the following three fragments."}, {"title": "Lambda Phages as Vectors .txt", "text": "So fragment one and fragment three, the side fragments, are also known as the arms."}, {"title": "Lambda Phages as Vectors .txt", "text": "And this is the center of the middle, fragment number two."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, what we can do is we can essentially separate these DNA molecules and then we can remove the fragment number two."}, {"title": "Lambda Phages as Vectors .txt", "text": "And instead of fragment number two, we can place some type of target DNA molecule that we actually want to copy."}, {"title": "Lambda Phages as Vectors .txt", "text": "And we can connect these two fragments onto the size of the target DNA molecule so that the actual size of the DNA does not change compared to the DNA of that lambda phage that we initially extracted."}, {"title": "Lambda Phages as Vectors .txt", "text": "Now, how can we connect these two fragments or these three fragments?"}, {"title": "Lambda Phages as Vectors .txt", "text": "Well, we can use a special enzyme, special catalytic protein known as DNA ligase."}, {"title": "Lambda Phages as Vectors .txt", "text": "So what DNA ligase does, as we'll see in a future lecture, it basically uses ATP molecules to create phosphodiasta bonds between the fragments here and this fragment here."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so ultimately, when we mix these three fragments with DNA ligase, we produce recombinant DNA that is about the same size as this original DNA molecule that came from that lambda phage."}, {"title": "Lambda Phages as Vectors .txt", "text": "And now we can take this DNA molecule and place it back into that lambda phage."}, {"title": "Lambda Phages as Vectors .txt", "text": "And the lambda phage can be mixed in with our E. Coli cells."}, {"title": "Lambda Phages as Vectors .txt", "text": "And if the environmental conditions are right, what will happen is the lythogenic cycle will be followed, and the cell will basically divide many, many times."}, {"title": "Lambda Phages as Vectors .txt", "text": "And every time it divides, it essentially replicates that DNA molecule."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so, at the end, we essentially have a beaker with all these cells that contain many copies of the DNA molecule of interest."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so then we can essentially break the cells down, and we can extract that DNA molecule of interest."}, {"title": "Lambda Phages as Vectors .txt", "text": "And so, at the end, we have many copies of the DNA that we ultimately wanted to amplify in the first place."}, {"title": "Lambda Phages as Vectors .txt", "text": "So we can use these plasmids as vectors, and we can also use these landophages as vector molecules, as carriers of DNA fragments."}, {"title": "Initiation of Action Potential.txt", "text": "Neurons are specialized types of cells that can generate action potentials on the cell membrane of the exxon hillock."}, {"title": "Initiation of Action Potential.txt", "text": "Now, what exactly is an action potential and what is the mechanism by which our neuron generates that action potential?"}, {"title": "Initiation of Action Potential.txt", "text": "So in this lecture, we're going to discuss how we initiate the action potential."}, {"title": "Initiation of Action Potential.txt", "text": "In the next lecture, we're going to focus on the propagation of that axe potential, the movement of the axe potential along the axon of our neuron."}, {"title": "Initiation of Action Potential.txt", "text": "So let's begin by discussing a special type of protein found in the membrane of our neuron."}, {"title": "Initiation of Action Potential.txt", "text": "And this protein is known as the voltagegated ion channel."}, {"title": "Initiation of Action Potential.txt", "text": "Now, there are two types of voltagegated ion channels, and they differ in the type of ion that they allow to pass through."}, {"title": "Initiation of Action Potential.txt", "text": "So we have voltage gated sodium channels, which allow the passage of sodium ions."}, {"title": "Initiation of Action Potential.txt", "text": "And we have voltage gated potassium channels that allow the passage of potassium ions when these voltage gated channels are open."}, {"title": "Initiation of Action Potential.txt", "text": "Now, when our cell is at the resting membrane potential, which is around negative 70 millivolts, our channels, the voltage gated ion channels, are closed."}, {"title": "Initiation of Action Potential.txt", "text": "Now, why exactly do we call these channels voltage gated ion channels?"}, {"title": "Initiation of Action Potential.txt", "text": "Well, they're called this because they basically respond to changes in voltage."}, {"title": "Initiation of Action Potential.txt", "text": "So when the voltage changes across our cell membrane, these voltage gated ion channels can basically open up."}, {"title": "Initiation of Action Potential.txt", "text": "And when they open up, they allow the flow of our ions."}, {"title": "Initiation of Action Potential.txt", "text": "So these voltage gated ion channels can open if the voltage changes."}, {"title": "Initiation of Action Potential.txt", "text": "Now, let's suppose that we have our neuron, the axon hillock of the neuron, that is at the resting membrane potential."}, {"title": "Initiation of Action Potential.txt", "text": "So at negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "Now, let's suppose we apply a stimulus onto the cell membrane of the neuron."}, {"title": "Initiation of Action Potential.txt", "text": "And this stimulus is equal to, or it exceeds the threshold value, which is around, usually around negative 45 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "So the threshold's value is basically the value of the stimulus that has to be just right so that the action potential is generated."}, {"title": "Initiation of Action Potential.txt", "text": "So once we reach our threshold value, this threshold voltage of about negative 45 millivolts will signal the voltage gated sodium channels to actually open up."}, {"title": "Initiation of Action Potential.txt", "text": "And as soon as they open up, our sodium ions will begin to flow."}, {"title": "Initiation of Action Potential.txt", "text": "The question is in which direction will the sodium ions travel?"}, {"title": "Initiation of Action Potential.txt", "text": "So let's take a look at the following diagram, which describes what I just said."}, {"title": "Initiation of Action Potential.txt", "text": "So before the stimulus, we have our cell membrane of the neuron that is basically at the resting membrane potential."}, {"title": "Initiation of Action Potential.txt", "text": "So at negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "And at this point, the inside of the cell, this region, will contain a negative charge."}, {"title": "Initiation of Action Potential.txt", "text": "The outside will contain a positive charge."}, {"title": "Initiation of Action Potential.txt", "text": "Now, we know that outside of the cell, we have a higher concentration of sodium ions than on the inside of the cell."}, {"title": "Initiation of Action Potential.txt", "text": "So as soon as our stimulus reaches our threshold value, that will open up our sodium, our sodium voltage gated channels."}, {"title": "Initiation of Action Potential.txt", "text": "And when they open up, this is known as our depolarization period."}, {"title": "Initiation of Action Potential.txt", "text": "So what will begin to happen is the sodium ions will begin to move down their electrochemical gradient."}, {"title": "Initiation of Action Potential.txt", "text": "So because they contain a positive charge and the inside is negatively charged, they will move this way from the outside to the inside."}, {"title": "Initiation of Action Potential.txt", "text": "And because our concentration is high on the outside and low on the inside, they will move into our cell."}, {"title": "Initiation of Action Potential.txt", "text": "And this is known as the electrochemical gradient."}, {"title": "Initiation of Action Potential.txt", "text": "So, since the concentration of sodium is higher on the outside than the inside, and because the inside the cell is negatively charged, our sodium ions will move down their electrochemical gradient into the cell."}, {"title": "Initiation of Action Potential.txt", "text": "Now, why do we call this our depolarization period?"}, {"title": "Initiation of Action Potential.txt", "text": "Well, we call it the depolarization period because the inside of the cell basically becomes positive."}, {"title": "Initiation of Action Potential.txt", "text": "Why?"}, {"title": "Initiation of Action Potential.txt", "text": "Well, as our sodium ions flow into the cell, our sodium ions each carry a positive charge."}, {"title": "Initiation of Action Potential.txt", "text": "And as the concentration of our sodium ions inside increases, the amount of positive charge also increases."}, {"title": "Initiation of Action Potential.txt", "text": "So eventually, the inside will become positive, the outside will become negative, and that will reverse or depolarize our cell membrane."}, {"title": "Initiation of Action Potential.txt", "text": "It will reverse the polarity of that membrane."}, {"title": "Initiation of Action Potential.txt", "text": "So once again, the opening of these channels will make the membrane much more permeable to sodium ions than to potassium ions."}, {"title": "Initiation of Action Potential.txt", "text": "And the high influx of sodium into our cytoplasm, the cell will make the inside of the cell positive and the outside negative."}, {"title": "Initiation of Action Potential.txt", "text": "And this will reverse the polarity."}, {"title": "Initiation of Action Potential.txt", "text": "So it will depolarize our cell membrane, because before, we have negative charge inside, now we have a positive charge inside."}, {"title": "Initiation of Action Potential.txt", "text": "Now, so the inside of the cell will become positive."}, {"title": "Initiation of Action Potential.txt", "text": "But what exactly is the magnitude of our positive charge?"}, {"title": "Initiation of Action Potential.txt", "text": "Well, when the inside of the cell reaches a positive voltage of about positive 45 million volt at this point, this will signal our voltage gated sodium channels to close."}, {"title": "Initiation of Action Potential.txt", "text": "And at the same time, it will signal the voltage gated potassium channels to actually open up."}, {"title": "Initiation of Action Potential.txt", "text": "And at this point, this basically ends depolarization, and it starts repolarization."}, {"title": "Initiation of Action Potential.txt", "text": "So once again, when the inside of the cell reaches our voltage of positive 45 millivolts, the voltage gated sodium channels will be shut, and they will be inactivated."}, {"title": "Initiation of Action Potential.txt", "text": "And what that basically means, even if our sodium channels are actually open, what happens is a spherical protein attached to this channel basically moves in and closes our entrance."}, {"title": "Initiation of Action Potential.txt", "text": "And even though it's open, the entrance is shut."}, {"title": "Initiation of Action Potential.txt", "text": "And so our sodium ions cannot actually move out or in to our cell."}, {"title": "Initiation of Action Potential.txt", "text": "So at the same time, this membrane voltage will signal the voltage gated potassium channels to actually open up and become active."}, {"title": "Initiation of Action Potential.txt", "text": "And now these potassium ions will basically move down their electrochemical gradient."}, {"title": "Initiation of Action Potential.txt", "text": "So, because we have a high concentration of potassium inside, and because we have a negative charge on the outside, these positively charged potassium ions will move down their electrochemical gradient and to the outside of our cell."}, {"title": "Initiation of Action Potential.txt", "text": "Now, the reason we call it repolarization period is because this period basically attempts to return our membrane potential back to its resting potential."}, {"title": "Initiation of Action Potential.txt", "text": "And that's because the positive charge begins to decrease on the inside as the positively charged potassium leave the inside and travel to the outside."}, {"title": "Initiation of Action Potential.txt", "text": "So as soon as the voltage gated potassium channels open, the potassium ions will move down the electrochemical gradient to the outside of the cell, to this region here."}, {"title": "Initiation of Action Potential.txt", "text": "Now, the membrane will once again become more permeable to our potassium than to sodium."}, {"title": "Initiation of Action Potential.txt", "text": "And the sodium basically rushes out of the cell and this will make the inside more negative and the outside more positive."}, {"title": "Initiation of Action Potential.txt", "text": "Now, once our voltage of the membrane decreases back to the threshold value of about negative 45 millivolts, some of the inactivated sodium channels will begin to recover."}, {"title": "Initiation of Action Potential.txt", "text": "So they will begin to close, but now they're no longer inactivated."}, {"title": "Initiation of Action Potential.txt", "text": "And this part will become important when we'll discuss the absolute refractory period and the relative refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "Now, at this point, our permeability of the membrane to potassium is actually higher than normal."}, {"title": "Initiation of Action Potential.txt", "text": "And this is exactly what causes our voltage of the cell to drop below the resting voltage in this period, when our voltage of the membrane drops slightly below the resting membrane potential."}, {"title": "Initiation of Action Potential.txt", "text": "This is known as the hyperpolarization period."}, {"title": "Initiation of Action Potential.txt", "text": "Now, to return the neuron to return the membrane of the neuron back to the resting membrane potential, which is equal to about negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "Now, we have to use energy, we have to use ATP, and we have to use a special type of pump, a special type of ATPase pump ATPase pump known as the sodium potential or the potassium sodium ATPase pump."}, {"title": "Initiation of Action Potential.txt", "text": "And what the potassium sodium ATPase pump does is it actively pumps three sodiums out of the cell, so against electrochemical gradient and two potassium into the cell against the electrochemical gradient."}, {"title": "Initiation of Action Potential.txt", "text": "And this eventually returns our membrane back to the resting membrane potential of around negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "So, everything we just discussed so far basically is summarized in the following graph."}, {"title": "Initiation of Action Potential.txt", "text": "So let's suppose the y axis is our voltage given in millivolts, and the x axis is time."}, {"title": "Initiation of Action Potential.txt", "text": "So basically what happens is this is the resting membrane potential of about negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "This is our threshold value of about negative 45 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "Now, if we apply stimulus onto the membrane of the neuron at the exxon hillock, and if the stimulus is equal to or exceeds this threshold value, then that will cause, that will signal the sodium voltage gated channels to actually open up."}, {"title": "Initiation of Action Potential.txt", "text": "So at this point, they open up and this causes the depolarization of our membrane."}, {"title": "Initiation of Action Potential.txt", "text": "So basically, as the sodium ions move down their electrochemical gradient and as they move into the cell, that causes the inside to go from negative to positive and the outside to go from positive to negative, as shown in this diagram."}, {"title": "Initiation of Action Potential.txt", "text": "And that basically increases our cell voltage from negative 70 millivolts to about positive 45 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "And this process is known as depolarization."}, {"title": "Initiation of Action Potential.txt", "text": "Now, when we reach the positive 45 millivolt value, the sodium channels will close, they will become inactivated while the potassium channels will begin to open."}, {"title": "Initiation of Action Potential.txt", "text": "And now no longer will the sodium move outside, but the potassium no longer will the sodium move inside, but the potassium will begin to move outside."}, {"title": "Initiation of Action Potential.txt", "text": "At this point, the inside will become negative again."}, {"title": "Initiation of Action Potential.txt", "text": "And so this will decrease as shown by this curve."}, {"title": "Initiation of Action Potential.txt", "text": "So this is known as the repolarization period."}, {"title": "Initiation of Action Potential.txt", "text": "It's the period by which the cell attempts to return the membrane back to the resting potential."}, {"title": "Initiation of Action Potential.txt", "text": "Now, because at this particular point, let's say at this point, our potassium, the membrane of the cell, is more permeable to potassium than normal."}, {"title": "Initiation of Action Potential.txt", "text": "That means it will go slightly below our resting potential."}, {"title": "Initiation of Action Potential.txt", "text": "And this is known as the hyperpolarization period."}, {"title": "Initiation of Action Potential.txt", "text": "And this is shown by this period here."}, {"title": "Initiation of Action Potential.txt", "text": "Now, when we have the hyperpolarization period, our sodium, potassium, Atpace pump will begin to pump."}, {"title": "Initiation of Action Potential.txt", "text": "By using ATP, molecules will begin to pump our three sodiums outside of the cell and potassium into the cell against electrochemical gradient."}, {"title": "Initiation of Action Potential.txt", "text": "And that's exactly why we need to use energy."}, {"title": "Initiation of Action Potential.txt", "text": "So basically, this will ultimately return our potential of the membrane back to the resting membrane potential of about negative 70 millivolts."}, {"title": "Initiation of Action Potential.txt", "text": "So this is known as our action potential."}, {"title": "Initiation of Action Potential.txt", "text": "So one last thing that I want to mention about our action potential is the fact that our action potential is all or nothing."}, {"title": "Initiation of Action Potential.txt", "text": "So our action potential is all or nothing."}, {"title": "Initiation of Action Potential.txt", "text": "And that means it either takes place or it doesn't."}, {"title": "Initiation of Action Potential.txt", "text": "So if the stimulus is high enough, then our action potential will take place."}, {"title": "Initiation of Action Potential.txt", "text": "If it's low, it will not take place."}, {"title": "Initiation of Action Potential.txt", "text": "If it's below the threshold value, that will not take place."}, {"title": "Initiation of Action Potential.txt", "text": "That's exactly what we mean by all or nothing."}, {"title": "Initiation of Action Potential.txt", "text": "It either takes place or it doesn't."}, {"title": "Initiation of Action Potential.txt", "text": "Now, this also means that no matter how high the stimulus actually is, the amplitude or the magnitude of this wave will be exactly the same."}, {"title": "Initiation of Action Potential.txt", "text": "So even if the stimulus is very, very high, this value, the height of the curve, will not change."}, {"title": "Initiation of Action Potential.txt", "text": "So by increasing the stimulus, we are not affecting the amplitude of our action potential."}, {"title": "Initiation of Action Potential.txt", "text": "What we are doing is we're increasing the frequency, we're increasing the frequency of oscillation of the action potential."}, {"title": "Initiation of Action Potential.txt", "text": "So instead of having one action potential in this time period, by increasing the stimulus, we're basically increasing the number of action potentials within this period."}, {"title": "Initiation of Action Potential.txt", "text": "So instead of one, we might have two or three action potentials take place within the same exact time period."}, {"title": "Initiation of Action Potential.txt", "text": "Now, the last thing that I want to mention is something called the refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "So we have an absolute refractory period and we have a relative refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "So the absolute refractory period is the period between this point and this point."}, {"title": "Initiation of Action Potential.txt", "text": "So remember, at this point, our sodium voltage gated ions begin to recover."}, {"title": "Initiation of Action Potential.txt", "text": "They begin to go from the inactivated state to the closed state."}, {"title": "Initiation of Action Potential.txt", "text": "So basically, between the initiation point when the stimulus is applied and before our inactivated sodium channels begins to recover, this is known as the absolute refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "And this is the period at which if we apply a stimulus, no matter how high the stimulus is, our action potential will not begin again."}, {"title": "Initiation of Action Potential.txt", "text": "We will not begin to initiate an action potential in the absolute refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "Now, we also have the relative refractory period, and this is this region here."}, {"title": "Initiation of Action Potential.txt", "text": "So this entire region from this point to this point is known as the relative refractory period."}, {"title": "Initiation of Action Potential.txt", "text": "Because if we apply a very high stimulus at this point, an action potential can be achieved."}, {"title": "Initiation of Action Potential.txt", "text": "So that's exactly why I mentioned the fact that as the voltage membrane reaches the threshold value of negative 45, so as it goes back to this value at this point, our inactivated sodium channels begins to recover."}, {"title": "Initiation of Action Potential.txt", "text": "So basically, this vehicle region, the protein begins to it leaves and our membrane, our channel, basically closes and once again it is able to activate itself if the stimulus is high enough."}, {"title": "Initiation of Action Potential.txt", "text": "And that's exactly why at the relative refractory period, if the stimulus is high, we can basically achieve another action potential."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "The final complex of the electron transport chain is complex four."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this is what we're going to focus on in this lecture."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, complex four is also known as cytochrome C oxidase."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And along complex four, what happens is the electrons are transferred from cytochrome C molecules onto oxygen."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So we generate water molecules, and we also help establish a proton electrical chemical gradient that will be used by ATP synthase to actually generate those high energy ATP molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, complex four contains two important groups."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "One of the group are the heme groups, and the other groups are copper atoms."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, we have two heme groups, heme A and heme A three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And we have three copper atoms."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Two of these three copper atoms basically associate with one another to form the copper A, copper A center."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And the third, the other copper atom we call copper B, actually associates with the heme A three to form the heme A three copper B center."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this is where we're going to basically reduce that oxygen to form water molecules, as we'll see in just a moment."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So let's actually go through the steps of how this process takes place and how these electrons are transferred from the reduced cytochrome C molecules that we produced along complex three onto the oxygen to form the water molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So let's begin with diagram number one."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So this is our inner mitochondrial membrane."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "This is the matrix, and this is the intermembrane space."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, we generate cytochrome C molecules in their reduced form along complex three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And then the cytochrome C in its reduced form, dissociates from complex three and travels and binds onto complex four."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And once it binds onto complex four, it transfers an electron initially to the copper A, copper A center."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Then the electron goes on to heme A, and then it moves on to heme A three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And that electron ultimately ends up being transferred onto the copper B, and it reduces the copper B."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, what happens is let me grab purple."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "What happens is we have our copper in its two plus states."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And when it gains a single electron, so we have a single electron coming in."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And when it gains that electron, it is basically reduced into copper plus."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So anytime the copper in this diagram abstracts an electron, it binds an electron, it is reduced."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So it goes from its oxidized form to its reduced form."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this is exactly what happens in this diagram when this copper B gains an electron."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And it also happens when this copper A gains an electron."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, notice in the diagram we actually have two of these cytochrome C molecules in their reduced form."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And that's because what happens is first a single cytochrome binds onto this section, giving off an electron."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "The electron ultimately ends up reducing this copper B."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Then that oxidized, cytochrome C leaves and a second reduced cytochrome C binds and gives off an electron."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So ultimately, we have two of these cytochrome C molecules, in their reduced form, being oxidized, give off two electrons."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "One of the electron ultimately ends up reducing the copper B, and the other electron ultimately ends up reducing the heme A three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So this should be the heme A three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And so we summarize this step in the following way."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So, we have two reduced cytochrome C molecules give off a total of two electrons."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So one electron per cytochrome C molecule."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "One of the electron stops at the copper B group, reducing it, as discussed here, and the other basically stops at the heme A three, reducing that heme A three."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And once these two groups are in their reduced form, only then can they actually bind oxygen."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So in the next step, in diagram two, we have an oxygen, and the oxygen is the same oxygen molecule that we essentially breathe in from the environment."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "The oxygen is basically used to form something called a peroxide bridge between this heme A three and this copper B."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So once the heme A three and the copper B are in their fully reduced form, and a diatomic oxygen molecule is actually abstracted, and it is used to actually build a peroxide bridge between this structure and this structure here."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, once we form this bridge, what happens next is, from the matrix of the mitochondria, two protons are abstracted, and those two protons are actually used to help break this bond."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "But before the two protons are used, two more of these reduced cytochrome C molecules are actually oxidized by protein complex four."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So two of these cytochrome C's are actually oxidized."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So they release two electrons."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "One of the electrons ends up on this copper."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "The other electron ends up on this heme A three group."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And when those two electrons are abstracted at the same time, two protons are picked up by this protein by this complex force structure from the matrix of the mitochondria."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this allows us to break this bridge between this oxygen and this oxygen here."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So we form the copper hydroxide group and the heme A three hydroxide group."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So in step three, two more reduced cytochrome C molecules are oxidized to transfer an additional two electrons into our system."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And two H plus two H plus ions are also obtained from the matrix of the mitochondria to help us break that peroxide bond, this bond here, and ultimately form these two structures."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And once we form these two structures, two more protons are abstracted from the matrix, and those two protons are basically used to form two water molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So one of these protons is picked up by, let's say, this hydroxide group, and the other proton is picked up by this hydroxide group."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And so these two bonds are formed."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "These two bonds are broken."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "We regenerate these two groups in their original initial oxidized form, and we also form the two water molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So this is the final step."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "Now, by the way, as these electrons are basically moved from the cytochrome seed to these two final groups."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And as we ultimately form the two water molecules, a total of four protons for hydrogen ions are essentially pumped from the matrix of the mitochondria to the intermembrane space."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this is shown in the following diagram."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So this is basically the summary of these four steps."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So once again, in the final step, in step four, the abstraction of two more hydrogen ions to a protons from the matrix helps oxidize the heme A three and the copper B group back to their original oxidized states."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "In the case of copper B, we basically oxidize it back into the copper two plus form."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "In the process, we also use those two protons to actually generate two water molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And this is basically the summary of these four steps that take place on complex four."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So let's take a look at this summary."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So essentially, we have a total of four individual reduced cytochrome C molecules that come and interact with complex four."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And they interact one by one."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So initially, we have two interacting here and then we have two interacting here to give us a total of four cytochrome C reduced molecules so they're oxidized into their oxidized form."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "In the process, a single oxygen molecule is used."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "The oxygen that we breathe in from the environment and four protons are taken up from the matrix of the mitochondria and we use the oxygen and the four protons to basically generate the two water molecules in the process."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "This protein, complex four, also acts as a proton pumps and it helps us generate that electrochemical gradient for protons that we're going to use by ATP synthase to actually generate those high energy ATP molecules."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "So from the matrix, we essentially pump out four of these protons and so that our concentration in the interim membrane space for the protons is greater compared to the matrix."}, {"title": "Complex IV of Electron Transport Chain .txt", "text": "And as we'll see in a future lecture, that proton gradient will ultimately be used to actually oxidatively phosphorylate the ATP molecules to form the high energy ATP molecules."}, {"title": "Introduction to Glycogen .txt", "text": "The next topic that we're going to focus on will be glycogen metabolism."}, {"title": "Introduction to Glycogen .txt", "text": "So let's begin by defining what glycogen actually is."}, {"title": "Introduction to Glycogen .txt", "text": "Well, glycogen is simply the way that we store glucose inside the cells of our body."}, {"title": "Introduction to Glycogen .txt", "text": "So we essentially update glucose when we eat food."}, {"title": "Introduction to Glycogen .txt", "text": "And then the glucose, once it, once it makes its way into the cells of our body, we transform glucose into glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "So glycogen is the storage form of glucose."}, {"title": "Introduction to Glycogen .txt", "text": "Now, glycogen is actually a very long polymer of glucose molecules and it contains branching points."}, {"title": "Introduction to Glycogen .txt", "text": "And these branching points are a result of alpha one six glycocitic linkages or alpha one six glycocitic bonds."}, {"title": "Introduction to Glycogen .txt", "text": "So there are two types of alpha linkages in glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "We have alpha one four glycocitic bonds that essentially hold adjacent glucose molecules in glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "And we also have the alpha one six glycositic bonds, which are those branching points in glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "So if we take a random section of glycogen, this is basically what we might see."}, {"title": "Introduction to Glycogen .txt", "text": "Notice we have these one four glycocitic bonds, which are basically bonds between the first carbon of one glucose monomer and the fourth carbon of the adjacent glucose monomer."}, {"title": "Introduction to Glycogen .txt", "text": "So we have one alpha one, we have one alpha one four glycocitic bond here, another one here, third one here, fourth one here, fifth one here, and so forth."}, {"title": "Introduction to Glycogen .txt", "text": "And we also have these branching points which are a result of the alpha one six glycocytic bonds."}, {"title": "Introduction to Glycogen .txt", "text": "And that's because we have a bond between the first carbon of this glucose and the 6th carbon of the adjacent glucose."}, {"title": "Introduction to Glycogen .txt", "text": "So, once again, glycogen is the storage form of glucose."}, {"title": "Introduction to Glycogen .txt", "text": "It's the way we store the glucose molecules inside the cells of our body."}, {"title": "Introduction to Glycogen .txt", "text": "Glycogen is a long polymer of glucose molecules that branches about every ten glucose residues."}, {"title": "Introduction to Glycogen .txt", "text": "And glycogen consists of two types of alpha linkages."}, {"title": "Introduction to Glycogen .txt", "text": "We have the alpha one four glycocitic linkages and the alpha one six glycocitic bombs."}, {"title": "Introduction to Glycogen .txt", "text": "Now, if we examine the cells of our body, there are two types of cells that are responsible for storing glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "We have the hepatitis, the liver cells, and we also have the skeleton muscle cells."}, {"title": "Introduction to Glycogen .txt", "text": "Now, cells such as our liver cells are responsible for actually regulating and maintaining the glucose levels inside our blood."}, {"title": "Introduction to Glycogen .txt", "text": "Now, why is it important to maintain a proper glucose level inside our blood?"}, {"title": "Introduction to Glycogen .txt", "text": "Well, one reason is because cells such as our brain cells depend solely and almost entirely on glucose molecules for energy."}, {"title": "Introduction to Glycogen .txt", "text": "And so what that means is the brain cells need to take the glucose from the blood to actually use the glucose as an energy source."}, {"title": "Introduction to Glycogen .txt", "text": "And that's why the liver must actually maintain and regulate the proper concentration of glucose inside our blood."}, {"title": "Introduction to Glycogen .txt", "text": "So, for instance, if our blood level glucose is very low, then what these liver cells will do is they will break down the glycogen as we'll talk about in a future lecture, into Glucose release the glucose inside the Blood."}, {"title": "Introduction to Glycogen .txt", "text": "And that will increase the level of glucose to the correct level."}, {"title": "Introduction to Glycogen .txt", "text": "So cells such as liver cells can use glycogen to regulate blood glucose levels of the body."}, {"title": "Introduction to Glycogen .txt", "text": "This is important because cells such as brain cells depend almost entirely on glucose for energy."}, {"title": "Introduction to Glycogen .txt", "text": "Now, what about skeleton muscle cells?"}, {"title": "Introduction to Glycogen .txt", "text": "Because not only do liver cells store glucose as glycogen, but our skeleton muscle cells also store the glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "Well, the skeleton muscle cells are responsible primary for actually using the glycogen to break it down to glucose and use that glucose in glycolysis to actually form ATP molecules so that we can carry out different types of voluntary motion, for instance, moving my hand back and forth."}, {"title": "Introduction to Glycogen .txt", "text": "So our body also depends on glycogen breakdown during periods of rapid activity, for example, sprinting."}, {"title": "Introduction to Glycogen .txt", "text": "And the glucose obtained from glycogen can be used to produce energy under anaerobic conditions."}, {"title": "Introduction to Glycogen .txt", "text": "And this is a very important distinction because other sources of energy, for instance fatty acids, depend on oxygen."}, {"title": "Introduction to Glycogen .txt", "text": "But in the case of glycogen, we can actually break down glycogen into glucose and produce energy without using oxygen."}, {"title": "Introduction to Glycogen .txt", "text": "So glycogen can be stored in two types of cells."}, {"title": "Introduction to Glycogen .txt", "text": "So we have the liver cells and skeleton muscle cells and the glycogen molecules, the glycogen polymers are actually stored in these tiny granules found throughout the cytoplasm of the liver and the skeleton muscle cells."}, {"title": "Introduction to Glycogen .txt", "text": "So this is basically what glycogen actually looks like."}, {"title": "Introduction to Glycogen .txt", "text": "And as I mentioned before, the liver cells use the glycogen primarily to actually regulate and maintain the proper levels of glucose inside our blood, while the skeleton muscle cells actually use the glycogen to break it down to glucose, to use it as a rapid energy source for sudden and strain use activity."}, {"title": "Introduction to Glycogen .txt", "text": "Now, in the lectures to come, we're going to discuss glycogen metabolism and we can break down glycogen metabolism into subcategories."}, {"title": "Introduction to Glycogen .txt", "text": "So we have the degradation of glycogen, so the breakdown of glycogen, and we also have the synthesis of glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "Now, if we examine the breakdown of glycogen, the degradation of glycogen, we can actually categorize that process into three different steps."}, {"title": "Introduction to Glycogen .txt", "text": "So we have the release of glucose one six phosphate from glycogen."}, {"title": "Introduction to Glycogen .txt", "text": "So we actually take the glycogen that contains, let's say, n number of glucose molecules and we release a single glucose one phosphate and we basically form a modified glucose, a modified glycogen that now contains N minus one glucose monomers."}, {"title": "Introduction to Glycogen .txt", "text": "Now, once we form this glycogen that contains one less glucose molecule, we actually have to remodel, we have to restructure that glycogen so that we can further break down that glycogen and release many more glucose one six phosphate molecules."}, {"title": "Introduction to Glycogen .txt", "text": "Now, in the final step, we take the glucose one six phosphate and we transform it into glucose six phosphate."}, {"title": "Introduction to Glycogen .txt", "text": "And the pathway that glucose six phosphate follows basically depends on the conditions inside our body and the cell type that the glycogen actually is found in."}, {"title": "Introduction to Glycogen .txt", "text": "For instance, if we're talking about hepatitis, our liver cells remember, the liver cells basically are responsible for regulating the levels of glucose inside our blood."}, {"title": "Introduction to Glycogen .txt", "text": "So what happens inside our liver cells is the glucose six phosphate is actually transformed into glucose molecules, and the glucose is then released into the blood plasma of our cardiovascular system, and that might increase the level of glucose inside our blood."}, {"title": "Introduction to Glycogen .txt", "text": "Now, if we're inside, for instance, our skeleton muscle cells, the skeleton muscle cells can use that glucose to actually form ATP molecules to carry out different types of active and strainuse activities."}, {"title": "Introduction to Glycogen .txt", "text": "And that requires glycolysis."}, {"title": "Introduction to Glycogen .txt", "text": "So the glucose six phosphate can basically be broken down to form ATP molecules and Pyruvate molecules in glycolysis."}, {"title": "Introduction to Glycogen .txt", "text": "And remember, glycolysis is an anaerobic process."}, {"title": "Introduction to Glycogen .txt", "text": "It takes place in the absence or in the presence of oxygen because it doesn't require oxygen."}, {"title": "Introduction to Glycogen .txt", "text": "Now, another pathway that glucose six phosphate can actually follow is a pathway known as the pentose phosphate path."}, {"title": "Introduction to Glycogen .txt", "text": "We'll talk about this in much more detail in Electro To Come."}, {"title": "Introduction to Glycogen .txt", "text": "So these are the three steps that the breakdown of glycogen can actually be broken down to."}, {"title": "Introduction to Glycogen .txt", "text": "And we'll talk about these in much more detail in Electro to Come."}, {"title": "Introduction to Glycogen .txt", "text": "Now, if we want to synthesize glycogen from glucose, the glucose molecules must first be activated."}, {"title": "Introduction to Glycogen .txt", "text": "And we activate glucose molecules by transforming those glucose molecules into UDP glucose, where UDP stands for urine diphosphate glucose."}, {"title": "Introduction to Glycogen .txt", "text": "And we'll talk about this in much more detail in Electric to Come."}, {"title": "Structure of the Human Ear .txt", "text": "In the same analogous way that the human eye is capable of capturing light and transforming light into electrical signals that the brain uses to create an image of our surroundings."}, {"title": "Structure of the Human Ear .txt", "text": "The human ear uses mechanical waves, pressure waves in the air, to basically transform them into electrical signals."}, {"title": "Structure of the Human Ear .txt", "text": "And then the brain uses those electrical signals to create sound."}, {"title": "Structure of the Human Ear .txt", "text": "And that's exactly why these mechanical waves are also known as sound waves."}, {"title": "Structure of the Human Ear .txt", "text": "So let's discuss how the mechanical wave actually propagates through the ear."}, {"title": "Structure of the Human Ear .txt", "text": "Let's discuss the structures of the ear and how the ear transforms the mechanical wave into electrical signals."}, {"title": "Structure of the Human Ear .txt", "text": "So the ear can be generalized, it can be broken down into three sections."}, {"title": "Structure of the Human Ear .txt", "text": "We have the outer ear, we have the middle ear, and we have the inner ear."}, {"title": "Structure of the Human Ear .txt", "text": "Now let's begin with the outer ear."}, {"title": "Structure of the Human Ear .txt", "text": "The outer ear basically contains a section known as the pinna, or the oracle."}, {"title": "Structure of the Human Ear .txt", "text": "So this entire section, including our ear lobe, is known as arabina."}, {"title": "Structure of the Human Ear .txt", "text": "Now, the pinna, what it basically does is it captures all the energy that is carried by our mechanical wave and it directs that mechanical wave into the ear canal."}, {"title": "Structure of the Human Ear .txt", "text": "And because the pinna has such a large surface area, it basically acts to amplify the force that our pressure wave actually creates."}, {"title": "Structure of the Human Ear .txt", "text": "So the human ear can detect variations in air pressure known as mechanical waves."}, {"title": "Structure of the Human Ear .txt", "text": "The pina, also known as the Oracle, acts to capture much of the energy of the mechanical wave and transmits that mechanical wave through the ear canal, which is basically this portion here."}, {"title": "Structure of the Human Ear .txt", "text": "So the ear canal is also part of the outer portion of the ear."}, {"title": "Structure of the Human Ear .txt", "text": "Now, the mechanical wave then moves along the ear canal and towards the end of our ear canal."}, {"title": "Structure of the Human Ear .txt", "text": "And at the end of the ear canal, we have the beginning of the middle ear."}, {"title": "Structure of the Human Ear .txt", "text": "So we have the propagating mechanical wave."}, {"title": "Structure of the Human Ear .txt", "text": "Some type of disturbance in the air initiates this propagating wave, our mechanical wave."}, {"title": "Structure of the Human Ear .txt", "text": "It eventually is captured by the pin of the ear and directed into the ear canal."}, {"title": "Structure of the Human Ear .txt", "text": "And we have this amplification process taking place."}, {"title": "Structure of the Human Ear .txt", "text": "The pin of the ear amplifies the wave by about times two."}, {"title": "Structure of the Human Ear .txt", "text": "Now, when our mechanical wave travels through this region, through the ear canal, inside the ear canal, we have many air molecules."}, {"title": "Structure of the Human Ear .txt", "text": "And as these air molecules vibrate back and forth, they eventually cause their eardrum, also known as our tympanic membrane, which is basically a membrane of a sort, the vibrations of the air molecules inside the ear that causes our membrane, the eardrum, to vibrate as well."}, {"title": "Structure of the Human Ear .txt", "text": "So at the end of the ear canal, the mechanical wave hits and vibrates the eardrum, our tympanic membrane."}, {"title": "Structure of the Human Ear .txt", "text": "Now, notice that the area of the eardrum is much smaller than the area of the pinna, this outside covering of our ear."}, {"title": "Structure of the Human Ear .txt", "text": "Now, we know from physics that the pressure outside the ear is exactly the same, that the pressure is inside this region."}, {"title": "Structure of the Human Ear .txt", "text": "But what is different is our area, because the area inside our eardrum, the area of the eardrum, is so much smaller than the area of the pin."}, {"title": "Structure of the Human Ear .txt", "text": "That implies because the force, the pressure is the same, our force must be much greater on the eardrum than on the outside of the ear."}, {"title": "Structure of the Human Ear .txt", "text": "And so we have a mechanical advantage."}, {"title": "Structure of the Human Ear .txt", "text": "So this concept in physics is known as a mechanical advantage."}, {"title": "Structure of the Human Ear .txt", "text": "So not only does the pina actually amplify that wave, the eardrum also amplifies the wave by increasing the force that is felt on the membrane as a result of that mechanical wave."}, {"title": "Structure of the Human Ear .txt", "text": "Now, this eardrum is connected directly to a bone known as the malleus."}, {"title": "Structure of the Human Ear .txt", "text": "So inside the middle portion of the ear, we have the eardrum, and we have these three bones that collectively are known as the obstacles."}, {"title": "Structure of the Human Ear .txt", "text": "So we have the malleus, we have the incas, and we have the staples."}, {"title": "Structure of the Human Ear .txt", "text": "Now, each one of these bones is smaller than the other one."}, {"title": "Structure of the Human Ear .txt", "text": "It has a smaller lever arm."}, {"title": "Structure of the Human Ear .txt", "text": "So basically, these three bones act as a lever system."}, {"title": "Structure of the Human Ear .txt", "text": "And as the force is transmitted from the Malleaus to the incas, to our staples, our force increases as a result of that decrease in the lever arm, decrease in our displacement."}, {"title": "Structure of the Human Ear .txt", "text": "And so that means we also have an amplification process taking place within this lever system."}, {"title": "Structure of the Human Ear .txt", "text": "And the force that is created by that pressure weight is increased as we go along these three bones."}, {"title": "Structure of the Human Ear .txt", "text": "So we have amplification taking place at the pinnam, we have amplification taking place at the eardrum, and we have amplification taking place at these three octaves, at these three bones."}, {"title": "Structure of the Human Ear .txt", "text": "The question is, why exactly do we want this amplification to take in the first place?"}, {"title": "Structure of the Human Ear .txt", "text": "So, recall from physics, whenever a mechanical wave is propagating through air and then it hits some type of liquid boundary, there is a good amount of resistance that exists at that boundary."}, {"title": "Structure of the Human Ear .txt", "text": "And to actually transmit our mechanical wave from air into liquid, we have to amplify our force."}, {"title": "Structure of the Human Ear .txt", "text": "So basically, inside the inner portion of the ear, we no longer have air."}, {"title": "Structure of the Human Ear .txt", "text": "We have a fluid type, a liquid of a type known as the periomph."}, {"title": "Structure of the Human Ear .txt", "text": "And as this air fluid boundary, we have a considerable amount of resistance to the mechanical waves."}, {"title": "Structure of the Human Ear .txt", "text": "And to overcome this resistance, we have to amplify our force."}, {"title": "Structure of the Human Ear .txt", "text": "And that's exactly we amplify the force at the pina."}, {"title": "Structure of the Human Ear .txt", "text": "We then amplify the force at the ear drum, and we amplify the force at our three bones, the malleus, the incas, and the staples."}, {"title": "Structure of the Human Ear .txt", "text": "Now, at the pina, we amplified by about times two."}, {"title": "Structure of the Human Ear .txt", "text": "At the eardrum, we amplified by about times 15."}, {"title": "Structure of the Human Ear .txt", "text": "And at these three bones, we amplified by about times three."}, {"title": "Structure of the Human Ear .txt", "text": "So together we amplified by two times 15, times three."}, {"title": "Structure of the Human Ear .txt", "text": "So about 90 times as much."}, {"title": "Structure of the Human Ear .txt", "text": "And that is equivalent to about 20 decibels."}, {"title": "Structure of the Human Ear .txt", "text": "So now let's move on to our inner portion of the ear."}, {"title": "Structure of the Human Ear .txt", "text": "So the staples is connected to another membrane that is part of the inner ear known as our oval window."}, {"title": "Structure of the Human Ear .txt", "text": "So this membrane, connected to the staples bone, is known as the oval window."}, {"title": "Structure of the Human Ear .txt", "text": "So as the pressure, the pressure wave hits the eardrum, it causes each one of these bones to basically vibrate."}, {"title": "Structure of the Human Ear .txt", "text": "And the vibration of the staples applies a force on the oval window and that causes that window, that membrane, to basically vibrate and move back and forth."}, {"title": "Structure of the Human Ear .txt", "text": "And as it vibrates, it causes the liquid inside to basically vibrate and forth."}, {"title": "Structure of the Human Ear .txt", "text": "It initiates a mechanical wave inside our fluid known as the paralymp, inside this cochlear region."}, {"title": "Structure of the Human Ear .txt", "text": "So this entire spiral region is known as the cochlea."}, {"title": "Structure of the Human Ear .txt", "text": "And as the pressure wave moves into the cochlea, it bounces off and moves back, eventually hitting the round window."}, {"title": "Structure of the Human Ear .txt", "text": "The round window is a second membrane inside our cochlea that basically helps the propagation and the creation of that mechanical wave."}, {"title": "Structure of the Human Ear .txt", "text": "So recall that one main difference between air and liquid is that liquid is not easily compressed."}, {"title": "Structure of the Human Ear .txt", "text": "So inside this cochlear region, if we didn't have these membranes, the pressure wave would not be able to travel because we would not be able to compress that liquid."}, {"title": "Structure of the Human Ear .txt", "text": "But because of the vibrating round window, and because of the vibrating oval window, we basically have this propagated mechanical wave inside the cockpit."}, {"title": "Structure of the Human Ear .txt", "text": "So if the round window or if the oval window becomes rigid, meaning it's not going to vibrate as much, that means our wave inside would not be as strong, and that implies we would not be able to hear as well."}, {"title": "Structure of the Human Ear .txt", "text": "So the reason we're able to hear well is because these windows, these membranes, are flexible and they're able to oscillate and move back and forth."}, {"title": "Structure of the Human Ear .txt", "text": "So as the pressure wave is carried through our cochlea, inside the cochlea, we have a region known as the organ of corte."}, {"title": "Structure of the Human Ear .txt", "text": "And at the organ of corte, we basically have specialized types of sensory cells known as hair cells."}, {"title": "Structure of the Human Ear .txt", "text": "And these hair cells contain these extensions known as Microville."}, {"title": "Structure of the Human Ear .txt", "text": "And these Microville extensions basically are capable of accepting these pressure waves."}, {"title": "Structure of the Human Ear .txt", "text": "And as a result of the vibration of the Microville, they basically depolarize the membrane of the hair cells."}, {"title": "Structure of the Human Ear .txt", "text": "And when the hair cells depolarize, they create an action potential, an electrical signal that basically travels through the car clear nerve and into the brain."}, {"title": "Structure of the Human Ear .txt", "text": "So inside the inner ear, the mechanical wave is transmitted into the fluid of the inner ear via the oval window, the membrane that basically is connected to the staples that begins to vibrate."}, {"title": "Structure of the Human Ear .txt", "text": "As it vibrates, it sends out our pressure wave that eventually vibrates our round window, also found in this region right below our oval window."}, {"title": "Structure of the Human Ear .txt", "text": "Now, these pressure variations in the fluid cause the hair cells to depolarize, and the action potential travels through the cochlear nerve and up to our brain."}, {"title": "Structure of the Human Ear .txt", "text": "So let's suppose these are the hair cells that are found inside the organ of corte found inside the cochlea."}, {"title": "Structure of the Human Ear .txt", "text": "And as the pressure waves hit these hair cells, the Microville, these extensions, hair like extensions, basically vibrate and they cause the depolarization of the cell membrane and that initiates an action potential which then travels through these exons, through our cochlear nerve and eventually into the brain."}, {"title": "Structure of the Human Ear .txt", "text": "Now, the last thing I want to talk about is something called the semicircular canals."}, {"title": "Structure of the Human Ear .txt", "text": "So inside the person, inside each ear, we basically have three semicircular canals."}, {"title": "Structure of the Human Ear .txt", "text": "And each one of these three semicircular canals basically lie along the three different axes, along the X, y and z axes."}, {"title": "Structure of the Human Ear .txt", "text": "So the semicircular canal, just like the cochlea, contains its own fluid."}, {"title": "Structure of the Human Ear .txt", "text": "And the fluid in a semicircular canal is known as our endolmp endolymph."}, {"title": "Structure of the Human Ear .txt", "text": "So as this fluid experiences our variation and pressure the mechanical wave, this causes the specialized hair cells found inside a semicircular canal."}, {"title": "Structure of the Human Ear .txt", "text": "So we see that we not only have hair cells inside the cochlea, we also have hair cells inside the semicircular canal, but these hair cells are slightly different."}, {"title": "Structure of the Human Ear .txt", "text": "So basically, these hair cells depolarize and they send the action potential, the signal, through its own nerve, known as our vestibular nerve."}, {"title": "Structure of the Human Ear .txt", "text": "And this basically connects with the cochlear nerve to form this nerve that then goes up to the brain and the brain basically analyzes and creates that sound that we hear."}, {"title": "Structure of the Human Ear .txt", "text": "Now, there are three semicircular canals and they help us with balance and allow us to actually detect acceleration as well as deceleration."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The next topic we're going to discuss in relation to the structure of the cell is the cytoskeleton."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, the cytoskeleton is a network of protein fibers that permeate all of the cell and it basically functions to give the cell structure as well as motility."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So in a way we can imagine that the cytoskeleton is like the bone structure of our body body."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It gives the cell its structure, it gives the cell its shape."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It also gives the cell the ability to resist different types of forces and pressures."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "But the cytoskeleton is more than that."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Not only is it a scaffolding system, it's also a highway system."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It gives the cell the ability to move things within that cell and it gives the cell the ability to organize the organelles and structures found within that cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So the cytoskeleton is a very important structure."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, there are three different types of fibers that are found within the cytoskeleton."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "We have microfilaments, we have intermediate filaments and also microtubules."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And let's begin by discussing the microfilaments."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The microfilaments are the thinnest of the three types of protein fibers and their diameter ranges from six to 7."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "They are basically composed entirely of one type of linear protein known as actin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And one common example of the use of microfilaments is in the contraction of cells and specifically in the contraction of muscle cells, one type of cell found in our bodies."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So basically during muscle contraction what happens is there is an interaction taking place between the actin found in our microfilament as well as a different type of protein known as meiosin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So myosin basically grabs the act and it pulls on it."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So it walks on it and this creates our contraction of the muscle cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, microfilament contain a negative end as well as a positive end."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So let's suppose this is the negative end and this is our positive end and the actin essentially grows beginning from our positive end."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And the negative end is attached to some type of structure within the cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, as our actin grows from the positive end of our microfilament eventually it pushes against some type of structure within the cell, for example, the cell membrane."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And this gives the cell the ability to resist tensile forces."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So microfilaments give the cell tensile strength."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So we see that not only are they responsible for our contraction of cells such as the muscle cells, they also stabilize the shape and structure of our cell and they give our cell ten style strength."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, let's move on to the second type of fiber known as the intermediate filament."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And these are known as intermediates because they're slightly greater in diameter than the smallest type of microfilin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So our diameter of intermediate filaments is about 10 nm."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So these fibers are actually composed of several types of different proteins and are slightly thicker than the microfilaments that we discussed in this section here."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, just like the microfilaments, these intermediate filaments also give the cell tensile strength."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "They increase the stability of the cell and give the cell its shape as well as its structure."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, one important difference between microfilaments and intermediate filaments is intermediate filaments are also found in the nucleus of our cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So intermediate filaments compose the nuclear lamina which is basically the fiber skeleton system found within our nucleus."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So that's one major difference between microfilaments and our intermediate filaments."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "But both types of filaments give the cell structure, they give the cell the shape and increase the tensile strength of our cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So basically, if we try to pull on the cell what keeps the cell from being split are these types of fibers the microfiliminants and our intermediate filaments."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, let's move on to the thickest type of filament fiber known as the micro tubules."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So microtubules are the largest of the three and are rigid hollow tubes made of a protein known as tubulin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And there are two versions of tubulin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "We have alpha as well as beta tubulin and together the alpha and the beta tubulin proteins which are globular proteins, they basically create a helical structure, structure that winds as shown."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So we have this winding in a helical like fashion and we create a hollow center."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So this structure here is the microtubule."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So notice that the actin and the intermediate filament."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So the microfilaments and intermediate filaments do not contain a hollow center but the micro tubules do contain a hollow center and that's exactly why they're called tubules because they create this hollow like tube."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, just like our microfilaments, our micro tubules which are 23 nm in diameter so notice they are larger than the microfilaments or the intermediate filaments."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The microtubules have a positive end as well as the negative end and the positive end is the end from where our microtubule grows."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The negative end inside an animal cell is usually found within a region given by MTOC where MTOC stands for the microtubule organizing center."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And within our eukaryotic animal cells this is known as our centrosome."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So it's the centrosome region that contains our centrioles."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So essentially our microtubules are made within our centrosome."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, if the centrosome is responsible for a cell division that implies that the microtubules are also involved in cell division and that's exactly right."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "One function of our microtubule is to basically separate our chromosomes during cell division."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So the microtubules are responsible for creating the metonic spindle that is formed during cell division."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, another function of microtubule is to basically transport things within the cell so we can imagine the microtubules to be the highway system within our cell so we can move things from one location to a different location within the cell as a result of these network of highways our microtubules."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, another important function of microtubules is the formation of specialized structures that help the cell move and these structures include our flagella as well as cilia."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, the flagella inside Eukaryotes is made of this tubulin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "But inside Prokaryotes, our flagella is not made from tubulin, so it's not made from microtubules."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It's made from a different type of protein known as flagellin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And we're going to discuss the difference between the flagellin, Cypriots and Eukaryotes in a different lecture."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So don't worry about that just yet."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So now that we discuss the three different types of fibers that are found within the cytoskeleton of the eukaryotic cell, let's basically summarize our findings."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Let's discuss what each type is and what each type does."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So let's begin with the microfiling."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The microfilamentant is composed of a single protein known as actin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The protein is linear and so we form this linear type of structure and it's the thinnest type of structure."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It's about six to 7 nm in length."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, the function of our microfiling is in muscle contraction, in phagocytosis, in tensile strength and cytoplasmic streaming."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So cytoplasmic streaming basically refers to the amoeboid like movement of our cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Phagocytosis refers to our invagination and engulfing of extracellular materials using the cell membrane."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And tensile strength basically means our cell is able to resist tensile forces and tensile pressures."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now let's move on to our intermediate filament."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The intermediate filament has an intermediate thickness."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It's about 10."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Several different types of proteins are found within our intermediate filament."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, the special thing about intermediate filaments is that not only are they found within a cytoplasm they're also found within the nucleoplasm within our nucleus and they're also found outside our cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So the function of intermediate filaments is to give our cell tensile strength and increase the stability of our cell structure."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "The intermediate filaments, because they're found outside our cell are also involved in creating structures between different cells so binding cells together."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And finally, the microtubule, the thickest and the largest and the strongest type of fiber found in our skeleton."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It has a thickness of about 23."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It's composed of one type of protein tubulent that comes in two forms."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "We have alpha and beta tubulin."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "So basically the alpha and beta globular tubulent proteins create a helical structure that is hollow at the center and that's why we call it a tubule."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "Now, the function of microtubules is to increase the compressive strength so we see that microfilaments and intermediate filaments give our cell the ability to resist pulling."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "But our micro tubules give the cells the ability to resist compression so it gives increases the cells compression rest of strength."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "It also is involved in forming the mitotic spindle and it's involved in forming cilia fluagella as well as involved in intracellular movements, basically moving things within our cell."}, {"title": "Microfilaments, Intermediate Filaments, and Microtubules .txt", "text": "And these are the three different types of protein fibers found within the cytoskeleton of our Eukaryotic cell."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Hemoglobin is the primary carrier of oxygen inside our blood system."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, the affinity of hemoglobin for oxygen can be affected by five different factors."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And we're going to summarize what these factors are."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we're going to examine PH, temperature, carbon dioxide, two, three by phosphoglycerate, as well as carbon monoxide."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "We're also going to discuss how these different factors affect the oxygen hemoglobin dissociation curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So let's begin with factor number one, the PH of our blood plasma."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So let's take a look at the following diagram."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So this is the cell found inside our tissue."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And let's suppose the tissue is exercising."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So it has a high rate of metabolism."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what that means is it produces a high concentration of carbon dioxide molecules as a wasteful."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Byproduct now, these carbon dioxide molecules diffuse across the cell membrane into the extracellular matrix, and they travel into the blood plasma of the nearby capillary."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So this is the wall of our capillary."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, when the CO2 molecules enter the blood plasma then travel into the red blood cell."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, the majority of the carbon dioxide in the red blood cells is transformed into bicarbonate ions and hydrogen ions."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So by increasing the amount of CO2 inside the red blood cell, we also in turn increase the amount of hydrogen ions inside our red blood cells."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And because hydrogen ions, the concentration of hydrogen ions, determines the PH of our blood plasma, and what that means is a higher concentration of hydrogen ions means a more acidic environment and so a lower PH."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, what exactly is the effect that hydrogen has on hemoglobin?"}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Well, it turns out that hydrogen ions can actually bind onto special allosteric sites found on our hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And by binding to hemoglobin, the hydrogen ions effectively decrease the affinity of hemoglobin for oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "That means the hydrogen ions make it much more likely that the hemoglobin will release that oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So what that means is, because our affinity of hemoglobin to oxygen actually decreases, more of that oxygen is released into the cells of our tissues."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So this effect, this phenomenon is known as the Bore effect."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what the Bore effect does is it ultimately shifts the entire curve to the right side."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So a decrease in our PH is the same thing as an increase in the hydrogen ion concentration."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what this does is it shifts the oxygen hemoglobin curve to the right side."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And to see what we mean, let's take a look at the following diagram."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "The following graph."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So, the y axis is the present saturation of hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And the x axis is the partial pressure of oxygen in the tissues given in millimeters of Mercury."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, the blue curve describes the dissociation curve for when we don't have any of these factors in place."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So this is the normal dissociation curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "But if we increase our hydrogen ion concentration, thereby decreasing our PH, what that does is it shifts the entire curve to the right side and we get the following dashed curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what that means is, at the same exact partial pressure of oxygen, we're going to have a smaller concentration percent saturation of hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And so more of that oxygen will be released to the cells of our tissue."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, what about the temperature?"}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So when our cells are carrying out many metabolic processes, they don't only produce carbon dioxide as a byproduct, they also produce thermal energy."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And this thermal energy is transferred into the blood plasma of our capillaries."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what it does is it increases the temperature of the environment within our capillaries."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, by increasing the temperature of our solution, we ultimately affect the affinity of hemoglobin to oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Because the hemoglobin is now at a higher temperature, it's moving at a higher kinetic energy."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So that means it's not able to hold the oxygen as well as before."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what that means is more of that oxygen will be released by the hemoglobin into the blood, and more of that oxygen will end up in the cells of our tissue."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So just like decreasing the PH, increasing the temperature will also shift the oxygen hemoglobin dissociation curve to the right side, as seen in the following diagram."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So decreasing the PH, which is the same thing as increasing the H plus ion, has the same effect as increasing the temperature of our solution inside our capillaries."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, what about carbon dioxide itself?"}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we already discussed the Bore effect, and we said that the majority of the carbon dioxide produced by the cells is absorbed by the red blood cells."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And then those red blood cells convert the majority of that CO2 into H plus ions and bicarbonate ions."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "But actually, a small percentage of that carbon dioxide, when it actually enters the red blood cells, goes on directly to the hemoglobin and binds directly to the hemoglobin at specific regions."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And once CO2 binds onto the hemoglobin, what it does is it decreases hemoglobin's ability to bind to oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And once again, less oxygen will be bound to our hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And more oxygen will be ultimately released to the red blood cells, to the tissues, to the cells inside our exercising tissues."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And this effect is known as the whole Dane effect."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So an increase in the CO2 concentration, in the partial pressure concentration of CO2 inside this area, the red blood cells basically shifts the curve once again to the right side."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we see that increasing the hydrogen ion concentration, increasing the temperature, and increasing the partial pressure of carbon dioxide."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "The concentration of carbon dioxide will shift the entire curve to the right side."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what that means is more of that oxygen will be delivered to the tissues of our body."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, what about something called two three BPG?"}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So two, three BPG is two three biphosphoglycerate."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And two three biphosphoglycerate is a naturally occurring intermediate in the process of glycolysis."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we produce two, three BPG when our cells use glucose and break down glucose for ATP."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So within our cells that are exercising, they have a high rate of metabolism."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "They produce an excess of two, three BPG molecules."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "These molecules can pass along the membrane into the matrix, and then eventually, they end up within the blood plasma and move into the red blood cells."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, once the two, three BPG are inside the red blood cells, they go on to directly interact with hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "They bind to a special side between the two beta subunes of hemoglobin, and they create a conformational change."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And by binding to hemoglobin and creating that conformational change, they decreased a lower vicinity of hemoglobin for oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And once again, this allows for more oxygen to actually be unloaded, and more oxygen ends up in the cells of our tissue."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And once again, increasing the concentration of two, three BPG will cause a rise work shift on our oxygen hemoglobin dissociation curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we see that increasing four of these different things will shift the curve to the right, and that will make it more likely for a hemoglobin to unload that oxygen and deliver more oxygen to the cells of our tissues."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we have increase in H plus ion concentration, increase in temperature, increase in the concentration of CO2, and increase in two, three BPG."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "That all creates a ripe work shift in the hemoglobin dissociation curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, the final factor I'd like to discuss is carbon monoxide."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, carbon monoxide is actually produced naturally inside our body, but it is produced in very, very small amounts."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So the CO2, because it's produced in very small amounts in our body, does not actually affect the hemoglobin in any adverse way."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "But we produce carbon monoxide in much greater concentrations via different types of processes that take place outside our body."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "For example, cars produce CO2, and smoking also produces CO2."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So carbon monoxide, as it turns out, is actually a competitive inhibitor of hemoglobin, and it competes with oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And in fact, it is 250 times more likely to actually bind to the heme group of hemoglobin than oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Now, by binding to hemoglobin, the carbon monoxide creates a conformational change that ultimately increases the affinity of hemoglobin for oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "It makes hemoglobin much more likely to bind oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what that means is, by binding to our hemoglobin Co, carbon monoxide ultimately causes the hemoglobin to not be that likely to release oxygen to the tissues."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And so, as a result, the tissues will receive less oxygen."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Less oxygen will be delivered to the cells of our tissue."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And what this means is when carbon monoxide binds to our hemoglobin, it causes a leftward shift in our hemoglobin curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And not only that, it also lowers the actual curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And that's because carbon monoxide binds to the heme groups, and that means it actually lowers the oxygen carrying capacity of our hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "And that's why we get the following curve."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "For when we have a high concentration of carbon monoxide inside our body."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So we have a left work shift on this side, and this entire curve essentially is moved down."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "Because carbon monoxide lowers hemoglobin's oxygen carrying capacity, it actually binds onto the heme group, and that prevents other oxygens to bind to the heme groups of hemoglobin, and so it decreases the amount of oxygen oxygen that can be carried by our hemoglobin."}, {"title": "Factors that Affect Hemoglobin Dissociation curve.txt", "text": "So these are the five different factors that ultimately affect the affinity of hemoglobin for oxygen and affect our oxygen hemoglobin dissociation curve."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "The process by which the cells of our body replicate DNA molecules is very complicated."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "In fact, it involves over 20 different types of proteins and enzymes that work together and coordinate the synthesis of that replicated DNA molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now, in 158, an individual by the name of Arthur Kornberg and his team essentially isolated and studied especially specific type of protein involved in the replication process of E. Coli cells."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And this protein became known as DNA polymerase."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "In fact, inside our body, we also use DNA polymerase to synthesize replicated DNA molecules."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So in this lecture, what we're going to discuss is how the DNA polymerase actually works."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And we're going to discuss what the DNA polymerase needs to actually synthesize that DNA molecule during the replication process."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So let's begin by looking at the general equation that describes how DNA polymerase actually works."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So let's suppose inside our cell, we are replicating the DNA molecule and so far we have N number of nucleotides in our DNA polynucleotide chain."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So we have N number of nucleotides in the DNA molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now, if we want to add one more nucleotide, we actually have to take the dNTP, the deoxy nucleotide triphosphate, and add it onto the DNA molecule in the process."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "What we do is we form a phosphodiather bond between this molecule and this molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so what we do is we extend the DNA chain by one."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so now we have N plus one number of nucleotides."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And in the process, every time we form the phosphor diastabond, we release a PP molecule where PP stands for Pyrophosphate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So what the DNA polymerase molecule does is it catalyzes the formation of a phosphor diester bond by adding a deoxy nucleotide triphosphate, the dNTP, onto that growing polypeptide chain."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And in the process, every time we add the deoxyribonucleotide onto that growing chain in a stepwise fashion, we release the Pyrophosphate molecule and we'll discuss what the Pyrophosphate molecule is in much more detail when we discuss the replication process."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So in this lecture, our goal is simply to discuss what the general function of DNA polymerase is."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now, for DNA polymerase to actually function effectively, it has to have three different things."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So A, B and C and D. We simply discuss one important fact about the DNA polymerase molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So let's begin with A."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So, in the same way that if we want to build a building, we have to have the bricks, the building blocks to build that building, to build a polynucleotide chain, we have to have the dNTP molecules, the deoxy nucleotide triphosphates."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And there are four different types of dNTP molecules."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "We have deoxy adenosine, five prime triphosphate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "We have deoxy guanosine, five prime triphosphate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "We have deoxy pyridine, five prime triphosphate, and we have the thymidine, five prime triphosphate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So for the DNA polymerase to actually build and extend the DNA polynucleotide chain, it has to have those four nucleotides swimming around in that solution."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Without those nucleotides, it will not be able to build our structure in the same way that we cannot build a building without the bricks, the building blocks."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Let's move on to B."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So, DNA polymerase requires a template DNA strand and that's because it's the template DNA strand that essentially provides the blueprint, the instructions to build that replicated strand of DNA."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And this is analogous to the following scenario."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So let's suppose we have a construction worker and the construction worker has to build a building."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now the construction worker cannot build that building without having the blueprint that was created by the architect."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And in the same exact analogous way, the template DNA strand is that architect that provides the blueprint, the instructions to actually build the structure that polynucleotide chain."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So DNA polymerase obtains its instructions from the preexisting DNA template that is found in that double helical structure."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So remember, in that double helix we have two of these template strands that basically run in an anti parallel direction."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And when we replicate DNA molecules, those two strands essentially separate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And when they separate, we can use DNA polymerase can use those templates to synthesize those new replicated polynucleotide chains."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So the DNA polymerase can only add new nucleotides onto that growing polypeptide chain as long as the new nucleotides are complementary to the basis down on that template DNA molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now let's move on to C. Another thing that DNA polymerase actually needs is a primer."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So with the primer, we can initiate that DNA replication process."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now, what exactly is a primer?"}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Well, a primer is simply a sequence of nucleotides that are already attached onto that DNA template."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And what that primer has is a free three prime hydroxyl group that can basically create that first phosphodia ester bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And we'll see exactly how that looks like in just a moment."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So there are three things that DNA polymerase needs."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "It needs the building blocks, the deoxy nucleuside, triphosphate molecules, and we have four different types."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "It actually needs that blueprint and that's the template DNA strand that exists in that double helical structure of DNA found inside our nuclei, C. It also needs a primer because the primer must exist for us to extend and build that phosphodiaester bond as we'll see in just a moment."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "It also actually needs magnesium ions because these magnesium ions essentially increase the efficiency of these DNA polymerase molecules."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And we'll discuss that in much more detail when we'll discuss the DNA replication process."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now D, so D is more of a fact about DNA polymerase molecules."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And what D tells us is DNA polymerase can actually correct its own mistakes."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So if the DNA polymerase accidentally mismatches a base, it can actually go back, remove that base and put in the correct base that it basically mismatched."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And what that means is the DNA polymerase rarely makes mistakes."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And when it does make a mistake, it can basically fix that mistake on its own accord."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "In fact, for every 100 million nucleotides that the DNA polymerase lays down correctly, it only makes one mistake and that's a very, very high accuracy."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So DNA polymerase has the ability to remove and replace nucleotides that have been incorrectly placed."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "This means that DNA polymerases rarely make mistakes and when they do, they can fix the mistakes on their own."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So let's take a look at the following diagram which basically describes how we form the phosphor diaster body."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And as we discuss this, we can imagine that the DNA polymerase molecule hovers about this position and catalyzes the formation of this phosphodiastor bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So here we have the DNA template that we're going to use to basically pair up the correct complementary basis."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And this template is needed to actually form that polynucleotide chain correctly."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So this is the DNA template, this is the three end and this is the five end."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now this is the primer."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And the primer basically contains the sequence of nucleotides."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And on the final nucleotide, we have the sugar with a base that contains this free three prime hydroxyl group."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So if we are to label these carbons here, this is carbon number one, carbon number two, carbon number three, four and five."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so this three position carbon contains a free hydroxyl group that can nucleophilically attack this phosphorus atom of this triphosphate group."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And this is the phosphodiastic bond that is formed that we spoke about earlier."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So essentially, we have the DNA polymerase essentially hoving over this molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And when this nucleotide so this is one of the dNTP nucleotides that we spoke about earlier."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "The dNTP molecule comes in close proximity as long as this base is complementary to this base."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So we have to use the DNA template molecule to basically figure out which base is complementary to this base."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And only then will this form a strong enough interaction for this to actually remain in place."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And when that takes place, the RNA polymerase molecules, as well as other proteins involved and other enzymes involved, essentially catalyze the nucleophilic addition of this phosphodia bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So we have these electrons attacking this phosphate and that kicks off this bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so this is this molecule that is formed here, the Pyrophosphate."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "It is broken."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And then we form that bond between this molecule and between this oxygen and this P atom."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so we form that phosphodia Esther bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "Now notice as we form the polynucleotide chain, we form that chain from the five N to the three N. And in fact, the DNA molecule, the DNA polymerase always forms that polynucleotide chain in this direction, beginning at the three end and traveling towards that or beginning the five end and traveling towards the three end."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "So once again, DNA polymerase catalyzes the formation of the phosphor diester bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And the three prime, a hydroxyl group of the sugar on the primer nucleophilicly attacks the innermost phosphorus atom of this triphosphate group of the dNTP molecule that we are base pairing with this base found on the DNA template."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And so this forms our phosphodiator bond."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "We extend our DNA molecule by one nucleotide."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "In the process, we release the pyrophosphate molecule."}, {"title": "DNA Polymerase and Catalysis of Phosphodiester Bond.txt", "text": "And as we'll see in a future lecture, it's the formation and the breaking of that phosphol, of that pyrophosphate molecule that drives this replication process forward."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Gene mapping is the process that involves finding the positions of genes on chromosomes and also determining what the distance is between the genes on a given chromosome."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, typically in genetics and biology we express the distance between any two genes on a given chromosome by using special units known as Map units or recombination units."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So these two terms are basically used interchangeably."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "They mean the same exact thing."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, as we'll see in just a moment, to actually calculate the Map units the distance between our two genes and Map units we have to calculate the percent recombination between those two genes."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So to see exactly what we mean by that, let's take a look at the following example."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "In this example, we're going to discuss how to calculate the percent recombination between two genes and how to use the percent recombination to find what the Map units are, what the distance is in Map units between those two genes."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So let's begin by taking a look at the following diagram."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So in this diagram, what we're basically doing is we're taking two types of fruits lies."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So in this example, we're going to study fruit flies."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, we're going to study two types of traits and we're going to assume that the traits are in fact linked."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we're going to study the color trait which is linked to our wing type trait."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have two types of colors and two types of wings."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "We have the color gray, which is dominant over the color black and the color gray is given by uppercase uppercase g. The color black is given by lowercase g. By the same exact token, we have two types of wing types."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "We have normal wings and we have vestigial wings."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, normal wings which are functional are given by uppercase N and vestigial wings, which are nonfunctional, are given by lowercase N. So in this example, in this experiment, we're basically mating a female individual that is homozygous dominant for the color trade and homozygous recessive for the wing trade with a male individual."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we're mating this with a male individual that is homozygous recessive for the color and homozygous dominant for the wing type."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, in a what is the genotype of the f one generation offspring that is produced when we make these two individuals?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "To actually determine what the genotype is, we first have to answer the question what are the gametes produced?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "What are the gametes that are produced by these two types of individuals?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So let's begin with our female individual."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have uppercase G, uppercase G, lower case and lowercase N. So uppercase G, uppercase G, lower case and lowercase N. And before they actually mates, they have to produce our gametes, the sex cells."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And in this case, because we have female, these are going to be X cells."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, because we're assuming these genes are linked, that means they're located on the same exact chromosome."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And in this particular case, if you carry out the process of Meiosis, we only have one type of gamete that can actually form."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And that gamete will have a chromosome that contains an upper case G, a lowercase N. So this is our X cell, and this is equivalent to basically redrawing it in the following diagram."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have this chromosome that contains lowercase ng and uppercase G, lower case ng, an uppercase G gene."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And so 100% of our gametes will look like this."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Okay?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now we're crossing it with a male that is lowercase G, lowercase G, uppercase and uppercase N. And likewise, by the same exact reasoning, if we carry out the process of Meiosis, we'll see that only one type of gamete can actually be formed in this particular case."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "In fact, 100% of the gametes will have this genotype, as shown."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So lowercase g, uppercase n. So it's a sperm cell."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So let's designate that with this squiggly line."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we can either designate it this way or by using the chromosome symbol."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have lowercase G, uppercase N, okay?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 100% of these genes will basically look like this."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So this produces this sperm cell."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "This produces this X cell."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "When they combine to form the Zygote, we basically form."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So this chromosome combines with this chromosome, and we form the following Zygote that contains uppercase G, lowercase N. So uppercase G and lowercase N. And then we have lowercase G uppercase, and that comes from this, right?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have lowercase N. So let's write that like so, sorry, uppercase N, then we have lowercase N here."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So lowercase N, uppercase G that came from the female, and lowercase G that came from the male."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And so this will be the genotype of all the offspring produced in the F one generation."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So f one generation genotype."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Okay, now let's move on to Part B."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "In Part B, when we mate an F one generation female, so what that means is we take a female that has the same genotype as the f one generation."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And what that basically means is this is the f one generation."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have a female that has a genotype that is uppercase G, lower case G, uppercase N, lowercase N, and we make this with a homozygous recessive male that is homozygous recessive for both traits."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So homozygous recessive for both traits means we have lowercase G, lowercase G, lowercase N, lowercase N. So when we mate or cross an F one generation female, this individual here with a homozygous recessive male, this individual here, we obtain 2000 offspring."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have 2000 individual fruit flies."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, if we assume that the traits, the color trait and this wing type trade are linked, that means they are located on the same chromosome, but we assume no crossing over actually took place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "What will be the expected genotype distribution between those 2000 offspring that are produced?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So basically, the entire point of Part B is to note that no genetic recombination actually takes place because no Crossing Over takes place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So once again, to determine what the genotypes of the offsprings are we have to find what the gametes that are produced are so we have two types of gametes in this particular case, the question is why?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Well, because no crossing over actually took place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And what that basically means is the same two gametes that were combined to produce this f one offspring."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So, namely, this gamete."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And this gamete will be produced in this particular case because no new recombinant gametes are actually formed because no crossing over actually took place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And so when Meiosis actually takes place so we replicate these, then they divide to form haploid cells."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Those Haploid cells divide."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "What we form are a gamete that contains uppercase g, lowercase M, and a gamete that contains a lowercase g, uppercase N. So one of these gametes will contain a chromosome that has uppercase g. So uppercase G, lowercase N, right?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Why?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Well, because this individual contains these two chromosomes meiosis takes place, separates them and so we have uppercase g, lower case N and then this one has the other one lowercase g, uppercase N so lowercase g, uppercase N and so 50% of the gametes will have this genotype and the other 50 will have that genotype."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 50% this, 50% that."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, in this particular case, things are quite simple because we only we only form one type of sperm cell that contains uppercase g, lower case g, lower case N. So lowercase g, lower case N. And that is 100% of the offspring."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And so this always forms this."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "But this can form two."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, if this combines with this, what we basically form is offspring number one that contains well, we basically have uppercase g, lowercase g, or it should be uppercase g with this green color and lowercase g with this green color and then lowercase and lowercase N. So lowercase N, lowercase N. The second type of offspring that is produced is so if this combines with this, we have lowercase g, lower case g, uppercase and lowercase N. And because this is 50% and 100%, so .5 times one gives us zero."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Five."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So a half of the 2000 or 1000 of the offspring will have this."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And the other 1000 are going to have this genotype right over here."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 1000 of the offspring will have this genotype here."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "The other 1000 will have this genotype here."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, what exactly is the phenotype of this?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Well, upper case G is dominant over lowercase G, so that means we have gray wingless because we're going to have vestigial non functional wings."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And then we have lowercase g. Lower case G is black and uppercase and lowercase N is normal wings because uppercase N is dominant over lowercase N. So we have functional wings."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 1000 are gray wingless."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "The other thousand are black and winged."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, this is if we assume that no Crossing Over took place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "But crossing over does normally take place."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And that's exactly what we discussed in part three."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Suppose that the actual F two distribution was as follows instead of having this hypothetical distribution because crossing over does take place we produce this distribution."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So notice that now not only do we have the gray and wingless and the black and winged as we have in this case we also have the gray winged and the black winged."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And these two here are actually the recombinant offsprings and they are produced as a result of crossing over as a result of the production of recombinant chromosomes."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we are given that eight, nine, five are gray wingless, 905 are black wing but 110 are gray wings and 90 are black wingless."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "To make a total of if we sum these up, we obtain 2000 offspring."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So the question is what is the recombination frequency between the two traits the color traits and that wing type trait?"}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And to find the recombination frequency, also known as percent recombination what we basically do is we sum up all the offspring that are recombinant."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 110 plus 90."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 110 plus 90, this is the total number of offspring that are recombinant and we divide it by the total number of offspring."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So 2000 offspring and what we get is 200 divided by 2000."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And that gives us, once we reduce it to one 10th and that's equivalent to 0.1."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, this is our recombination frequency."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And to find the percent recombination we basically multiply 0.1."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we multiply zero."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "One times 100% and we get 10% is our percent recombination between those two genes."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "It basically tells us how many of those offspring are a result of the process of crossing over."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "Now, we can use this to calculate what the recombination units are or the mapping units."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And to basically do that we have to remember that one Map unit or one recombination unit is equal to 1% recombination."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So we have 1%."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "And so by using this ratio, this proportion we know that because we have 10% recombination that means we've have ten Map units or ten recombination units between those two genes."}, {"title": "Gene Mapping, Percent Recombination and Map Units .txt", "text": "So what that means is if we examine our chromosome along that chromosome we have, let's say this gene right here, that is our."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we know that the plasma membrane is a fluidlike structure."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And what determines the fluidity is the relative movement of all the molecules, the phospholipids and proteins that exist within that membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So the more movement we have, the more fluid that membrane is."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "The less movement we have, the more rigid that membrane is."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, if the fluidity is determined by the relative movement, what determines the relative movement itself?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, the relative movement of the molecules within the membrane is determined by the strength of the attractions, the non covalent intermolecular bonds that exist between the phospholipids, the molecules in the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So you might imagine that in a membrane in which we have more fluidity, we have more movement."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And what that means is the attractions are not very strong."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "But in a membrane in which the attractions between the molecules is strong, that means we're going to have less movement."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so the membrane will be more rigid."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so we see that the stronger the interactions between the molecules in the membrane, the stronger these intermolecular bonds are, the more rigid the membrane is."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And conversely, the weaker the interactions are, the less rigid and more fluid that membrane actually is."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's take a look at the following graph."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And let's imagine what happens to a membrane as we go from a low temperature to a high temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So as we increase the temperature of the environment in which the membrane is in, so the y axis is the fluidity of the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "As we go higher up along the y axis, the fluidity increases."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "As we go lower along that y axis, the rigidity increases."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, the x axis is the temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So on this side, we have a low temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "As we go along the x axis, the temperature increases until we get to a high temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's suppose we have a rigid structure, a rigid membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we're at a low temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "What begins to happen as we actually increase that temperature?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, as we increase the temperature, we're essentially transferring kinetic energy to the molecules, the lipids and the proteins within that membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so these phospholipids basically move with a greater velocity."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because they move with a greater velocity, those intermolecular bonds that are holding that rigid structure, the well defined and order structure, basically cannot maintain that rigidity any longer."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And eventually, what happens is at a specific temperature called the melting temperature, there's a phase transition that takes place."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And the collapse of that well defined and order structure basically leads into that fluid state."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So as the temperature is increased, there's a sharp transition from the rigid state here to the fluid state here."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And this temperature, the melting temperature, is the temperature at which this phase transition actually takes place."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And if we look on the microscopic level, we see that as the temperature is raised, the kinetic energy of the lipids and other molecules increases."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And as a result, the intermolecular non covalent bonds holding the lipids can no longer maintain a packed and well ordered, well defined structure."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so as a result of the collapse of this rigid structure, the well defined structure, we basically create a more fluid and less ordered structure."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we go from the rigid state to that fluid state."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's suppose we have two membranes, one membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "In one membrane, we have strong intermodal interactions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "In the other membrane, we have weak intermolecular interactions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So how do you think the melting temperature of these two systems will compare?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, in the membrane where we have stronger intermolecular interactions, that membrane will have a higher melting temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Why?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, because a higher amount of energy."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So high temperature must actually be used to actually get that well defined structure that exists due to those intermolecular interactions to actually collapse."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so we conclude that a membrane with strong intermolecular interactions will have a higher melting temperature than a membrane with weaker ones."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So again, a stronger or stronger interactions basically implies a more rigid, more well defined and ordered structure and that implies a higher melting temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, we know that membrane fluidity is determined by the relative movement of those lipids and the other molecules in the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And the relative movement is determined by the strength of those inter molecular interactions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "But what determines the strength of those intermolecular interactions within the membrane?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, three things."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Number one is the length of fatty acid chains."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Number two is degree of unsaturation."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So how many double bonds we find in those hydrocarbon chains of the fatty acids and three, the concentration of cholesterol."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's discuss how each one of these actually affects the strength of the intermolecular interactions within the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And let's begin with length of fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's compare these two adjacent fatty acids and these two adjacent fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So these one are clearly longer than this particular case."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because of the difference in length, we see that in this particular case we have many more interactions, intermolecular interactions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "To be more specific, we have many more London dispersion forces that can potentially form in this case than in this case."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And what that means is if we have a membrane that consists of these fatty acids and one that consists of these fatty acids, the overall strength of the intermolecular interactions in this particular membrane will be greater than in this particular case."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so in such a case, the membrane will be more rigid and will have a higher melting temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So longer fatty acids can form more lung dispersion forces than shorter ones."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Therefore, the presence of longer fatty acids decreases the fluidity, makes the membrane more rigid and increases the melting temperature because we have to input more energy to break those lung dispersion forces than in this particular case."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, what about the double bonds?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's compare."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "We have this system in which we have four adjacent phospholipid molecules in which we don't have any double bonds."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And such a system is said to be a saturated system."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, let's suppose we compare this to this case in which we have these for phospholipids that have the same exact length."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "But now we add CIS double bonds."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's suppose we add a single CIS double bond into this molecule."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "How exactly will that determine or change the fluidity of the membrane?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, in this particular case, we have a well defined structure."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because of this well defined structure, the adjacent hydrocarbon chains of these adjacent phospholipid molecules can actually interact very well and form many of these London dispersion forests."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "But in this particular case, because of the CIS double bond, we have a kink, we essentially have this bend in the chain."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because of that bend, the interactions are not as strong and not as extensive as in this particular case."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we simply have less of these interactions taking place."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because of that, if we have less interactions taking place, what that basically means is the fluidity in this particular case will increase and the melting temperature will decrease."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we see that saturated fatty acids create a well structured arrangement of hydrocarbon chains."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And these straight chain hydrocarbons can form stronger and more extensive intermolecular bonds with the nearby fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And this favors rigidity."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "It basically decreases fluidity and it raises the melting temperature."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, a cyst double bond like the one shown here."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So in systems that are unsaturated and contain a cyst double bond, we see that that bond creates a kink, a bend in that structure, and this interferes with the well defined structure of that membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so this favors membrane fluidity, it decreases the rigidity and lowers the melting temperature of that system."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we see that increasing the length of our fatty acid chains and removing those says double bonds basically makes the membrane more rigid and increases the melting temperature of that membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, in bacterial cells, bacterial cells tend to basically use these two factors to control and regulate the rigidity or fluidity of the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So they usually increase the number or decrease the number of these double bonds."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, in animal cells, we normally use cholesterol."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So let's see how cholesterol can be used to basically regulate the rigidity of the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So remember, cholesterol molecules are steroid molecules."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "They contain four fused chains or four fused rings, as shown in the following diagram."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So these are phospholipid molecules."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "These are glycophosolipids that contain these sugar components."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "These are cholesterol molecules, and this is some type of transmembrane integral protein."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, when cholesterol fits into the structure of the membrane, it actually interferes with the structure of these fatty acids because of the difference in shape."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So cholesterol interferes with the regular interactions of the fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "However, because the cholesterol molecule, by being present inside that membrane, because it basically stimulates formation of complexes between the cholesterol molecules and these glycophosolipid molecules, like the one shown here, they basically are responsible for forming these very important structures we call lipid rafts."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So what exactly is a lipid raft?"}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Well, basically a lipid raft is a section of the membrane that contains a high concentration of cholesterol molecules as well as the glycophospholipids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And because we have a high concentration of these lipids within the area of the membrane, what that does is ultimately it increases the rigidity and makes that membrane less fluid."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Because if in a given section, if we're in that lipid rack region, we have many more of these large molecules."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So cholesterol molecules are relatively large, and these glycophosolipids are also very large, and they're packed densely to this region."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "That area will have a lower amount of movement."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so if we have lower movement, that means we have more of these interactions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so that will increase, make that membrane more rigid."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Now, on top of that, even though the membrane is more rigid in the presence of cholesterol, what these lipid wraps also do, and what cholesterol does in general, is it basically increases the resistance of the membrane to this transition transition phase that we spoke of earlier."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So instead of having this steep slope, the slope is slightly flatter."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And what that means is the membrane is able to resist these transition phases."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we see that cholesterol, even though it interferes with the regular interactions of fatty acids, because cholesterol seems to actually form complexes with glycos single lipids, a type of glyco phospholipid."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "We see that because they form these complexes."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "These complexes, in turn, form these lipid ramps."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And what that does is it makes the membrane slightly less fluid, so more rigid, but at the same time, it makes it much more resistant to actually phase transitions."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And so when there's a change in temperature taking place, that membrane is less likely to actually transition between these two stages."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And that's very important to maintaining homeostasis inside the cells of our body."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So cholesterol is basically used in animal cells, in our own cells to regulate the fluidity of the membrane and is also used to basically regulate the transition from the rigid state to the fluid state or vice versa."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "So we conclude that there are three different things that basically allow the that basically influence the fluidity of the membrane."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Number one is the length of fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "Number two is the number of fatty, the number of double bonds that we have on those fatty acids."}, {"title": "Cholesterol and Fatty Acids Regulate membrane Fluidity .txt", "text": "And number three, the concentration of cholesterol within the membrane of our cells."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "When we break down amino acids inside our liver, we essentially remove that alpha amino group."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And what we have left over is a carbon skeleton."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So in this lecture and the next several lectures, what I'd like to focus on is the fate of that carbon skeleton."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So when we metabolize amino acids and we form that carbon skeleton by removing that alpha amino group, one exactly happens to that carbon skeleton."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So all the carbon skeletons that we form, when we metabolize the 20 different types of amino acids inside our liver cells, all those carbon skeletons lead to one of seven different molecules."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And all these seven molecules are intermediates of the metabolic pathway, the metabolic system that allows us to generate high energy ATP molecules."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So let's recall some basic facts about metabolic pathways."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Let's begin with the citric acid cycle."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So this is our citric acid cycle."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And inside our liver, the point of the citric acid cycle is to help us generate oxyloacetate."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Why?"}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Because oxalo acetate is ultimately the starting material to produce glucose via gluconeogenesis as it takes place inside our liver cell."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So if we can form any one of these intermediate molecules, that can ultimately help us form oxalo acetate, and that can lead to glucose production."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, inside our liver, we can actually use Pyruvate to basically form oxalo acetate."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And this pathway is catalyzed by the enzyme Pyruvate carboxylase."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And so what that means is we can use Pyruvate to actually help us generate glucose, because if we transform Pyruvate to oxaloacetate, we can then use this in gluconeogenesis to help us form glucose."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, what about this pathway here?"}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So, if we take pyruvate, the second fate of Pyruvate is to undergo decarboxylation."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So the enzyme pyruvate carboxylase transforms pyruvate into acetylcoenzyme a."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, what happens to acetylco enzyme A?"}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Well, we can use acetylcoenzyme A to help us generate fatty acids, but we can also use acetylcoenzyme A to help us generate ketone bodies."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So by transforming acetyl coenzyme A to acetoacetalco enzyme A, this ultimately can be transformed into ketone bodies."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, one fact that you have to remember is acetylco enzyme A cannot be used, at least inside humans, to actually generate glucose molecules."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And what that means is, even though it seems like we can use acetyl coenzyme A, transform it into the citric acid cycle, ultimately form oxalo acetate, and then form glucose via glucoinogenesis, that is not actually true."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And the reason is the following."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "When we use acetyl coenzyme A and we feed it into the citric acid cycle, we actually use up a single oxalo acetate."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So we use a single oxylacetate combined with acetytl coenzyme A, and we form citrates."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And so ultimately, even though we do form oxalo acetate at the end, we use up one oxalo acetate at the beginning, and the net result is zero."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So what that means is we cannot use acetylco enzyme A to help us form glucose in our liver."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, let's focus on all these different amino acids."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So basically, if we metabolize an amino acid, and the carbon skeleton of that amino acid is used to form any one of these intermediates here, or Pyruvate, these are known as glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So glucogenic amino acids are those amino acids that, when metabolized, help us form intermediates that ultimately lead to the production of glucose."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So that includes all these, these and these."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So, for example, let's take tryptophan."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Tryptophan, if it follows a specific pathway, that will ultimately lead to the production of pyruvate."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, Pyruvate basically goes this way via the pyruvate carboxylase enzyme that forms oxalo acetate, and that then helps to form glucose via glucomgenesis."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, if we look at aspartate, for example, aspartate can be transformed into oxalo acetate, and we actually looked at this example in a previous lecture, and then the oxylacetade goes on to form glucose via glucaniogenesis."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So all of these amino acids are known as glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, if we look at these, these and these ultimately helps us form these two molecules."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And so these can then be used to form ketone bodies."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So these are known as ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So all of these are ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, the only ones that are solely strictly ketogenic are actually leucine and lysine."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Why?"}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Well, because tryptophan, if it follows one pathway, we can form acetylco enzyme A, in which case it's ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "In a different pathway, it can form acetoacetalco enzyme A."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Again, it's ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "But in this pathway, it helps us form pyruvate."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And Pyruvate goes this way to help us form glucose."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, we can also go this way, of course, and this will be ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "But if we look strictly on this pathway, this pathway is glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So tryptophan is both glucogenic and ketogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So the only ones which are only ketogenic are leucine and lysine."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "This is the list of all the glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Only we have 14."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And this is the list of both ketogenic and glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So as we saw earlier, we have tryptophan, but we also have isolucine, phenylalanine and tyrosine."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So my suggestion, if you're going to memorize these, memorize these two and these four, but don't memorize this, because if you memorize these two, the other 14, which essentially must be glucogenic only."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, one caveat, however, is the way I've listed is I have 14 glucogenic and four under both."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Sometimes you're going to see three anine listed under both."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So that means we have 13 here, not including three anine, and five here, including three anine."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "And that's simply because of the way you define glucogenic."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So if you define glucogenic one way, the three anine ends up being here."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "If you define a different way, the three ane ends up being here."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "Now, that's really not too important."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "What's important here is to notice that the majority of the amino acids that are metabolized inside our liver actually end up being metabolized into glucose, because 14, or in some cases 13, essentially end up being transformed into glucose, and then that glucose can be used to help our cells generate high energy ATP molecule."}, {"title": "Introduction to glucogenic and ketogenic amino acids .txt", "text": "So in the next several lectures, we're basically going to look at the actual pathways that lead to all these different intermediates when we actually metabolize the 20 amino acids."}, {"title": "Autonomic Nervous System .txt", "text": "The peripheral nervous system of the human body is broken down into two."}, {"title": "Autonomic Nervous System .txt", "text": "We have our somatic nervous system and the autonomic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "Previously we discussed our somatic system and we said that the somatic nervous system consists of two divisions."}, {"title": "Autonomic Nervous System .txt", "text": "We have the sensory division and the motor division."}, {"title": "Autonomic Nervous System .txt", "text": "And in the same exact way, the autonomic nervous system system also consists of the sensory division and the motor division."}, {"title": "Autonomic Nervous System .txt", "text": "But in the case of the autonomic nervous system the motor division is even further subdivided into two."}, {"title": "Autonomic Nervous System .txt", "text": "We have the sympathetic and the parasympathetic systems."}, {"title": "Autonomic Nervous System .txt", "text": "Now before we actually discuss these two individual systems, let's discuss what the difference is between our somatic and autonomic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "Now the somatic nervous system basically innervates skeletal muscle, skeletal tissue."}, {"title": "Autonomic Nervous System .txt", "text": "And that means our somatic nervous system is responsible for our voluntary movement."}, {"title": "Autonomic Nervous System .txt", "text": "So what allows me to move my arm back and forth is the fact that inside my arm I have skeletal tissue that is innovated by our somatic nervous system, our skeletal muscle."}, {"title": "Autonomic Nervous System .txt", "text": "And that's exactly what allows me to move my hand back and forth."}, {"title": "Autonomic Nervous System .txt", "text": "Now what about the autonomic nervous system?"}, {"title": "Autonomic Nervous System .txt", "text": "Well, the autonomic nervous system innervates cardiac muscle and smooth muscle and then also innervates different types of glands found inside our body."}, {"title": "Autonomic Nervous System .txt", "text": "So that means the autonomic nervous system controls the race, the beating of the heart and also controls, for example, the dilation and constriction of our blood vessels."}, {"title": "Autonomic Nervous System .txt", "text": "So it's the autonomic nervous system that controls all our involuntary movement, movement that we cannot actually control."}, {"title": "Autonomic Nervous System .txt", "text": "Now the somatic nervous system consists of our electrical pathways that only have one neuron."}, {"title": "Autonomic Nervous System .txt", "text": "But in the case of the autonomic we usually have two neurons in our electrical pathway."}, {"title": "Autonomic Nervous System .txt", "text": "We have a pre ganglionic neuron and a post ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "Now in the case of the somatic system we only use the cetylcholine neurotransmitter."}, {"title": "Autonomic Nervous System .txt", "text": "In the autonomous case we use acetylcholine as well as in some cases epinephrine and norepinephrine."}, {"title": "Autonomic Nervous System .txt", "text": "So now let's discuss the sympathetic and the parasympathetic divisions of the autonomic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "Now let's begin with our sympathetic case."}, {"title": "Autonomic Nervous System .txt", "text": "Let's suppose we're casually walking in the park and all of a sudden we have a dog that begins to chase us."}, {"title": "Autonomic Nervous System .txt", "text": "Now, if we choose to run away from that dog or if we choose to fight that dog off, in either case it's the sympathetic nervous system that actually kicks in."}, {"title": "Autonomic Nervous System .txt", "text": "So let's suppose we decide to run away."}, {"title": "Autonomic Nervous System .txt", "text": "Now as we begin to run, what begins to happen is more blood begins to pump to our skeletal muscles so that we can run away."}, {"title": "Autonomic Nervous System .txt", "text": "And as more blood is being pumped to our muscle, those muscles are basically using more energy creating more ATP molecules and they need more oxygen."}, {"title": "Autonomic Nervous System .txt", "text": "And so the rate of our respiration increases as well as the rate of our heart."}, {"title": "Autonomic Nervous System .txt", "text": "Now as we begin to run, we have to see where we're going."}, {"title": "Autonomic Nervous System .txt", "text": "And so that means our pupils increase, they dilate so that more light gets into our eye and we can better see where we're actually running to."}, {"title": "Autonomic Nervous System .txt", "text": "So we see that our sympathetic nervous system this is the division of the autonomic nervous system that is responsible for the fight or flight response."}, {"title": "Autonomic Nervous System .txt", "text": "This includes dilating our pupils, increasing the heart as well as our breathing rate and increasing the mouth that we sweat."}, {"title": "Autonomic Nervous System .txt", "text": "So that's because when we sweat we're basically expelling the byproduct our energy."}, {"title": "Autonomic Nervous System .txt", "text": "So as we produce more ATP in our muscles, that creates more energy, more thermal energy as a byproduct."}, {"title": "Autonomic Nervous System .txt", "text": "And to keep our temperature of the body at the same temperature, we have to expel that energy."}, {"title": "Autonomic Nervous System .txt", "text": "And we do that by the process of sweating."}, {"title": "Autonomic Nervous System .txt", "text": "Now, when we're running, we don't have to worry about digestion."}, {"title": "Autonomic Nervous System .txt", "text": "We don't want to have to worry about digestion because our body basically needs to use the majority of the energy to basically run instead of digest."}, {"title": "Autonomic Nervous System .txt", "text": "And so what happens is that decreases our digestive rate and at the same time, it inhibits peristalsis because parastosis is the movement of our food products through our small intestine for the process of absorption."}, {"title": "Autonomic Nervous System .txt", "text": "So when we essentially begin to run, we don't want to worry about digestion or peristalsis."}, {"title": "Autonomic Nervous System .txt", "text": "So the sympathetic nervous system shuts down these processes."}, {"title": "Autonomic Nervous System .txt", "text": "It decreases their rate."}, {"title": "Autonomic Nervous System .txt", "text": "So the overall effect of our sympathetic nervous system is to basically increase the blood flow to our heart, to our cardiac muscle, as well as to our skeletal muscle."}, {"title": "Autonomic Nervous System .txt", "text": "So the blood vessels that carry the blood to our cardiac and skeletal muscle increase in size."}, {"title": "Autonomic Nervous System .txt", "text": "They dilate."}, {"title": "Autonomic Nervous System .txt", "text": "But the blood vessels that carry the blood to our digestive tract basically decrease in size."}, {"title": "Autonomic Nervous System .txt", "text": "They constrict because our rate of activity decreases inside the gastrointestinal system."}, {"title": "Autonomic Nervous System .txt", "text": "So now that we know what the job and function of the sympathetic nervous system is let's actually discuss the pathway of the electrical signal along the neurons inside the sympathetic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "So we have two neurons in our pathway."}, {"title": "Autonomic Nervous System .txt", "text": "The first neuron is known as our pre ganglionic neuron and the second neuron is known as the post ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "Now, all pre ganglionic neurons in a sympathetic nervous system begin in the spinal cord of our body."}, {"title": "Autonomic Nervous System .txt", "text": "So the cell, body and the dendrites of the pre ganglionic neuron are found in our spinal cord when they actually exit."}, {"title": "Autonomic Nervous System .txt", "text": "When the axon exits our spinal cord, it always exits from the front side, known as our ventral side."}, {"title": "Autonomic Nervous System .txt", "text": "And the axon of the pre ganglionic neuron is relatively short compared to our axon of the post ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "Now, at the first synapse between our pre ganglionic and the post ganglionic cell of the sympathetic nervous system we use acetylcholine as our neurotransmitter to pass that signal from our pre to our post ganglionic cell."}, {"title": "Autonomic Nervous System .txt", "text": "Now, when the action potential is carried all the way to the exxon terminal of the post ganglionic cell at the synapse between our exxon terminal the post ganglionic cell and the cell of our effector organ."}, {"title": "Autonomic Nervous System .txt", "text": "In this case, we use a different neurotransmitter."}, {"title": "Autonomic Nervous System .txt", "text": "We either use Epinephrine or we use Norepinephrine."}, {"title": "Autonomic Nervous System .txt", "text": "So once again, in the case of the sympathetic nervous system, every single pre ganglionic cell begins in our spinal cord and we'll see this is not the case in the parasympathetic system."}, {"title": "Autonomic Nervous System .txt", "text": "Now, there is an exception to this rule."}, {"title": "Autonomic Nervous System .txt", "text": "So inside the sympathetic nervous system, we usually have two of these neurons."}, {"title": "Autonomic Nervous System .txt", "text": "We have a pre and opposed ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "But there is one exception."}, {"title": "Autonomic Nervous System .txt", "text": "The electrical signal that is carried from the spinal cord to our adrenal medulla is carried by only a single neuron, by one pre ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "So the pre ganglionic neuron basically carries that electric signal all the way to our adrenal medulla without using the pose ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "And our neurotransmitter in that case is still acetylcholine."}, {"title": "Autonomic Nervous System .txt", "text": "So now let's move on to our parasympathetic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "So in many different ways, the parasympathetic nervous system basically reverses these effects."}, {"title": "Autonomic Nervous System .txt", "text": "So let's suppose we just ate and we basically ate."}, {"title": "Autonomic Nervous System .txt", "text": "We sit down and we begin watching TV."}, {"title": "Autonomic Nervous System .txt", "text": "So what begins to take place?"}, {"title": "Autonomic Nervous System .txt", "text": "So as we're watching our television, we're not basically using our muscles as much."}, {"title": "Autonomic Nervous System .txt", "text": "So that means we do not have to worry about producing ATP to move our muscles, to contract our muscles."}, {"title": "Autonomic Nervous System .txt", "text": "So what the parasympathetic system does is it basically decreases the rate of the heart and it decreases our respiration rate, basically the opposite of what the sympathetic nervous system did."}, {"title": "Autonomic Nervous System .txt", "text": "Because we're not sweating as much, we don't have to worry about sweating as in this case."}, {"title": "Autonomic Nervous System .txt", "text": "So our sweating basically drops at the same time because we just ate."}, {"title": "Autonomic Nervous System .txt", "text": "We have to digest our food and we have to absorb our food, the nutrients inside the small intestine."}, {"title": "Autonomic Nervous System .txt", "text": "So what happens is the digestion rate basically increases."}, {"title": "Autonomic Nervous System .txt", "text": "Our excretory system is working much more than before and we're no longer inhibiting, we're inducing our peristalis so that we can actually move that food along our small intestine."}, {"title": "Autonomic Nervous System .txt", "text": "So the parasympathetic division of our autonomic nervous system is responsible for the rest and digest activities."}, {"title": "Autonomic Nervous System .txt", "text": "This means it increases the flow of blood to our digestive organs and excretory system."}, {"title": "Autonomic Nervous System .txt", "text": "So that means the blood vessels carrying blood to our digestive organs increases in size, they dilate, while our blood vessels that carry our blood to our skeletal tissue decreases in size."}, {"title": "Autonomic Nervous System .txt", "text": "And so we have a decrease in blood flow because we don't have to worry about moving our arms or legs."}, {"title": "Autonomic Nervous System .txt", "text": "We're not actually running, we're sitting down and we're watching television."}, {"title": "Autonomic Nervous System .txt", "text": "So this is what the parasympathetic nervous system does."}, {"title": "Autonomic Nervous System .txt", "text": "Now, in the same exact way that we discussed our pathway of the electrical signal, let's discuss the pathway in the parasympathetic case."}, {"title": "Autonomic Nervous System .txt", "text": "So in the case of the sympathetic nervous system, our pre ganglionic neuron always begins in our spinal cord."}, {"title": "Autonomic Nervous System .txt", "text": "But in this case, it can begin in a spinal cord or it also can begin in the brain."}, {"title": "Autonomic Nervous System .txt", "text": "So the cell body begins in our brain or spinal cord."}, {"title": "Autonomic Nervous System .txt", "text": "And now the axon is relatively long."}, {"title": "Autonomic Nervous System .txt", "text": "So the axon is long compared to the axon of the post ganglionic cell."}, {"title": "Autonomic Nervous System .txt", "text": "So we still have our pre ganglionic cell that synapses with the post ganglionic cell."}, {"title": "Autonomic Nervous System .txt", "text": "And in this case our neurotransmitter is also acetylcholine."}, {"title": "Autonomic Nervous System .txt", "text": "Now we have a short post ganglionic axon."}, {"title": "Autonomic Nervous System .txt", "text": "In this case we had a long one."}, {"title": "Autonomic Nervous System .txt", "text": "And now our synapse between the post ganglionic neuron and the fact the organ uses acetylcholine as a neurotransmitter, in this case we use epinephrine or norepinephrine."}, {"title": "Autonomic Nervous System .txt", "text": "So this is a second difference between our sympathetic and parasympathetic nervous system."}, {"title": "Autonomic Nervous System .txt", "text": "So the pre ganglionic neuron begins either in a spinal cord or in the brain."}, {"title": "Autonomic Nervous System .txt", "text": "It then carries our electrical signal via a long axon to our synapse that uses acetylcholine."}, {"title": "Autonomic Nervous System .txt", "text": "And then the signal is passed down to this one and at this location it uses our acetylcholine once again."}, {"title": "Autonomic Nervous System .txt", "text": "So the major difference between our sympathetic and the parasympathetic is in the parasympathetic, both synapses use acetylcholine."}, {"title": "Autonomic Nervous System .txt", "text": "In this case, only the pre uses our acetylcholine."}, {"title": "Autonomic Nervous System .txt", "text": "The post uses epinephrine."}, {"title": "Autonomic Nervous System .txt", "text": "In this case we have a long pre ganglionic and a short post ganglionic."}, {"title": "Autonomic Nervous System .txt", "text": "Here we have a short pre ganglionic and a long pre ganglionic."}, {"title": "Autonomic Nervous System .txt", "text": "In the sympathetic case it always begins in a spinal cord while in this case it begins either in the brain or in our spinal cord."}, {"title": "Autonomic Nervous System .txt", "text": "Now, in the parasympathetic case we always have a pre ganglionic and opposed ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "In the case of the sympathetic we usually have a pre and opposed ganglionic."}, {"title": "Autonomic Nervous System .txt", "text": "But in the case of the signal being transferred into our adrenal medulla we only have a single neuron."}, {"title": "Autonomic Nervous System .txt", "text": "In the pathway we have the pre ganglionic neuron."}, {"title": "Autonomic Nervous System .txt", "text": "And once again, our sympathetic nervous system is responsible for monitoring and regulating the activities related with the fight or flight responses."}, {"title": "Autonomic Nervous System .txt", "text": "But in the parasympathetic case we basically regulate the rest and digest activities."}, {"title": "Autonomic Nervous System .txt", "text": "And the major difference between our somatic and the autonomic is the somatic controls our skeletal movement, so, voluntary movement but the autonomic controls all the movement that involuntary such as increasing our heart rate, dilating or constricting our pupils or blood vessels, controlling our rate of digestion and so forth."}, {"title": "Deamination of Amino Acids .txt", "text": "Once proteins are broken down into their individual amino acid constituents, what happens to those amino acids next?"}, {"title": "Deamination of Amino Acids .txt", "text": "What is the fate of amino acids once proteins are actually degraded?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, for the most part, the amino acid can be used in biosynthetic processes to form new molecules."}, {"title": "Deamination of Amino Acids .txt", "text": "For example, we can use amino acids to build proteins."}, {"title": "Deamination of Amino Acids .txt", "text": "We can use amino acids to build nucleotide bases."}, {"title": "Deamination of Amino Acids .txt", "text": "But let's suppose we have all the proteins that we want, and we have all the nucleotide bases that our cells can actually use."}, {"title": "Deamination of Amino Acids .txt", "text": "What happens to any extra leftover amino acids?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, you might be thinking we can store those amino acids for later use."}, {"title": "Deamination of Amino Acids .txt", "text": "So in the same way that we can store glucose as glycogen, and we can store extra fatty acids as triglycerides, can we store extra amino acids inside our cells?"}, {"title": "Deamination of Amino Acids .txt", "text": "And the answer is simply no."}, {"title": "Deamination of Amino Acids .txt", "text": "Our cells do not have a way to actually store any excess amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "And so what must happen to these extra amino acids is they must be broken down."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, the majority of the breakdown of amino acids occurs inside our liver."}, {"title": "Deamination of Amino Acids .txt", "text": "But other cells, such as muscle cells, can also break down amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "For example, inside our muscle cell, we basically break down branch chain amino acids such as leucine, isoleucine, and valine."}, {"title": "Deamination of Amino Acids .txt", "text": "So let's take a look at how we actually break down amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, we have different ways by which we break down different amino acids, but let's begin by focusing on this two step process here."}, {"title": "Deamination of Amino Acids .txt", "text": "So essentially, the goal in the breakdown of amino acids is first we have to remove that amino group from that amino acid to form our ammonia."}, {"title": "Deamination of Amino Acids .txt", "text": "The ammonium ultimately is fed into the urea cycle, and that removes that ammonium from the body and the leftover carbon skeleton that we have left over."}, {"title": "Deamination of Amino Acids .txt", "text": "After this process occurs, that is used to form energy molecules, and we'll talk about that in electra to come."}, {"title": "Deamination of Amino Acids .txt", "text": "So this is a two step process by which first we take the amino acid."}, {"title": "Deamination of Amino Acids .txt", "text": "We undergo a transamination step in which we basically transfer this green group onto a different molecule."}, {"title": "Deamination of Amino Acids .txt", "text": "We form glutamate."}, {"title": "Deamination of Amino Acids .txt", "text": "And the second step, we actually have that diamondation step."}, {"title": "Deamination of Amino Acids .txt", "text": "So we deaminate, we remove the alpha amino group, and we form the ammonium, at which point this ammonium can now be fed into the urea cycle."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, let's begin by focusing on just this reaction here."}, {"title": "Deamination of Amino Acids .txt", "text": "So we have transamination."}, {"title": "Deamination of Amino Acids .txt", "text": "transamination is catalyzed by an enzyme known as aminotransferase, and we also call it transaminase."}, {"title": "Deamination of Amino Acids .txt", "text": "But in this lecture, we're going to refer to it as simply aminotransferase."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, Aminotransferase, as we'll talk about in more detail in the next lecture, uses an important coenzyme, a vitamin B six derivative known as peridoxylphostate."}, {"title": "Deamination of Amino Acids .txt", "text": "So a periodoxyl phosphate needs to be present for this enzyme to actually be effective."}, {"title": "Deamination of Amino Acids .txt", "text": "If we have deficiency in this coenzyme here, this enzyme will not function correctly."}, {"title": "Deamination of Amino Acids .txt", "text": "So this is a general process that takes place."}, {"title": "Deamination of Amino Acids .txt", "text": "We begin with some target amino acid that we have too much of."}, {"title": "Deamination of Amino Acids .txt", "text": "So we want to break this down."}, {"title": "Deamination of Amino Acids .txt", "text": "We reacted with an alpha ketoacid, and we basically form these two products here."}, {"title": "Deamination of Amino Acids .txt", "text": "So we transfer this green group, the alpha amino group, onto this group here, remove this oxygen, and we form these two molecules."}, {"title": "Deamination of Amino Acids .txt", "text": "So we form another amino acid, which is actually a glutamate, as we have in this diagram here, and we form this alpha keto acid."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, this molecule can basically be used for energy purposes, as we'll see in a future lecture."}, {"title": "Deamination of Amino Acids .txt", "text": "But this molecule must further undergo a process, the diamondation step, to basically generate that free ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "So let's look at two examples of these processes."}, {"title": "Deamination of Amino Acids .txt", "text": "So we have different aminotransferases, and two common examples are alanine and aspartate aminotransferases."}, {"title": "Deamination of Amino Acids .txt", "text": "So, as you might imagine, in this particular case, the beginning amino acid is alanine."}, {"title": "Deamination of Amino Acids .txt", "text": "In this case, it's aspartate."}, {"title": "Deamination of Amino Acids .txt", "text": "So in both cases, the alpha keto acid is alpha ketoglutrate."}, {"title": "Deamination of Amino Acids .txt", "text": "So we use this molecule to basically transfer this green alpha amino group onto the alpha ketoglutrate."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, when we remove the alpha amino group, this green group from alanine, we basically form pyruvate."}, {"title": "Deamination of Amino Acids .txt", "text": "When we do the same thing for aspartate, we form oxalo acetate."}, {"title": "Deamination of Amino Acids .txt", "text": "But because these two molecules are exactly the same, when we transfer that green group onto alpha key to glutarate, we basically form the glutamate."}, {"title": "Deamination of Amino Acids .txt", "text": "And it's the glutamate that goes on to undergo the oxidative diamondation step to basically abstract that ammonium, as we'll see in just a moment."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, the last thing I'd like to mention about this process is it goes both ways."}, {"title": "Deamination of Amino Acids .txt", "text": "So we can go this way, but we also go in reverse."}, {"title": "Deamination of Amino Acids .txt", "text": "So this reaction actually exists in equilibrium."}, {"title": "Deamination of Amino Acids .txt", "text": "And why is that important?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, it's important the following way."}, {"title": "Deamination of Amino Acids .txt", "text": "So going this way, our cells can break down allenine and aspartate and other amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "But going in reverse, that actually gives us a way to form new amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "So we can begin with these molecules and go on to form alanine, or aspartate if our cell actually needs to do that."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, let's go on to step number two."}, {"title": "Deamination of Amino Acids .txt", "text": "So the oxidative diamondation step."}, {"title": "Deamination of Amino Acids .txt", "text": "So once we transfer that amino group from the target amino acid onto the alpha key to glutary to form the glutamate, what is the fate of that glutamate?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, what we want to do is we want to deaminate the glutamate."}, {"title": "Deamination of Amino Acids .txt", "text": "And this happens in a two step process."}, {"title": "Deamination of Amino Acids .txt", "text": "So we have a dehydrogenation, and then we have this hydrolysis reaction."}, {"title": "Deamination of Amino Acids .txt", "text": "So we take the glutamate, and we basically want to remove this h here and this h here."}, {"title": "Deamination of Amino Acids .txt", "text": "We also want to remove two electrons."}, {"title": "Deamination of Amino Acids .txt", "text": "And so we form a pi bond between this carbon and this nitrogen."}, {"title": "Deamination of Amino Acids .txt", "text": "And so this is actually an oxidation reaction reaction, oxidation reduction reaction."}, {"title": "Deamination of Amino Acids .txt", "text": "And so the molecule that we use as a coenzyme is NAD."}, {"title": "Deamination of Amino Acids .txt", "text": "Plus, now the enzyme that catalyze this step is no longer this enzyme."}, {"title": "Deamination of Amino Acids .txt", "text": "It's a different enzyme known as glutamate dehydrogenase."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, glutamate dehydrogenase is interesting because it not only uses NAD plus, but it can also use instead of the NAD plus, NADP plus."}, {"title": "Deamination of Amino Acids .txt", "text": "So we can replace this with NADP plus, but ultimately we use this or the enzyme uses this to basically remove the two electrons and the h to form the NADH."}, {"title": "Deamination of Amino Acids .txt", "text": "We also remove the h plus and we form a double bond between carbon and the nitrogen, and we form this shift based intermediate shown here."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, in the second step, we actually have the diamondation step, or we can also see it as a hydrolysis step because we use a water to basically hydrolyze and remove that Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "And so we replace the nitrogen, h two with an oxygen and we abstract that Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "So we take the two HS from here and the two HS from the water, and we form that Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "And we also form the alpha ketoglutrate as the final product."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, one interesting thing about glutamate dehydrogenase is that it is found in the mitochondria."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, why is that important?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, the final product form of this process is Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "And Ammonium is a very toxic substance."}, {"title": "Deamination of Amino Acids .txt", "text": "And so if Ammonium was readily formed in the styroplasm, that can actually damage the cell."}, {"title": "Deamination of Amino Acids .txt", "text": "And so to prevent that from actually happening, our cell sequesters the glutamate dehydrogenase in the mitochondria and it basically keeps that Ammonium inside the mitochondria, preventing it from actually damaging the cell."}, {"title": "Deamination of Amino Acids .txt", "text": "Another important thing about this reaction is the same thing we mentioned here."}, {"title": "Deamination of Amino Acids .txt", "text": "These arrows go both ways."}, {"title": "Deamination of Amino Acids .txt", "text": "And so we can basically go this way, but if the conditions change, we can also go this way."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, under normal conditions, the reaction actually goes forward."}, {"title": "Deamination of Amino Acids .txt", "text": "Why?"}, {"title": "Deamination of Amino Acids .txt", "text": "Well, because normally, every time we for the Ammonium product, that Ammonium is used up in the urea cycle."}, {"title": "Deamination of Amino Acids .txt", "text": "And so if we continually use up this final product, that will drive this reaction forward."}, {"title": "Deamination of Amino Acids .txt", "text": "So if we summarize these two reactions, the transamination and the oxidative deamination, we basically form this diagram here."}, {"title": "Deamination of Amino Acids .txt", "text": "So we begin with the target amino acid, and we have the alpha key to glutrate."}, {"title": "Deamination of Amino Acids .txt", "text": "As we saw in this particular case, this is catalyzed by aminotransferase."}, {"title": "Deamination of Amino Acids .txt", "text": "And so we ultimately form a glutamate and the alpha key to acid, in this case, pyruvate, in this case, oxalo acetate."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, in the second step, that is catalyzed by glutamate dehydrogenase, the glutamate reacts with the NAD plus or NADP plus and water to basically form the alpha key to gluterate and that Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "And so this Ammonium then goes into the urea cycle."}, {"title": "Deamination of Amino Acids .txt", "text": "It is used up, and so this reaction is driven in this direction."}, {"title": "Deamination of Amino Acids .txt", "text": "So we see that the majority of amino acids inside our cells, more specifically our liver cells, hepatics basically undergo this two step process to deaminate that amino acid."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, other amino acids such as Serene and three anine undergo other processes, processes to basically deaminate it."}, {"title": "Deamination of Amino Acids .txt", "text": "So in this case, we have a two step process that deaminates the amino acid."}, {"title": "Deamination of Amino Acids .txt", "text": "But for Serene and three anine, this is a single step process and it's catalyzed by single enzyme, a dehydrates."}, {"title": "Deamination of Amino Acids .txt", "text": "So we call it a dehydrates because there is a dehydration reaction that precedes a deamination reaction, as we'll see in just a moment."}, {"title": "Deamination of Amino Acids .txt", "text": "So for serine, we have serine dehydrates that basically deaminates the serine into Pyruvate and that forms Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "For three enine, we form alpha, ketobutyrate, and the ammonium, the Ammonium goes into the urea cycle."}, {"title": "Deamination of Amino Acids .txt", "text": "These can be used for energy purposes."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, to see exactly what happens, let's focus on this reaction here."}, {"title": "Deamination of Amino Acids .txt", "text": "Reaction one."}, {"title": "Deamination of Amino Acids .txt", "text": "So we begin with our serine."}, {"title": "Deamination of Amino Acids .txt", "text": "And this enzyme dehydrates basically allows us to undergo a dehydration step."}, {"title": "Deamination of Amino Acids .txt", "text": "And so what happens is this hydroxide group combines with an H atom, this H atom here, to basically form a double bond between this carbon, this carbon, and we form this high energy intermediate molecule."}, {"title": "Deamination of Amino Acids .txt", "text": "Now, this high energy intermediate molecule is unstable, and so it rarely converts into this final product."}, {"title": "Deamination of Amino Acids .txt", "text": "And this is our diamondation step."}, {"title": "Deamination of Amino Acids .txt", "text": "So this diamondation step is similar to this one here because we also use water in this hydrolysis step."}, {"title": "Deamination of Amino Acids .txt", "text": "So we essentially allow this group here to be kicked off."}, {"title": "Deamination of Amino Acids .txt", "text": "We form that Ammonium, and that Ammonium then goes into the urea cycle."}, {"title": "Deamination of Amino Acids .txt", "text": "So this is basically the process by which we deaminate amino acids."}, {"title": "Deamination of Amino Acids .txt", "text": "And by deaminating the amino acids, we basically form carbon skeletons and we form Ammonium."}, {"title": "Deamination of Amino Acids .txt", "text": "The Ammonium can be used in the urea cycle, and that carbon skeleton can be used to basically form energy molecules, as we'll see in a future lecture."}, {"title": "Deamination of Amino Acids .txt", "text": "So we see that some of those amino acids are basically deaminated in a two step process, in an indirect process, while other amino acids undergo this process in which we have a single step process by which we deaminate that amino acid."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "The final type of purification technique that we're going to focus on is the twodimensional gel electrophoresis."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And this is actually something that we spoke about already."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "It's simply a combination of two different types of protein purification techniques."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So in twodimensional gel electrophoresis, we take our mixture of proteins and we first expose it to isoelectrofocusing."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "We separate the proteins based on their isoelectric point."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So the PH value at which that particular protein basically has a net charge of zero."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And after that, we expose that solution, that mixture of proteins, to the process of SDS polyacrylamide gel electrophoresis, also known as SDS Page."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So P is the first letter."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Then we have the A."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Then we have the g then we have the E. So SD eight SDS page So isoelectric focusing can be combined with SDS polyacrylamide geelectrophrases, or SDS Page to create a more effective and more efficient way of purifying our crude mixture of proteins."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And to see exactly what we mean, let's take a look at the following two steps."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Now, we're not going to focus too much on each one of these steps because we spoke about these in detail in previous lectures."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "We're simply going to show you the fact that we can combine these two techniques to basically create a more effective method."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So, in the first step, we take our crude mixture of proteins found in the following beaker, and we expose it to isoelectric focusing."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So remember, in isoelectric focusing, we essentially have this gel."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And that gel contains a PH gradient."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So on one side, we have a low PH acidic, and that's when we have many of these positively charged H ions."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And so we have a positive charge on this end."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "On the other side, we have a low concentration of H plus ions."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "We have a high PH, a basic environment."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "We have a negative charge."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And so when we take this mixture of proteins and dump them onto the gel, they will begin to separate on the basis of their net charge."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And so they will essentially continue moving as a result of that electric field."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And they will stop moving when their net charge is zero."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And that is what we call the isoelectric point."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So a mixture of proteins is first exposed to isoelectric focusing."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "This separates the proteins based on their isoelectric point."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So the PH value at which the net charge on the protein is zero."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So if two or more proteins, however, have the same pi value, they will be found on the same exact band in this diagram."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So we have 12345 of these different bands."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And what each of these bands basically means, we have either a single or many proteins within each one of these bands."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "For example, let's suppose we're looking at this band."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Here what this band basically means."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "A single protein or many proteins exist along the following region."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And all these proteins basically have the same exact isoelectric point, the same exact pi value."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And the same thing is true for these other bands, as shown."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Now, if we take this horizontal slap and we place it into our SDS Page setup, we can now separate our proteins based on size."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So this is one direction, the horizontal direction of separation, and this is our vertical direction of separation."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And that's why this is called a two dimensional gel electrophoresis process, because we separate along the x axis, then along the y axis, and those are two different dimensions."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So once we take this and place it into our electrophoresis setup, we see that what begins to happen is they begin to migrate down towards the positively charged end of this SDS Page setup."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And so if any one of these bands consists of different proteins that have different mass values, that are different sizes, we're going to be able to separate them along the vertical direction based on their size."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So in this case, we separate them based on their isoelectric point, but in this case, we separate them based on their mass, based on their size."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So we see that this slab, this band, consists of at least four different proteins, because these four different proteins contain different size values, different masses."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Likewise, the second band consists of at least two proteins, the third band consists of at least one, two, three proteins."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "The fourth band consists of at least three proteins, and the fifth band consists of at least five different proteins."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Now, it's not to say that we don't have more proteins here."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "For example, the reason to say we have at least five proteins in this section is because two proteins that have the same exact isoelectric point can also have the same exact mass."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "And so each one of these sections, each one of these individual bands can consist of two or more proteins, but it also can consist of only a single protein."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "To basically determine if we have more proteins in each one of these sections, we have to carry out some other type of purification process that separates the proteins based on some other type of property."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So in the second method, the horizontal gel lane that contains the protein, so this entire gel lane is placed onto the SDS Page apparatus."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So SDS polyacrylamide gel electrophoresis apparatus, the proteins now begin to move as a result of that electric field in the perpendicular direction with respect to the direction in this case."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So here we have along the x axis, and here we have movement along the y axis."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So the x axis is perpendicular to the y axis, so they begin to move downward."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "This will separate the proteins that have identical pi values based on their different masses, different sizes."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So we conclude that the two dimensional gel electrofreezes process is a highly effective method that separates the mixtures of the mixture proteins based on two different properties, so their isoelectric point and their size."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So the horizontal direction is the isoelectric point."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "It separates the proteins based on the PH at which they have a net charge of zero, and the second vertical dimension basically separates them based on size."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "So this is the process of two dimensional gel electrophoresis."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "It combines isoelectric focusing and st polyacrylamide gel electrophree."}, {"title": "Two Dimensional Gel Electrophoresis.txt", "text": "Source simply SDS Page."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Previously, we discussed a neuron, and we said that a neuron is the basic functional unit of the nervous system."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "It's a specialized type of cell that is capable of generating action potentials."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And it generates the action potentials on the cell membrane, and it moves the electrical signal along the axon and passes that electric signal down to adjacent cells."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And by this method, our cells can communicate with one another in a direct and rapid fashion over very short distances."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, before we actually describe how the neuron generates the action potential and what the action potential is, let's describe the cell membrane of the neuron."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "When the neuron is at rest, that is, when it is not generating any action potential."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this is known as the resting membrane of our neuron."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, the resting membrane contains a certain voltage difference."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "There is a certain voltage difference between the inside and the outside of the cell, and this is known as the resting membrane potential."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So, once again, the resting membrane potential is the voltage difference or the electric potential difference between the inside and the outside of a neuron that is not generating any action potential."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So let's begin by looking at the following diagram."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this diagram describes the relative concentrations of sodium ions and potassium ions on the outside and inside of the neuron cell membrane."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this is the phospholipid bilayer, the membrane of the neuron, let's say, found on the exxon hillock where the action potential is generated."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "But, of course, no action potential is being generated in this particular case."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this is the outside portion of the cell."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "It's the extracellular portion of the membrane."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "This is the inside portion of the cell, the cytoplasmic side of our membrane."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, these red dots describe sodium ions, and these purple dots describe our potassium ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And each one of these ions are cat ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "That means they each have a positive charge of one."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, notice we have many more of these red dots on the outside than on the inside, and many more of these purple dots on the inside than on the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So that implies that when the membrane is resting, when it is not generating any action potential, we have many more sodium ions on the outside than on the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And conversely, we have many more potassium on the inside than on the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And this table describes what the concentrations are."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So for sodium on the inside, we have 15 millimolar."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And for the outside, we have 150 millimolar."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So the ratio is ten to one."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So for every one sodium we find on the inside, we have ten sodium ions on the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, for potassium, it's the opposite."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "We have more."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "On the inside, we have 130 millimolar, and only five millimolar on the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So the ratio is 26 to one."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "For every one potassium we find on the outside, we have 26 potassiums on the inside of the resting membrane of our neuron."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, this picture doesn't actually describe everything correctly because we also have other ions that bear a negative charge."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we also have chloride ions, we have bicarbonate, and we have proteins that all have negative charge and they're found on the inside as well as on the outside of the cell."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, we're going to begin by assuming something called electroneutrality."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So electroneutrality means that all the negative charges cancel out all the positive charges on the inside, and likewise all the negative charges of all the negatively charged ions cancel out all the positive charges of all the positively charged ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this is known as electron neutrality."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So the outside and the inside are neutral with respect to the charge."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we're going to begin by assuming that."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now the question is let's take a look at the following concentration amount."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we have many more of these sodiums on the outside than on the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And that means if the sodium ions can somehow flow across the membrane, they would travel from the high concentration the outside to the low concentration the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And likewise, if these potassium ions could somehow travel across the membrane, they would travel from the high concentration the inside to the low concentration the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, of course, because these ions contain positive charges, we know that they cannot actually diffuse across the membrane."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, what the membrane actually contains is special proteins that facilitate the diffusion passively of these ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And we have many more of these potassium membrane proteins than the sodium membrane proteins."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And that implies that our membrane is much more permeable to potassium than it is to sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And that implies that our potassium will travel across the membrane much more at a much higher rate than our sodium will."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So once again, the membrane of the neuron is naturally much more permeable to potassium than to the sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "This means that the membrane contains more protein channels that facilitate our passive diffusion of potassium than of sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And therefore more potassium ions will leave the cell, then compared to our sodium ions will enter our cell."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this is described in the following diagram."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we have these facilitated transfer proteins."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "We have the ones that transport our potassium from the inside to the outside, from a high to a low concentration."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And we have these transfer proteins that transport our sodium from the high from the outside to the low to the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And we also have proteins that actually actively transport our potassium and sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And we're going to discuss these in much more detail in the next several lectures."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "This is known as the ATPase protein."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, the question that we want to basically ask next is the following."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So, we begin by assuming that the charge on the outside and the inside is exactly the same."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "It's zero."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So that means the voltage difference between the outside and inside is zero."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "But we know that the voltage is not zero."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "If we actually try to find what the voltage is using some type of instrument, we'll see that it's not zero."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So the question is, what exactly is the voltage difference between the cell membrane of a resting membrane and how is it generated?"}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So, let's begin."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "For the time being."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Let's begin by assuming that the cell is only permeable to our potassium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So as potassium leaves the cell, it travels from the inside to the outside via these proteins that passively diffuse our molecules, our ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So as our potassium leaves the cell, we have less positively charged ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And so the positive charge will decrease and the inside will become more negative."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "At the same time as these potassiums are being pumped into the outside, the outside will gain a certain positive charge."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So as the positive charge builds up on the outside, the electric force begins to force the potassium back inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we build up our positive charge on the outside, and that drives via an electric force, these potassiums slowly back inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And eventually when the electric force, due to the positive charge build up on the outside is exactly the same as the force that is pushing our potassiums to the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "As a result of the concentration gradient, when these two forces are exactly the same and point in the opposite direction, equilibrium is reached."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And when equilibrium is reached, we have this concentration of our potassium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So let's try to use this concentration and the nursed equation to calculate what the voltage difference is."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So remember when we discussed the chemistry of neurons?"}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "We said that the Neuron is basically a concentration cell."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And we can use the nurse equation to calculate what the voltage difference is between the inside and the outside of the cell due to our potassium ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So 2.3 multiplied by R, the Gas constant 8.3, 114 multiplied by T, the temperature Inside the body."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So that's 310 Degrees Kelvin, or Simply 310 Kelvin divided by Z, which is basically one in this case divided by F farades constant, which is about 96,500."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, the concentration of potassium outside, according to our table, is five millimolar."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And outside or inside, is 130 millimolar."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we have five on top and 130 on the bottom."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we have log of this ratio multiplied by this."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "We plug in our values and we get negative zero point 87 volts or equivalently."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "If we multiply this by 1000, we get negative 87 millivolts."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we see that this would be our voltage difference, the electric potential difference between the inside and the outside portion of the resting membrane of the neuron."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "If the permeability of the membrane to sodium was zero, So we know that this is not actually the resting potential, the resting membrane potential, the voltage difference."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Because our membrane is not only permeable to potassium, as we assumed here, but it's also permeable to sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So what will happen?"}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Well, basically, as Our potassium is being pumped to the outside, the sodium will also begin to slowly pump to the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, the rate at which our sodium is brought to the inside is much smaller, and so that means much less of those sodiums will be brought to the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Then the potassiums will be brought to the outside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So the sodium will flow naturally from the high concentration, the outside to the low concentration to the inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And the way that that takes place is via these special proteins that passively pump these ions."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Now, this means that if we move positive charge from the outside of the cell to the inside of the cell, this inside will become slightly more positive, that is, slightly less negative."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So this value of negative 87 millivolts will become more positive because this membrane is slightly permeable to our sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And so some of these sodiums will be brought to the inside, and so this will become more positive."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And that's exactly why the actual value for the voltage difference of the rustic membrane is around negative 70 millivolts."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Because the membrane is not only permeable to our potassium, it's also slightly permeable to our sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we see that these potassiums are brought to the outside, and that makes the inside negative."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "At the same time, these sodiums are brought to the inside at a much smaller rate, so this becomes slightly more positive."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And so what the actual voltage difference between the inside and outside?"}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Is?"}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "It's negative 70 millivolts."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So that means the inside has a negative charge and the outside has a positive charge."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "So we began by assuming electron neutrality, but now we know that the resting membrane potential inside has a negative charge, while the outside contains a positive charge."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And what created this difference in charge is basically this movement on equal movement of sodium as well as potassium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "Potassium is more permeable than sodium."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And so we have many more of these potassiums flowing outside than our sodium traveling inside."}, {"title": "Resting Membrane Potential of Neuron.txt", "text": "And that's why our value is negative 70 millivolts."}, {"title": "Covalent Modification and Phosphorylation Part II .txt", "text": "It amplifies the effects and amplifies the amount of product that we form at the end."}, {"title": "Covalent Modification and Phosphorylation Part II .txt", "text": "And finally, just like we can activate the enzyme defosphorylation, we have these enzymes known as protein phosphatases that can ultimately reverse the effects of protein kinase and basically defosphorylate that reaction."}, {"title": "Covalent Modification and Phosphorylation Part II .txt", "text": "So we see that this phosphorylation is actually a reversible process."}, {"title": "Covalent Modification and Phosphorylation Part II .txt", "text": "We can phosphorylate it, but at the same time we can use a different reaction mechanism and a different enzyme to actually defosphorylate and reverse the effects of these protein kinases."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Eukaryotic cells can divide by either one of two methods."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "If we're talking about somatic eukaryotic cells, then those divide via mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "If we're talking about gametocides, those divide via meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, mitosis is the process by which a somatic cell divides into two genetically identical deployed daughter cells cells, and the chromosome number remains exactly the same."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So if we begin with 46 chromosomes in a human somatic cell, we produce 46 chromosomes in the daughter cell, and this is mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, in meiosis, we basically have a single gametocide, divides into four genetically different haploid cells."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And that basically means if we begin with 46 chromosomes in our gametocide, our daughter cells will contain 23 chromosomes in each one of the four daughter cells, and this is known as meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, both mitosis and meiosis consist of a process of phase known as anaphase."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And during anaphase, we have the separation of chromosomes or the equal separation of chromosomes to both sides of our cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And this process is known as disjunction."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, just like any other biological process, disjunction is also prone to mistakes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And one mistake that can take place during this junction is an unequal or an incorrect separation of chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And this is known as nondisjunction."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So non disjunction is the process by which the chromosomes actually fail to separate correctly or equally during anaphase of either mitosis or mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And this results in cells that have an incorrect number of chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So in human somatic cells, we know that if we begin with 46 chromosomes, we have to produce cells that also consists of 46 chromosomes and any variations to this number."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "For example, if we produce 45 chromosomes or 47 chromosomes, this leads to a condition known as anapply."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, let's discuss how none disjunction actually takes place in mitosis as well as in meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's begin with mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, mitosis actually consists of four individual phases."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "We have ProPhase, metaphase, anaphase, and telephase."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And we also have the process of cytokinesis that actually divides the cell membrane and the cytoplasm of our cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, during the process of s phase of interphase, which takes place right before mitosis, we actually replicate each one of our chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's suppose we begin with a cell that consists of one, two, three chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So during interphase, we have to replicate each one of the chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And that's exactly why each one of these chromosomes consist of two identical chromatids known as cystochromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So chromosome one consists of one two identical cystic chromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And the same thing is true for chromosome number two and chromosome number three."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So, for this particular cell, we have three chromosomes lined up at the center at metaphase of mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "In the case of human somatic cells, we actually have 46 of these chromosomes lined up at the center during metaphase of mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So at metaphase, we basically line up all our chromosomes along the center, as shown, and the two centrioles are found on opposite sides."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And the centriole synthesize fibers known as spindle fibers."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And if disjunction actually takes place correctly, what happens is each spindle fiber attaches to each side of our chromosome."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So when our separation takes place, we have an equal separation of chromosomes to both sides of the cells."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So these chromatids will end up on that side, and these chromatids will end up on the other side."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, in the case of nondisjunction, during anaphase of mitosis, what can happen is a spindle fiber might incorrectly attach itself or not attach itself at all to the centromere portion of our chromosome, or the centromere might not actually divide correctly, and this can lead to the process of nondisjunction."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So in this case, we basically have our mitotic spindle fiber not binding to this side of chromosome number one."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And what happens is, when anaphase takes place and when we have the separation, this entire chromosome that consists of two individual cystochromatids will end up on the left side of the cell, while this side will consist of only one two cystochromatids, as shown."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So when we have telephase and cytokinesis take place and we produce our two daughter cells, one of these daughter cells, we will have an extra chromatid, while the other one will have one less chromatid than normal."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And this basically causes a variation of the correct number of chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And both of these cells have the condition known as anapply."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So nondisjunction can occur in somatic cells during the process of mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "At the beginning of anaphase, the spindle fibers begin to pull on the cystochromatids in an attempt to separate those chromatids equally to opposite poles of the cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, none disjunction takes place when the centromere holding our two chromatids fails to break or the spinal fiber actually fails to attach to one end of the chromosome."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And both chromatids in that chromosome are pulled to the same side of the cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "In this case, to the left side of the cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now let's move on to nondisjunction taking place in meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, meiosis is a slightly more complicated process because it actually consists of two individual stages."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So gametosites are those cells that undergo meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And meiosis actually involves two stages meiosis one and meiosis two."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And because each one of these individual stages contains its own anaphase, there are two locations where nondisjunction can take place during the process of meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's begin with anaphase one of meiosis one."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's suppose we're at metaphase, and let's suppose that our cell consists of six chromosomes and not three chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So we take our gamethocide that consists of six chromosomes in human cells."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "We basically have 23 pairs of these tetris found at the center of our cell in metaphase."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's suppose this is metaphase one of meiosis one, and we have the six chromosomes, and we have these three tetris."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So each one of these pairs are homologous chromosomes that have undergone a genetic recombination process known as crossing over."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Basically, line up at the center of our cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, once again, what we can have is the spindle fiber basically fails to actually attach to one side of the tetris."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And what happens when anaphase takes place?"}, {"title": "Nondisjunction of Chromosomes .txt", "text": "These tetris are not correctly separated."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So what should happen if this junction takes place correctly is each one of these tetrades is separated correctly."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So this goes here, this goes here."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "These two go this way, and these two go this way."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "But what actually takes place is this entire tetrad."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "The pair of homologous chromosomes, or recombinant chromosomes end up being dragged to the left side of the cell."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So when our cell division actually takes place, one of our daughter cells consists of one extra chromosome and two extra chromatids while the other cell consists of one less chromosome and two less chromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So during the beginning of anaphase one of meiosis one, the tetras are pulled apart to opposite poles."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "nondisjunction will cause a tetra to move to one side, ultimately leading to a cell with one extra chromosome and two extra chromatids, while the other cell will contain one less chromosome and two less chromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, let's move on to meiosis two."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, meiosis two contains its own process of anaphase that is known as anaphase two."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, if nondisjunction takes place, in anaphase II of meiosis, one of the daughter cells will have an extra chromatid while one will have one less chromatid than the normal number."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So to see what we mean, let's suppose we have this process that actually takes place correctly."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So let's assume meiosis one takes place correctly and we produce a daughter cell that consists of three of these chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "That itself consists of two cystochromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So each chromosome consists of its own set of chromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So now these chromatids are not cystochromatids, meaning they're not identical, as we saw in this case because in meiosis, we have the process of crossing over that takes place."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So once again, let's suppose a spindle fiber does not correctly attach to the centromere of one of these chromosomes."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And during the process of anaphase, we have the separation."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "But the separation is unequal."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Our distribution of chromosomes is unequal."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "This entire chromosome that consists of two individual chromatids are pulled to one side."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And so eventually, when our cytokinetis takes place, we have two of these daughter cells."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, one of them contains one extra chromatid while the other one contains one less chromatid."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "So we see that this process of nondisjunction, which is basically the unequal separation of chromosomes to both sides of our cell, can take place in mitosis as well as in meiosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, because mitosis consists of one anaphase, nondisjunction takes place only at one location during our cell cycle of mitosis or cell division of mitosis."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "But in meiosis, because we have two individual anaphase processes, we have anaphase one and anaphase two, there are two places where nondisjunction can actually take place."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And when nondisjunction actually takes place, in Meiosis One."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "That can lead to more serious problems than when it takes place in meiosis two."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Because in this case, we're producing a cell with two extra chromatids and with two less chromatids."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "But in this case, we're producing a cell with one extra and one less chromatid."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Now, what kind of problems can this cause?"}, {"title": "Nondisjunction of Chromosomes .txt", "text": "Well, whenever a cell is missing a set of genes, a set of DNA, that means it cannot actually synthesize certain types of proteins."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And that can lead to many problems."}, {"title": "Nondisjunction of Chromosomes .txt", "text": "And we'll talk more about the actual problems when we discuss genetics."}, {"title": "Electrochemical Gradient.txt", "text": "One of the many important functions of the cell membrane of a cell is to create an electrochemical gradient between the side to solve the inside of the cell and the outside of the cell, the extracellular fluid."}, {"title": "Electrochemical Gradient.txt", "text": "Now, the question is not how we create the electrochemical gradient."}, {"title": "Electrochemical Gradient.txt", "text": "We're going to discuss that in the next lecture."}, {"title": "Electrochemical Gradient.txt", "text": "The question is what exactly is is electrochemical gradient?"}, {"title": "Electrochemical Gradient.txt", "text": "So before we discuss the different modes of cell transport, let's define what an electrochemical gradient is."}, {"title": "Electrochemical Gradient.txt", "text": "So let's begin with a concentration gradient or a chemical concentration gradient."}, {"title": "Electrochemical Gradient.txt", "text": "So let's recall a concept from physics."}, {"title": "Electrochemical Gradient.txt", "text": "We know that in physics, according to Brownian motion, if we take a molecule and place it inside a fluid, the molecule will collide with the atoms or molecules of that fluid."}, {"title": "Electrochemical Gradient.txt", "text": "And as a result, that molecule in the fluid will experience random and rapid motion."}, {"title": "Electrochemical Gradient.txt", "text": "So let's conduct the following thought experiment."}, {"title": "Electrochemical Gradient.txt", "text": "Let's suppose we take a container shown in the black region."}, {"title": "Electrochemical Gradient.txt", "text": "And inside that container we have a certain fluid."}, {"title": "Electrochemical Gradient.txt", "text": "So the atoms of that fluid are shown by these blue dots."}, {"title": "Electrochemical Gradient.txt", "text": "So let's suppose we take twelve molecules."}, {"title": "Electrochemical Gradient.txt", "text": "Six of those molecules are molecule A."}, {"title": "Electrochemical Gradient.txt", "text": "And we place those six molecules onto the left side of our container."}, {"title": "Electrochemical Gradient.txt", "text": "And the other six molecules, let's call a molecule B, are found on the right side of that fluid filled container."}, {"title": "Electrochemical Gradient.txt", "text": "Now, separating the left and the right side is a semi permeable membrane that allows both of these molecules to basically pass through."}, {"title": "Electrochemical Gradient.txt", "text": "The question is, what exactly will take place over time?"}, {"title": "Electrochemical Gradient.txt", "text": "Well, over time, we're going to get the following case in which we're going to have equal amounts of molecule A on both sides and equal amounts of molecule B on both sides."}, {"title": "Electrochemical Gradient.txt", "text": "Basically, as a result of Brownian motion, molecules A and molecules B will be in a constant state of motion."}, {"title": "Electrochemical Gradient.txt", "text": "And based on the law of entropy, the most mathematically probable state of our system is in which we have an even amount of molecules on each side."}, {"title": "Electrochemical Gradient.txt", "text": "So this is the most probable state."}, {"title": "Electrochemical Gradient.txt", "text": "And if we begin with state number one, where we have all the A molecules on the left side, all the B molecules on the right side, eventually we will develop the following state."}, {"title": "Electrochemical Gradient.txt", "text": "So we say that molecule A moves down the concentration gradient from a higher concentration to a lower concentration."}, {"title": "Electrochemical Gradient.txt", "text": "So notice we had no molecules A on the right side."}, {"title": "Electrochemical Gradient.txt", "text": "And so A will move naturally from this location to this location."}, {"title": "Electrochemical Gradient.txt", "text": "And likewise the B molecules will move down their concentration gradient from a higher concentration to a lower concentration in the opposite direction of A."}, {"title": "Electrochemical Gradient.txt", "text": "And eventually we will have an equilibrium that will exist and our concentration gradient will basically cease to exist."}, {"title": "Electrochemical Gradient.txt", "text": "Now, according to Brownian motion, molecules A and molecules B will still move across our semipermeable membrane, but there will be no net change."}, {"title": "Electrochemical Gradient.txt", "text": "So we take six molecules A and place them on the left side of a fluid filled container."}, {"title": "Electrochemical Gradient.txt", "text": "We also take six molecules B and place them on the right end of our container."}, {"title": "Electrochemical Gradient.txt", "text": "These two sides are separated by semipermeable membrane that allows both of these molecules to move with ease."}, {"title": "Electrochemical Gradient.txt", "text": "Now, entropy dictates that after a while the most mathematically probable case will be a system in which we have these two molecules even out."}, {"title": "Electrochemical Gradient.txt", "text": "So basically, we have the same molecules A on this side as on that side and the same number of B molecules on this side as on that side."}, {"title": "Electrochemical Gradient.txt", "text": "We conclude that molecules tend to naturally move from a high concentration to a low concentration."}, {"title": "Electrochemical Gradient.txt", "text": "So given situation A, we say that there exists a chemical concentration gradient and both molecules travel down their perspective, chemical concentrate their respective chemical concentration gradient."}, {"title": "Electrochemical Gradient.txt", "text": "Molecule A travels from the left side, where we have a high concentration, to the right side, where we have a low concentration and molecule B moves in the opposite from a high concentration the right side to the left side, where we have a low concentration."}, {"title": "Electrochemical Gradient.txt", "text": "And this is known as the chemical concentration gradient or simply our concentration gradient."}, {"title": "Electrochemical Gradient.txt", "text": "Now, what about the electrical gradient?"}, {"title": "Electrochemical Gradient.txt", "text": "Well, in this case, molecule A and molecule B were both neutral."}, {"title": "Electrochemical Gradient.txt", "text": "They had no charge."}, {"title": "Electrochemical Gradient.txt", "text": "Suppose our molecules now have a charge."}, {"title": "Electrochemical Gradient.txt", "text": "So when molecules have electric charge, there can also be an electric gradient."}, {"title": "Electrochemical Gradient.txt", "text": "And the electric gradient is a result of the electric repulsive and attractive forces that exist in nature."}, {"title": "Electrochemical Gradient.txt", "text": "So this is basically a result of Brownian motion and the law of entropy."}, {"title": "Electrochemical Gradient.txt", "text": "And this is a result of the electric forces that exist in nature both positive or both attractive and repulsive electric forces."}, {"title": "Electrochemical Gradient.txt", "text": "So let's suppose we look at situation three."}, {"title": "Electrochemical Gradient.txt", "text": "In situation three, we have six C molecules that each have a positive one charge."}, {"title": "Electrochemical Gradient.txt", "text": "And on the other side, the right side, we have 6D molecules that each have a negative one charge."}, {"title": "Electrochemical Gradient.txt", "text": "Once again, we are separated by a semipermeable membrane that allows both of these molecules to pass through."}, {"title": "Electrochemical Gradient.txt", "text": "So in this case, molecule C has a positive charge and molecule D has a negative charge."}, {"title": "Electrochemical Gradient.txt", "text": "Both molecules will move down their electrical gradient and this movement is a result of the electric attractive and repulsive forces that exist in nature."}, {"title": "Electrochemical Gradient.txt", "text": "Molecule C moves to the right while molecule D will move to the left until the electric charge basically equilibriates between our two sides."}, {"title": "Electrochemical Gradient.txt", "text": "So in this case, we have a positive six charge."}, {"title": "Electrochemical Gradient.txt", "text": "In this case, we have a negative six charge and we have the separation of our charge."}, {"title": "Electrochemical Gradient.txt", "text": "Now eventually, after some time passes as a result of the tractive forces between the positive and negative as well as the repulsive forces between the negatives and the positives, we basically have the following situation in which we have no charge, no net charge."}, {"title": "Electrochemical Gradient.txt", "text": "On the left side, we have three D and three C. And so the charges cancel out and no charge on this side because they cancel out."}, {"title": "Electrochemical Gradient.txt", "text": "And so in this scenario, we no longer have an electric gradient."}, {"title": "Electrochemical Gradient.txt", "text": "In the same way, in this case, we no longer have our concentration gradient."}, {"title": "Electrochemical Gradient.txt", "text": "Now, if we combine the concentration gradient with the electrical gradient, we get the electrochemical gradient."}, {"title": "Electrochemical Gradient.txt", "text": "So the electrochemical gradient basically combines these two different types of gradients."}, {"title": "Electrochemical Gradient.txt", "text": "So notice that in this case, we also had a concentration gradient because we have no molecule C on the right side."}, {"title": "Electrochemical Gradient.txt", "text": "All the molecules C were on this side."}, {"title": "Electrochemical Gradient.txt", "text": "So on top of these molecules moving to the right side as a result of an electric gradient, because there is an attraction between the positive and negative, these C molecules will also move to the right side because they will move from a high C concentration to a low C concentration."}, {"title": "Electrochemical Gradient.txt", "text": "So this concept, this scenario actually incorporates both the concentration gradient and our electrical gradient."}, {"title": "Electrochemical Gradient.txt", "text": "So at the end, we have an even amount of molecules on both sides, and the charges are also in equilibrium."}, {"title": "Electrochemical Gradient.txt", "text": "We have no net charge here and no net charge here."}, {"title": "Electrochemical Gradient.txt", "text": "And this is the electrochemical gradient."}, {"title": "Electrochemical Gradient.txt", "text": "So basically, one of the purposes of our cell membrane is to create an electrochemical gradient."}, {"title": "Electrochemical Gradient.txt", "text": "And there are different modes by which our cell membrane actually allows the molecules or ions to pass through across the cell membrane."}, {"title": "Electrochemical Gradient.txt", "text": "And we'll discuss that in more detail in the next lecture."}, {"title": "Start and Stop Codons .txt", "text": "The ribosomes are the cells machinery that synthesizes proteins from RNA molecules in a process known as translation."}, {"title": "Start and Stop Codons .txt", "text": "So we essentially have the mRNA chain, the ribosome attaches onto the mRNA chain and reads the codons on the mRNA chain and brings those amino acids and builds that polypeptide chain that are essentially complementary to those codons."}, {"title": "Start and Stop Codons .txt", "text": "Now, how exactly does the ribosome actually know where to begin and where to end the process of translation on that mRNA molecule?"}, {"title": "Start and Stop Codons .txt", "text": "Well, in prokaryotic cells and eukaryotic cells we have the specific sequences of nucleotides."}, {"title": "Start and Stop Codons .txt", "text": "These codons known as start codons and stop codons."}, {"title": "Start and Stop Codons .txt", "text": "And these are used to essentially initiate and terminate the process of translation."}, {"title": "Start and Stop Codons .txt", "text": "So let's briefly discuss how this takes place in prokaryotes and eukaryotes."}, {"title": "Start and Stop Codons .txt", "text": "So in prokaryotic cells, such as bacterial cells, we have this specific sequence of nucleotides, Aug and less commonly CUG that essentially code for the beginning of that process."}, {"title": "Start and Stop Codons .txt", "text": "So Aug and C UG are the start codons."}, {"title": "Start and Stop Codons .txt", "text": "Now, in prokaryotic cells, in bacterial cells, this is not enough to actually initiate the process of translation."}, {"title": "Start and Stop Codons .txt", "text": "What has to happen is we have to have this specific sequence of nucleotides that is rich in puree nucleotides known as the Shine Delgarno sequence that has to be found about ten nucleotides upstream to the left of the first Aug sequence."}, {"title": "Start and Stop Codons .txt", "text": "So as shown on the following diagram."}, {"title": "Start and Stop Codons .txt", "text": "So let's imagine this is the mRNA molecule inside that particular bacterial cell."}, {"title": "Start and Stop Codons .txt", "text": "So we have this Aug sequence, Aristocodon, and about ten nucleotides upstream to the left we have this sequence rich in pure nucleotides known as the Shine Dalgarno sequence."}, {"title": "Start and Stop Codons .txt", "text": "And what happens is a specific rRNA molecule, ribosomal RNA."}, {"title": "Start and Stop Codons .txt", "text": "The 16s ribosomal RNA of that ribosome has a complementary nucleotide sequence that is complementary to the Shine Dolgarno sequence."}, {"title": "Start and Stop Codons .txt", "text": "And that's exactly why that ribosomal RNA can attach itself onto the Shindal Garno sequence."}, {"title": "Start and Stop Codons .txt", "text": "And once it attaches itself, it essentially forms that entire complex, the ribosome complex."}, {"title": "Start and Stop Codons .txt", "text": "And it stimulates a tRNA molecule, a transfer RNA molecule to bring an activated amino acid we call formal methionine or FMet."}, {"title": "Start and Stop Codons .txt", "text": "And so the Aug actually codes for this methionine molecule."}, {"title": "Start and Stop Codons .txt", "text": "And the formal methionine looks like this."}, {"title": "Start and Stop Codons .txt", "text": "The formal simply means we have this group attached onto the central carbon as shown in the following diagram."}, {"title": "Start and Stop Codons .txt", "text": "So once that molecule, the rRNA, binds onto the Shine Del Garner sequence, it forms that complex, it stimulates the tRNA to bring this form of methionine onto that Aug and that essentially establishes the reading frame of that mRNA molecule."}, {"title": "Start and Stop Codons .txt", "text": "Now, what do we mean by the reading frame or establishing the reading frame?"}, {"title": "Start and Stop Codons .txt", "text": "Well, what that means is we essentially establish all the codon sequences that we're going to read on that mRNA molecule."}, {"title": "Start and Stop Codons .txt", "text": "So this becomes our first codon and this is essentially the methionine molecule."}, {"title": "Start and Stop Codons .txt", "text": "Then we have CUC, then we have UCC, then we have Ugg and so forth."}, {"title": "Start and Stop Codons .txt", "text": "And so once we know that this is our first codon, the next triplet nucleotide sequence is codon number two."}, {"title": "Start and Stop Codons .txt", "text": "Then the next one is codon number three and so forth."}, {"title": "Start and Stop Codons .txt", "text": "Now, in eukaryotic cells, such as human cells, we have the methionine tRNA complex."}, {"title": "Start and Stop Codons .txt", "text": "So the transfer RNA molecule attached to that activated methionine molecule essentially reads our mRNA molecule."}, {"title": "Start and Stop Codons .txt", "text": "And when it reaches the first aug that is closer to the five N, it attaches onto that and initiates the process of protein synthesis."}, {"title": "Start and Stop Codons .txt", "text": "Now, how exactly do we terminate this process of translation?"}, {"title": "Start and Stop Codons .txt", "text": "Well, there are these proteins, these enzymes known as release factors."}, {"title": "Start and Stop Codons .txt", "text": "And these release factors, they essentially move along the mRNA molecule and they bind to these special stop codons."}, {"title": "Start and Stop Codons .txt", "text": "And remember when we discussed genetic code, we said there are three different stop codons."}, {"title": "Start and Stop Codons .txt", "text": "We have UAAG, UAG and UGA."}, {"title": "Start and Stop Codons .txt", "text": "These three codons essentially stimulate these release factors to bind onto that stop codon."}, {"title": "Start and Stop Codons .txt", "text": "And that essentially causes the dissociation of that ribosome complex."}, {"title": "Start and Stop Codons .txt", "text": "And that essentially concludes and terminates that synthesis of that particular polypeptide chain."}, {"title": "Start and Stop Codons .txt", "text": "So to see what we mean, let's take a look at the following diagram."}, {"title": "Start and Stop Codons .txt", "text": "So this is the eukaryotic mRNA molecule."}, {"title": "Start and Stop Codons .txt", "text": "So we initiate the process of protein synthesis when the methionine tRNA complex brings that methionine onto the aug, then we establish the reading frame."}, {"title": "Start and Stop Codons .txt", "text": "And then the ribosome essentially reads every codon one at a time in a sequential manner until we reach this stop codon, UAA."}, {"title": "Start and Stop Codons .txt", "text": "Now, once we reach UA, the release factors bind onto the UAA sequence and that causes the dissociation of this polypeptide chain."}, {"title": "Start and Stop Codons .txt", "text": "So this is the first amino acid."}, {"title": "Start and Stop Codons .txt", "text": "And then we have many other amino acids."}, {"title": "Start and Stop Codons .txt", "text": "And this is the final amino acid that contains that carboxyl terminal group."}, {"title": "Start and Stop Codons .txt", "text": "And once we reach this, this essentially dissociates the polypeptide chain associates from the mRNA molecule and from that ribosome."}, {"title": "Start and Stop Codons .txt", "text": "So this is how we essentially initiate and terminate the process of translation."}, {"title": "Start and Stop Codons .txt", "text": "And we'll discuss this in much more detail when we'll actually discuss how translation takes place in prokaryotic and eukaryotic cells."}, {"title": "Introduction to Proteases.txt", "text": "The enzymes of our body use a combination of different mechanisms to carry out their catalytic function, to speed up the rates of biological reactions."}, {"title": "Introduction to Proteases.txt", "text": "And the four major mechanisms of action that we spoke of previously include Covalent catalysis acidbased catalysis, metal ion catalysis and catalysis by proximity and orientation."}, {"title": "Introduction to Proteases.txt", "text": "And so, to demonstrate these mechanisms, we're going to begin our discussion on the first group of protein enzymes used inside our body, namely the proteases."}, {"title": "Introduction to Proteases.txt", "text": "So what exactly is a protease?"}, {"title": "Introduction to Proteases.txt", "text": "Well, a protease is a protein enzyme."}, {"title": "Introduction to Proteases.txt", "text": "It's an enzyme molecule that is a protein that catalyzes the hydrolysis, the breaking of peptide bonds and peptide bonds, also known as amide bonds are the bonds that hold amino acids together in any protein molecule, in any polypeptide chain."}, {"title": "Introduction to Proteases.txt", "text": "Now, why would we need to actually break a peptide bond in the first place?"}, {"title": "Introduction to Proteases.txt", "text": "Well, for instance, if we ingest some food particle that is a macromolecule for instant protein, then we have to be able to break down that food protein molecule into its individual constituent amino acids."}, {"title": "Introduction to Proteases.txt", "text": "So that once we have those amino acids, we can either use the amino acids to actually form, let's say, ATP molecules, or we can also use the amino acids to actually form brand new proteins and brand new enzymes."}, {"title": "Introduction to Proteases.txt", "text": "Now, the second reason as to why we need to be able to break a peptide bond is because our cells actually need to be able to recycle protein molecules."}, {"title": "Introduction to Proteases.txt", "text": "For instance, if, let's say, a cell needs to decrease the number of protein channels found in the cell membrane, it has to be able to remove those protein channels and then digest those protein channels."}, {"title": "Introduction to Proteases.txt", "text": "And so inside the cells, we have these digestive enzymes in the same way that we have digestive enzymes inside our small intestine as well as inside our stomach."}, {"title": "Introduction to Proteases.txt", "text": "And these digestive enzymes are proteases."}, {"title": "Introduction to Proteases.txt", "text": "They are used to break down and recycle the proteins found inside our cells."}, {"title": "Introduction to Proteases.txt", "text": "And finally, as we'll discuss in much more detail in the future, these proteases are also actually used in proteolytic cleavage and that is used to activate or sometimes deactivate important biological pathways and biological molecules."}, {"title": "Introduction to Proteases.txt", "text": "So as we'll see in the future lecture, these different types of digestive enzymes are actually themselves activated by other proteases."}, {"title": "Introduction to Proteases.txt", "text": "So the digestive enzymes inside our stomach, for example, aren't always functioning."}, {"title": "Introduction to Proteases.txt", "text": "But as soon as we ingest food, those enzymes are activated by proteolytic cleavage, by other protease molecules."}, {"title": "Introduction to Proteases.txt", "text": "So these are the three major reasons as to why we have to be able to break a peptide bond."}, {"title": "Introduction to Proteases.txt", "text": "Now, the next question is why do we have to use a catalyst?"}, {"title": "Introduction to Proteases.txt", "text": "Why do we need to use an enzyme for this reaction to actually take place inside our body?"}, {"title": "Introduction to Proteases.txt", "text": "Well, as it turns out, as we'll see in just a moment, the rate at which the reaction takes place is very, very low."}, {"title": "Introduction to Proteases.txt", "text": "So let's take a look at this particular reaction."}, {"title": "Introduction to Proteases.txt", "text": "So we have the peptide bond between the carbon and nitrogen shown in purple."}, {"title": "Introduction to Proteases.txt", "text": "And what this describes is the hydrolysis of the peptide bond."}, {"title": "Introduction to Proteases.txt", "text": "So ultimately the water molecule acts as a nucleophile, this carbon acts as an electrophile."}, {"title": "Introduction to Proteases.txt", "text": "And what happens is this nucleophilically attacks the carbon and ultimately displaces that amide bond, the peptide bond."}, {"title": "Introduction to Proteases.txt", "text": "And notice that the arrow pointing this way is longer than the arrow pointing in reverse."}, {"title": "Introduction to Proteases.txt", "text": "And what that means is equilibrium will lie towards the product side and that implies that the products are lower in energy and more stable than the reactants."}, {"title": "Introduction to Proteases.txt", "text": "So we see that even though this reaction is thermodynamically favorable, it doesn't take place at a very high rate without the use of the protease enzyme."}, {"title": "Introduction to Proteases.txt", "text": "Now, why doesn't it take place at a very high rate?"}, {"title": "Introduction to Proteases.txt", "text": "Well, as it turns out, water by itself is not a strong enough nucleophile to actually attack the carbon and the carbon is not a strong enough electrophile and this has to do with the strength of this amide bond."}, {"title": "Introduction to Proteases.txt", "text": "So as it turns out, this bond here shown as a single bond, is not actually a single bond."}, {"title": "Introduction to Proteases.txt", "text": "This peptide bond contains a double bond."}, {"title": "Introduction to Proteases.txt", "text": "Nature double bond character, as can be seen by drawing these two lewis dot structures."}, {"title": "Introduction to Proteases.txt", "text": "So this is the first lewis dot structure, but the other lewis dot structure is described by this diagram."}, {"title": "Introduction to Proteases.txt", "text": "And so if these two electrons essentially go on to form a pi bond, so let's use blue."}, {"title": "Introduction to Proteases.txt", "text": "So we have these two electrons basically form this pi bond."}, {"title": "Introduction to Proteases.txt", "text": "Here."}, {"title": "Introduction to Proteases.txt", "text": "We get the following diagram."}, {"title": "Introduction to Proteases.txt", "text": "And so these two electrons in this pipeline between the carbon and oxygen basically go on onto the orbital around the oxygen and we form a negative charge on the oxygen, a positive charge on a nitrogen, but at the same time we have a double bond between the carbon and that nitrogen."}, {"title": "Introduction to Proteases.txt", "text": "So we see that although this bond isn't exactly a double bond, it's also not exactly a single bond."}, {"title": "Introduction to Proteases.txt", "text": "It's somewhere in between because these two resonance stabilized structure describes the actual structure of that peptide bond which is somewhere in between."}, {"title": "Introduction to Proteases.txt", "text": "So because we have a greater electron density that is fluctuating in between the carbon and nitrogen, we have more electrons fluctuating between those two atoms."}, {"title": "Introduction to Proteases.txt", "text": "The electrons of the oxygen will not be able to get to that carbon because of electron, electron repulsion."}, {"title": "Introduction to Proteases.txt", "text": "And that's exactly what we mean by the carbon simply will not be a good enough electrophile and this oxygen on the water will not be a good enough nucleophile for this reaction to take place at a high enough rate even though these products are more stable and lower in energy than these reactants."}, {"title": "Introduction to Proteases.txt", "text": "So we see that although this reaction is thermodynamically favorable, it occurs at an extremely slow rate."}, {"title": "Introduction to Proteases.txt", "text": "And this has to do with the double bond character of peptide bonds."}, {"title": "Introduction to Proteases.txt", "text": "In this diagram we see that the resonance stabilized structure of peptide bonds make the carbon, this carbon here less susceptible to nucleophilic attack by water."}, {"title": "Introduction to Proteases.txt", "text": "Because of this resonance stabilization, the electrons fluctuate around the carbon and nitrogen as a result of the double bond character and that essentially electrostatically repels the electrons of that water molecule."}, {"title": "Introduction to Proteases.txt", "text": "And therefore in order for this reaction to actually take place at a high enough rate inside our body and in order for us to be able to quickly and effectively break down these peptide bonds we have to use these enzymes, these proteases."}, {"title": "Introduction to Proteases.txt", "text": "Proteases."}, {"title": "Introduction to Proteases.txt", "text": "As we'll see in the next several electros actually make water a much better nucleophile and they make the carbon a much better electrophile."}, {"title": "Introduction to Proteases.txt", "text": "They make these reactants much more reactive and that facilitates this hydrolysis reaction."}, {"title": "Introduction to Proteases.txt", "text": "Now we can actually categorize proteases into different categories."}, {"title": "Introduction to Proteases.txt", "text": "And these are five categories of proteases."}, {"title": "Introduction to Proteases.txt", "text": "We have seren proteases, we have cystine proteases, we have metalloprotiases and we have aspartape proteases."}, {"title": "Introduction to Proteases.txt", "text": "And we'll discuss these in much more detail in the next several lectures."}, {"title": "Introduction to Proteases.txt", "text": "And we also have thirianine proteases."}, {"title": "Introduction to Proteases.txt", "text": "So let's very quickly discuss these four of the five protease molecules."}, {"title": "Introduction to Proteases.txt", "text": "So let's begin with serine proteases."}, {"title": "Introduction to Proteases.txt", "text": "And by the way, the major difference between these different proteases is the presence of a specific type of residue inside the active side of that enzyme."}, {"title": "Introduction to Proteases.txt", "text": "So in the case of seren proteasis from the name you might guess that inside that active side it's a serene molecule, a serine amino acid that plays the nucleochilic role of nucleophilically attacking or breaking that peptide bond."}, {"title": "Introduction to Proteases.txt", "text": "And so it's the serine that ultimately catalyzes that reaction."}, {"title": "Introduction to Proteases.txt", "text": "Now in addition to that serene, as we'll see in the next lecture, there are other additional residues present in the active side that also assist in the catalysis process as we'll discuss in the next lecture."}, {"title": "Introduction to Proteases.txt", "text": "Now, what are some examples of senior proteases and what are some of their roles?"}, {"title": "Introduction to Proteases.txt", "text": "So let's begin with some digestive enzymes."}, {"title": "Introduction to Proteases.txt", "text": "So we have trypsin, we have chimetrypsin, we also have elastase."}, {"title": "Introduction to Proteases.txt", "text": "And these three are digestive enzymes found inside our small intestine which basically play the role of breaking down the proteins that we ingest."}, {"title": "Introduction to Proteases.txt", "text": "We also have cum proteases involved in the blood coagulation process and we'll discuss these in much more detail when we'll discuss the blood cascade."}, {"title": "Introduction to Proteases.txt", "text": "And so these are thrombin and plasmid."}, {"title": "Introduction to Proteases.txt", "text": "Now inside our immune system we have the complement system and one important serum protease, part of the complement system is known as the complement C one."}, {"title": "Introduction to Proteases.txt", "text": "And finally, serum proteases also play a role in reproduction."}, {"title": "Introduction to Proteases.txt", "text": "So when we discuss sperm cells, we said that on the tip of sperm cells are these structures we call acrosomes."}, {"title": "Introduction to Proteases.txt", "text": "And inside the acrosomes are digestive enzymes and these digestive enzymes are known as acrosoma proteases."}, {"title": "Introduction to Proteases.txt", "text": "And these are examples of serene proteases."}, {"title": "Introduction to Proteases.txt", "text": "So serene proteases are involved in biological processes such as digestion."}, {"title": "Introduction to Proteases.txt", "text": "So trypsin chymatripsin, elastase, blood coagulation, thrombin and plasma."}, {"title": "Introduction to Proteases.txt", "text": "We have immunity, so the complement C one."}, {"title": "Introduction to Proteases.txt", "text": "And we also have reproduction, namely acrosoma protease which are the enzymes which are needed to basically digest a hole inside the membrane covering of that excel so the sperm cell can move inside that X cell to form that zygote."}, {"title": "Introduction to Proteases.txt", "text": "Now, we also have not only serum proteases, we have cysteine proteases aspertal or aspartate proteases and metalloprotiases."}, {"title": "Introduction to Proteases.txt", "text": "So as you might infer from the title, cysteine proteases basically contain a cysteine residue that plays that nucleosilic role of attacking that peptide bond and catalyzing this hydrolysis reaction."}, {"title": "Introduction to Proteases.txt", "text": "Now, cysteine proteases such as cat space and cathepsen are involved in programmed cell death, also known as epitosis."}, {"title": "Introduction to Proteases.txt", "text": "And this is basically an immune response that our body has."}, {"title": "Introduction to Proteases.txt", "text": "And this process is also involved in a normal embryological development of that human embryo."}, {"title": "Introduction to Proteases.txt", "text": "Now, other evidence also suggests that we have 16 proteases that are involved in bone remodeling as well as MHC class two processing."}, {"title": "Introduction to Proteases.txt", "text": "And remember, MHC class two is a protein complex found on certain cells, immune cells of our body where MHC stands for the major historic compatibility class two complex."}, {"title": "Introduction to Proteases.txt", "text": "Now, these cysteine proteases are also found in many other organisms and they are found predominantly in fruits."}, {"title": "Introduction to Proteases.txt", "text": "And so papaya type of fruit contains a special cysteine protease known as papain."}, {"title": "Introduction to Proteases.txt", "text": "Now let's move on to aspartyl or aspartate proteases as well as metallic proteases."}, {"title": "Introduction to Proteases.txt", "text": "So once again from the title, from that name you can infer that instead of having Serene or cysteine inside these active sites of these enzymes, we have aspartic acid."}, {"title": "Introduction to Proteases.txt", "text": "In fact, these enzymes contain two so a pair of aspartic acids."}, {"title": "Introduction to Proteases.txt", "text": "And as we'll discuss in a future lecture, one of those residues takes away an H atom and the other residue basically is used to increase the nucleophilic character of that particular substrate molecule."}, {"title": "Introduction to Proteases.txt", "text": "And Renan or Renin is basically an example of an aspartal protease that is involved in increasing or decreasing so regulating the blood pressure inside our body."}, {"title": "Introduction to Proteases.txt", "text": "And we also have another example, namely Pepsin."}, {"title": "Introduction to Proteases.txt", "text": "And Pepsin is once again an example of a digestive enzyme."}, {"title": "Introduction to Proteases.txt", "text": "It's used to break down the proteins that we ingest into our body."}, {"title": "Introduction to Proteases.txt", "text": "And finally we have metalloprotease."}, {"title": "Introduction to Proteases.txt", "text": "And these are simply enzymes proteases that actually utilize a metal atom, a metal ion to basically catalyze that hydrolysis reaction."}, {"title": "Introduction to Proteases.txt", "text": "And two examples of such metalloproteases are carboxy peptidis a which an example of a digestive enzyme."}, {"title": "Introduction to Proteases.txt", "text": "We'll focus on it in much more detail in future lecture."}, {"title": "Introduction to Proteases.txt", "text": "And we also have a bacterial enzyme known as thermalycin."}, {"title": "Introduction to Proteases.txt", "text": "So we don't have inside our body but certain bacterial cells have the thermolycine protease molecule that is used to break down peptide bonds inside that bacterial cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now I'd like to focus on a signal transduction pathway that involves insulin."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, before we take a look at the details of the pathway, let's discuss what insulin is, what it does and when our body actually uses it."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So let's suppose we just had a meal and the meal is rich in carbohydrates."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And what that means is our body will begin to break down the carbohydrates, the polysaccharides, into their individual units, glucose molecules."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And so following a meal that is rich in carbohydrates, we see that inside our blood, the glucose levels will begin to increase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And the rise in concentration of glucose in the blood can actually be very dangerous, very toxic to our body."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And so what the body does is it responds by stimulating the beta cells of the eyelids of Langerhine that are part of the pancreas to release insulin molecules into the blood."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And insulin is a small peptide hormone."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what insulin does is it initiates this signal transduction pathway."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And the signal transduction pathway is actually very complicated, very complex and very extensive."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And so what I'd like to focus on in this lecture is actually a small section of this insulin signal transduction pathway that stimulates the absorption of the glucose by the cells and a subsequent transformation of the glucose into the glycogen form."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this is what I'd like to focus on in this lecture."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So let's see exactly how that takes place."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, let's begin by focusing on the structure of the receptor that actually binds insulin."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So insulin binds onto a receptor we call the insulin receptor."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And the insulin receptor actually is a diamond that consists of two identical chains, one chain and a second identical chain."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And each one of these chains themselves consists of two individual units."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "We have the alpha unit shown here in purple, and this beta unit shown here in pink."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, the alpha unit is attached onto the beta unit by a disulfide bridge shown here."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we have one bridge shown here and another bridge shown on that adjacent identical chain."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what exactly is the function of the alpha and the beta units?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Well, the two alpha units, which are, by the way, found on the outside of the cell, the extracellular environment basically create the pocket, the region of space that binds the insulin."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And so that exists on the outside of the cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, these beta submunes not only spam the entire membrane shown here, but they also have components found on the inside the cytoplasmic side of the cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And these two regions of the beta soviets basically contain a very important section that gives this receptor its activity."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And this section contains the tyrosine protein kinase domains."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, a tyrosine protein kinase is basically an enzyme, a protein that phosphorylates tyrosine amino acids on target proteins and enzymes."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And we'll see what those are used for in just a moment."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this is what the insulin receptor actually looks like."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, notice there's an important difference between this insulin receptor and the receptors that we spoke of previously."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So, for instance, in our discussion on the epinephrine signaling pathway we said that that pathway actually uses G proteins and those receptors are known as G coupled protein receptors."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "But in this particular case, for the case of insulin we don't actually use any G proteins."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Instead, we actually have protein kinases found within the structure of this receptor."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what happens when the insulin actually binds?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So insulin is the primary messenger of this particular pathway and the insulin shown in orange binds into this cavity that is created by these two alpha units."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once the insulin actually moves in these two structures the alpha units actually close in."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And as they close in, they seal off this region so that the insulin cannot actually detach."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "On top of that, they also cause these two beta subunits to basically move closer together."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, as these two beta subunits move closer together the activation region of one of the beta subunits actually moves into the active side of the other beta Subun."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And this causes a cross phosphorylation process in which both of these beta units are actually phosphorylated in the presence of ATP."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And what that does is it activates this insulin receptor."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And because of the fact that this receptor itself contains a tyrosine protein kinase we also called the insulin receptor, the insulin receptor protein kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So once again, when the insulin primary messenger, a peptide hormone, moves into its cavity that is created by the two alpha subunits the closure of the two alpha chains causes the two beta chains to move closer together and this leads to crossfosphorylation as shown here and here."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "That basically changes the confirmation of those beta subunits and that activates those beta subunits."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we see the binding of the insulin on one side of that receptor activates it on the other side and so that signal can basically be transduced passed down from the outside to the inside of that cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what actually happens when these two regions are phosphorylated?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this beta submune and the other beta submune well, remember, what the tyrosine protein kinase does is it phosphorylates."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "It attaches a phosphoryl group onto tyrosine residues and some of these tyrosine residues that are phosphorylated actually begin to act as attachment points for other proteins namely an important protein known as IRS which stands for insulin receptor substrate."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So one of the phosphorylated tyrosine residues on the insulin receptor more specifically this one over here basically attracts a protein called the insulin receptor substrate or simply IRS."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once the IRS and in this particular case, we call it IRS One because we actually have another one called IRS Two which exists in a different pathway that we're not going to look in this lecture."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "But IRS One basically attaches onto this phosphorylated residue and once it is attached because it moves in close proximity to the active side of that activated receptor kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "This green structure, the IRS itself is phosphorylated at four tyrosine residues."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So upon binding, the IRS itself is phosphorylated by the insulin receptor kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what is the point of asphorylating this region?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And in general, what exactly is the function of the IRS one structure?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Well, the IRS protein is not actually a protein that activates something in the pathway."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Instead, what it does is it functions as an adaptive protein."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So IRS molecules are called adaptive proteins."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Why?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Well, because instead of activating anything, they actually act as attachment points for other enzymes, other proteins."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So instead the phosphorylated IRS."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So instead of activating anything, they phosphorylates the phosphorylated."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "IRS basically acts as an attachment point for a lipid kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And remember, lipid kinases are protein kinase that take a phosphoryl group from ATP and they move it onto some type of fat molecule, some type of lipid molecule."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And to be more specific, the lipid kinase that this actually attaches to is known as phosphonosatide three kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we have the phosphorylation of these four residues on this iris molecule causes this molecule here, phosphorositi Three kinase to actually attach."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So the phosphorusati three kinase contains a regulatory region, shown here, that attaches onto the phosphorylated residue of the IRS molecule."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once this attachment takes place, that causes the active side of this lipid kinase to move in in close proximity with respect to the membrane."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this is the active side of this phosphor nosetide kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once that active side moves there, it causes the phosphorylation of a specific type of fat molecule that exists within the membrane known as Pip two."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, when did we see Pip Two previously?"}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Well, we actually spoke about Pip Two in our discussion on the phosphornosatide cascade."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And we said that Pip two, Pip Two stands for phosphatididylin nosetal 45 diphosphate."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this molecule contains a polar region that points towards the cytoplasmic side and a non polar region that consists of two tails that lies within the membrane."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "Now, what this lipid kinase does is it basically attaches a phosphoryl group."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "It takes a phosphoryl group from an ATP molecule and it places that phosphoryl group onto the Pip two and that creates Pip Three."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So Pip Two stands for phosphatidolinotitol four, five, diphosphate, but Pip Three stands for phosphateidolinosatoll three, four, five triphosphate."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And so we see that this phosphor noseattype three kinase phosphorylates the third carbon on this Pip Two to form the Pip three."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once we form the Pip three, the Pip Three basically moves along the membrane and eventually ends up on a protein known as Pip Three."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So pip three dependent protein kinase."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once it binds onto this protein kinase, this protein kinase, shown in green, is able to activate an important effect of molecule important protein kinase known as protein kinase B, also known as AKT."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we see that phosphor, nototide three kinase, phosphorylates the Pip Two into Pip three that then travels along the membrane to activate a protein kinase we call Pip Three dependent protein kinase or simply PDK One."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this is PDK One and once PDK is activated by the binding of the Pip Three to this kinase, it then goes on and activates this structure here, which is the inactive form of protein kinaseb also known as AKT."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So AKT One is activated and once this is activated, it can basically diffuse across the cell membrane."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So this protein kinase B, AKT, is not actually bound to the cell membrane and it can move anywhere within the cytoplasm of that particular cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And what this AKT does is what the protein kinase B does is two things."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "It actually activates enzymes which are responsible for transforming glucose into Glycogen and it also stimulates these protein transporters to move into the membrane and cause the reabsorption of glucose into the cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we see that the PDK One then activates the protein kinase B we also call AKT."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And this kinase is not membrane down and it can move anywhere around that cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And it does two things."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "It stimulates the movement of glucose membrane transporters to that cell membrane, which increases the uptake of glucose from the blood and into the cytoplasm of that cell."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And once the glucose is inside the cell, that this same AKT alsophosphorylates to activate specific enzymes which are responsible for actually transforming those glucose molecules into Glycogen molecules."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So the Glycogen can actually be stored in cells such as skeletal muscle cells and fat cells and so forth."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So we see that the major difference between the insulin signal transduction pathway and the pathways we discussed up to this point is that this insulin pathway actually involves a protein kinase present in the actual structure of the receptor that is involved in this pathway."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "So before we only focused on G coupled protein receptors, but now we see that other receptors exist that don't use the G proteins and instead they use these protein kinases."}, {"title": "Insulin Signal Transduction Pathway .txt", "text": "And in this particular case it's a tyrosine protein kinase."}, {"title": "Michaelis menten Equation .txt", "text": "In our previous discussion we focus on the following graph and we said that the graph describes how the rate of the enzyme in an enzyme catalyze reaction changes when we change when we increase the substrate concentration."}, {"title": "Michaelis menten Equation .txt", "text": "So as we increase the substrate concentration, as we make the Xvalue greater we see that the yvalue, the reaction velocity v naught, the rate at which the enzyme catalyzed the reaction basically increases and it follows the following blue curve."}, {"title": "Michaelis menten Equation .txt", "text": "So initially at the beginning of that reaction, we have a relatively straight line, a straight slope, and then the slope begins to decrease and it levels off and eventually it begins to approach asymptotically the maximum velocity, the maximum rate of that enzymes activity, this red horizontal line."}, {"title": "Michaelis menten Equation .txt", "text": "And notice the blue curve is never going to pass that v max value."}, {"title": "Michaelis menten Equation .txt", "text": "Now, we also were able to actually derive the equation, the mathematical expression that describes the blue curve and this is known as the Michaelis Methan equation and this is the Michaelis Methane equation."}, {"title": "Michaelis menten Equation .txt", "text": "So this equation describes this blue curve here."}, {"title": "Michaelis menten Equation .txt", "text": "So v knot is the y coordinate."}, {"title": "Michaelis menten Equation .txt", "text": "That's the velocity, the rate at which the enzyme catalyzes that reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And this is equal to the product of a constant V max."}, {"title": "Michaelis menten Equation .txt", "text": "This Y value here multiplied by this ratio, the substrate concentration, the X value divided by Km, the Mikaela's constant."}, {"title": "Michaelis menten Equation .txt", "text": "Plus, once again, the X value, the substrate concentration."}, {"title": "Michaelis menten Equation .txt", "text": "Now, what we want to explore in this lecture is the meaning behind this equation."}, {"title": "Michaelis menten Equation .txt", "text": "What physiological meaning does this equation actually have and does this equation correctly describe this blue curve?"}, {"title": "Michaelis menten Equation .txt", "text": "So this is what we basically want to answer in this question."}, {"title": "Michaelis menten Equation .txt", "text": "Now what we want to explore first is the meaning behind the Km terms."}, {"title": "Michaelis menten Equation .txt", "text": "So Km is known as the Michaela's constant."}, {"title": "Michaelis menten Equation .txt", "text": "The question is what is the physiological meaning of this Km value?"}, {"title": "Michaelis menten Equation .txt", "text": "Well, to answer this question we're going to begin by making a simplification."}, {"title": "Michaelis menten Equation .txt", "text": "And the reason we want to make the simplification is to basically figure out the meaning behind Km."}, {"title": "Michaelis menten Equation .txt", "text": "Now, because Km appears in the denominator we can see that the units of Km are the same as that for the concentration of the substrate."}, {"title": "Michaelis menten Equation .txt", "text": "And so what we're going to assume initially is we're going to set the Km value equal to the substrate concentration and we'll see why we do that in just a moment."}, {"title": "Michaelis menten Equation .txt", "text": "So if we set Km equal to the substrate concentration then this denominator can be simplified from Km plus this to simply the concentration of S plus the concentration of S, where Km has been replaced with the concentration of S. So V naught is equal to v max multiplied by this ratio."}, {"title": "Michaelis menten Equation .txt", "text": "Now, the denominator can be combined to basically combine these two quantities."}, {"title": "Michaelis menten Equation .txt", "text": "So it's as if we have x plus x and that gives us two x."}, {"title": "Michaelis menten Equation .txt", "text": "So that means we have v max multiplied by the concentration of S divided by two multiplied by the concentration of S. And notice these two quantities can now be canceled out and we simply have v Naught is equal to v max divided by two."}, {"title": "Michaelis menten Equation .txt", "text": "And this is a very important physiological it carries very important physiological meaning."}, {"title": "Michaelis menten Equation .txt", "text": "What this tells us is when the Michael is constant is equal to the substrate concentration, that particular x value, we see that the rate of that enzyme, the velocity of that enzyme is exactly half of the maximum velocity of that enzyme."}, {"title": "Michaelis menten Equation .txt", "text": "So if we look on the following y axis, this is the maximum velocity, this is the zero velocity."}, {"title": "Michaelis menten Equation .txt", "text": "So the velocity in the middle is the v max divided by two."}, {"title": "Michaelis menten Equation .txt", "text": "And if we draw that horizontal line and when that line touches that curve, we then draw a vertical line down that gives us the Y coordinate known as the Michael's constant Km."}, {"title": "Michaelis menten Equation .txt", "text": "So basically the Mikala's constant Km describes the substrate concentration, the x value at which the rate, the velocity of that enzyme's activity is exactly half of its maximum velocity, v max."}, {"title": "Michaelis menten Equation .txt", "text": "So if Km is equal to the substrate concentration, then V Naught is equal to v max divided by two."}, {"title": "Michaelis menten Equation .txt", "text": "So that's the meaning behind Km."}, {"title": "Michaelis menten Equation .txt", "text": "Km basically describes the situation when exactly half of all the active sites are filled with the substrate."}, {"title": "Michaelis menten Equation .txt", "text": "And we'll talk much more about that in the next lecture."}, {"title": "Michaelis menten Equation .txt", "text": "Now let's move on to two and three."}, {"title": "Michaelis menten Equation .txt", "text": "In two and three, we basically want to show that this Mikayla's methane equation actually correctly describes this blue curve here."}, {"title": "Michaelis menten Equation .txt", "text": "So let's begin by going to the beginning of that chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So at the beginning of the chemical reaction at a time of approximately zero, we know that the substrate concentration is very, very low."}, {"title": "Michaelis menten Equation .txt", "text": "So the substrate concentration is somewhere around this value here at the beginning of that chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "Now let's compare the substrate concentration at the beginning to the Km value."}, {"title": "Michaelis menten Equation .txt", "text": "Clearly the Km has a much higher value than the substrate concentration at the beginning."}, {"title": "Michaelis menten Equation .txt", "text": "And so we're going to begin by making the following assumption."}, {"title": "Michaelis menten Equation .txt", "text": "So when the time is approximately equal to zero at the beginning of that chemical reaction, the Km value is much greater than the concentration of that substrate."}, {"title": "Michaelis menten Equation .txt", "text": "And so what that means is this sum, the Km value plus the substrate concentration is simply approximately equal to the Km value because this is much greater than this."}, {"title": "Michaelis menten Equation .txt", "text": "This is approximately equal to zero compared to this."}, {"title": "Michaelis menten Equation .txt", "text": "And so Km is approximately Km plus the subsequent is approximately equal to Km."}, {"title": "Michaelis menten Equation .txt", "text": "So this is approximately equal to zero."}, {"title": "Michaelis menten Equation .txt", "text": "Now the point of making this simplification was to basically simplify this equation because what we actually want to do in step two is we actually want to describe the equation that describes how the curve behaves at the beginning of that particular reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So V Naught is equal to v max multiplied by this ratio."}, {"title": "Michaelis menten Equation .txt", "text": "And because our denominator is Km plus the subsid concentration and as a result of this assumption we see that our denominator simply becomes Km."}, {"title": "Michaelis menten Equation .txt", "text": "So this is approximately equal to v max multiplied by the substrate concentration divided by Km."}, {"title": "Michaelis menten Equation .txt", "text": "Now instead of having the Km underneath this term, let's bring it underneath the V max term."}, {"title": "Michaelis menten Equation .txt", "text": "And this is the equation that we have."}, {"title": "Michaelis menten Equation .txt", "text": "And so this equation is the equation that describes activity the rate of that enzyme at the beginning of that chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And notice what this equation actually looks like."}, {"title": "Michaelis menten Equation .txt", "text": "So based on the curve here, we see that at the beginning of the reaction, the curve."}, {"title": "Michaelis menten Equation .txt", "text": "So from about this point in time to, let's say about this point in time, the curve looks like a straight line."}, {"title": "Michaelis menten Equation .txt", "text": "And in fact, this equation also describes an equation that looks like a straight line."}, {"title": "Michaelis menten Equation .txt", "text": "So remember, a straight line has the following general form."}, {"title": "Michaelis menten Equation .txt", "text": "So y, the Y coordinate is equal to and the slope multiplied by x the x coordinate plus b the y intercept."}, {"title": "Michaelis menten Equation .txt", "text": "Now B in this particular case is zero."}, {"title": "Michaelis menten Equation .txt", "text": "So this is zero and it cancels out."}, {"title": "Michaelis menten Equation .txt", "text": "Now M is the slope that's v max divided by Km, x is a substrate concentration and Y is simply the velocity, the rate of that enzyme."}, {"title": "Michaelis menten Equation .txt", "text": "So we see that this equation correctly describes the behavior of the enzyme at the beginning of that reaction."}, {"title": "Michaelis menten Equation .txt", "text": "Not only that, but this equation also describes a reaction that has first order."}, {"title": "Michaelis menten Equation .txt", "text": "So remember in our discussion on the rate law we said that if the rate law looks like this, then our reaction is in fact a first order reaction where V is the rate of that particular reaction, k is the rate constant and this is a substitute concentration."}, {"title": "Michaelis menten Equation .txt", "text": "And this coefficient, this exponent of one basically describes a first order reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And this looks like this or this looks like this where V is v naught, k is V max divided by Km and this quantity is equal to this."}, {"title": "Michaelis menten Equation .txt", "text": "So what that basically means is at the beginning of that chemical reaction we see that the rate, the velocity of that enzymes activity is directly proportional to the substrate concentration."}, {"title": "Michaelis menten Equation .txt", "text": "So that is what we mean by a first order reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So notice that this is a straight line and also a first order reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And this implies that the rate of the reaction is directly proportional to the substrate concentration at the beginning of that chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So this equation correctly describes the behavior at the beginning of that chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "Now what about at the end of the chemical reaction?"}, {"title": "Michaelis menten Equation .txt", "text": "So in part two we basically discussed when the substrate concentration was very low."}, {"title": "Michaelis menten Equation .txt", "text": "But what if the substrate concentration is very high?"}, {"title": "Michaelis menten Equation .txt", "text": "Can this equation correctly describe the behavior of that particular enzyme?"}, {"title": "Michaelis menten Equation .txt", "text": "And this is what we do in part three."}, {"title": "Michaelis menten Equation .txt", "text": "So we can also use the Michael's Methane equation to describe the enzyme activity towards the end of that reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So when the substrate concentration is very, very high."}, {"title": "Michaelis menten Equation .txt", "text": "So now we're basically going to use the same argument as in this case, but we're going to reverse because at the end of the reaction so when we have a very, very high concentration of substrate that means the Km value is much smaller than the substrate concentration."}, {"title": "Michaelis menten Equation .txt", "text": "So for example, if we're somewhere here along the X axis, this quantity, this concentration is much higher than Km."}, {"title": "Michaelis menten Equation .txt", "text": "And so what that means is towards the end we see that the concentration of S is much, much higher than the value of Km."}, {"title": "Michaelis menten Equation .txt", "text": "And so by the same logic that we used here, the sum of Km and the substrate concentration is about equal to simply the substrate concentration."}, {"title": "Michaelis menten Equation .txt", "text": "And so if we take this mechanics methane equation it will simplify itself to this."}, {"title": "Michaelis menten Equation .txt", "text": "So V knot is equal to V max divided by the ratio."}, {"title": "Michaelis menten Equation .txt", "text": "The denominator is approximately equal to this."}, {"title": "Michaelis menten Equation .txt", "text": "And now these two quantities cancel out and we simply see that V Naught is equal to V max."}, {"title": "Michaelis menten Equation .txt", "text": "So what that means is as we continually add concentration of as we continually increase the concentration of S, eventually our V knot will be the V max."}, {"title": "Michaelis menten Equation .txt", "text": "And once we reach the V max, it doesn't matter if we add more of that substrate."}, {"title": "Michaelis menten Equation .txt", "text": "Adding more substrate will not have any effect on the rate of that enzyme catalyzed reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And that can be seen from this equation."}, {"title": "Michaelis menten Equation .txt", "text": "So v naught is equal to v max."}, {"title": "Michaelis menten Equation .txt", "text": "V Naught is equal to V max is an equation that describes a rate law that has a 0th order."}, {"title": "Michaelis menten Equation .txt", "text": "Remember, V is equal to K multiplied by the concentration to the 0th power."}, {"title": "Michaelis menten Equation .txt", "text": "This is a zero Th order chemical reaction."}, {"title": "Michaelis menten Equation .txt", "text": "And so what that means is this will cancel out because anything to the zero is one and so D equals K and V Naught is V and V max is the K value."}, {"title": "Michaelis menten Equation .txt", "text": "And what that means is by changing the concentration, the substrate when we have a very high substrate concentration that will not affect the rate of that enzyme catalyzed reaction."}, {"title": "Michaelis menten Equation .txt", "text": "So once again, this tells us that the velocity approaches a maximum as the substrate concentration increases."}, {"title": "Michaelis menten Equation .txt", "text": "And this describes a zero order reaction."}, {"title": "Michaelis menten Equation .txt", "text": "This means that increasing the substrate concentration will not actually affect the rate of that chemical reaction when we're very far along the X axis to the right."}, {"title": "Michaelis menten Equation .txt", "text": "So this is the meaning of the Michaelis Methan equation."}, {"title": "Michaelis menten Equation .txt", "text": "And in the next lecture we're going to discuss the meaning behind the Km value in much more detail."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "What about glycolysis?"}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So when we have low mass of ATP, we want to produce ATP."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so these are the enzyme, these are the allosteric effect, they're shown in blue that activate the process of glycolysis under low energy conditions."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So in this particular case, if we have lots of Amp, the same Amp that inactivates this actually activates the phosphor fructose kinase."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "On top of that, the st fructose 26 bisphosphate that inactivates this actually activates this."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So this molecule is activated by these two Alastairs effectors and pyruvate kinase is activated by the build up of fructose six bisphosphate."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Now, why does that actually make sense?"}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Well, if these two molecules activate the activity of phosphorptokinase, we're going to basically create many more fructose one six bisphosphate."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And as this molecule builds up in the concentration, it will depend on pyruvate kinase to transform these ultimately into pyruvate."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so to basically make sure we don't have a continual buildup of the fructose one six bisphosphate, it creates a positive feedback loop and the f 15 bisphosphate molecule actually activates that pyruvate kinase and that activates the process of glycolysis."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So let's summarize our results."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So, when the cell has a low level of ATP relative to Amp, that means it basically has a low energy charge and it has a relatively high amount of Amp."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so what that means is we want to produce more of the ATP and we want to use less of the ATP."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "So Gluconeogenesis is shut down, but Glycolysis is activated."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so we see that on the glycolytic pathway we have phosphorptokinase being activated by Amp and f 26 BP, while pyruvate kinase is activated by fructose one six bisphosphate."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "On the other hand, fructose one six bisphosphate is inactivated by these two molecules, amp and f 26 BP."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "The pet carboxylates and the pyruvate carboxylates are both inactivated by ADP."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so we conclude that when ATP is plentiful in a cell, the gluconeogenic process gluconeogenesis predominates, while when ATP is scarce, glycolysis is the process that predominates."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Now, one more thing I want to mention before we discuss how glucose affects these two processes in the next lecture is the following."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Sometimes you'll hear that Latitude's principle basically dictates which one of these processes will actually take place."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And that's not exactly right."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "We cannot use legit Lee's principle to explain why either this process takes place or the other process takes place."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Why?"}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "Well, because legit Lee's principle is used strictly for those reactions which are at equilibrium."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And if a reaction is at equilibrium, that means the gifts free energy in that process is zero."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "But we know in gluconeogenesis and in glycolysis, these two processes both release a Gibbs free release GIBS free energy."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And that means neither of these processes are actually at equilibrium."}, {"title": "Reciprocal Regulation of Gluconeogenesis and Glycolysis .txt", "text": "And so we cannot use Leslie Lee's principle to explain why this process takes place and the other one doesn't actually take place."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Previously, we focused on the oxygen binding curve of myoglobin and hemoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And we saw that in the case of myoglobin, myoglobin binds oxygen very strongly."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "It has a very high affinity for oxygen, and it binds oxygen in a noncooperative fashion."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "On the other hand, we saw that the shape for our hemoglobin curve was a sigmoidal shape."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And this, this describes the cooperative behavior of hemoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So even though hemoglobin has a lower affinity for oxygen than myoglobin, hemoglobin is able to bind oxygen in a cooperative fashion."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that's exactly why our body prefers to use hemoglobin as the carrier and the transport of oxygen inside our body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, that discussion was a more qualitative approach."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now let's take a look at a more quantitative approach as to why our body actually uses hemoglobin instead of myoglobin as the transporter and carrier of oxygen from the lungs to the tissues of our body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So let's begin by recalling some basic biological facts."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Inside our lungs, the partial pressure of oxygen is about 100 mercury inside our resting tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "When we're not exercising, the partial pressure drops to 40 mercury."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And inside our exercising tissue, for example, if we're swimming or running, our partial pressure drops to about 20 mercury."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So we want to use these values and the oxygen dissociation curves for myoglobin and hemoglobin to basically show why hemoglobin is a much better carrier of oxygen than myoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So let's begin with the hemoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So this red curve describes the oxygen dissociation curve for hemoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So as we go from right to left, from the lungs to our tissue, our hemoglobin essentially unloads and releases that oxygen."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So let's begin inside our lungs."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And let's suppose we're going from the lungs to our resting tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So the lungs have a partial pressure of 100 mercury, and the corresponding Y value at this point is about zero 98."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So that means about 98% of the hemoglobin is fully saturated inside our lungs."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, when the hemoglobin travels down to our resting tissue, which is at a pressure of about 40 mercury, the corresponding Y value is about zero point 77."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that means about 77% of that hemoglobin is fully saturated with oxygen inside our resting tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, what that tells us is when the hemoglobin goes from the lungs to the resting tissue, there is a difference of about 21%."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And what that means is 21% of that oxygen of that hemoglobin has successfully unloaded and released the oxygen to the resting cells of our body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So this is how much oxygen can be unloaded by the hemoglobin when it goes from the lungs to the resting tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, what about if we're exercising?"}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "How much can hemoglobin deliver if our tissues are exercising?"}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Well, in the case of the exercising tissue, the partial pressure is at 20 mercury."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And we see that because we have this sigmoidal shape curve, there is a drastic drop in our fractional saturation of hemoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So we go from here to about here."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And this wide valley corresponds to about zero point 32."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that means when our tissue is exercising, 32% of that hemoglobin is fully saturated with oxygen."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And so now, when we go from the lungs to our exercising tissue, there is a difference of 98% -32%."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So 66% and that means 66% of the hemoglobin has unloaded and released that oxygen to the cells of our body that are exercising."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that is a lot of oxygen."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that means hemoglobin can successfully deliver the oxygen to our tissues of the body from the lungs."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, what about myoglobin?"}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Well, let's do the same exact thing for myoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So in the case of myoglobin, so let's take out a marker."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "In the case of myoglobin, we begin once again at the lungs, just the same way we begin here at the lungs."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So, at the lungs, we have 100 million meter of mercury and that corresponds to about 98% to zero."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "98 fractional saturation or 98% of the myoglobin is saturated in the lungs, which is the same value as for the hemoglobin case."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "But look what happens when we go down to this value which corresponds to the resting tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "There is only a very, very small drop in a fractional saturation of myoglobin when we go from the lungs to the resting tissue, about 1% difference."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that means only about 1% of that myoglobin has successfully unloaded that oxygen into the tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that's a very, very small amount."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "It's simply not enough for those cells in the resting tissue to actually use the oxygen to create enough ATP."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Now, if we examine the difference between the lungs and the exercising tissue, so going from the lungs to this point, this point corresponds to value of about zero point 91."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So that means 91% of the myoglobin is saturated in exercising tissue of our body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And so 98 -91 gives us a difference of about 7% so this is a tremendous difference."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "7% would not be enough for our body to actually create enough ATP molecules and to use the ATP molecules for the various processes."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that's precisely why it's the hemoglobin molecule and not the myoglobin that our body actually prefers as the carrier of oxygen, because it's the hemoglobin that can successfully unload enough oxygen."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "21% in this case, and 66% in this case, to our cells of the body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "Our myoglobin simply has too high of an affinity for oxygen and it will not be able to successfully unload enough oxygen to the resting tissue or to our exercising tissue."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And that's exactly why it's myoglobin that is used as the storage protein that stores oxygen inside our muscle cells."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "But it's the hemoglobin that is used as the carrier, because it binds oxygen in a non cooperative fashion, which gives it a sigmoidal shape and it is able to successfully unload enough oxygen to the tissues of our body."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "So once again, we see that hemoglobin's cooperative behavior allows it to unload much more oxygen successfully to the tissues than myoglobin."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And this is why our body prefers to use hemoglobin as a transporter for oxygen inside our cardiovascular system, inside our bloodstream."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And myoglobin simply has too high of an attraction to oxygen."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "It binds it way too strongly."}, {"title": "Hemoglobin vs Myoglobin as Oxygen Carrier .txt", "text": "And so what that means is it's will not be able to unload enough oxygen to the cells of either the resting tissue or the exercising tissue of our body."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "In order to build fatty acid chains, we have to begin with acetylco enzyme A molecules, because ultimately, when we're synthesizing fatty acid chains, we're combining many acetylco enzyme A molecules together."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, where do we get our supply of acetylco enzyme A molecules?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Well, we obtain it in the matrix of the mitochondria via processes such as the beta oxygen oxidation of fatty acids."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We also generate acetylco enzyme A molecules via the decarboxylation of pyruvate, the catabolism of certain amino acids, as well as the breakdown of ketone bodies."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "But ultimately, this acetylco enzyme A molecule is found in the matrix of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And that poses a problem, because fatty acid synthesis takes place in the cytoplasm of the cell."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "But these acetylco enzyme A molecules are located in the matrix of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So we have to be able to move these acetylco enzyme A molecules from the matrix into the cytoplasm cell to actually initiate the process of fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, there's a problem with moving acetyl coenzyme A molecules across the membrane of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And the problem is it's water soluble."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So if we look at the acetyl coenzyme A molecule, the coenzyme a component of the acetyl coenzyme A molecule prevents that acetyl group from actually moving across the inner mitochondrial membrane."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so to ultimately allow the movement of that acetyl coenzyme A molecule across, we have to remove that coenzyme A."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so what happens is we transfer this CETL group onto oxalo acetate in the process that is catalyzed by citrate synthase to form the citrate molecule."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And now we can move that citrate across the inner and then the outer membrane of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so this, if we recall, is simply the step number one in the citric acid cycle."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, before we move on to the next steps of this process, actually moving it across the membrane of the mitochondria and then seeing what happens inside the cytoplasm, let's discuss which conditions actually lead to the synthesis of fatty acid."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So what conditions do we have to have in the matrix of the mitochondria to actually promote the process of fatty acid synthesis?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So, in the matrix of the mitochondria, by the way, this is our matrix, our cytoplasm, the inner and the outer membrane of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So we know that in the matrix we have the citric acid cycle and electron transport chain basically generating ATP molecules."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so when we have high levels of ATP inside the matrix of the mitochondria, we don't want to actually produce any more ATP molecules."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We want to stop the process of ATP synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so what happens is, when there are high levels of ATP in the matrix of mitochondria, that ATP act as an allosteric inhibitor of one of the enzymes of the citric acid cycle."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So which enzyme?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Isocytrade dehydrogenase."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "isocitric dehydrogenase basically transforms isocitrate into alpha ketoglutrate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And when we have high levels of ATP, it blocks the activity of this enzyme and that leads to a build up of isocitrate in the matrix of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, isocitrate, if recalled back to the citric acid cycle, can be interconverted into citrate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So it basically converts back and forth."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "But if we have high levels of isocitrate, we're also going to see an accumulation of citrate molecules and this will promote fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So high levels of ATP and high levels of citrate molecules basically stimulates the process of fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And that makes sense because we need ATP and we need citrate to actually begin the process of fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So once again, what actually promotes what stimulates fatty acid synthesis?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Well, when the level of ATP in the matrix is high, this means that we no longer need to actually synthesize any more ATP."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And therefore the ATP will create a negative feedback loop that will inhibit isocitrate dehydrogenase."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this causes a build up, is citrate, which in turn causes a build up of citrate molecules."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And once we actually form citrate, which involves transferring acetyl, the Cetil group from acetyl co enzyme onto oxalacetate, then that citrate can actually move across the inner and the outer membrane of the mitochondria and into the cytoplasm of that cell."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So in step three, we have citrate is then transported across the membrane and into the cytoplasm of that cell."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, the citrate itself is not actually used in the fatty acid synthesis process."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We have to actually obtain that acetylcoanson a back."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so what happens is we have a process in which we take that citrate and we form back that oxylo acetate that we begin with."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And we also generate an acetyl co enzyme a molecule."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this is carried out by the enzyme we call ATP, citrate lyase."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So in order to regenerate the CETL co enzyme a inside of plasma, the enzyme ATP Citrate Liaase, uses an ATP and a co enzyme to reform the acetyl coenzyme A and that oxalo acetate as the byproduct."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So this is the reaction shown here."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So we have the citrate that is now on the cytoplasmic side, we have a coenzyme a that is different than the coenzyme a that we had here because remember, in this process, the coenzyme a was essentially kicked off."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We combine these two by hydrolyzing ATP and we form an acetyl coenzyme a and the oxalo acetate a."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So ultimately, what actually moved across the membranes of the mitochondria are the oxalo acetate and the Cecil group that was attached onto oxalo acetate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And it's the Cecil group that will ultimately be used to synthesize those fatty acids."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So it's this acetyl coenzyme a that will now go on to help synthesize fatty acid molecules as we'll discuss in the next several lectures."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, what about this oxalo acetate?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "What is the fate of this oxylo acetate?"}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Well, now we actually have to transform the oxalo acetate into a molecule that can move across the membrane back onto the matrix of the mitochondria so that we can recycle and reuse that oxylo acetate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "The problem is, oxyloacetate cannot simply diffuse across the membrane of the mitochondria."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And we have to transform that oxyloacetate in a two step process into pyruvate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So let's see how this actually takes place."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So we have oxalo acetate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We basically reduce oxylacetate by using the reduction power of NADH to form a malate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this is step number five."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So the oxalo acetate cannot cross the mitochondrial membrane."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Therefore, to return back to the matrix, it is first transformed into malade by malade dehydrogenase."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this requires NADH."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And so we produce NAD plus in this process."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, once we form malade, an important process takes place that allows us not only to form the pyruvate that can now move across the matrix, across the membrane of the mitochondria, but we also generate NADPH and NADPH."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this is important, as we'll see in just a moment, because this is the NADPH that we're going to use in the fatty acid synthesis process."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So next, the malate undergoes an oxidative decorboxylation step that is catalyzed by the enzyme NADP plus linked malate enzyme, also known as malik enzyme."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And this reaction is important because not only does it give us a way to actually move that molecule across the membrane of the mitochondria, it also generates that NADPH that will be used in fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So, malade in the presence of NADP plus and this enzyme, NADP plus linked malade enzyme, is transformed into pyruvate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "We essentially release the carbon dioxide and we form the NADPH."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And it's this NADPH that will be used by fatty acid synthesis."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "In fact, this is the major pathway that produces the highest number of NADPH molecules that will be used by the fatty acid synthesis process."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "The remaining Nadphs will be produced via the pentose phosphate pathway."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "Now, once we form pyruvate, it moves across the membranes of the mitochondria into the matrix."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And inside the matrix, we use pyruvate carboxylase to transform the pyruvate into oxalo acetate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So the pyruvate can now move across the membrane into the matrix, where it is transformed into oxyloacetate."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "So this is the process by which we ultimately move that acetyl group from the matrix of the mitochondria into the cytoplasm, so that now we can use that acetyl group to actually elongate and form those fatty acid chains."}, {"title": "Initiation of Fatty Acid Synthesis.txt", "text": "And just like I said in the beginning, what stimulates or promotes the process of fatty acid synthesis are high levels of ATP and Citrate in the matrix of the mitochondria."}, {"title": "Glycogen Breakdown .txt", "text": "Before the cells of our body, such as liver cells or skeleton muscle cells, can actually use their supply of glucose."}, {"title": "Glycogen Breakdown .txt", "text": "They have to release the glucose from glycogen because inside our body we store glucose in the form we call glycogen."}, {"title": "Glycogen Breakdown .txt", "text": "So the question that I would like to address in this lecture is how exactly do we break down glycogen inside the cells of our body?"}, {"title": "Glycogen Breakdown .txt", "text": "Well, glycogen, glycogen breakdown, also known as glycogen degradation, is the process by which we carry out three different steps to basically release the glucose molecule from glycogen."}, {"title": "Glycogen Breakdown .txt", "text": "And this process actually involves four different enzymes, as we'll see in just a moment."}, {"title": "Glycogen Breakdown .txt", "text": "So let's discuss the first step of glycogen breakdown."}, {"title": "Glycogen Breakdown .txt", "text": "Now, the first step is known as phosphoralysis, and this process is catalyzed by an enzyme known as glycogen phosphorylase."}, {"title": "Glycogen Breakdown .txt", "text": "Now, glycogen phosphorylase uses an orthophosphate molecule to actually cleave to break an alpha one four glycosytic bond between a terminal glucose molecule that contains a free hydroxyl group on the fourth carbon and the JSON glucose molecule."}, {"title": "Glycogen Breakdown .txt", "text": "And this can be seen in the following picture."}, {"title": "Glycogen Breakdown .txt", "text": "So we essentially have our first step of glycogen breakdown."}, {"title": "Glycogen Breakdown .txt", "text": "So on the left side we have the reactant, the glycogen molecule that contains, let's suppose, N number of glucose molecules."}, {"title": "Glycogen Breakdown .txt", "text": "And to simplify the diagram of only drawn two of these glucose molecules."}, {"title": "Glycogen Breakdown .txt", "text": "Now, this is the terminal glucose molecule that contains the free hydroxyl group on carbon number four of the glucose."}, {"title": "Glycogen Breakdown .txt", "text": "And so this is the alpha one four glycocitic bond that will be cleaved by the glycogen phosphorlase."}, {"title": "Glycogen Breakdown .txt", "text": "Now, the other reactant of this particular reaction is the orthophosphate."}, {"title": "Glycogen Breakdown .txt", "text": "The orthophosphate actually acts as a nuclear file that cleaves this alpha one four glycocitic bond to basically form these two product molecules."}, {"title": "Glycogen Breakdown .txt", "text": "We have a glucose one phosphate and we have the glycogen that now contains one less glucose because we removed this terminal glucose molecule here."}, {"title": "Glycogen Breakdown .txt", "text": "Now we have this glycogen that contains N minus one number of glucose molecules."}, {"title": "Glycogen Breakdown .txt", "text": "Now, inside the cells of our body, this reaction is a product favorite reaction and that's because of two important reasons."}, {"title": "Glycogen Breakdown .txt", "text": "Number one is this reaction is energetically favorable."}, {"title": "Glycogen Breakdown .txt", "text": "Why?"}, {"title": "Glycogen Breakdown .txt", "text": "Well, recall that if we want to transform glucose into glucose one phosphate, we actually have to utilize and hydrolyze an ATP molecule."}, {"title": "Glycogen Breakdown .txt", "text": "So normally if we want to transform glucose into glucose one phosphate, we have to use an ATP molecule."}, {"title": "Glycogen Breakdown .txt", "text": "But let's see what happens in this particular reaction."}, {"title": "Glycogen Breakdown .txt", "text": "In this reaction we do release a glucose molecule, we take off the terminal glucose."}, {"title": "Glycogen Breakdown .txt", "text": "In the process, we add up a spoil group without actually hydrolyzing an ATP molecule and this creates an energetically favorable process."}, {"title": "Glycogen Breakdown .txt", "text": "So we essentially bypass the process of using an ATP molecule by releasing the glucose in the glucose one phosphate form."}, {"title": "Glycogen Breakdown .txt", "text": "Now, the other reason why this reaction is product favorite is because inside our cells we generally have a much higher concentration of the orthophosphate reactive molecule than the glucose one phosphate product."}, {"title": "Glycogen Breakdown .txt", "text": "In fact, the ratio of orthophosphate to this product is about 100 to one."}, {"title": "Glycogen Breakdown .txt", "text": "And so because of that, because we have so much more of the reactants, that means that will drive this reaction toward the right side."}, {"title": "Glycogen Breakdown .txt", "text": "So this process, step one of glycogen breakdown, proceeds toward the right side, toward the product side."}, {"title": "Glycogen Breakdown .txt", "text": "Because the cell contains a higher concentration of orthophosphate compared to glucose one phosphate, and because the formation of glucose one phosphate bypasses the usage of the ATP, it forms directly the glucose one phosphate from that glucose."}, {"title": "Glycogen Breakdown .txt", "text": "And this is in fact energetically favorable."}, {"title": "Glycogen Breakdown .txt", "text": "Now let's move on to step number two."}, {"title": "Glycogen Breakdown .txt", "text": "So in step number two, what we ultimately want to do is, oh, and by the way, the glucose one phosphate that we form as a product in step one will actually be used in step three."}, {"title": "Glycogen Breakdown .txt", "text": "But the glycogen and minus one is actually used in step two."}, {"title": "Glycogen Breakdown .txt", "text": "And what step two does is it restructures, it remodels the glycogen."}, {"title": "Glycogen Breakdown .txt", "text": "It basically puts it into a form so that the glycogen phosphoralase can continue acting on it, cleaving it and releasing the glucose one phosphate molecule."}, {"title": "Glycogen Breakdown .txt", "text": "So the reason for that is simple."}, {"title": "Glycogen Breakdown .txt", "text": "The glycogen phosphorase is limited to what it can actually do."}, {"title": "Glycogen Breakdown .txt", "text": "The glycogen phosphorolase can only cleave alpha one four glycocitic bonds."}, {"title": "Glycogen Breakdown .txt", "text": "It cannot cleave alpha one six glycocitic bonds."}, {"title": "Glycogen Breakdown .txt", "text": "In fact, it stops cleaving the alpha one four glycocitic bonds for residues for glucose molecules away from the branching point, the nearest alpha one six glycocitic bond."}, {"title": "Glycogen Breakdown .txt", "text": "So glycogen phosphoralase, the enzyme that catalyzes step one of glycogen breakdown, can only cleave alpha one four glycocitic bonds."}, {"title": "Glycogen Breakdown .txt", "text": "It does not cleave alpha one six glycocitic bonds that are found in glycogen."}, {"title": "Glycogen Breakdown .txt", "text": "In fact, this enzyme stops four residues away from the nearest branching point."}, {"title": "Glycogen Breakdown .txt", "text": "And we'll talk more about that in this particular diagram."}, {"title": "Glycogen Breakdown .txt", "text": "Now, step number two can actually be broken down into two different steps and that's because step number two utilizes two different types of enzymes."}, {"title": "Glycogen Breakdown .txt", "text": "One of these enzymes is known as transferase and the other enzyme is known as alpha 13 glucosidase."}, {"title": "Glycogen Breakdown .txt", "text": "Now, in eukaryotic cells, these two enzymes are actually found on a single enzyme."}, {"title": "Glycogen Breakdown .txt", "text": "So in eukaryotic cells we have this single bifunctional enzyme that contains these two different types of enzymes, transferase and alpha 116 glucosedase, these two different types of catalytic sites that basically catalyze two different types of reactions."}, {"title": "Glycogen Breakdown .txt", "text": "So let's begin by examining transferase and what it actually does."}, {"title": "Glycogen Breakdown .txt", "text": "So suppose we have the following glycogen molecules."}, {"title": "Glycogen Breakdown .txt", "text": "So it's a simple molecule with a single alpha one six glycocitic bond."}, {"title": "Glycogen Breakdown .txt", "text": "So these bonds here are the alpha one four glycocitic bonds and this bond here is the alpha one six glycocitic bond."}, {"title": "Glycogen Breakdown .txt", "text": "Now remember what I said about glycogen phosphorase."}, {"title": "Glycogen Breakdown .txt", "text": "It can only cleave alpha one four glycocitic bonds and it stops cleaving the alpha one four glycocitic bonds when it gets to four residues away from the nearest branching point."}, {"title": "Glycogen Breakdown .txt", "text": "The nearest alpha one six glycocitic bonds."}, {"title": "Glycogen Breakdown .txt", "text": "So on this particular section, we have 1234 glucose residues."}, {"title": "Glycogen Breakdown .txt", "text": "And so the glycogen phosphorase will no longer be able to cleave these alpha one four glycocity bonds because it's only four away from this branching point."}, {"title": "Glycogen Breakdown .txt", "text": "And so to fix that problem, what transferase does is it takes this region of three residues away from this section and moves it shifts us onto this region here."}, {"title": "Glycogen Breakdown .txt", "text": "So it basically forms the following product."}, {"title": "Glycogen Breakdown .txt", "text": "So it removes this and extends this linear section by three glucose molecules."}, {"title": "Glycogen Breakdown .txt", "text": "So transphrase catalyzes the shift of three glucose residues from one branch, this branch, to the other branch, this branch here."}, {"title": "Glycogen Breakdown .txt", "text": "And this process basically leaves a single glucose molecule that is attached to this entire region by an alpha one six glycocitic bond."}, {"title": "Glycogen Breakdown .txt", "text": "Now, this is where alpha one six glucosidase actually comes into place, comes into play, because what this enzyme does is it is able to cleave that alpha one six glycocitic bond."}, {"title": "Glycogen Breakdown .txt", "text": "So the alpha one six glucosidase cleaves this alpha one six glycocitic bond and releases this free glucose."}, {"title": "Glycogen Breakdown .txt", "text": "And that free glucose is then transformed by hexokinase to form the glucose one phosphate, which then goes on to step three, as we'll see in just in a moment."}, {"title": "Glycogen Breakdown .txt", "text": "And we also form this product."}, {"title": "Glycogen Breakdown .txt", "text": "Now, notice that when we go from this molecule to this molecule, we essentially remove the branching points."}, {"title": "Glycogen Breakdown .txt", "text": "We basically transform the branched polymer of glycogen to a linear polymer of glycogen."}, {"title": "Glycogen Breakdown .txt", "text": "And now this only contains the alpha 114 glycosytic bonds that can be cleaved by glycogen phosphorase."}, {"title": "Glycogen Breakdown .txt", "text": "And so once we form this linear glycogen in step two, the glycogen phosphorase moves on to this glycogen and begins breaking these alpha one four glycocitic bonds and those glucose one phosphate molecules produce, then go on to step three."}, {"title": "Glycogen Breakdown .txt", "text": "And so let's move on to step three and let's see what happens in step three."}, {"title": "Glycogen Breakdown .txt", "text": "Now in step three, we basically transform the glucose one phosphate into glucose six phosphate."}, {"title": "Glycogen Breakdown .txt", "text": "The reason we need to do that is because the glucose six phosphate can go on to basically react in different types of pathways."}, {"title": "Glycogen Breakdown .txt", "text": "For instance, in skeleton muscle cells, the glucose six phosphate can undergo glycolysis to form ATP."}, {"title": "Glycogen Breakdown .txt", "text": "In liver cells, the glucose six phosphate can be transformed into glucose and then released into the blood to help regulate the blood plasma, the glucose blood plasma concentration and so forth."}, {"title": "Glycogen Breakdown .txt", "text": "Now, the enzyme that catalyzes step three is phosphoglucom mutates."}, {"title": "Glycogen Breakdown .txt", "text": "Remember that a mutase basically transfers a group from one location to a different location on that same molecule."}, {"title": "Glycogen Breakdown .txt", "text": "So what phosphorluca mutase actually does is it transfers that phosphoryl group from carbon number one to carbon number six."}, {"title": "Glycogen Breakdown .txt", "text": "Now we begin with glucose one phosphate and we end with glucose six phosphate."}, {"title": "Glycogen Breakdown .txt", "text": "But what we actually don't show in this diagram is that we actually have an intermediate molecule involved and that intermediate molecule is glucose 116 bisphosphate."}, {"title": "Glycogen Breakdown .txt", "text": "So if we examine the active side of this enzyme, phosphogluca mutase, we're going to see a modified serine residue."}, {"title": "Glycogen Breakdown .txt", "text": "And that Serene residue actually plays a catalytic role of catalyzing this reaction."}, {"title": "Glycogen Breakdown .txt", "text": "So inside the active side of this enzyme, we have a serine that has been modified."}, {"title": "Glycogen Breakdown .txt", "text": "We attached a phosphoryl group onto that Serene."}, {"title": "Glycogen Breakdown .txt", "text": "So before this reaction actually begins, that serine contains the phosphoryl group."}, {"title": "Glycogen Breakdown .txt", "text": "And so when this reaction takes place, that phosphoryl group is transferred from the Serene residue onto carbon six of this glucose, forming that glucose one six bisphosphate intermediate."}, {"title": "Glycogen Breakdown .txt", "text": "Now, in the next step of this process, this phosphoryl group is transferred from carbon one onto so from carbon one of the glucose 116 bisphosphate onto that Serene residue."}, {"title": "Glycogen Breakdown .txt", "text": "And what that does is it regenerates the active side of this phosphoglucomutase enzyme and it forms that glucose six phosphate."}, {"title": "Glycogen Breakdown .txt", "text": "So we see that glycogen breakdown."}, {"title": "Glycogen Breakdown .txt", "text": "Glycogen degradation consists of three major steps and involves four major enzymes."}, {"title": "Glycogen Breakdown .txt", "text": "In step one, the entire goal is to release that glucose in the glucose one phosphate form."}, {"title": "Glycogen Breakdown .txt", "text": "In step two, the entire goal is to remodel restructure that glycogen so that the glycogen phosphorlase could actually continue breaking down the glycogen and releasing those glucose one phosphate molecules."}, {"title": "Glycogen Breakdown .txt", "text": "And in step three, the entire goal is to transform all those glucose one phosphate molecules into a form, namely glucose six phosphate."}, {"title": "Glycogen Breakdown .txt", "text": "That can then go on and carry out some type of particular process."}, {"title": "Glycogen Breakdown .txt", "text": "In liver cells, the process is regulating blood glucose levels."}, {"title": "Glycogen Breakdown .txt", "text": "In skeletal muscle cells, the process is generating ATP via glycolysis."}, {"title": "Properties of Enzymes .txt", "text": "The next topic in our study of biochemistry is enzyme."}, {"title": "Properties of Enzymes .txt", "text": "So what exactly is an enzyme?"}, {"title": "Properties of Enzymes .txt", "text": "What's the purpose of enzymes?"}, {"title": "Properties of Enzymes .txt", "text": "And what are some facts that you have to know about enzymes in general?"}, {"title": "Properties of Enzymes .txt", "text": "So this is what we're going to discuss in this lecture."}, {"title": "Properties of Enzymes .txt", "text": "So an enzyme is basically a biological molecule with remarkable capabilities."}, {"title": "Properties of Enzymes .txt", "text": "What they do is they catalyze all of their different types of biological processes and reactions that take place inside our cells."}, {"title": "Properties of Enzymes .txt", "text": "And without the enzymes catalyzing the reactions, cellular processes would essentially hold to a rate that would make life impossible, at least in the way that we know life today."}, {"title": "Properties of Enzymes .txt", "text": "So the first thing you have to know about enzymes is an enzyme is a biological molecule that catalyzes speeds up the rate of reactions."}, {"title": "Properties of Enzymes .txt", "text": "Now, in our discussion on hemorrglobin, we mentioned one important enzyme, namely carbonic anhydrase."}, {"title": "Properties of Enzymes .txt", "text": "And we said that it was carbonic anhydrase that essentially speeds up and allows the conversion of carbon dioxide into its polar form, namely bicarbonate ions."}, {"title": "Properties of Enzymes .txt", "text": "And this is exactly what allows us to actually store the carbon dioxide inside our blood plasma."}, {"title": "Properties of Enzymes .txt", "text": "So carbonic anhydrates essentially hydrates."}, {"title": "Properties of Enzymes .txt", "text": "So it combines carbon dioxide with water to produce carbonic acid."}, {"title": "Properties of Enzymes .txt", "text": "And carbonic acid, being a relatively strong acid, will dissociate into these two polar ions, hydrogen ions and bicarbonate ions."}, {"title": "Properties of Enzymes .txt", "text": "Now, carbonic anhydrates is a very efficient, very effective enzyme, like most enzymes are."}, {"title": "Properties of Enzymes .txt", "text": "In fact, this molecule can convert."}, {"title": "Properties of Enzymes .txt", "text": "The enzyme can transform 1 million of these carbon dioxide molecules every single second."}, {"title": "Properties of Enzymes .txt", "text": "So it increases the rate by 1 million compared to its uncategorized form."}, {"title": "Properties of Enzymes .txt", "text": "So this enzyme basically helps us transform the non polar carbon dioxide that cannot dissolve inside our blood into a form that can be dissolved inside our blood."}, {"title": "Properties of Enzymes .txt", "text": "And that's precisely what allows us to effectively and quickly get rid of the carbon dioxide from the cells and eventually expelled by the lungs of our body."}, {"title": "Properties of Enzymes .txt", "text": "Now, fact number two about enzymes."}, {"title": "Properties of Enzymes .txt", "text": "Enzymes typically transform one form of energy into a much more useful form of energy."}, {"title": "Properties of Enzymes .txt", "text": "And one example is the process of photosynthesis, which takes place in plants."}, {"title": "Properties of Enzymes .txt", "text": "So inside plants, we have a variety of different types of enzymes that essentially transform."}, {"title": "Properties of Enzymes .txt", "text": "They harvest or capture the energy that is stored in electromagnetic radiation that comes from the sun, namely light."}, {"title": "Properties of Enzymes .txt", "text": "So they transform the energy that is stored in light into energy stored in the chemical bonds of glucose and sugar molecules."}, {"title": "Properties of Enzymes .txt", "text": "Now, humans and other animals then eat that glucose, and they themselves use enzymes in the process we're going to discuss eventually the process is glycolysis, Pyruvate decarboxylation, and then the Krebs cycle."}, {"title": "Properties of Enzymes .txt", "text": "So basically, in these processes, we have many different enzymes that essentially catalyze the transformation of the energy stored in the chemical bonds of glucose into the energy that is stored in the proton gradient that exists across the membrane of mitochondria and then the energy stored in that membrane in the electrochemical gradient due to the protons found across the mitochondrial membrane."}, {"title": "Properties of Enzymes .txt", "text": "That energy transformed into energy stored in the bonds of ATP molecules adenosine triphosphates."}, {"title": "Properties of Enzymes .txt", "text": "And we'll discuss that in much more detail eventually."}, {"title": "Properties of Enzymes .txt", "text": "So we see that these enzymes are very, very good at transforming one form of energy that we can't use into a form that we can use, and that is what enzymes do."}, {"title": "Properties of Enzymes .txt", "text": "Number three enzymes typically do not act alone, and they require additional molecules."}, {"title": "Properties of Enzymes .txt", "text": "And these molecules are known as Cofactors."}, {"title": "Properties of Enzymes .txt", "text": "So Cofactors are helping molecules that are needed for the enzymes to actually function effectively and efficiently."}, {"title": "Properties of Enzymes .txt", "text": "So when an enzyme is not bound to its Cofactor, we call the enzyme apoenzyme."}, {"title": "Properties of Enzymes .txt", "text": "But when the Cofactor is bound to the APO enzyme, we call that a hollow enzyme."}, {"title": "Properties of Enzymes .txt", "text": "So the hollow enzyme is simply an enzyme bound to its Cofactor."}, {"title": "Properties of Enzymes .txt", "text": "Now, we have many, many different types of Cofactors, as we'll eventually see."}, {"title": "Properties of Enzymes .txt", "text": "But we can categorize Cofactors into two groups, into two categories."}, {"title": "Properties of Enzymes .txt", "text": "We have metal ions and we also have organic molecules known as coenzymes that are usually formed from vitamins."}, {"title": "Properties of Enzymes .txt", "text": "Now, one example of a metal ion that acts as a cofactor for carbonic and hydrates is the zinc atom."}, {"title": "Properties of Enzymes .txt", "text": "And we'll talk about that in detail in a future electra."}, {"title": "Properties of Enzymes .txt", "text": "Now, coenzymes can bind onto proteins either strongly or weakly."}, {"title": "Properties of Enzymes .txt", "text": "And if we have a coenzyme that is bound very tightly to the enzyme that is known as a prosthetic group number four enzymes are extremely efficient and extremely specific molecules."}, {"title": "Properties of Enzymes .txt", "text": "And what that means is enzymes only bind to specific substrate specific molecules and they carry out either a single reaction or a set of reactions that are closely related to one another."}, {"title": "Properties of Enzymes .txt", "text": "So enzymes bind to specific reactants."}, {"title": "Properties of Enzymes .txt", "text": "We also call substrates and catalyze a single reaction or a set of related reactions."}, {"title": "Properties of Enzymes .txt", "text": "And enzymes are highly efficient and limit the number of unwanted products."}, {"title": "Properties of Enzymes .txt", "text": "So, for example, in the case of carbonic and hydrates, carbonic and hydrates binds the CO2 and the water, and the CO2 is the substrate."}, {"title": "Properties of Enzymes .txt", "text": "Now, CO2 can react with water in many different ways."}, {"title": "Properties of Enzymes .txt", "text": "For example, in this particular case, we saw that we can produce sugar molecules and oxygen molecules."}, {"title": "Properties of Enzymes .txt", "text": "And these are unwanted products, at least in this particular case."}, {"title": "Properties of Enzymes .txt", "text": "So what carbonic and hydrase does is it ensures that we form only a single type of product."}, {"title": "Properties of Enzymes .txt", "text": "We do not form any unwanted products in our reaction."}, {"title": "Properties of Enzymes .txt", "text": "So enzymes are highly specific."}, {"title": "Properties of Enzymes .txt", "text": "Another example of a highly specific enzyme that carries out a set of related reactions is tryptin."}, {"title": "Properties of Enzymes .txt", "text": "So Trypsin is found in our digestive system."}, {"title": "Properties of Enzymes .txt", "text": "It's a digestive enzyme."}, {"title": "Properties of Enzymes .txt", "text": "And what it does is it binds to polypeptides, to proteins that we ingest into our body."}, {"title": "Properties of Enzymes .txt", "text": "And it basically carries out a set of two closely related reactions."}, {"title": "Properties of Enzymes .txt", "text": "In one of the reactions, it basically cleaves peptide bonds on the carboxyl side of lysine."}, {"title": "Properties of Enzymes .txt", "text": "In the other reaction, it binds and cleaves."}, {"title": "Properties of Enzymes .txt", "text": "On the carboxyl side of the arginine amino acid so this trypsin has a single type of has a single type of substrate, namely the polypeptide and it carries out two sets, two types of very similar reactions in one reaction and Cleaves lysine on the carboxyl side in the other reaction cleaves Arginine on the carboxyl side."}, {"title": "Properties of Enzymes .txt", "text": "Now, number five nearly all enzymes are proteins."}, {"title": "Properties of Enzymes .txt", "text": "So long ago we essentially thought that all enzymes were proteins."}, {"title": "Properties of Enzymes .txt", "text": "But now we know that some enzymes are actually RNA molecules."}, {"title": "Properties of Enzymes .txt", "text": "So RNA molecules, certain RNA molecules also have the ability to catalyze reactions as we'll see eventually."}, {"title": "Properties of Enzymes .txt", "text": "And the last thing we're going to mention about enzymes is enzymes are not actually used up or not depleted in chemical reactions."}, {"title": "Properties of Enzymes .txt", "text": "And if enzymes are changed or altered in some way in the reaction at the end of that reaction the enzyme will assume its original shape and original structure."}, {"title": "Properties of Enzymes .txt", "text": "So enzymes are not used up and remain unchanged at the end of the reaction."}, {"title": "Properties of Enzymes .txt", "text": "Now, this is not to say that enzymes during the reaction are unchanged in some way."}, {"title": "Properties of Enzymes .txt", "text": "They might be changed, their structure might be changed."}, {"title": "Properties of Enzymes .txt", "text": "But at the end of the reaction when the enzyme releases the substrate it assumes its original structure and its original shape."}, {"title": "Properties of Enzymes .txt", "text": "So these are the six facts you have to remember about enzymes."}, {"title": "Properties of Enzymes .txt", "text": "Enzymes greatly increase the rate at which reactions take place."}, {"title": "Properties of Enzymes .txt", "text": "Enzymes typically help transform one form of energy into much useful form of energy."}, {"title": "Properties of Enzymes .txt", "text": "Three enzymes do not function alone and they typically do not."}, {"title": "Properties of Enzymes .txt", "text": "And they typically need these helper."}, {"title": "Properties of Enzymes .txt", "text": "Molecules we call cofactors."}, {"title": "Properties of Enzymes .txt", "text": "Number four enzymes are highly specific."}, {"title": "Properties of Enzymes .txt", "text": "They bind specific substrates and carry out only a single reaction or a set of reactions that are similar as we saw in the case of trypsin number five nearly all enzymes are proteins."}, {"title": "Properties of Enzymes .txt", "text": "Some enzymes are RNA molecules."}, {"title": "Properties of Enzymes .txt", "text": "And number six enzymes are not depleted."}, {"title": "Properties of Enzymes .txt", "text": "They are not changed at the end of the reaction."}, {"title": "Properties of Enzymes .txt", "text": "They remain exactly the same."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's continue the process of analyzing pedigrees."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So so far we discussed pedigrees that describe diseases that are sex link recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We also looked at those pedigrees that describe autosomal recessive traits."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now let's take a look at the following pedigree that will describe autosomal dominant traits."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So what we want to basically show in this lecture is that whatever the disease is that is described by this pedigree, it cannot be sex linked dominant and it cannot be sex link recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And we want to show that this could be autosomal dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So show that a disease described by the following pedigree cannot be sex link recessive and sex linked dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So as always, to show that it's not something, we have to begin by assuming that it is that."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's begin by assuming that it is sex length."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Let's say recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So it's sex length recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And what that basically means is we have an x uppercase B that basically describes the normal gene, and then we have the x lowercase B that describes the gene for that disease."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So if this were true, if it is sex link recessive, then what that means is this female individual must be x lowercase b, x lowercase B and this individual, because it's a male and it's normal, that means we must have x uppercase B and y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's actually carry out the following crossing process between these two individuals and let's discuss what the distribution is of the genotypes of the offspring produce."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And let's see if that's consistent with information given to us in this pedigree."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So remember, this is generation one, these are the individuals of generation two, and these are the individuals of generation three."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have, this individual produces either this sperm cell or this sperm cell."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This produces only one type of xcel, x lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's continue this punitive square."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we basically have x uppercase b, x lowercase b."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have x uppercase b, x lowercase b."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have x uppercase by, x uppercase by."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now notice what this punning square is telling us."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "It tells us that 100% of the offspring that are produced, the male offspring, so this one and this one must actually exhibit that particular disease phenotype, because we have x lowercase by and x lowercase by."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now that is consistent with this individual because this individual must be x lowercase by to actually display that disease phenotype."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "But this individual does not display that phenotype, it is male."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So that means it must be x uppercase by."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And this genotype cannot exist if we cross these two individuals as shown in the following pundit square."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so what that means is this pedigree cannot describe a disease that is sex link recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So it can't be sex link recessive as a result of this inconsistency between the pedigree analysis and the pun and square analysis."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's continue and let's move on to the sex length dominant and let's show that this cannot be sex length dominant, so it can't be this."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's put an X over A."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "What about B?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now let's assume that it's sex linked dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Can it be sex linked dominant?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Well, if it's sex linked dominant, what that means is this individual, so this individual will have the disease, will have the phenotype for that disease, this individual will have the phenotype for that disease."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And it also means that this individual will also have the disease for that particular phenotype for that particular disease, all other individuals."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have X lowercase by and X lowercase BX lowercase B, these individuals will be normal."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So with this in mind, let's fill out the following pedigree."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have a male that is normal, and the only time that a male is normal is this, right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have X lowercase B and Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And here we also have a normal male."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this must be X lowercase by."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This by the same reasoning, must be X lowercase by, and this must be X lowercase B Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This must be X lowercase B and Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "The only time that a female is normal is when they have this particular genotype."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have a normal female here, that means we have X lowercase by, x lowercase by."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This is a normal female as well."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This is a normal female and this is a normal female."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And then we have the other one."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So here we have a male that carries, that, has that phenotype or that disease."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So that means it's uppercase B and Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This one must also be X uppercase B and Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This must be X uppercase B y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now this individual and this individual can either be this trade or this trade because we have two different possibilities."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's actually carry out the pudding square to see if these are possible right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So the choices here are either X uppercase VX uppercase B, or we have X uppercase VX lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And here the choices are also X uppercase VX uppercase B, or X uppercase VX lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's move on to this one over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we're crossing this one with this one."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Let's see what we produce."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's assume that first, let's assume that the individual is this right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "If the individual was this, then we have the Xcel."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So one type of Xcel, which is that, and then we have this type of sperm cell or this one from the male parent."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so if we carry out this crossing process, we get X uppercase B, x lowercase B, x uppercase B, x lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And actually we don't have to do well, yeah, let's continue, let's finish this up."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So X-B-Y-X-B-Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So from this information, what this tells us is every single individual produced in this case must carry that particular phenotype for that disease."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And we know that is not consistent with the information that is given to us because these two individuals don't carry that particular phenotype as described by this pun and square."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we know it cannot be this genotype here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So, okay, now we know that."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Let's continue into the next one."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Let's suppose the genotype is in fact this one right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So now let's carry out the pun and square for that."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have X uppercase B, we have X lowercase B, and we have X lowercase by for our sperm cells here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have X uppercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have x lowercase b, x lowercase b, x lowercase b, x uppercase B-Y-X lowercase b y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay, so this actually makes sense because we have a 25 chance that a 25% chance that this individual is formed, which we have right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have a 25% chance that this individual is formed and a 25% chance that this individual is formed."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And that's consistent with these individuals in the following pedigree."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So that works as long as this is this individual right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay, now let's move on to this case."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We have x uppercase B-Y-X lowercase b. X lowercase b."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "If we carry out the punning square, we'll see that these individuals do in fact work."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So because X B can be donated by one parent, XB can be donated by the other parent."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we can in fact form this individual."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And likewise, if the Y is donated by the male parent, XB is donated by the other one, we form this individual right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So to determine if it is sex link dominant, we have to show that all these actually make sense."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we're crossing this individual with this individual."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So what do we get?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Well, we have X uppercase B and Y."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So from this individual we have X lowercase BX, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so when we cross, we get X uppercase B, lowercase BX, uppercase BX, lowercase B, and right away we should see that that's a problem."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And that's a problem because we form this female right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So according to the pedigree, we have this female individual that contains both lowercase B's on both of those X chromosomes."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "But in this particular Punnett square, we see that is impossible because 100% of those females must be heterozygous and so they must express that disease, that phenotype, and that is inconsistent with this particular information."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so it cannot be sex link dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So he basically answered our question."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now we want to show that it could be autosomal dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's remove all these, all the scrap work that we did to basically show that it wasn't sex linked."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And now we're going to follow the same exact step to show that it could be autosomal dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So I guess we can hopefully you wrote that information down or you can rewind it if you like."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay, so we want to now show that it is possible."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This pedigree can describe autosomal dominance."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And what that means is, so uppercase B, uppercase B or uppercase B, lower case B will basically describe that disease gene or disease."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "It will describe, I should say the disease phenotype."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And the only time we don't have phenotype for the disease is lowercase B, lower case B, okay?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we don't have a disease here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this must be lowercase B, lower case B, this must be lowercase B, lower case B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This must be lowercase b. Lowercase b?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So every one that appears normal basically is lowercase B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this one is lowercase B, and this one is lowercase B as well."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Now all the ones that have the Z's are either this or that."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this can be either uppercase B, uppercase B, or it can be uppercase B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This can be uppercase B, uppercase B or uppercase B. Lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "This one is uppercase B, uppercase B or lowercase B, lower case B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And the same thing with these two."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Okay, so these are kind of the possibilities of our genotype."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's actually pick one and see that they are consistent."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's begin with these two phenotypes here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So when we cross BB with BB, the only type of phenotype that we form is obviously lowercase B, lowercase B, and that is absolutely consistent with these two individuals here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Both of the individuals don't show that disease phenotype and so they're lowercase B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this actually works out."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "What about this case?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Well, notice that this individual cannot be uppercase B, uppercase B, because if it were uppercase B uppercase B, what that means is these two individuals would be heterozygous and so that is not true."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "What about if it's this?"}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "Well if it's this, then we have BB, we have lowercase B, lowercase B, and so what this would produce is it would produce 50% heterozygous, so 50% heterozygous and 50% homozygous recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And that is consistent with our results."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "We see that the only time this works out is if this individual's upper case B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "In that case this works out, this works out and this also works out."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And this must be this individual, it can't be that homozygous dominant."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So now we have uppercase B, lowercase B that is crossed with lowercase B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let's say uppercase B. Uppercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "No, that is not true."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So now he wants to basically show this one."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have the male individual, uppercase B, lowercase B, those are the sperm cells and these are the X cells, lowercase B, lowercase B."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so we have the following mating process take place and we have heterozygous and we have homozygous recessive."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "And so these are the possibilities of these offspring right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So we have BB, which is consistent with this one and is consistent with this one right over here."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So this should have been BB and the other case is this one, which is once again consistent with these cases."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "As long as we assume that it can't be this, it can't be this, and it can't be this."}, {"title": "Pedigree Analysis for Autosomal Dominant Traits .txt", "text": "So let me just."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "The next big topic that we're going to focus on will be glucose metabolism."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And in this lecture, I'd like to basically introduce what this concept actually is, what it involves and what it attempts to actually achieve."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So let's begin by describing, generally speaking, what glucose metabolism is."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So glucose metabolism is the process by which our body, ourselves, basically try to transform the energy that is stored in the chemical bonds of the sugar molecule, the glucose, into the energy that is stored in the bonds of ATP molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Because ultimately it's not the glucose molecules, but the ATP molecules that are used by the cells to carry out many different types of processes."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "For instance, creating electrochemical gradients by using membrane pumps or using ATP to basically contract muscle."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So contraction of muscle, it can be skeleton muscle or cardiac muscle or smooth muscle, uses ATP molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, what types of processes actually make up glucose metabolism?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So the first process that we're going to look at will be glycolysis."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And glycolysis is the process by which the glucose molecules present in a cytoplasm are broken down into Pyruvate molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So two Pyruvate molecules are net result of two ATP molecules which can be used by the cell to carry out some type of process as well as NADH molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And we'll discuss what those are in a future lecture."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "But ultimately, glycolysis produces these byproduct molecules we call pyruvates."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, glycolysis is an anaerobic process and what that means is it does not require oxygen to actually take place."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So whether or not we have oxygen doesn't actually matter because glycolysis doesn't actually use oxygen."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, in the absence of oxygen under anaerobic conditions, when we don't have plenty of oxygen present inside the cell, these Pyruvate molecules will undergo a process known as fermentation."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, some cells in nature undergo alcohol fermentation and that produces ethanol from the Pyruvate."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Other organisms, for instance, cells of our body undergo lactic acid fermentation and that transforms the Pyruvate into lactic acid or the conjugate base of lactic acid is lactate."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So inside our body, when the cells of our body don't have enough oxygen, they will take the pyruvates and transform them into lactic acid molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, what happens if there is oxygen present in the cells of our body?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Well, in the case of aerobic conditions, when we have oxygen present in the cell, the Pyruvate molecules will move into the mitochondria of the cell."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so this is our mitochondria."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And inside the mitochondria, we have processes such as Pyruvate decarboxylation as well as the citric acid cycle and the electron transport chain found on the inner membrane of that mitochondria actually uses those oxygen molecules to ultimately transform the Pyruvate into carbon dioxide molecules as well as ATP molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "In fact, the majority of ATP molecules produced by our cells are formed in the process that takes place inside the mitochondria."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, this is known as aerobic cellular respiration."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "An aerobic cellular respiration includes not only the processes that take place in the mitochondria, but also actually includes glycolysis itself."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "But glycolysis is itself an anaerobic process."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "This takes place regardless of whether or not we actually have o, two molecules present in our cell."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, let's suppose the cell has plenty of ATP molecules to actually go around and so it doesn't actually want to produce any more ATP molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "What happens in this situation?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So in this situation, because we don't actually want to break down the glucose molecules, we want to store the glucose molecules in a form that basically will not be broken down."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so we take the individual glucose molecules and we transform them into their polysaccharide form we call glycogen."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, what about these pyruvate molecules and these lactate molecules?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "What happens to them in the case that we have many, many ATP inside our body?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So in this case, these pyruvate molecules or lactic acid molecules are transformed back into glucose and then the glucose is stored in a form we call glycogen."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And the process by which we transform these pyruvates and lactic acid molecules back into glucose is known as gluconeogenesis."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So glucose means glucose, neo means new molecules, and genesis means the formation."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So the formation of these new glucose molecules by using the pyruvate or the lactic acid molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now we see that glycolysis breaks down the glucose, but gluconeogenesis uses these byproducts to reform that glucose molecule."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So one goes this way and the other one goes in reverse."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So if the cell needs to break down glucose and produce ATP molecules, then what it does is basically shuts off gluconeogenesis."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "But if the cell has plenty amounts of ATP molecules and it doesn't actually want to break down the glucose, then gluconeogenesis is more likely to actually take place."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "In fact, we see that glycolysis and gluconeogenesis do not actually take place at the same exact moment in time."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So when one process is activated, the other process is usually inhibited and vice versa."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So now we know the general idea of what glucose metabolism actually is."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "But how does that glucose actually make its way into the cells of our body?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Or more generally, how does the glucose actually make its way into our body in the first place?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Well, via the ingestion of food."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So if we eat a meal that is rich in carbohydrates, that's how the glucose actually makes its way into our body."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So there are two types of sugar molecules carbohydrates that we typically ingest."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So carbohydrates polysaccharides that come from plants, and carbohydrates polysaccharides that come from animals."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, for instance, if we eat a piece of chicken, that chicken not only has protein and fat, it also contains polysaccharides carbohydrates store in a form we call glycogen, which is the same form that we mentioned just a moment ago."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, if we ingest things like pasta or bread or cereal, these are actually polysaccharides that come from plants."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so what we're ingesting is starch."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And there are two types of starch."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So we have amylose and amylopectin."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So one of them is basically a linear helical structure that's the amylose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And the amylopectin is like the glycogen, actually a branched form of starch."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, we see that these polysaccharides are inherently too large to actually fit into our cells, and they're too large to actually move around and transport in the blood plasma."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so before these large polysaccharides actually make their way into the blood plasma of our body and into our cells, these carbohydrates must be broken down into smaller components."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "In fact, they must be broken down into these individual glucose molecules before the cells can actually uptake those glucose molecules and store the glucose as glycogen, or break down the glucose to form ATP molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So the question is, what are these enzymes, digestive enzymes, proteases, that basically break down these carbohydrates into their individual monomeric form?"}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Well, we have many different types of enzymes, and I've listed six enzymes, actually seven enzymes on the board."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And let's begin with a salivary alpha amylase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So salivary simply means it exists in a saliva."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So when we eat food and where we're chewing the food, that saliva actually contains a specific type of digestive enzyme and proteins known as alpha amylase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And what the alpha amylase does is it begins to cleave alpha one four glycocity linkages that exist in the starch as well as glycogen."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So this begins the cleavage of alpha one four glycocity linkages in the mouth, and this breaks it down to smaller polysaccharides and oligosaccharides."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, from the mouth, it moves via the esophagus, eventually makes its way into our stomach."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, in the stomach, nothing actually breaks down."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So what that means is the actual glycocitic linkages, the bonds don't break down in the stomach, but once it makes its way into the small intestine, that's when the rest of that digestion actually takes place, because the pancreas produces a specific type of carbohydrate digestive enzyme known as pancreatic alpha amylase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And this is much more potent and much more powerful than the salivary alpha amylase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So the pancreatic alpha amylase also is able to break down those same alpha one four glycocytic linkages, but this actually breaks down the polysaccharide into either disaccharides or trisaccharides."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So in the case of starch or glycogen, we basically break down these individual polysaccharides into maltose molecules, which are disaccharides."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "That consists of two glucose or trisaccharides, that consists of three glucose known as maltotrios."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, the actual cells on the epithelium of the small intestine actually contain these secretory vesicles, these granules that themselves contain enzymes."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so these are the enzymes that they basically have."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So we have Maltase, we have alpha glucosedase, we have alpha dextrinase, we have sucrase and lactase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And all of these enzymes are basically specific to the type of molecules and type of bonds they actually cleave."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So, for instance, in the case of Maltase, maltase is released by the cells on the brush border, and this enzyme basically breaks down the Maltose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So here we said the pancreatic alpha amylase breaks down the ligosaccharides and polysaccharides that could not be broken down by the salivary alpha amylase into Maltose or Maltotria."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And these Maltose molecules are broken down by these maltase enzymes at the brush border of our epithelium of the small intestine."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And once the Maltose is broken down into the glucose constituents, then the glucose can actually be taken by the cell by using a special type of glucose transporter, as we'll discuss in a future lecture."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, we also mentioned the meltotrios, and we have another type of enzyme, a different enzyme known as alpha glucose, a dase, that basically breaks down the meltotrials into the three constituent glucose molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And only then can the glucose molecules can actually make their way into the cell of our body."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Then we also have alpha dextronose or dextrinase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, in the case of alpha dextronate, so let's go back to starch and glycogen."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So if we discuss so if we ingest the amylopectin version of starch or glycogen, we know that these two types of polysaccharides not only have the alpha one four glycocity bonds, they also have the alpha one six glycocytic bonds."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And the alpha amylase found in our mouth and the alpha amylase found in our small intestine that is produced by the pancreas, these cannot break down those alpha one six linkages."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And that's where this alpha dextronase actually comes into play."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So the alpha dextronase basically breaks down the limited xray, which is basically those oligosaccharides that contain the alpha one six bonds which were not broken down by either of these two types of enzymes."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so it's this one that breaks down these dextrin molecules, breaks down those alpha one six linkages, breaks the molecules into their individual constituent glucose molecules, and then the glucose is ingested into our cell."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, glucose molecules are not the only sugar molecules that we actually ingest into our body."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "We can also ingest, for instance, galactase we can ingest or galactose we can ingest fructose and so forth."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so we have many other examples of enzymes that are used to break down these specific types of glycosytic bonds."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So we have Succeed, which basically breaks down the glycocitic bond between fructose and sugar and fructose and glucose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So when fructose and glucose combined, they form sucrose, and sucrase breaks down sucrose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So sucrose is essentially a mobile form of a carbohydrate sugar molecule found inside plants."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So when we eat plants, we can also actually eat these sucrose molecules."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And so Succeed is responsible for breaking down sucrose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Now, we also have lactase."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So lactase is essentially a digestive enzyme that breaks down lactose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And lactose is a disaccharide that consists of glucose and galactose."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And lactose we obtain from dairy products, from milk."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So if we drink milk inside milk, we'll find these lactose disaccharides."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "And it's the lactose that breaks down these disaccharides into their individual monomers."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "So once all these different types of enzymes and many more, they basically break down all the different types of carbohydrates inside the small intestine."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "Only then can these actually make their way into the cytoplasm of our cells and into the blood via this process of transport."}, {"title": "Introduction to Glucose Metabolism .txt", "text": "By using these special types of membrane transport protein molecules."}, {"title": "Sanger Sequencing of DNA .txt", "text": "In biochemistry, it's very useful to be able to determine what the sequence of nucleotides in some DNA molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Because if we know what the sequence of nucleotides is, that will give us information about how gene expression takes place and what types of proteins are produced."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, what's the process by which we can actually sequence our DNA molecule?"}, {"title": "Sanger Sequencing of DNA .txt", "text": "Well, the process is known as Sanger dioxine method, or simply Sanger DNA sequencing."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, before we discuss the steps of this process, let's discuss an important molecule used in this process and let's see why it is actually used."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So the molecule is this molecule here."}, {"title": "Sanger Sequencing of DNA .txt", "text": "It's called two prime, three prime dioxy nucleuside triphosphate or simply Ddntp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, this molecule is almost identical to a normal deoxy nucleuside triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "The only difference is the sugar component contains a three prime carbon that does not contain a hydroxyl group."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So remember, in a normal deoxy nucleus triphosphate, the presence of the hydroxyl group on the three prime carbon allows DNA polymerase to actually form a phosphodiastor bond with the next nucleotide in line."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So in the process of DNA synthesis, when we're replicating a DNA strand, the DNA polymerase needs this hydroxyl group to be present on the three prime carbon to actually form the phosphodiaester bond."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And if that hydroxyl group is not present, as in this case, it will not be able to form that phospholdiaester bond."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so DNA replication would essentially stop."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so what this DD NTP molecule is used for in this method is to basically stop the process of DNA replication."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And we'll see why that's important towards the end of this lecture."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So let's move on to these four steps."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So, in step one of the standard DNA sequencing, we have to actually obtain that DNA molecule that we want to sequence."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So let's suppose we have a double stranded DNA molecule as shown on the board."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, the second step of this process will involve DNA replication."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And remember, DNA replication only takes place if the two strands of DNA have separated."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So, in step one, what we essentially want to do is we want to denature the double helix structure of the DNA."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We want to separate the two strands of DNA, and the way that we're going to separate them is by adding sodium hydroxide."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So remember, a base or an acid, if we mix the DNA in either a basic or acidic solution, in this case a basic, the base will essentially ionize the bases of our DNA molecule and that will disrupt and break the hydrogen bonds."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so if we take the double strand DNA molecule and we add sodium hydroxide, we produce these two individual strands of DNA."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, one of these single strands of DNA can actually be chosen for the sequencing process."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, it doesn't matter which one of these DNA strands we choose, because if we choose this one, for example, then once we determine the sequence of this DNA strand, we can easily determine what the sequence of the other strand is because these two strands are complementary."}, {"title": "Sanger Sequencing of DNA .txt", "text": "They have complementary base pairing."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So the G bases with our C and the A bases with our T. So once we know this sequence, we know what the other sequence is simply by the base parent process."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So let's choose this single stranded DNA molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We isolate it, we place it into our beaker that contains only this molecule here."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And then we move on to step number two."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And in step number two, we want to basically replicate this DNA molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so what that means is we need three different things."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We need a DNA primer, we need DNA polymerase and we need the building blocks, the four types of normal deoxy nucleotide triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So in step two, the solution containing the single strand of DNA, this one here is mixed with number one or a a labeled radioactively labeled DNA primer."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we need the DNA primer basically for that DNA polymerase to actually work."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Because remember, the DNA polymerase will only initiate replication if the primer is present."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And what that means is we have to know what this initial sequence is on that DNA molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Because to build the DNA primer, we have to know what the complementary sequence is to this group here."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So if this is ACG, then we have to build a primer that contains a sequence TGC."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so we can build that in a laboratory."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And we also radioactively label that DNA primer because that will basically allow us to pinpoint exactly where that molecule is when we undergo the process of gel electrophoresis."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we add a label DNA primer that is complementary to the three end of that single stranded DNA molecule that we want to sequence."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So this is the three end of that DNA molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And remember, DNA polymerase reads from three to five and it builds from five to three."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And that's why this is the end that we actually want to build the DNA primer for."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we add the DNA polymerase and we also add the four types of deoxy nucleus diet triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we add dATP dGTP dCTP and TTP."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And finally, the important component in the standard died oxy method is a tiny amount of one of the four types of Ddntp molecules."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Remember, we have four different types that can exist and that's because we have four different types of bases."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So this base could be Adamine, it could be Guanine, it could be Cytosine, or it could be Thymine."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so we have four different types of Ggntp molecules."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And in step two, we have to add a tiny amount, about 1% with respect to the other nucleoside triphosphates of a specific dig deoxy nucleuside triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we don't add all four types, we only add one type."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, why is that important?"}, {"title": "Sanger Sequencing of DNA .txt", "text": "Well, let's see what that actually does by examining the following diagram."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we essentially take this DNA molecule, the single strand, and we mix it with these four components."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have the radioactively labeled DNA primer that is complementary to the three end."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We have the four types of deoxy nucleuside triphosphates."}, {"title": "Sanger Sequencing of DNA .txt", "text": "These four ones shown here, we have the DNA polymerase, and we have a very small amount."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So let's say about 1% of the Ddatp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So that's the specific Ddntp that we're going to choose for this specific experiment, for that specific beaker."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, what will begin to happen?"}, {"title": "Sanger Sequencing of DNA .txt", "text": "Well, what will happen is the complementary DNA primer will hybridize itself to this section here as shown in the following diagram."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So this is our DNA primer."}, {"title": "Sanger Sequencing of DNA .txt", "text": "It will form these base pairs as shown in the following diagram."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So T base pairs with a G, base pairs with C, and C base pairs with G. And then the DNA polymerase will bind onto the primer and it will use the hydroxyl group on this cytosine to basically form that first phosphodiaester bond."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so it will take a thymine."}, {"title": "Sanger Sequencing of DNA .txt", "text": "It will take this molecule here to basically form the first base."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Then it will move on onto the second base, which is a T, and that will basically form an A."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, we have two types of A's that we can use."}, {"title": "Sanger Sequencing of DNA .txt", "text": "One of them is the normal deoxy adenosine triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "The other one is a dioxy adenosine triphosphate."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the dioxia adenosine triphosphate does not contain a hydroxyl group on the third prime carbon."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And what that means is if that DNA polymerase actually uses the Ddatp to place this base, it will not be able to continue that DNA replication process because that molecule does not have the hydroxyl group that is needed to produce the phosphor diester bond with the next base."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so if this A comes from the Ddatp, this process will end and this will be the molecule that we will synthesize."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And this is why we have fragment number one, molecule number one."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, because we only have 1% of this Ddatp, this DNA polymerase will only sometimes use the Ddatp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Usually it's going to use the normal dATP molecule."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And if it uses the normal dATP that contains the hydroxyl, then it will continue synthesizing those fossil diester bonds and so we can produce fragment number two."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So if this was normal, then it will continue."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So the DNA polymerase would add the thymine, then the guanine, then the cytosine, then the thiamine."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And now it comes to a T. So that means there is once again the possibility for an A."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the A can either come from this normal dATP or the abnormal Ddatp that lacks the hydroxyl."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And if it's this group here, then once again we will stop the synthesis and this fragment will be produced."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, if it wasn't that molecule, then we would add the next."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So if the A was normal, the normal dATP, it would produce the next nucleotide in line."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so the next one is also an A because this is a T. So once again, this is an A."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And now we have a possibility between this one or this one."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And let's suppose it's once again the ggatp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so it will stop it once again after this because it lacks that hydroxyl."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so at the end in our mixture, in beaker number one, after we conduct step number two with the DD ATP, these are the other three fragments that will be present inside our beaker number one."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now we take that beaker number one and we place it into SDS page."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So SDS polyacrylamide gel electrophoresis."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So this is our setup, and we have four different wells."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, well, number one, we label as the Ddatp, because this is step two, where we use the DD ATP."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We take the mixture and we place it into well number one, lane number one."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And we allow these to separate based on their masses."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Remember, in gel electrophoresis, the smaller our molecule is, the farther down it will move along that gel."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So if this is molecule one, Two and Three, this band will be for molecule One."}, {"title": "Sanger Sequencing of DNA .txt", "text": "This band will be for molecule Two."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And this band, the highest up, will be the largest molecule, molecule Three."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, we continue the same process three more times."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the second time around, we use a different Dgntp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "The third time around, we use yet another ggntp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the final fourth time, we use the final Dgntp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So let's suppose the second time around, instead of using the DG ATP, we used Ddgtp."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so instead of having the fragments where we stopped on the A's, we're going to have the fragments where we stop on the g's."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so, because we only have two CS, so this C doesn't count because it's part of the primer."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have one C and we have a second C. So the complementary would have a g here and a g here."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we only form two fragments."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And this lane would contain two bands because we only contain two fragments with different sizes."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Then we repeat the process."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Instead of using this one, we use DDCT."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So C, that means we have to count up the GS here, not including this one, because it's part of the primer."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have one g, we have two GS."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And that means we're going to have two complementary CS."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we're going to have two different fragments once again, one, two."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And finally, if we use this one, we have to look for our adenine."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have to look for the adenine."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have one, two, three and four."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We should have four fragments."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And that's exactly what we get in this particular case."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So basically, in step three, we take step two and we repeat that same step three different times with the other three Ddntps."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And in step four, once the four reactions are completed, we run gel electrophoresis."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Each reaction mixture is placed into a lane."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So lane one, lane two, lane three, lane four."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the results are then transferred onto a polymer sheet."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And then we use X ray order radiography to basically determine exactly where those radioactively labeled fragments actually were."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And so this is the diagram that we get."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Now, how can we use this to actually determine what the sequence of that initial DNA molecule is?"}, {"title": "Sanger Sequencing of DNA .txt", "text": "Well, we know what the first three nucleotides are because that's the primer."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we have T, G and C. So the question is, what are these remaining nucleotides here?"}, {"title": "Sanger Sequencing of DNA .txt", "text": "Well, let's try to use the following setup to base determine what the sequence is."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So we know that the farther down along our page, the the smaller our fragment is and the closer the nucleotide sequence is to the beginning."}, {"title": "Sanger Sequencing of DNA .txt", "text": "And the fragment all the way at the bottom basically describes this right over here."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So that means the first nucleotide following the primer is the one lowest at the bottom."}, {"title": "Sanger Sequencing of DNA .txt", "text": "So this and according to this graph, according to this setup, the lowest one at the bottom corresponds to a T. So this one is a T. The next one is we have an A."}, {"title": "Sanger Sequencing of DNA .txt", "text": "The next one is so let's make it a little bit bigger."}, {"title": "Sanger Sequencing of DNA .txt", "text": "We have a T. We have an A."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Then we have a T. Next we have, next we have a C. Next we have a T. Then we have two A's, one and two."}, {"title": "Sanger Sequencing of DNA .txt", "text": "Then we have a T, then we have a G, and then we have a C. And so this is the."}]